Chapter 48 : Hepatitis A Virus

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • PDF
    1.52 MB
  • XML
    350.08 Kb
  • HTML
    315.89 Kb

Preview this chapter:
Zoom in

Hepatitis A Virus, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819439/9781555819422.ch48-1.gif /docserver/preview/fulltext/10.1128/9781555819439/9781555819422.ch48-2.gif


Hepatitis A is an acute, self-limiting infection of the liver by hepatitis A virus (HAV), an enterically transmitted, hepatotropic member of the picornavirus family. Although HAV infection may occasionally result in fulminant hepatitis and death, it is not recognized to cause persistent infection or chronic hepatitis, even in severely immunocompromised individuals.

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Highlighted Text: Show | Hide
Loading full text...

Full text loading...



Image of FIGURE 1

Click to view


Electron micrographs of HAV. (A) Immune electron micrograph of HAV particles from human stool reacted with convalescent serum. The particles are heavily coated with and aggregated by antibody. Both “full” and “empty” particles can be seen. (B) An immune electron micrograph showing particles from human stool reacted with a preinfection serum. The 27- to 28-nm particles are nearly devoid of antibody and some fine structure can be seen. (C) Quasi-enveloped eHAV particles (panels a–d) and a nonenveloped HAV virion purified by density gradient centrifugation from supernatant fluids of infected Huh-7 cell cultures. The density of the fractions containing the particles is shown below the images. (A) and (B) Reprinted from Richman DD, Whitley RJ, Hayden FG (ed) , 3rd ed, with permission. (C) (Reprinted from reference with permission of the publisher.)

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Click to view


HAV genome organization and polyprotein processing cascade. The positive-strand RNA genome of HAV is approximately 7.5 kilobases (kb) in length and contains a single long open reading frame (ORF, box) flanked by relatively short 5′ and 3′ untranslated regions (UTRs, solid lines) as shown. The 5′ UTR is covalently linked at the 5′ end to the genome-linked protein VPg (otherwise known as 3B), and contains a highly structured internal ribosome entry site (IRES) that drives 5′ cap-independent translation of the polyprotein encoded by the ORF. The 3′ UTR terminates in a lengthy poly(A) sequence. The HAV polyprotein is co- and posttranslationally processed by the viral protease 3C (red box) that cleaves the polyprotein and its derivatives at sites indicated by the red triangles, producing both the structural (P1, turquoise) and nonstructural proteins (P2+P3, tan and red) that go to form the capsid and replicase complex, respectively. Yet-to-be-identified protease activities cause a final maturation cleavage in the VP0 (VP4+VP2) capsid protein, and trim the C-terminal pX domain off of VP1, during late stages in viral maturation.

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Click to view


X-ray crystallographic structure of the HAV capsid. Overall structure of the HAV capsid as deduced from X-ray crystallographic studies of formalin-inactivated vaccine virus (27). (A) Left: Accessible surface of the capsid, showing residues contributed by VP1 as red, VP2 green, and VP3 blue (60 copies of each are present within one capsid). VP4 is internal and is not seen. Right: Electrostatic surface of the capsid; red=negative charge, blue=positive charge, white=neutral. Yellow dots are sulfate ions. (B) Overlay of folded VP2 structure of HAV with that of VP2 protein from (left) cricket paralysis virus (CrPV) and (right) the mammalian picornavirus, foot-and-mouth virus (FMDV), showing prominent domain-swap paralleling structure in the insect virus. (C) Structural phylogeny of the HAV capsid showing its intermediate position between that of other mammalian picornaviruses and distantly related viruses such as CrPV. (Reprinted from reference with permission of the publisher.)

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Click to view


Biogenesis of quasi-enveloped eHAV virions (11). Several hypothetical mechanisms may account for the release of quasi-enveloped virions from hepatocytes. The most likely mechanism for eHAV biogenesis involves (a) the recruitment of assembled intracellular HAV capsids to cytoplasmic multivesicular bodies (MVBs) by protein components of the cellular ESCRT (ndosomal orting omplex equired for ransport) system such as ALIX, followed by the budding of capsids into MVBs such that they become enclosed in membranes within the MVB. Movement of the MVB to the plasma membrane and fusion of the outer MVB membrane and plasma membrane then delivers eHAV to the extracellular environment. Alternatively, (b) ESCRT-associated proteins might mediate release of eHAV directly at the plasma membrane. A third possibility (c) is that HAV capsids are engulfed in autophagosomes for transport to either MVBs or the plasma membrane. Loss of the eHAV membrane after egress from the cell (d) leads to the production of naked, nonenveloped virions. (Reprinted from reference with permission of the publisher.)

