1887

Chapter 42 : Influenza Virus

Authors: Frederick G. Hayden, Peter Palese
Content Type: Reference
Publication Year: 2009

Category: Viruses and Viral Pathogenesis

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Preview Magnify
Zoom in
Zoomout

Influenza Virus, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815981/9781555814250_Chap42-1.gif /docserver/preview/fulltext/10.1128/9781555815981/9781555814250_Chap42-2.gif

Abstract:

Homologous recombination between corresponding RNA segments of different influenza viruses has not been observed, in contrast to the high frequency of recombination observed among the genomes of positive-sense RNA viruses, like polioviruses, and retroviruses. The virulence and host range of influenza viruses relate to the surface glycoproteins, as well as to other viral proteins. Zoonotic influenza virus infections are also spread by these routes through direct and indirect exposures and perhaps rarely by gastrointestinal infection. Influenza virus RNA is readily detected on fomites, and virus retains infectiousness longer on hard, nonporous surfaces, in low humidity, and at cooler temperatures, but the importance of transmission via fomites is unclear. Pathogenicity and cell tropism of influenza viruses relate in part to the hemagglutinin (HA) cleavability by particular host cell enzymes. Serine proteases, presumably derived from host epithelial cells, cleave the HA precursor molecule into HA1 and HA2 to render human influenza viruses infectious. Currently, use of inactivated influenza vaccine is the most important measure for reducing influenza virus-related morbidity and mortality. Drug recipients may experience subclinical infection, which usually confers protection against infection by the same strain. As antiviral chemoprophylaxis does not interfere with the immune response to inactivated vaccine, they can be administered concurrently. However, concurrent use of any anti-influenza antiviral drug might interfere with the immunogenicity of live attenuated influenza virus vaccines (LAIV).

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42

Key Concept Ranking

Influenza A virus Subtype H5N1
0.46046156
0.46046156
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Influenza Virus
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815981.ch42-1,webId=/content/author/10.1128/9781555815981.ch42-1,properties={foaf_givenname=Frederick G., foaf_name=Frederick G. Hayden, foaf_surname=Hayden}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815981.ch42-2,webId=/content/author/10.1128/9781555815981.ch42-2,properties={foaf_givenname=Peter, foaf_name=Peter Palese, foaf_surname=Palese}]]
Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
/content/10.1128/9781555815981.ch42.ch42fig01
FIGURE 1
Circulation of human influenza A, B, and C viruses. Solid lines indicate that strains have been isolated and characterized. Three different influenza A virus HA subtypes (H1, H2, and H3) and two NA subtypes (N1 and N2) were identified in humans during the 20th century. The RNA genome of the extinct pandemic 1918 virus has been sequenced from RNA fragments in formalin-fixed and frozen tissue samples from 1918 victims following RT-PCR ( ). The virus was then reconstructed in the laboratory by reverse genetics (solid square) ( ).
10.1128/9781555815981/f0944-01_thmb.gif
10.1128/9781555815981/f0944-01.gif
Image of FIGURE 1
FIGURE 1

Circulation of human influenza A, B, and C viruses. Solid lines indicate that strains have been isolated and characterized. Three different influenza A virus HA subtypes (H1, H2, and H3) and two NA subtypes (N1 and N2) were identified in humans during the 20th century. The RNA genome of the extinct pandemic 1918 virus has been sequenced from RNA fragments in formalin-fixed and frozen tissue samples from 1918 victims following RT-PCR ( ). The virus was then reconstructed in the laboratory by reverse genetics (solid square) ( ).

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555815981.ch42.ch42fig02
FIGURE 2
(A) Schematic diagram of an influenza A virus. HA, NA, and M2 are transmembrane proteins anchored in the lipid membrane of the virus. Inside the lipid membrane is a layer of the M1 protein. The RNP core consists of the different RNA segments which are covered by NP molecules. In addition, they carry an RNA-dependent RNA polymerase complex (P proteins). The RNA segments possess a panhandle-fork-corkscrew structure which appears to be stabilized by base pairing between the 3′ and 5′ ends of the RNAs. NEP is also part of the viral core structure. (B) Schematic depiction of influenza virus HA. Antigenic changes cluster into five highly variable regions (A to E) surrounding the receptor-binding pocket. The latter is too small to allow ingress of antibody and remains conserved. See Color Plate 25 depicting the interaction of neutralizing antibody with HA. (Panel B courtesy of Robert Webster, St. Jude Children’s Hospital, Memphis, TN.)
10.1128/9781555815981/f0945-01_thmb.gif
10.1128/9781555815981/f0945-01.gif
Image of FIGURE 2
FIGURE 2

(A) Schematic diagram of an influenza A virus. HA, NA, and M2 are transmembrane proteins anchored in the lipid membrane of the virus. Inside the lipid membrane is a layer of the M1 protein. The RNP core consists of the different RNA segments which are covered by NP molecules. In addition, they carry an RNA-dependent RNA polymerase complex (P proteins). The RNA segments possess a panhandle-fork-corkscrew structure which appears to be stabilized by base pairing between the 3′ and 5′ ends of the RNAs. NEP is also part of the viral core structure. (B) Schematic depiction of influenza virus HA. Antigenic changes cluster into five highly variable regions (A to E) surrounding the receptor-binding pocket. The latter is too small to allow ingress of antibody and remains conserved. See Color Plate 25 depicting the interaction of neutralizing antibody with HA. (Panel B courtesy of Robert Webster, St. Jude Children’s Hospital, Memphis, TN.)

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555815981.ch42.ch42fig03
FIGURE 3
(A) Genetic map of influenza A/PR/8/34 (H1N1) virus. Purified RNAs were separated on a polyacrylamide gel; assignment of genes coding for one or two viral proteins is indicated. (B) Plasmid-only rescue of infectious influenza virus. Twelve plasmids are introduced into mammalian cells: four plasmids lead to expression of the viral proteins required for viral RNA replication (PA, PB1, PB2, and NP), and eight plasmids express precise copies of the eight viral RNA segments (PA, PB1, PB2, HA, NP, NA, M, and NS). The resulting viral RNAs are replicated and transcribed by the reconstituted influenza virus RNA-dependent RNA polymerase. Recombinant infectious influenza virus is generated 48 to 72 h after transfection of cells ( ). Recently, several improvements of the plasmid-only rescue for influenza A viruses have been introduced ( ). Also, reverse-genetics systems for influenza B and C viruses have been successfully developed ( ).
10.1128/9781555815981/f0947-01_thmb.gif
10.1128/9781555815981/f0947-01.gif
Image of FIGURE 3
FIGURE 3

(A) Genetic map of influenza A/PR/8/34 (H1N1) virus. Purified RNAs were separated on a polyacrylamide gel; assignment of genes coding for one or two viral proteins is indicated. (B) Plasmid-only rescue of infectious influenza virus. Twelve plasmids are introduced into mammalian cells: four plasmids lead to expression of the viral proteins required for viral RNA replication (PA, PB1, PB2, and NP), and eight plasmids express precise copies of the eight viral RNA segments (PA, PB1, PB2, HA, NP, NA, M, and NS). The resulting viral RNAs are replicated and transcribed by the reconstituted influenza virus RNA-dependent RNA polymerase. Recombinant infectious influenza virus is generated 48 to 72 h after transfection of cells ( ). Recently, several improvements of the plasmid-only rescue for influenza A viruses have been introduced ( ). Also, reverse-genetics systems for influenza B and C viruses have been successfully developed ( ).

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555815981.ch42.ch42fig04
FIGURE 4
Reassortment of influenza A viruses leading to a new pandemic strain. Coinfection of the same cell with a human H2N2 (thin lines) virus and an animal (avian) strain with an H3 HA (thick lines) results in reassortment. The H3N2 virus responsible for the pandemic in 1968 is postulated to derive its PB1 and H3 genes (thick lines) from the animal strain and its remaining six RNAs, including the N2 gene, from the H2N2 parent (thin lines) ( ).
10.1128/9781555815981/f0948-01_thmb.gif
10.1128/9781555815981/f0948-01.gif
Image of FIGURE 4
FIGURE 4

Reassortment of influenza A viruses leading to a new pandemic strain. Coinfection of the same cell with a human H2N2 (thin lines) virus and an animal (avian) strain with an H3 HA (thick lines) results in reassortment. The H3N2 virus responsible for the pandemic in 1968 is postulated to derive its PB1 and H3 genes (thick lines) from the animal strain and its remaining six RNAs, including the N2 gene, from the H2N2 parent (thin lines) ( ).

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555815981.ch42.ch42fig05
FIGURE 5
Replication of influenza virus. For a description of different replication steps, see the text.
10.1128/9781555815981/f0948-02_thmb.gif
10.1128/9781555815981/f0948-02.gif
Image of FIGURE 5
FIGURE 5

Replication of influenza virus. For a description of different replication steps, see the text.

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555815981.ch42.ch42fig06
FIGURE 6
Transcription and replication of influenza virus RNAs. (A) The 3′-terminal 15 nt and the 5′-terminal 22 nt of an NS gene (vRNA) are shown. The 3′-terminal 12 nt and the 5′-terminal 13 nt are highly conserved among influenza virus RNAs. The six U’s at the 5′ end are part of the polyadenylation signal. Transcription leads to a polyadenylated mRNA which is primed by short capped RNA molecules derived from nascent cellular transcripts and terminates at the stretch of six U’s near the 5′ end of the incoming vRNA. Full-length cRNAs are copied from vRNAs and are then used as templates for the generation of new vRNA molecules. All RNAs are shown as linear molecules. (B) The vRNA is represented here by a panhandle-fork structure. The 3′ and 5′ ends are postulated to base pair, but it is not known which RNA structure (panhandle-fork-corkscrew) is the predominant one in vivo.
10.1128/9781555815981/f0949-01_thmb.gif
10.1128/9781555815981/f0949-01.gif
Image of FIGURE 6
FIGURE 6

Transcription and replication of influenza virus RNAs. (A) The 3′-terminal 15 nt and the 5′-terminal 22 nt of an NS gene (vRNA) are shown. The 3′-terminal 12 nt and the 5′-terminal 13 nt are highly conserved among influenza virus RNAs. The six U’s at the 5′ end are part of the polyadenylation signal. Transcription leads to a polyadenylated mRNA which is primed by short capped RNA molecules derived from nascent cellular transcripts and terminates at the stretch of six U’s near the 5′ end of the incoming vRNA. Full-length cRNAs are copied from vRNAs and are then used as templates for the generation of new vRNA molecules. All RNAs are shown as linear molecules. (B) The vRNA is represented here by a panhandle-fork structure. The 3′ and 5′ ends are postulated to base pair, but it is not known which RNA structure (panhandle-fork-corkscrew) is the predominant one in vivo.

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555815981.ch42.ch42fig07
FIGURE 7
Influenza activity in the United States, 1995 to 2007, based on isolates reported to the Influenza Branch, CDC. Influenza activity has occurred each year during this interpandemic period, often with mixtures of influenza A subtypes and/or B viruses. (Figure kindly provided by Lynnette Brammer and Joe Bresee, Influenza Division, CDC.)
10.1128/9781555815981/f0952-01_thmb.gif
10.1128/9781555815981/f0952-01.gif
Image of FIGURE 7
FIGURE 7

Influenza activity in the United States, 1995 to 2007, based on isolates reported to the Influenza Branch, CDC. Influenza activity has occurred each year during this interpandemic period, often with mixtures of influenza A subtypes and/or B viruses. (Figure kindly provided by Lynnette Brammer and Joe Bresee, Influenza Division, CDC.)

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555815981.ch42.ch42fig08
FIGURE 8
Pneumonia and influenza (P%I) deaths presented as a percentage of total deaths in the United States, 2002 to 2007. Total deaths and those attributed to pneumonia and influenza deaths are reported weekly from 122 cities in the United States to the CDC. Excess mortality above the epidemic threshold has been seen particularly in association with influenza A (H3N2) subtype activity. (Figure kindly provided by Lynnette Brammer and Joe Bresee, Influenza Division, CDC.)
10.1128/9781555815981/f0954-01_thmb.gif
10.1128/9781555815981/f0954-01.gif
Image of FIGURE 8
FIGURE 8

Pneumonia and influenza (P%I) deaths presented as a percentage of total deaths in the United States, 2002 to 2007. Total deaths and those attributed to pneumonia and influenza deaths are reported weekly from 122 cities in the United States to the CDC. Excess mortality above the epidemic threshold has been seen particularly in association with influenza A (H3N2) subtype activity. (Figure kindly provided by Lynnette Brammer and Joe Bresee, Influenza Division, CDC.)

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555815981.ch42.ch42fig09
FIGURE 9
Photomicrographs of lung tissue from patients with primary influenza A viral pneumonia. Histologic sections were stained with hematoxylin and eosin and were viewed at an original magnification of approximately ×125. (A) Intra-alveolar hemorrhage with erythrocytes and exudate filling alveoli; (B) extensive hyaline membrane formation; (C) early regenerative phase with a metaplastic epithelium. (Figure kindly provided by Phillip Feldman, Department of Pathology, University of Virginia.)
10.1128/9781555815981/f0956-01_thmb.gif
10.1128/9781555815981/f0956-01.gif
Image of FIGURE 9
FIGURE 9

Photomicrographs of lung tissue from patients with primary influenza A viral pneumonia. Histologic sections were stained with hematoxylin and eosin and were viewed at an original magnification of approximately ×125. (A) Intra-alveolar hemorrhage with erythrocytes and exudate filling alveoli; (B) extensive hyaline membrane formation; (C) early regenerative phase with a metaplastic epithelium. (Figure kindly provided by Phillip Feldman, Department of Pathology, University of Virginia.)

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555815981.ch42.ch42fig10
FIGURE 10
Sequential chest radiographs from a 30-year-old nonimmunocompromised female with acute influenza A virus pneumonia. (A) Her symptoms began 1 day before first radiograph, which shows right middle and bilateral lower lobe infiltrates. Her respiratory status deteriorated rapidly and she required mechanical ventilation but survived. (B) The second radiograph, taken approximately 24 h after admission, shows diffuse infiltrates.
10.1128/9781555815981/f0961-01_thmb.gif
10.1128/9781555815981/f0961-01.gif
Image of FIGURE 10
FIGURE 10

Sequential chest radiographs from a 30-year-old nonimmunocompromised female with acute influenza A virus pneumonia. (A) Her symptoms began 1 day before first radiograph, which shows right middle and bilateral lower lobe infiltrates. Her respiratory status deteriorated rapidly and she required mechanical ventilation but survived. (B) The second radiograph, taken approximately 24 h after admission, shows diffuse infiltrates.