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5

Click to view


HAV replication cycle. (a) HAV interacts with a cellular receptor (possibly HAVCR1/TIM-1) at the basolateral membrane of the hepatocyte, is internalized, and (b) the viral genome is released into the cytoplasm; (b) the positive-strand RNA genome is translated in a cap-independent IRES-driven manner, resulting in a polyprotein that is (d) proteolytically processed to generate nonstructural proteins involved in genome replication (2B, 2C, 3AB, 3D) and the protease (3C), as well as capsid proteins (see Fig. 2 ). Changes in intracellular membranes are induced by 2BC, resulting in assembly of the nonstructural proteins into a membrane-bound replicase complex that (e) directs the synthesis of a complementary minus-strand RNA intermediate (blue) that is then used as template to (f) generate multiple new copies of positive-strand RNA (red). These newly synthesized positive-strand RNAs can (g) be directed to engage in additional translation or RNA synthesis or (h) packaged into capsids to generate intracellular viral progeny. These newly assembled viral particles (i) are recruited to multivesicular bodies for ultimate release from the infected cells across either (j) the apical plasma membrane into the biliary canaliculus (as shown) or across the basolateral membrane into the hepatic sinusoids (not shown). (Adapted from Martin A, Lemon SM, 2006 with permission of the publisher.)

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 6

Click to view


Composite graph depicting HAV infection in an intravenously inoculated, experimentally infected chimpanzee (105). (A) Innate immune response: minimal increases in serum IFN-α occur during the first weeks of the infection in association with the transient presence of plasmacytoid dendritic cells (pDCs) in liver sinusoids and minimal intrahepatic expression of interferon-stimulated genes (ISGs) such as IFIT1 and ISG15. These early responses diminish prior to the peak in viral replication. (B) Intracellular cytokine staining shows that the virus-specific CD4+ T cell response (bottom) is more robust than the virus-specific CD8+ T cell cytokine or tetramer-specific response (top), and that the CD4+ T cell response correlates better with viral control. (C) IgM and total anti-HAV antibody responses detected in enzyme-linked immunosorbent assays. The total anti-HAV is measured in a blocking assay, where 100% indicates high-titer antibody. (D) Relative viral RNA abundance (GE=genome equivalents) in serum, liver tissue, and feces determined by reverse transcription polymerase chain reaction assays. Results are layered onto serum alanine transferase values that show a sharp spike indicative of acute liver injury at 4 weeks post inoculation. (Reprinted from reference with permission of the publisher.)

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 7

Click to view


Electron micrographs of a marmoset hepatocyte during acute hepatitis A. The arrows in the upper panel point to cytoplasmic vesicles containing probable HAV capsids. The lower panel is a higher powered view of one of the vesicles more clearly showing viruslike particles. Bar=500 nm in the upper panel and 100 nm in the lower. Courtesy of Yohko Shimizu.

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 8

Click to view


Photomicrograph of a liver section from a patient with acute hepatitis A, showing inflammation of the portal and periportal areas by lymphocytes coupled with lobular disarray and hepatocellular ballooning degeneration (cytoplasmic vacuolization). (Hematoxylin and eosin stain; original magnification 40x). (Adapted from Martin A, Lemon SM, 2006 with permission of the publisher.)

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 9

Click to view


Estimated global prevalence of hepatitis A virus, 2005. (Reprinted from reference with permission of the publisher.)

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 10

Click to view


Estimates of anti-HAV seroprevalence by age group and selected populations in different world regions, 1990 and 2005. Groups shown include those in Western Europe, South sub-Saharan Africa, North America (high income), and Oceania. The impact of changing standards of sanitation and immunization programs is evident in shifts in age-specific prevalence of anti-HAV antibody. No changes were estimated to have occurred in the African region. (Adapted from reference with permission of the publisher.)