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555815981.ch42
1. Akarsu, H.,, W. P. Burmeister,, C. Petosa,, I. Petit,, C. W. Muller,, R. W. Ruigrok, and, F. Baudin. 2003. Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2). EMBO J. 22: 4646– 4655.
2. Aoki, F. Y.,, G. Boivin, and, N. Roberts. 2007. Influenza virus susceptibility and resistance to oseltamivir. Antivir. Ther. 12 (4 Pt. B) : 603– 616.
3. Baskin, C. R.,, H. Bielefeldt-Ohmann,, A. Garcia-Sastre,, T. M. Tumpey,, N. Van Hoeven,, V. S. Carter,, M. J. Thomas,, S. Proll,, A. Solorzano,, R. Billharz,, J. L. Fornek,, S. Thomas,, C. H. Chen,, E. A. Clark,, K. Murali-Krishna, and, M. G. Katze. 2007. Functional genomic and serological analysis of the protective immune response resulting from vaccination of macaques with an NS1-truncated influenza virus. J. Virol. 81: 11817– 11827.
4. Bean, B.,, B. M. Moore,, B. Sterner,, L. R. Peterson,, D. N. Gerding, and, H. H. Balfour, Jr. 1982. Survival of influenza viruses on environmental surfaces. J. Infect. Dis. 146: 47– 51.
5. Beare, A. S.,, and R. G. Webster. 1991. Replication of avian influenza viruses in humans. Arch. Virol. 119: 37– 42.
6. Belser, J. A.,, X. Lu,, K. Szretter,, X. Jin,, L. M. Aschen-brenner,, S. Lee,, S. Hawley,, D. H. Kim,, M. P. Malakhov,, M. Yu,, F. Fang, and, J. M. Katz. 2007. DAS181, a novel sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection. J. Infect. Dis. 196: 1493– 1499.
7. Belshe, R.,, P. Mendelman,, J. J. Treanor,, J. King,, W. C. Gruber,, P. A. Piedra,, D. I. Bernstein,, F. G. Hayden,, K. Kotloff,, K. Zangwill,, D. Iacuzio, and, M. Wolff. 1998. Efficacy of a trivalent live attenuated intranasal influenza vaccine in children. N. Engl. J. Med. 338: 1405– 1412.
8. Belshe, R. B.,, K. M. Edwards,, T. Vesikari,, S. V. Black,, R. E. Walker,, M. Hultquist,, G. Kemble, and, E. M. Connor for the CAIV-T Comparative Efficacy Study Group. 2007. Live attenuated versus inactivated influenza vaccine in infants and young children. N. Engl. J. Med. 356: 685– 696.
9. Bernstein, D. I.,, K. M. Edwards,, C. L. Dekker,, R. Belshe,, H. K. B. Talbot,, I. L. Graham,, D. L. Noah,, F. He, and, H. Hill. 2008. Effects of adjuvants on the safety and immunogenicity of an avian influenza H5N1 vaccine in adults. J. Infect. Dis. 197: 1– 9.
10. Boone, S. A.,, and C. P. Gerba. 2005. The occurrence of influenza A virus on household and day care center fomites. J. Infect. 51: 103– 109.
11. Brankston, G.,, L. Gitterman,, Z. Hirji,, C. Lemieux, and, M. Gardam. 2007. Transmission of influenza A in human beings. Lancet Infect. Dis. 7: 257– 265.
12. Brundage, J. F. 2006. Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Infect. Dis. 6: 303– 312.
13. Buonagurio, D. A.,, T. M. Bechert,, C. F. Yang,, L. Shutyak,, G. A. D’Arco,, Y. Kazachkov,, H. P. Wang,, E. A. Rojas,, R. E. O’Neill,, R. R. Spaete,, K. L. Coelingh,, T. J. Zamb,, M. S. Sidhu, and, S. A. Udem. 2006. Genetic stability of live, cold-adapted influenza virus components of the FluMist(R)/CAIV-T vaccine throughout the manufacturing process. Vaccine 24: 2151– 2160.
14. Bush, R. M.,, C. A. Bender,, K. Subbarao,, N. J. Cox, and, W. M. Fitch. 1999. Predicting the evolution of human influenza A. Science 286: 1921– 1925.
15. Call, S. A.,, M. A. Vollenweider,, C. A. Hornung,, D. L. Simel, and, W. P. McKinney. 2005. Does this patient have influenza? JAMA 293: 987– 997.
16. Cauchemez, S.,, A. J. Valleron,, P. Y. Boelle,, A. Flahault, and, N. M. Ferguson. 2008. Estimating the impact of school closure on influenza transmission from sentinel data. Nature 452: 750– 754.
17. Centers for Disease Control and Prevention. 2007. Interim pre-pandemic planning guidance: community strategy for pandemic influenza mitigation in the United States—easy, targeted, layered use of nonpharmaceutical interventions. http://www.pandemicflu.gov/plan/community/community_mitigation.pdf.
18. Chemaly, R. F.,, H. A. Torres,, E. A. Aguilera,, G. Mattiuzzi,, M. Cabanillas,, H. Kantarjian,, V. Gonzalez,, A. Safdar, and, I. I. Raad. 2007. Neuraminidase inhibitors improve outcome of patients with leukemia and influenza: an observational study. Clin. Infect. Dis. 44: 964– 967.
19. Chen, W.,, P. A. Calvo,, D. Malide,, J. Gibbs,, U. Schubert,, I. Bacik,, S. Basta,, R. O’Neill,, J. Schickli,, P. Palese,, P. Henklein,, J. R. Bennink, and, J. W. Yewdell. 2001. A novel influenza A virus mitochondrial protein that induces cell death. Nat. Med. 7: 1306– 1312.
20. Colman, P. M. 1989. Influenza virus neuraminidase: enzyme and antigen, p. 175–218. In R. M. Krug (ed.), The Influenza Viruses. Plenum Press, New York, NY.
21. Colman, P. M.,, J. N. Varghese, and, W. G. Laver. 1983. Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature 303: 41– 44.
22. Couch, R. B.,, P. Winokur,, R. Brady,, R. Belshe,, W. H. Chen,, T. R. Cate,, B. Sigurdardottir,, A. Hoeper,, I. L. Graham,, R. Edelman,, F. He,, D. Nino,, J. Capellan, and, F. L. Ruben. 2007. Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects. Vaccine 25: 7656– 7663.
23. Crescenzo-Chaigne, B.,, and S. van der Werf. 2007. Rescue of influenza C virus from recombinant DNA. J. Virol. 81: 11282– 11289.
24. Davies, J. R.,, and E. A. Grilli. 1989. Natural or vaccine-induced antibody as a predictor of immunity in the face of natural challenge with influenza viruses. Epidemiol. Infect. 102: 325– 333.
25. De Benedictis, P.,, M. S. Beato, and, I. Capua. 2007. Inactivation of avian influenza viruses by chemical agents and physical conditions: a review. Zoonoses Public Health 54: 51– 68.
26. de Jong, M. D.,, C. P. Simmons,, T. T. Thanh,, V. M. Hien,, G. J. Smith,, T. N. Chau,, D. M. Hoang,, N. V. Chau,, T. H. Khanh,, V. C. Dong,, P. T. Qui,, B. V. Cam,, D. Q. Ha,, Y. Guan,, J. S. Peiris,, N. T. Chinh,, T. T. Hien, and, J. Farrar. 2006. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat. Med. 12: 1203– 1207.
27. de Jong, M. D.,, T. T. Thanh,, T. H. Khanh,, V. M. Hien,, G. J. D. Smith,, N. V. Chau,, B. V. Cam,, P. T. Qui,, D. Q. Ha,, Y. Guan,, J. S. M. Peiris,, T. T. Hien, and, J. Farrar. 2005. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N. Engl. J. Med. 353: 2667– 2672.
28. Deyde, V. M.,, X. Xu,, R. A. Bright,, M. Shaw,, C. Smith,, Y. Zhang,, Y. Shu,, L. Gubareva,, N. Cox, and, A. I. Klimov. 2008. Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide. J. Infect. Dis. 196: 249– 257.
29. Dodds, L.,, S. A. McNeil,, D. B. Fell,, V. M. Allen,, A. Coombs,, J. Scott, and, N. MacDonald. 2007. Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women. Can. Med. Assoc. J. 176: 463– 468.
30. Dowdle, W. R. 1999. Influenza A virus recycling revisited. Bull. W. H. O. 77: 820– 828.
31. Englund, J. A.,, R. E. Champlin,, P. R. Wyde,, H. Kantarjian,, R. L. Atmar,, J. J. Tarrand,, H. Yousuf,, H. Regnery,, A. I. Klimov,, N. Cox, and, E. Whimbey. 1998. Common emergence of amantadine and rimantadine resistant influenza A viruses in symptomatic immunocompromised adults. Clin. Infect. Dis. 26: 1418– 1424.
32. Epstein, J. M.,, D. M. Goedecke,, F. Yu,, R. J. Morris,, D. K. Wagener, and, G. V. Bobashev. 2007. Controlling pandemic flu: the value of international air travel restrictions. PLoS ONE 2 (5) : e401.
33. Ferguson, N. M.,, D. A. T. Cummings,, S. Cauchemez,, C. Fraser,, S. Riley,, A. Meeyai,, S. Iamsirithaworn, and, D. S. Burke. 2005. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature 437: 209– 214.
34. Fiers, W.,, M. De Filette,, A. Birkett,, S. Neirynck, and, W. Min Jou. 2004. A “universal” human influenza A vaccine. Virus Res. 103 (1–2) : 173– 176.