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 11

Click to view


Natural history of hepatitis A. The infection is typically acute in nature, with symptoms and signs of the infection usually occurring within 3 to 5 weeks of exposure. The sequence of events includes shedding of infectious HAV in feces and viremia, followed by increases in serum ALT activity (red line), and the appearance of IgM and IgG anti-HAV antibody responses (the latter typically measured as total anti-HAV antibody). (Adapted from Martin A, Lemon SM, 2006 with permission of the publisher.)

Citation: Williford S, Lemon S. 2017. Hepatitis A Virus, p 1165-1188. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch48
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Zuckerman AJ,. 1983. The history of viral hepatitis from antiquity to the present, p 332. In Deinhardt F, Deinhardt J (ed), Viral Hepatitis: Laboratory and Clinical Science. Marcel Dekker, New York.
2. Bancroft WH, Lemon SM, Gerety RJ. 1984. Hepatitis A from the military perspective, p 81100. In Hepatitis A. Academic Press, Orlando, Florida.
3. Havens WP Jr. 1945. Experiment in cross immunity between infectious hepatitis and homologous serum jaundice. Exp Biol Med 59:148150.
4. Neefe JR, Gellis SS, Stokes J Jr. 1946. Homologous serum hepatitis and infectious (epidemic) hepatitis; studies in volunteers bearing on immunological and other characteristics of the etiological agents. Am J Med 1:322.
5. Deinhardt F, Holmes AW, Capps RB, Popper H. 1967. Studies on the transmission of human viral hepatitis to marmoset monkeys. I. Transmission of disease, serial passages, and description of liver lesions. J Exp Med 125:673688.[PubMed]
6. Feinstone SM, Kapikian AZ, PurcelL RH. 1973. Hepatitis A: detection by immune electron microscopy of a viruslike antigen associated with acute illness. Science 182:10261028.[PubMed]
7. Provost PJ, Hilleman MR. 1979. Propagation of human hepatitis A virus in cell culture in vitro. Proc Soc Exp Biol Med 160:213221.[PubMed]
8. Najarian R, Caput D, Gee W, Potter SJ, Renard A, Merryweather J, Van Nest G, Dina D. 1985. Primary structure and gene organization of human hepatitis A virus. Proc Natl Acad Sci U S A 82:26272631.[PubMed]
9. Clemens R, Safary A, Hepburn A, Roche C, Stanbury WJ, Andre FE. 1995. Clinical experience with an inactivated hepatitis A vaccine. J InfectDis 171(Suppl 1):S44S49.
10. Werzberger A, Mensch B, Kuter B, Brown L, Lewis J, Sitrin R, Miller W, Shouval D, Wiens B, Calandra G, Ryan J, Provost P, Nalin D. 1992. A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children. N Engl J Med 327:453457.[PubMed]
11. Feng Z, Hirai-Yuki A, McKnight KL, Lemon SM. 2014. Naked viruses that aren't always naked: quasi-enveloped agents of acute hepatitis. Annu Rev Virol 1:539560.
12. Palmenberg AC, Semler B, Ehrenfeld E,. 1989. Sequence alignments of picornaviral capsid proteins, p 211241. In Semler B, Ehrenfeld E (ed), Molecular Aspects of Picornavirus Infection and Detection. American Society for Microbiology Press, Washington, DC.
13. Martin A, Lemon SM,. 2002. The molecular biology of hepatitis A virus, p 2350. In Ou J (ed), Hepatitis Viruses. Kluwer Academic Publishers, Norwell, MA.
14. Drexler JF, Corman VM, Lukashev AN, van den Brand JMA, Gmyl A, Brunink S, Rasche A, Seggewiss N, Feng H, Leijten LM, Vallo P, Kuiken T, Dotzauer A, Ulrich RG, Lemon SM, Drosten C Hepatovirus Ecology Consortium. 2015. Evolutionary origins of hepatitis A virus in small mammals. Proc Natl Acad Sci U S A 112:1519015195.