35. Fiore, A. E.,, D. K. Shay,, P. Haber,, J. Iskander,, T. M. Uyeki,, G. Mootrey,, J. S. Bresee, and, N. Cox for the Centers for Disease Control and Prevention. 2007. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. Morb. Mortal. Wkly. Rep. 56 (RR-6) : 1– 54.
36. Flick, R.,, and G. Hobom. 1999. Interaction of influenza virus polymerase with viral RNA in the ‘corkscrew’ conformation. J. Gen. Virol. 80(Pt. 10) : 2565– 2572.
37. Fodor, E.,, L. Devenish,, O. G. Engelhardt,, P. Palese,, G. G. Brownlee, and, A. Garcia-Sastre. 1999. Rescue of influenza A virus from recombinant DNA. J. Virol. 73: 9679– 9682.
38. Fodor, E.,, D. C. Pritlove, and, G. G. Brownlee. 1995. Characterization of the RNA-fork model of virion RNA in the initiation of transcription in influenza A virus. J. Virol. 69: 4012– 4019.
39. Fujii, K.,, Y. Fujii,, T. Noda,, Y. Muramoto,, T. Watanabe,, A. Takada,, H. Goto,, T. Horimoto, and, Y. Kawaoka. 2005. Importance of both the coding and the segment-specific noncoding regions of the influenza A virus NS segment for its efficient incorporation into virions. J. Virol. 79: 3766– 3774.
40. Fukuda, K.,, R. A. Levandowski,, C. B. Bridges, and, N. J. Cox. 2004. Inactivated influenza vaccine, p. 339–370. In S. A. Plotkin, and, W. A. Orenstein (ed.), Vaccines. Elsevier, Philadelphia, PA.
41. Garcia-Sastre, A. 2006. Antiviral response in pandemic influenza viruses. Emerg. Infect. Dis. 12: 44– 47.
42. Garcia-Sastre, A.,, and P. Palese. 1993. Genetic manipulation of negative-strand RNA virus genomes. Annu. Rev. Microbiol. 47: 765– 790.
43. Gianfrani, C.,, C. Oseroff,, J. Sidney,, R. W. Chesnut, and, A. Sette. 2000. Human memory CTL response specific for influenza A virus is broad and multispecific. Hum. Immunol. 61: 438– 452.
44. Glezen, W. P.,, and R. B. Couch. 1997. Influenza viruses, p. 473–505. In A. S. Evans and, R. A. Kaslow (ed.), Viral Infections of Humans. Plenum Medical Book Company, New York, NY.
45. Glezen, W. P.,, L. H. Taber,, A. L. Frank,, W. C. Gruber, and, P. A. Piedra. 1997. Influenza virus infections in infants. Pediatr. Infect. Dis. J. 16: 1065– 1068.
46. Gomolin, I. H.,, H. B. Leib,, N. H. Arden, and, F. T. Sherman. 1995. Control of influenza outbreaks in the nursing home: guidelines for diagnosis and management. J. Am. Geriatr. Soc. 43: 71– 74.
47. Gravenstein, S. M. M. C.,, P. M. Drinka,, D. M. Osterweil,, M. M. Schilling,, P. R. Krause,, M. M. Elliott,, P. P. Shult,, A. M. Ambrozaitis,, R. M. Kandel,, E. M. Binder,, J. M. Hammond,, J. M. McElhaney,, N. P. Flack,, J. P. Daly, and, O. M. Keene. 2005. Inhaled zanamivir versus rimantadine for the control of influenza in a highly vaccinated long-term care population. J. Am. Med. Directors Assoc. 6: 359– 366.
48. Gu, J.,, Z. Xie,, Z. Gao,, J. Liu,, C. Korteweg,, J. Ye,, L. T. Lau,, J. Lu,, Z. Gao,, B. Zhang,, M. A. McNutt,, M. Lu,, V. M. Anderson,, E. Gong,, A. C. H. Yu, and, W. I. Lipkin. 2007. H5N1 infection of the respiratory tract and beyond: a molecular pathology study. Lancet 370: 1137– 1145.
49. Hageman, J. C.,, T. M. Uyeki,, J. S. Francis,, D. B. Jernigan,, J. G. Wheeler,, C. B. Bridges,, S. J. Barenkamp,, D. M. Sievert,, A. Srinivasan,, M. C. Doherty,, L. K. McDougal,, G. E. Killgore,, U. A. Lopatin,, R. Coffman,, J. K. MacDonald,, S. K. McAllister,, G. E. Fosheim,, J. B. Patel, and, L. C. McDonald. 2006. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003–04 influenza season. Emerg. Infect. Dis. 12: 894– 899.
50. Hagen, M.,, T. D. Chung,, J. A. Butcher, and, M. Krystal. 1994. Recombinant influenza virus polymerase: requirement of both 5′ and 3′ viral ends for endonuclease activity. J. Virol. 68: 1509– 1515.
51. Hatakeyama, S.,, Y. Sakai-Tagawa,, M. Kiso,, H. Goto,, C. Kawakami,, K. Mitamura,, N. Sugaya,, Y. Suzuki, and, Y. Kawaoka. 2005. Enhanced expression of an α2,6-linked sialic acid on MDCK cells improves isolation of human influenza viruses and evaluation of their sensitivity to a neuraminidase inhibitor. J. Clin. Microbiol. 43: 4139– 4146.
52. Hayden, F. G. 1997. Prevention and treatment of influenza in immunocompromised patients. Am. J. Med. 102 (3A) : 55– 60.
53. Hayden, F. G.,, and F. Y. Aoki. 2005. Amantadine, rimantadine, and related agents, p. 705–729. In V. L. Yu,, G. Edwards,, P. S. McKinnon,, C. Peloquin, and, G. D. Morse (ed.), Antimicrobial Therapy and Vaccines. ESun Technologies, LLC, Pittsburgh, PA.
54. Hayden, F. G.,, and F. Y. Aoki. 2005. Influenza neuraminidase inhibitors, p. 773–789. In V. L. Yu,, G. Edwards,, P. S. McKinnon,, C. Peloquin, and, G. D. Morse (ed.), Antimicrobial Therapy and Vaccines. ESun Technologies, LLC, Pittsburgh, PA.
55. Hayden, F. G.,, R. S. Fritz,, M. Lobo,, G. Alvord,, W. Strober, and, S. E. Straus. 1998. Local and systemic cytokine responses during experimental human influenza A virus infection. J. Clin. Investig. 101: 643– 649.
56. Hayden, F. G.,, and A. T. Pavia. 2006. Antiviral management of seasonal and pandemic influenza. J. Infect. Dis. 194 (S2) : S119– S126.
57. Hayward, A. C.,, R. Harling,, S. Wetten,, A. M. Johnson,, S. Munro,, J. Smedley,, S. Murad, and, J. M. Watson. 2006. Effectiveness of an influenza vaccine programme for care home staff to prevent death, morbidity, and health service use among residents: cluster randomised controlled trial. Br. Med. J. 333: 1241– 1247.
58. Hoffmann, E.,, K. Mahmood,, Z. Chen,, C.-F. Yang,, J. Spaete,, H. B. Greenberg,, M. L. Herlocher,, H. Jin, and, G. Kemble. 2005. Multiple gene segments control the temperature sensitivity and attenuation phenotypes of ca B/Ann Arbor/1/66. J. Virol. 79: 11014– 11021.
59. Hoffmann, E.,, K. Mahmood,, C. F. Yang,, R. G. Webster,, H. B. Greenberg, and, G. Kemble. 2002. Rescue of influenza B virus from eight plasmids. Proc. Natl. Acad. Sci. USA 99: 11411– 11416.
60. Horimoto, T.,, and Y. Kawaoka. 2005. Influenza: lessons from past pandemics, warnings from current incidents. Nat. Rev. Microbiol. 3: 591– 600.
61. Ilyushina, N. A.,, E. Hoffmann,, R. Solomon,, R. G. Webster, and, E. A. Govorkova. 2007. Amantadineoseltamivir combination therapy for H5N1 influenza virus infection in mice. Antivir. Ther. 12: 363– 370.
62. Ison, M. G.,, L. V. Gubareva,, R. L. Atmar,, J. Treanor, and, F. G. Hayden. 2006. Recovery of drug-resistant influenza virus from immunocompromised patients: a case series. J. Infect. Dis. 193: 760– 764.
63. Jackson, D.,, A. Cadman,, T. Zurcher, and, W. S. Barclay. 2002. A reverse genetics approach for recovery of recombinant influenza B viruses entirely from cDNA. J. Virol. 76: 11744– 11747.
64. Jackson, D.,, H. J. Hossain,, D. Hickman,, D. R. Perez, and, R. A. Lamb. 2008. A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogenicity. Proc. Natl. Acad. Sci. USA 105: 4381– 4386.
65. Jameson, J.,, J. Cruz,, M. Terajima, and, F. A. Ennis. 1999. Human CD8+ and CD4+ T lymphocyte memory to influenza A viruses of swine and avian species. J. Immunol. 162: 7578– 7583.
66. Jin, H.,, B. Lu,, H. Zhou,, C. Ma,, J. Zhao,, C. F. Yang,, G. Kemble, and, H. Greenberg. 2003. Multiple amino acid residues confer temperature sensitivity to human influenza virus vaccine strains (Flumist) derived from cold-adapted A/Ann Arbor/6/60. Virology 306: 18– 24.
67. Johnson, N. P.,, and J. Mueller. 2002. Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic. Bull. Hist. Med. 76: 105– 115.
68. Kaiser, L.,, R. S. Fritz,, S. E. Straus,, L. Gubareva, and, F. G. Hayden. 2001. Symptom pathogenesis during acute influenza: interleukin-6 and other cytokine responses. J. Med. Virol. 64: 262– 268.
69. Kaiser, L.,, and F. G. Hayden. 1999. Hospitalizing influenza in adults. Curr. Clin. Top. Infect. Dis. 19: 112– 134.
70. Keyser, L. A.,, M. Karl,, A. N. Nafziger, and, J. S. Bertino. Jr. 2000. Comparison of central nervous system adverse effects of amantadine and rimantadine used as sequential prophylaxis of influenza A in elderly nursing home patients. Arch. Intern. Med. 160: 1485– 1488.
71. Kilbourne, E. D. 1987. Influenza. Plenum Medical Book Company, New York, NY.
72. Kobasa, D.,, S. M. Jones,, K. Shinya,, J. C. Kash,, J. Copps,, H. Ebihara,, Y. Hatta,, J. Hyun Kim,, P. Halfmann,, M. Hatta,, F. Feldmann,, J. B. Alimonti,, L. Fernando,, Y. Li,, M. G. Katze,, H. Feldmann, and, Y. Kawaoka. 2007. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 445: 319– 323.
73. Koelle, K.,, S. Cobey,, B. Grenfell, and, M. Pascual. 2006. Epochal evolution shapes the phylodynamics of interpandemic influenza A (H3N2) in humans. Science 314: 1898– 1903.
74. Lamb, R. A. 1983. The influenza virus RNA segments and their encoded proteins, p. 21. In P. Palese and, D. W. Kingsbury (ed.), Genetics of Influenza Viruses. Springer-Verlag, New York, NY.
75. Langmuir, A. D.,, T. D. Worthen,, J. Solomon,, C. G. Ray, and, E. Petersen. 1985. The Thucydides syndrome. A new hypothesis for the cause of the plague of Athens. N. Engl. J. Med. 313: 1027– 1030.
76. Lee, N.,, C. K. Wong,, P. K. S. Chan,, S. W. M. Lun,, G. Lui,, B. Wong,, D. S. C. Hui,, C. W. K. Lam,, C. S. Cockram,, K. W. Choi,, A. C. M. Yeung,, J. W. Tang, and, J. J. Y. Sung. 2007. Hypercytokinemia and hyperactivation of phospho-p38 mitogen-activated protein kinase in severe human influenza A virus infection. Clin. Infect. Dis. 45: 723– 731.
77. Leekha, S.,, N. Zitterkopf,, M. J. Espy,, T. F. Smith,, R. L. Thompson, and, P. Sampathkumar. 2007. Duration of influenza a virus shedding in hospitalized patients and implications for infection control. Infect. Control Hosp. Epidemiol. 28: 1071– 1076.
78. Leroux-Roels, I.,, A. Borkowski,, T. Vanwolleghem,, M. Drame,, F. Clement,, E. Hons,, J. M. Devaster, and, G. Leroux-Roels. 2007. Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. Lancet 370: 580– 589.
79. Lin, J. C.,, and K. L. Nichol. 2001. Excess mortality due to pneumonia or influenza during influenza seasons among persons with acquired immunodeficiency syndrome. Arch. Intern. Med. 161: 441– 446.
80. Lin, Y. P.,, M. Shaw,, V. Gregory,, K. Cameron,, W. Lim,, A. Klimov,, K. Subbarao,, Y. Guan,, S. Krauss,, K. Shortridge,, R. Webster,, N. Cox, and, A. Hay. 2000. Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship between H9N2 and H5N1 human isolates. Proc. Natl. Acad. Sci. USA 97: 9654– 9658.
81. Lofgren, E.,, N. H. Fefferman,, Y. N. Naumov,, J. Gorski, and, E. N. Naumova. 2007. Influenza seasonality: underlying causes and modeling theories. J. Virol. 81: 5429– 5436.
82. Lowen, A. C.,, S. Mubareka,, J. Steel, and, P. Palese. 2007. Influenza virus transmission is dependent on relative humidity and temperature. PloS Pathog. 3: 1470– 1476.
83. Lowen, A. C.,, S. Mubareka,, T. M. Tumpey,, A. Garcia-Sastre, and, P. Palese. 2006. The guinea pig as a transmission model for human influenza viruses. Proc. Natl. Acad. Sci. USA 103: 9988– 9992.
84. Luke, T. C.,, E. M. Kilbane,, J. L. Jackson, and, S. L. Hoffman. 2006. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann. Intern. Med. 145: 599– 609.
85. Ma, W.,, A. L. Vincent,, M. R. Gramer,, C. B. Brockwell,, K. M. Lager,, B. H. Janke,, P. C. Gauger,, D. P. Patnayak,, R. J. Webby, and, J. A. Richt. 2007. Identification of H2N3 influenza A viruses from swine in the United States. Proc. Natl. Acad. Sci. USA 104: 20949– 20954.
86. Maines, T. R.,, L. M. Chen,, Y. Matsuoka,, H. Chen,, T. Rowe,, J. Ortin,, A. Falcon,, N. T. Hien,, L. Q. Mai,, E. R. Sedyaningsih,, S. Harun,, T. M. Tumpey,, R. O. Donis,, N. J. Cox,, K. Subbarao, and, J. M. Katz. 2006. Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc. Natl. Acad. Sci. USA 103: 12121– 12126.
87. Markel, H.,, H. B. Lipman,, J. A. Navarro,, A. Sloan,, J. R. Michalsen,, A. M. Stern, and, M. S. Cetron. 2007. Nonpharmaceutical interventions implemented by US cities during the 1918–1919 influenza pandemic. JAMA 298: 644– 654.
88. Marsh, G. A.,, R. Hatami, and, P. Palese. 2007. Specific residues of the influenza A virus hemagglutinin viral RNA are important for efficient packaging into budding virions. J. Virol. 81: 9727– 9736.
89. Martin, K.,, and A. Helenius. 1991. Nuclear transport of influenza virus ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibits import. Cell 67: 117– 130.
90. Matsuzaki, Y.,, C. Abiko,, K. Mizuta,, K. Sugawara,, E. Takashita,, Y. Muraki,, H. Suzuki,, M. Mikawa,, S. Shimada,, K. Sato,, M. Kuzuya,, S. Takao,, K. Wakatsuki,, T. Itagaki,, S. Hongo, and, H. Nishimura. 2007. A nationwide epidemic of influenza c virus infection in Japan in 2004. J. Clin. Microbiol. 45: 783– 788.
91. Matsuzaki, Y.,, N. Katsushima,, Y. Nagai,, M. Shoji,, T. Itagaki,, M. Sakamoto,, S. Kitaoka,, K. Mizuta, and, H. Nishimura. 2006. Clinical features of influenza C virus infection in children. J. Infect. Dis. 193: 1229– 1235.
92. McElhaney, J. E.,, J. W. Hooton,, N. Hooton, and, R. C. Bleackley. 2005. Comparison of single versus booster dose of influenza vaccination on humoral and cellular immune responses in older adults. Vaccine 23: 3294– 3300.
93. McElhaney, J. E.,, D. Xie,, W. D. Hager,, M. B. Barry,, Y. Wang,, A. Kleppinger,, C. Ewen,, K. P. Kane, and, R. C. Bleackley. 2006. T cell responses are better correlates of vaccine protection in the elderly. J. Immunol. 176: 6333– 6339.
94. McGeer, A.,, K. Green,, A. Plevneshi,, A. Shigayeva,, N. Siddiqi,, J. Raboud, and, D. Low. 2007. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin. Infect. Dis. 45: 1568– 1575.
95. McMichael, A. 1994. Cytotoxic T lymphocytes specific for influenza virus. Curr. Top. Microbiol. Immunol. 189: 75– 91.
96. McMinn, P.,, A. Carrello,, C. Cole,, D. Baker, and, A. Hampson. 1999. Antigenic drift of influenza A (H3N2) virus in a persistently infected immunocompromised host is similar to that occurring in the community. Clin. Infect. Dis. 29: 456– 458.
97. Monto, A. S.,, S. Gravenstein,, M. Elliott,, M. Colopy, and, J. Schweinle. 2000. Clinical signs and symptoms predicting influenza infection. Arch. Intern. Med. 160: 3243– 3247.
98. Mulder, J.,, and J. E. Hers. 1972. Influenza. Wolters-Noordhoof, Groningen, The Netherlands.
99. Munster, V. J.,, E. de Witt,, D. van Riel,, W. E. Beyer,, G. F. Rimmelzwaan,, A. D. Osterhaus,, T. Kuiken, and, R. A. Fouchier. 2007. The molecular basis of the pathogenicity of the Dutch highly pathogenic human influenza A H7N7 viruses. J. Infect. Dis. 196: 258– 265.
100. Muraki, Y.,, T. Murata,, E. Takashita,, Y. Matsuzaki,, K. Sugawara, and, S. Hongo. 2007. A mutation on influenza C virus M1 protein affects virion morphology by altering the membrane affinity of the protein. J. Virol. 81: 8766– 8773.
101. Murphy, B. R.,, and M. L. Clements. 1989. The systemic and mucosal immune response of humans to influenza A virus. Curr. Top. Microbiol. Immunol. 146: 107– 116.
102. Murray, C. J.,, A. D. Lopez,, B. Chin,, D. Feehan, and, K. H. Hill. 2006. Estimation of potential global pandemic influenza mortality on the basis of vital registry data from the 1918–20 pandemic: a quantitative analysis. Lancet 368: 2211– 2218.
103. Mutsch, M.,, W. Zhou,, P. Rhodes,, M. Bopp,, R. T. Chen,, T. Linder,, C. Spyr, and, R. Steffen. 2004. Use of the inactivated intranasal influenza vaccine and the risk of Bell’s palsy in Switzerland. N. Engl. J. Med. 350: 896– 903.