15. Weitz M, Baroudy BM, Maloy WL, Ticehurst JR, Purcell RH. 1986. Detection of a genome-linked protein (VPg) of hepatitis A virus and its comparison with other picornaviral VPgs. J Virol 60:124130.[PubMed]
16. Brown EA, Day SP, Jansen RW, Lemon SM. 1991. The 5′ nontranslated region of hepatitis A virus RNA: secondary structure and elements required for translation in vitro. J Virol 65:58285838.[PubMed]
17. Tesar M, Harmon SA, Summers DF, Ehrenfeld E. 1992. Hepatitis A virus polyprotein synthesis initiates from two alternative AUG codons. Virology 186:609618.[PubMed]
18. Yang Y, Yi M, Evans DJ, Simmonds P, Lemon SM. 2008. Identification of a conserved RNA replication element (cre) within the 3Dpol-coding sequence of hepatoviruses. J Virol 82:1011810128.[PubMed]
19. Jia XY, Summers DF, Ehrenfeld E. 1993. Primary cleavage of the HAV capsid protein precursor in the middle of the proposed 2A coding region. Virology 193:515519.[PubMed]
20. Martin A, Escriou N, Chao SF, Girard M, Lemon SM, Wychowski C. 1995. Identification and site-directed mutagenesis of the primary (2A/2B) cleavage site of the hepatitis A virus polyprotein: functional impact on the infectivity of HAV RNA transcripts. Virology 213:213222.[PubMed]
21. Allaire M, Chernaia MM, Malcolm BA, James MNG. 1994. Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases. Nature 369:7276.[PubMed]
22. Probst C, Jecht M, Gauss-Müller V. 1997. Proteinase 3C-mediated processing of VP1-2A of two hepatitis A virus strains: in vivo evidence for cleavage at amino acid position 273/274 of VP1. J Virol 71:32883292.[PubMed]
23. Martin A, Bénichou D, Chao SF, Cohen LM, Lemon SM. 1999. Maturation of the hepatitis A virus capsid protein VP1 is not dependent on processing by the 3Cpro proteinase. J Virol 73:62206227.[PubMed]
24. Probst C, Jecht M, Gauss-Müller V. 1999. Intrinsic signals for the assembly of hepatitis A virus particles. Role of structural proteins VP4 and 2A. J Biol Chem 274:45274531.[PubMed]
25. Cohen L, Bénichou D, Martin A. 2002. Analysis of deletion mutants indicates that the 2A polypeptide of hepatitis A virus participates in virion morphogenesis. J Virol 76:74957505.[PubMed]
26. Anderson DA, Ross BC. 1990. Morphogenesis of hepatitis A virus: isolation and characterization of subviral particles. J Virol 64:52845289.[PubMed]
27. Wang X, Ren J, Gao Q, Hu Z, Sun Y, Li X, Rowlands DJ, Yin W, Wang J, Stuart DI, Rao Z, Fry EE. 2015. Hepatitis A virus and the origins of picornaviruses. Nature 517:8588.[PubMed]
28. Gosert R, Egger D, Bienz K. 2000. A cytopathic and a cell culture adapted hepatitis A virus strain differ in cell killing but not in intracellular membrane rearrangements. Virology 266:157169.[PubMed]
29. Teterina NL, Bienz K, Egger D, Gorbalenya AE, Ehrenfeld E. 1997. Induction of intracellular membrane rearrangements by HAV proteins 2C and 2BC. Virology 237:6677.[PubMed]
30. Paul AV, Rieder E, Kim DW, van Boom JH, Wimmer E. 2000. Identification of an RNA hairpin in poliovirus RNA that serves as the primary template in the in vitro uridylylation of VPg. J Virol 74:1035910370.[PubMed]
31. Yang Y, Liang Y, Qu L, Chen Z, Yi M, Li K, Lemon SM. 2007. Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor. Proc Natl Acad Sci U S A 104:72537258.[PubMed]