104. Myers, K. P.,, C. W. Olsen, and, G. C. Gray. 2007. Cases of swine influenza in humans: a review of the literature. Clin. Infect. Dis. 44: 1084– 1088.
105. Neirynck, S.,, T. Deroo,, X. Saelens,, P. Vanlandschoot,, W. M. Jou, and, W. Fiers. 1999. A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat. Med. 5: 1157– 1163.
106. Neumann, G.,, and Y. Kawaoka. 2006. Host range restriction and pathogenicity in the context of influenza pandemic. Emerg. Infect. Dis. 12: 881– 886.
107. Neumann, G.,, K. Shinya, and, Y. Kawaoka. 2007. Molecular pathogenesis of H5N1 influenza virus infections. Antivir. Ther. 12(4 Pt. B) : 617– 626.
108. Neumann, G.,, T. Watanabe,, H. Ito,, S. Watanabe,, H. Goto,, P. Gao,, M. Hughes,, D. R. Perez,, R. Donis,, E. Hoffmann,, G. Hobom, and, Y. Kawaoka. 1999. Generation of influenza A viruses entirely from cloned cDNAs. Proc. Natl. Acad. Sci. USA 96: 9345– 9350.
109. Neuraminidase Inhibitor Susceptibility Network. 2007. Monitoring of neuraminidase inhibitor resistance among clinical influenza virus isolates in Japan during the 2003–2006 influenza seasons. Wkly. Epidemiol. Rec. 82: 149– 150.
110. Neuzil, K. M.,, B. G. Mellen,, P. F. Wright,, E. F. Mitchel, Jr., and, M. R. Griffin. 2000. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N. Engl. J. Med. 342: 225– 231.
111. Ng, W. F.,, K. F. To,, W. W. L. Lam,, T. K. Ng, and, K. C. Lee. 2006. The comparative pathology of severe acute respiratory syndrome and avian influenza A subtype H5N1—a review. Hum. Pathol. 37: 381– 390.
112. Nichol, K. L.,, J. D. Nordin,, D. B. Nelson,, J. P. Mullooly, and, E. Hak. 2007. Effectiveness of influenza vaccine in the community-dwelling elderly. N. Engl. J. Med. 357: 1373– 1381.
113. Nicholson, K. G. 1998. Human influenza, p. 219–264. In K. G. Nicholson,, R. G. Webster, and, A. J. Hay (ed.), Textbook of Influenza. Blackwell Science Ltd., Oxford, United Kingdom.
114. Noyola, D. E.,, B. Clark,, F. T. O’Donnell,, R. L. Atmar,, J. Greer, and, G. J. Demmler. 2000. Comparison of a new neuraminidase detection assay with an enzyme immunoassay, immunofluorescence, and culture for rapid detection of influenza A and B viruses in nasal wash specimens. J. Clin. Microbiol. 38: 1161– 1165.
115. Ohmit, S. E.,, J. C. Victor,, J. R. Rotthoff,, E. R. Teich,, R. K. Truscon,, L. L. Baum,, B. Rangarajan,, D. W. Newton,, M. L. Boulton, and, A. S. Monto. 2006. Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines. N. Engl. J. Med. 355: 2513– 2522.
116. Olsen, B.,, V. J. Munster,, A. Wallensten,, J. Walden-strom,, A. D. M. E. Osterhaus, and, R. A. M. Fouchier. 2006. Global patterns of influenza A virus in wild birds. Science 312: 384– 388.
117. O’Neill, R. E.,, R. Jaskunas,, G. Blobel,, P. Palese, and, J. Moroianu. 1995. Nuclear import of influenza virus RNA can be mediated by viral nucleoprotein and transport factors required for protein import. J. Biol. Chem. 270: 22701– 22704.
118. O’Neill, R. E.,, J. Talon, and, P. Palese. 1998. The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins. EMBO J. 17: 288– 296.
119. Ong, A. K.,, and F. G. Hayden. 2007. John F. Enders Lecture 2006: antivirals for influenza. J. Infect. Dis. 196: 181– 190.
120. Ozawa, M.,, H. Goto,, T. Horimoto, and, Y. Kawaoka. 2007. An adenovirus vector-mediated reverse genetics system for influenza A virus generation. J. Virol. 81: 9556– 9559.
121. Palese, P. 2004. Influenza: old and new threats. Nat. Med. 10 (12 Suppl.) : S82– S87.
122. Palese, P.,, and M. Shaw. 2007. Orthomyxoviridae: the viruses and their replication, p. 1647–1689. In D. M. Knipe,, P. M. Howley,, D. E. Griffin,, R. A. Lamb,, M. A. Martin,, B. Roizman, and, S. E. Straus (ed.), Fields Virology, 5th ed. Lippencott Williams % Wilkins, Philadelphia, PA.
123. Pasick, J.,, K. Handel,, J. Robinson,, J. Copps,, D. Ridd,, K. Hills,, H. Kehler,, C. Cottam-Birt,, J. Neufeld,, Y. Berhane, and, S. Czub. 2005. Intersegmental recombination between the haemagglutinin and matrix genes was responsible for the emergence of a highly pathogenic H7N3 avian influenza virus in British Columbia. J. Gen. Virol. 86: 727– 731.
124. Peiris, J. S. M.,, M. D. de Jong, and, Y. Guan. 2007. Avian influenza virus (H5N1): a threat to human health. Clin. Microbiol. Rev. 20: 243– 267.
125. Peltola, V. T.,, K. G. Murti, and, J. A. McCullers. 2005. Influenza virus neuraminidase contributes to secondary bacterial pneumonia. J. Infect. Dis. 192: 249– 257.
126. Perez-Ruiz, M.,, R. Yeste,, M. J. Ruiz-Perez,, A. Ruiz-Bravo,, M. de la Rosa-Fraile, and, J. M. Navarro-Mari. 2007. Testing of diagnostic methods for detection of influenza virus for optimal performance in the context of an influenza surveillance network. J. Clin. Microbiol. 45: 3109– 3110.
127. Petric, M.,, L. Comanor, and, C. A. Petti. 2006. Role of the laboratory in diagnosis of influenza during seasonal epidemics and potential pandemics. J. Infect. Dis. 194 (Suppl. 2) : S98– S110.
128. Poehling, K. A.,, K. M. Edwards,, G. A. Weinberg,, P. Szilagyi,, M. A. Staat,, M. K. Iwane,, C. B. Bridges,, C. G. Grijalva,, Y. Zhu,, D. I. Bernstein,, G. Herrera,, D. Erdman,, C. B. Hall,, R. Seither, and, M. R. Griffin for the New Vaccine Surveillance Network. 2006. The underrecognized burden of influenza in young children. N. Engl. J. Med. 355: 31– 40.
129. Potter, C. W. 1998. Chronicle of influenza pandemics, p. 3–18. In K. G. Nicholson,, R. G. Webster, and, A. J. Hay (ed.), Textbook of Influenza. Blackwell Science Ltd., Oxford, United Kingdom.
130. Rasmussen, S. A.,, D. J. Jamieson, and, J. S. Bresee. 2008. Pandemic influenza and pregnant women. Emerg. Infect. Dis. 14: 95– 100.
131. Reichert, T. A.,, N. Sugaya,, D. S. Fedson,, W. P. Glezen,, L. Simonsen, and, M. Tashiro. 2001. The Japanese experience with vaccinating schoolchildren against influenza. N. Engl. J. Med. 344: 889– 896.
132. Rimmelzwaan, G. F.,, A. C. Boon,, J. T. Voeten,, E. G. Berkhoff,, R. A. Fouchier, and, A. D. Osterhaus. 2004. Sequence variation in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes. Virus Res. 103 (1–2) : 97– 100.
133. Rodriguez, W. J.,, C. B. Hall,, R. Welliver,, E. A. Simoes,, M. E. Ryan,, H. Stutman,, G. Johnson,, R. Van Dyke,, J. R. Groothuis,, J. Arrobio,, K. Schabel,, H. W. Kim,, R. H. Parrott, and, P. Pincus. 1994. Efficacy and safety of aerosolized ribavirin in young children hospitalized with influenza: a double-blind, multicenter, placebo-controlled trial. J. Pediatr. 125: 129– 135.
134. Rothbarth, P. H.,, J. Groen,, A. M. Bohnen,, R. de Groot, and, A. D. Osterhaus. 1999. Influenza virus serology—a comparative study. J. Virol. Methods 78(1–2) : 163– 169.
135. Roti, M.,, J. Yang,, D. Berger,, L. Huston,, E. A. James, and, W. W. Kwok. 2008. Healthy human subjects have CD4+ T cells directed against H5N1 influenza virus. J. Immunol. 180: 1758– 1768.
136. Russell, C. A.,, T. C. Jones,, I. G. Barr,, N. J. Cox,, R. J. Garten,, V. Gregory,, I. D. Gust,, A. W. Hampson,, A. J. Hay,, A. C. Hurt,, J. C. de Jong,, A. Kelso,, A. I. Klimov,, T. Kageyama,, N. Komadina,, A. S. Lapedes,, Y. P. Lin,, A. Mosterin,, M. Obuchi,, T. Odagiri,, A. D. M. E. Osterhaus,, G. F. Rimmelzwaan,, M. W. Shaw,, E. Skepner,, K. Stohr,, M. Tashiro,, R. A. M. Fouchier, and, D. J. Smith. 2008. The global circulation of seasonal influenza A (H3N2) viruses. Science 320: 340– 346.
137. Salgado, C. D.,, B. M. Farr,, K. K. Hall, and, F. G. Hayden. 2002. Influenza in the acute hospital setting. Lancet Infect. Dis. 2: 145– 155.
138. Salomon, R.,, E. Hoffmann, and, R. G. Webster. 2007. Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. Proc. Natl. Acad. Sci. USA 104: 12479– 12481.
139. Salvatore, M.,, A. Garcia-Sastre,, P. Ruchala,, R. I. Lehrer,, T. Chang, and, M. E. Klotman. 2007. α-Defensin inhibits influenza virus replication by cell-mediated mechanism(s). J. Infect. Dis. 196: 835– 843.
140. Schaffer, F. L.,, M. E. Soergel, and, D. C. Straube. 1976. Survival of airborne influenza virus: effects of propagating host, relative humidity, and composition of spray fluids. Arch. Virol. 51: 263– 273.
141. Schwarzmann, S. W.,, J. L. Adler,, R. J. Sullivan, and, W. M. Marine. 1971. Bacterial pneumonia during the Hong Kong influenza epidemic of 1968–1969. Arch. Intern. Med. 127: 1037– 1041.
142. Sidwell, R. W.,, D. L. Barnard,, C. W. Day,, D. F. Smee,, K. W. Bailey,, M. H. Wong,, J. D. Morrey, and, Y. Furuta. 2007. Efficacy of orally administered T-705 on lethal avian influenza A (H5N1) virus infections in mice. Antimicrob. Agents Chemother. 51: 845– 851.
143. Simonsen, L.,, M. J. Clarke,, L. B. Schonberger,, N. Arden,, N. J. Cox, and, K. Fukuda. 1998. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J. Infect. Dis. 178: 53– 60.
144. Simonsen, L.,, R. J. Taylor,, C. Viboud,, M. A. Miller, and, L. A. Jackson. 2007. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Infect. Dis. 7: 658– 666.
145. Skowronski, D.,, S. A. Tweed, and, G. De Serres. 2008. Rapid decline of influenza vaccine-induced antibody in the elderly: is it real, or is it relevant? J. Infect. Dis. 197: 490– 502.
146. Smith, G. J. D.,, X. H. Fan,, J. Wang,, K. S. Li,, K. Qin,, J. X. Zhang,, D. Vijaykrishna,, C. L. Cheung,, K. Huang,, J. M. Rayner,, J. S. M. Peiris,, H. Chen,, R. G. Webster, and, Y. Guan. 2006. Emergence and predominance of an H5N1 influenza variant in China. Proc. Natl. Acad. Sci. USA 103: 16936– 16941.
147. Stech, J.,, H. Garn,, M. Wegmann,, R. Wagner, and, H. D. Klenk. 2005. A new approach to an influenza live vaccine: modification of the cleavage site of hemagglutinin. Nat. Med. 11: 683– 689.
148. Subbarao, K.,, I. Klimov,, J. Katz,, H. Regnery,, W. Lim,, H. Hall,, M. Perdue,, D. Swayne,, C. Bender,, J. Huang,, M. Hemphill,, T. Rowe,, M. Shaw,, X. Xu,, K. Fukuda, and, N. Cox. 1998. Characterization of an avian influenza A(H5N1) virus isolated from a child with a fatal respiratory illness. Science 279: 393– 396.
149. Subbarao, K.,, and T. Joseph. 2007. Scientific barriers to developing vaccines against avian influenza viruses. Nat. Rev. Immunol. 7: 267– 278.
150. Sugaya, N.,, K. Mitamura,, M. Yamazaki,, D. Tamura,, M. Ichikawa,, K. Kimura,, C. Kawakami,, M. Kiso,, M. Ito,, S. Hatakeyama, and, Y. Kawaoka. 2007. Lower clinical effectiveness of oseltamivir against influenza B contrasted with influenza A infection in children. Clin. Infect. Dis. 44: 197– 202.
151. Sullivan, P. S.,, D. L. Hanson,, M. S. Dworkin,, J. L. Jones,, J. W. Ward, and the Adult and Adolescent Spectrum of HIV Disease Investigators. 2000. Effect of influenza vaccination on disease progression among HIV-infected persons. AIDS 14: 2781– 2785.
152. Taubenberger, J. K.,, A. H. Reid,, R. M. Lourens,, R. Wang,, G. Jin, and, T. G. Fanning. 2005. Characterization of the 1918 influenza virus polymerase genes. Nature 437: 889– 893.
153. Tecle, T.,, M. R. White,, E. C. Crouch, and, K. L. Hartshorn. 2007. Inhibition of influenza viral neuraminidase activity by collectins. Arch. Virol. 152: 1731– 1742.
154. Temperton, N. J.,, K. Hoschler,, D. Major,, C. Nicolson,, R. Manvell,, V. M. Hien,, D. Q. Ha,, M. de Jong,, M. Zambon,, Y. Takeuchi, and, R. A. Weiss. 2007. A sensitive retroviral pseudotype assay for influenza H5N1-neutralizing antibodies. Influenza Other Respir. Viruses 1: 105– 112.
155. Thompson, W. W.,, D. K. Shay,, E. Weintraub,, L. Brammer,, C. B. Bridges,, N. J. Cox, and, K. Fukuda. 2004. Influenza-associated hospitalizations in the United States. JAMA 292: 1333– 1340.
156. Thompson, W. W.,, L. Comanor, and, D. K. Shay. 2006. Epidemiology of seasonal influenza: use of surveillance data and statistical models to estimate the burden of disease. J. Infect. Dis. 194 (Suppl. 2) : S82– S91.
157. Treanor, J. J.,, J. D. Campbell,, K. M. Zangwill,, T. Rowe, and, M. Wolff. 2006. Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine. N. Engl. J. Med. 354: 1343– 1351.
158. Treanor, J. J.,, and F. G. Hayden. 2005. Viral infections, p. 867–919. In J. F. Murray and, J. A. Nadel (ed.), Textbook of Respiratory Medicine. W. B. Saunders Company, Philadelphia, PA.
159. Treanor, J. J.,, G. M. Schiff,, F. G. Hayden,, R. C. Brady,, C. M. Hay,, A. L. Meyer,, J. Holden-Wiltse,, H. Liang,, A. Gilbert, and, M. Cox. 2007. Safety and immunogenicity of a baculovirus-expressed hemagglutinin influenza vaccine: a randomized controlled trial. JAMA 297: 1577– 1582.
160. Tumpey, T. M.,, C. F. Basler,, P. V. Aguilar,, H. Zeng,, A. Solorzano,, D. E. Swayne,, N. J. Cox,, J. M. Katz,, J. K. Taubenberger,, P. Palese, and, A. Garcia-Sastre. 2005. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310: 77– 80.
161. Tumpey, T. M.,, T. R. Maines,, N. Van Hoeven,, L. Glaser,, A. Solorzano,, C. Pappas,, N. J. Cox,, D. E. Swayne,, P. Palese,, J. M. Katz, and, A. Garcia-Sastre. 2007. A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science 315: 655– 659.
162. van Riel, D.,, V. J. Munster,, E. de Wit,, G. F. Rimmelzwaan,, R. A. M. Fouchier,, A. D. M. E. Osterhaus, and, T. Kuiken. 2007. Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals. Am. J. Pathol. 171: 1215– 1223.
163. Wang, J. P.,, E. A. Kurt-Jones, and, R. W. Finberg. 2007. Innate immunity to respiratory viruses. Cell. Microbiol. 9: 1641– 1646.
164. Webster, R. G.,, and E. A. Govorkova. 2006. H5N1 influenza—continuing evolution and spread. N. Engl. J. Med. 355: 2174– 2177.
165. Wiley, D. C.,, and J. J. Skehel. 1987. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu. Rev. Biochem. 56: 365– 394.
166. World Health Organization. 2007. Clinical management of human infection with avian influenza A (H5N1) virus. http://www.who.int/csr/disease/avian_influenza/guidelines/ClinicalManagement07.pdf.
167. World Health Organization. 2008. WHO/ECDC frequently asked questions for oseltamivir resistance. http://www.who.int/csr/disease/influenza/oseltamivir_faqs/en/print.html.
168. Wright, P.,, G. Neumann, and, Y. Kawaoka. 2007. Orthomyxoviruses, p. 1691–1740. In D. M. Knipe,, P. M. Howley,, D. E. Griffin,, R. A. Lamb,, M. A. Martin,, B. Roizman, and, S. E. Straus (ed.), Fields Virology, 5th ed. Lippincott Williams % Wilkins, Philadelphia, PA.
169. Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. 2008. Update on avian influenza A (H5N1) virus infection in humans. N. Engl. J. Med. 358: 261– 273.
170. Yamada, S.,, Y. Suzuki,, T. Suzuki,, M. Q. Le,, C. A. Nidom,, Y. Sakai-Tagawa,, Y. Muramoto,, M. Ito,, M. Kiso,, T. Horimoto,, K. Shinya,, T. Sawada,, M. Kiso,, T. Usui,, T. Murata,, Y. Lin,, A. Hay,, L. F. Haire,, D. J. Stevens,, R. J. Russell,, S. J. Gamblin,, J. J. Skehel, and, Y. Kawaoka. 2006. Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature 444: 378– 382.
171. Yamashita, M.,, M. Krystal, and, P. Palese. 1989. Comparison of the three large polymerase proteins of influenza A, B, and C viruses. Virology 171: 458– 466.
172. Yun, N. E.,, N. S. Linde,, M. A. Zacks,, I. G. Barr,, A. C. Hurt,, J. N. Smith,, N. Dziuba,, M. R. Holbrook,, L. Zhang,, J. M. Kilpatrick,, C. S. Arnold, and, S. Paessler. 2008. Injectable peramivir mitigates disease and promotes survival in ferrets and mice infected with the highly virulent influenza virus, A/Vietnam/1203/04 (H5N1). Virology 374: 198– 209.