32. Lemon SM, Jansen RW, Newbold JE. 1985. Infectious hepatitis A virus particles produced in cell culture consist of three distinct types with different buoyant densities in CsCl. J Virol 54:7885.[PubMed]
33. Siegl G, Frösner GG, Gauss-Müller V, Tratschin JD, Deinhardt F. 1981. The physicochemical properties of infectious hepatitis A virions. J Gen Virol 57:331341.[PubMed]
34. Tesar M, Jia XY, Summers DF, Ehrenfeld E. 1993. Analysis of a potential myristoylation site in hepatitis A virus capsid protein VP4. Virology 194:616626.[PubMed]
35. Lemon SM, Jansen RW, Brown EA. 1992. Genetic, antigenic and biological differences between strains of hepatitis A virus. Vaccine 10(Suppl 1):S40S44.[PubMed]
36. Hughes JV, Stanton LW. 1985. Isolation and immunizations with hepatitis A viral structural proteins: induction of antiprotein, antiviral, and neutralizing responses. J Virol 55:395401.[PubMed]
37. Stapleton JT, Lemon SM. 1987. Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus. J Virol 61:491498.[PubMed]
38. Ping LH, Lemon SM. 1992. Antigenic structure of human hepatitis A virus defined by analysis of escape mutants selected against murine monoclonal antibodies. J Virol 66:22082216.[PubMed]
39. Feng Z, Hensley L, McKnight KL, Hu F, Madden V, Ping L, Jeong S-H, Walker C, Lanford RE, Lemon SM. 2013. A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. Nature 496:367371.[PubMed]
40. Jansen RW, Siegl G, Lemon SM. 1990. Molecular epidemiology of human hepatitis A virus defined by an antigen-capture polymerase chain reaction method. Proc Natl Acad Sci U S A 87:28672871.[PubMed]
41. Robertson BH, Jansen RW, Khanna B, Totsuka A, Nainan OV, Siegl G, Widell A, Margolis HS, Isomura S, Ito K, Ishizu T, Moritsugu Y, Lemon SM. 1992. Genetic relatedness of hepatitis A virus strains recovered from different geographical regions. J Gen Virol 73:13651377.[PubMed]
42. Cohen JI, Ticehurst JR, Purcell RH, Buckler-White A, Baroudy BM. 1987. Complete nucleotide sequence of wild-type hepatitis A virus: comparison with different strains of hepatitis A virus and other picornaviruses. J Virol 61:5059.[PubMed]
43. Paul AV, Tada H, von der Helm K, Wissel T, Kiehn R, Wimmer E, Deinhardt F. 1987. The entire nucleotide sequence of the genome of human hepatitis A virus (isolate MBB). Virus Res 8:153171.[PubMed]
44. Tsarev SA, Emerson SU, Balayan MS, Ticehurst J, Purcell RH. 1991. Simian hepatitis A virus (HAV) strain AGM-27: comparison of genome structure and growth in cell culture with other HAV strains. J Gen Virol 72:16771683.[PubMed]
45. Cohen JI, Rosenblum B, Ticehurst JR, Daemer RJ, Feinstone SM, Purcell RH. 1987. Complete nucleotide sequence of an attenuated hepatitis A virus: comparison with wild-type virus. Proc Natl Acad Sci U S A 84:24972501.[PubMed]
46. Jansen RW, Newbold JE, Lemon SM. 1988. Complete nucleotide sequence of a cell culture-adapted variant of hepatitis A virus: comparison with wild-type virus with restricted capacity for in vitro replication. Virology 163:299307.[CrossRef][PubMed]
47. Lemon SM, Murphy PC, Shields PA, Ping LH, Feinstone SM, Cromeans T, Jansen RW. 1991. Antigenic and genetic variation in cytopathic hepatitis A virus variants arising during persistent infection: evidence for genetic recombination. J Virol 65:20562065.[PubMed]
48. Nainan OV, Margolis HS, Robertson BH, Balayan M, Brinton MA. 1991. Sequence analysis of a new hepatitis A virus naturally infecting cynomolgus macaques (Macaca fascicularis). J Gen Virol 72:16851689.[PubMed]