Tables

Influenza Virus
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815981.ch42-1,webId=/content/author/10.1128/9781555815981.ch42-1,properties={foaf_givenname=Frederick G., foaf_name=Frederick G. Hayden, foaf_surname=Hayden}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815981.ch42-2,webId=/content/author/10.1128/9781555815981.ch42-2,properties={foaf_givenname=Peter, foaf_name=Peter Palese, foaf_surname=Palese}]]
Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
/content/10.1128/9781555815981.ch42.ch42tab01
TABLE 1
Influenza A virus RNA segments and proteins
Generic image for table
TABLE 1

Influenza A virus RNA segments and proteins

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
/content/10.1128/9781555815981.ch42.ch42tab02
TABLE 2
Recent examples of human illness due to infection by avian influenza viruses
Generic image for table
TABLE 2

Recent examples of human illness due to infection by avian influenza viruses

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
/content/10.1128/9781555815981.ch42.ch42tab03
TABLE 3
Influenza A virus pandemics and other important influenza events during the past century
Generic image for table
TABLE 3

Influenza A virus pandemics and other important influenza events during the past century

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
/content/10.1128/9781555815981.ch42.ch42tab04
TABLE 4
Target groups for influenza immunization
Generic image for table
TABLE 4

Target groups for influenza immunization

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
/content/10.1128/9781555815981.ch42.ch42tab05
TABLE 5
Comparison of seasonal inactivated vaccines and LAIV
Generic image for table
TABLE 5

Comparison of seasonal inactivated vaccines and LAIV

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42
/content/10.1128/9781555815981.ch42.ch42tab06
TABLE 6
Suggested dose regimens for antiviral administration in seasonal influenza
Generic image for table
TABLE 6

Suggested dose regimens for antiviral administration in seasonal influenza

Citation: Hayden F, Palese P. 2009. Influenza Virus, p 943-976. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch42

Back to top
This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error