49. Scholz E, Heinricy U, Flehmig B. 1989. Acid stability of hepatitis A virus. J Gen Virol 70:24812485.[PubMed]
50. Siegl G, Weitz M, Kronauer G. 1984. Stability of hepatitis A virus. Intervirology 22:218226.[PubMed]
51. Lemon SM, Amphlett E, Sangar D. 1991. Protease digestion of hepatitis A virus: disparate effects on capsid proteins, antigenicity, and infectivity. J Virol 65:56365640.[PubMed]
52. Parry JV, Mortimer PP. 1984. The heat sensitivity of hepatitis A virus determined by a simple tissue culture method. J Med Virol 14:277283.[PubMed]
53. Peterson DA, Hurley TR, Hoff JC, Wolfe LG. 1983. Effect of chlorine treatment on infectivity of hepatitis A virus. Appl Environ Microbiol 45:223227.[PubMed]
54. Lemon SM, Murphy PC, Smith A, Zou J, Hammon J, Robinson S, Horowitz B. 1994. Removal/neutralization of hepatitis A virus during manufacture of high purity, solvent/detergent factor VIII concentrate. J Med Virol 43:4449.[CrossRef][PubMed]
55. Mbithi JN, Springthorpe VS, Sattar SA. 1991. Effect of relative humidity and air temperature on survival of hepatitis A virus on environmental surfaces. Appl Environ Microbiol 57:13941399.[PubMed]
56. Binn LN, Bancroft WH, Lemon SM, Marchwicki RH, LeDuc JW, Trahan CJ, Staley EC, Keenan CM. 1986. Preparation of a prototype inactivated hepatitis A virus vaccine from infected cell cultures. J Infect Dis 153:749756.[PubMed]
57. Lanford RE, Feng Z, Chavez D, Guerra B, Brasky KM, Zhou Y, Yamane D, Perelson AS, Walker CM, Lemon SM. 2011. Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA. Proc Natl Acad Sci U S A 108:1122311228.[PubMed]
58. Zhou Y, Callendret B, Xu D, Brasky KM, Feng Z, Hensley LL, Guedj J, Perelson AS, Lemon SM, Lanford RE, Walker CM. 2012. Dominance of the CD4(+) T helper cell response during acute resolving hepatitis A virus infection. J Exp Med 209:14811492.[PubMed]
59. Mathiesen LR, Møller AM, Purcell RH, London WT, Feinstone SM. 1980. Hepatitis A virus in the liver and intestine of marmosets after oral inoculation. Infect Immun 28:4548.[PubMed]
60. Asher LVS, Binn LN, Mensing TL, Marchwicki RH, Vassell RA, Young GD. 1995. Pathogenesis of hepatitis A in orally inoculated owl monkeys (Aotus trivirgatus). J Med Virol 47:260268.[PubMed]
61. Brown EA, Jansen RW, Lemon SM. 1989. Characterization of a simian hepatitis A virus (HAV): antigenic and genetic comparison with human HAV. J Virol 63:49324937.[PubMed]
62. Hornei B, Kämmerer R, Moubayed P, Frings W, Gauss-Müller V, Dotzauer A. 2001. Experimental hepatitis A virus infection in guinea pigs. J Med Virol 64:402409.[PubMed]
63. Provost PJ, Giesa PA, McAleer WJ, Hilleman MR. 1981. Isolation of hepatitis A virus in vitro in cell culture directly from human specimens. Proc Soc Exp Biol Med 167:201206.[PubMed]
64. Daemer RJ, Feinstone SM, Gust ID, Purcell RH. 1981. Propagation of human hepatitis A virus in African green monkey kidney cell culture: primary isolation and serial passage. Infect Immun 32:388393.[PubMed]
65. Binn LN, Lemon SM, Marchwicki RH, Redfield RR, Gates NL, Bancroft WH. 1984. Primary isolation and serial passage of hepatitis A virus strains in primate cell cultures. J Clin Microbiol 20:2833.[PubMed]
66. Dotzauer A, Feinstone SM, Kaplan G. 1994. Susceptibility of nonprimate cell lines to hepatitis A virus infection. J Virol 68:60646068.[PubMed]
67. Brack K, Frings W, Dotzauer A, Vallbracht A. 1998. A cytopathogenic, apoptosis-inducing variant of hepatitis A virus. J Virol 72:33703376.[PubMed]
68. Provost PJ, Banker FS, Giesa PA, McAleer WJ, Buynak EB, Hilleman MR. 1982. Progress toward a live, attenuated human hepatitis A vaccine. Proc Soc Exp Biol Med 170:814.[PubMed]
69. Emerson SU, McRill C, Rosenblum B, Feinstone S, Purcell RH. 1991. Mutations responsible for adaptation of hepatitis A virus to efficient growth in cell culture. J Virol 65:48824886.[PubMed]
70. Funkhouser AW, Purcell RH, D'Hondt E, Emerson SU. 1994. Attenuated hepatitis A virus: genetic determinants of adaptation to growth in MRC-5 cells. J Virol 68:148157.[PubMed]
71. Emerson SU, Huang YK, Purcell RH. 1993. 2B and 2C mutations are essential but mutations throughout the genome of HAV contribute to adaptation to cell culture. Virology 194:475480.[PubMed]
72. Jansen RW, Newbold JE, Lemon SM, Zuckerman AJ,. 1988. Mutations in the capsid-encoding and 5’ nontranslated regions of the hepatitis A virus genome associated with adaptation of virus to growth in cell culture, p 3642. In Zuckerman AJ (ed), Viral Hepatitis and Liver Disease. Alan R. Liss, Inc., New York.
73. Cohen JI, Ticehurst JR, Feinstone SM, Rosenblum B, Purcell RH. 1987. Hepatitis A virus cDNA and its RNA transcripts are infectious in cell culture. J Virol 61:30353039.[PubMed]
74. Emerson SU, Lewis M, Govindarajan S, Shapiro M, Moskal T, Purcell RH. 1992. cDNA clone of hepatitis A virus encoding a virulent virus: induction of viral hepatitis by direct nucleic acid transfection of marmosets. J Virol 66:66496654.[PubMed]
75. Feng Z, Li Y, McKnight KL, Hensley L, Lanford RE, Walker CM, Lemon SM. 2015. Human pDCs preferentially sense enveloped hepatitis A virions. J Clin Invest 125:169176.[PubMed]
76. Kaplan G, Totsuka A, Thompson P, Akatsuka T, Moritsugu Y, Feinstone SM. 1996. Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus. EMBO J 15:42824296.[PubMed]
77. Feigelstock D, Thompson P, Mattoo P, Zhang Y, Kaplan GG. 1998. The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor. J Virol 72:66216628.[PubMed]
78. Silberstein E, Xing L, van de Beek W, Lu J, Cheng H, Kaplan GG. 2003. Alteration of hepatitis A virus (HAV) particles by a soluble form of HAV cellular receptor 1 containing the immunoglobin- and mucin-like regions. J Virol 77:87658774.[PubMed]
79. Jemielity S, Wang JJ, Chan YK, Ahmed AA, Li W, Monahan S, Bu X, Farzan M, Freeman GJ, Umetsu DT, Dekruyff RH, Choe H. 2013. TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine. PLoS Pathog 9:e1003232.[PubMed]
80. Dotzauer A, Gebhardt U, Bieback K, Göttke U, Kracke A, Mages J, Lemon SM, Vallbracht A. 2000. Hepatitis A virus-specific immunoglobulin A mediates infection of hepatocytes with hepatitis A virus via the asialoglycoprotein receptor. J Virol 74:1095010957.[PubMed]
81. Borman AM, Kean KM. 1997. Intact eukaryotic initiation factor 4G is required for hepatitis A virus internal initiation of translation. Virology 237:129136.[PubMed]
82. Gosert R, Chang KH, Rijnbrand R, Yi M, Sangar DV, Lemon SM. 2000. Transient expression of cellular polypyrimidine-tract binding protein stimulates cap-independent translation directed by both picornaviral and flaviviral internal ribosome entry sites in vivo. Mol Cell Biol 20:15831595.[PubMed]
83. Blank CA, Anderson DA, Beard M, Lemon SM. 2000. Infection of polarized cultures of human intestinal epithelial cells with hepatitis A virus: vectorial release of progeny virions through apical cellular membranes. J Virol 74:64766484.[PubMed]
84. Snooks MJ, Bhat P, Mackenzie J, Counihan NA, Vaughan N, Anderson DA. 2008. Vectorial entry and release of hepatitis A virus in polarized human hepatocytes. J Virol 82:87338742.[PubMed]
85. Schulman AN, Dienstag JL, Jackson DR, Hoofnagle JH, Gerety RJ, Purcell RH, Barker LF. 1976. Hepatitis A antigen particles in liver, bile, and stool of chimpanzees. J Infect Dis 134:8084.[PubMed]
86. Purcell RH, Feinstone SM, Daemer RJ, Baroudy BM,. 1984. Hepatitis A virus, p 932. In Vyas GN, Dienstag JL, Hoofnagle JH (ed), Viral Hepatitis and Liver Disease. Grune & Stratton, Inc, Orlando, FL.
87. Lemon SM, Binn LN, Marchwicki R, Murphy PC, Ping LH, Jansen RW, Asher LVS, Stapleton JT, Taylor DG, LeDuc JW. 1990. In vivo replication and reversion to wild type of a neutralization-resistant antigenic variant of hepatitis A virus. J Infect Dis 161:713.[PubMed]
88. Mathiesen LR, Drucker J, Lorenz D, Wagner JA, Gerety RJ, Purcell RH. 1978. Localization of hepatitis A antigen in marmoset organs during acute infection with hepatitis A virus. J Infect Dis 138:369377.[PubMed]
89. Shimizu YK, Mathiesen LR, Lorenz D, Drucker J, Feinstone SM, Wagner JA, Purcell RH. 1978. Localization of hepatitis A antigen in liver tissue by peroxidase-conjugated antibody method: light and electron microscopic studies. J Immunol 121:16711679.[PubMed]
90. Dienstag JL, Feinstone SM, Purcell RH, Hoofnagle JH, Barker LF, London WT, Popper H, Peterson JM, Kapikian AZ. 1975. Experimental infection of chimpanzees with hepatitis A virus. J Infect Dis 132:532545.[PubMed]
91. Teixeira MR Jr, Weller IVD, Murray A, Bamber M, Thomas HC, Sherlock S, Scheuer PJ. 1982. The pathology of hepatitis A in man. Liver 2:5360.[PubMed]
92. Cohen JI, Feinstone S, Purcell RH. 1989. Hepatitis A virus infection in a chimpanzee: duration of viremia and detection of virus in saliva and throat swabs. J Infect Dis 160:887890.[PubMed]
93. Ouzilou L, Caliot E, Pelletier I, Prévost M-C, Pringault E, Colbère-Garapin F. 2002. Poliovirus transcytosis through M-like cells. J Gen Virol 83:21772182.[PubMed]
94. Bromberg K, Newhall DN, Peter G. 1982. Hepatitis A and meningoencephalitis. JAMA 247:815.[PubMed]
95. Breningstall GN, Belani KK. 1995. Acute transverse myelitis and brainstem encephalitis associated with hepatitis A infection. Pediatr Neurol 12:169171.[PubMed]
96. Cadranel JF, Corpechot C, Di Martino V, Bernard B, Lunel F, Opolon P. 1996. Acute renal failure associated with nonfulminant hepatitis A viral infection. Am J Gastroenterol 91:22572258.[PubMed]
97. Martino R, Aebischer CC, Baehler P, Bianchetti MG. 1996. Acute renal failure complicating nonfulminant hepatitis A in childhood. Nephron 74:490.[PubMed]
98. Mishra A, Saigal S, Gupta R, Sarin SK. 1999. Acute pancreatitis associated with viral hepatitis: a report of six cases with review of literature. Am J Gastroenterol 94:22922295.[PubMed]
99. Fensterl V, Grotheer D, Berk I, Schlemminger S, Vallbracht A, Dotzauer A. 2005. Hepatitis A virus suppresses RIG-I-mediated IRF-3 activation to block induction of beta interferon. J Virol 79:1096810977.[PubMed]
100. Qu L, Feng Z, Yamane D, Liang Y, Lanford RE, Li K, Lemon SM. 2011. Disruption of TLR3 signaling due to cleavage of TRIF by the hepatitis A virus protease-polymerase processing intermediate, 3CD. PLoS Pathog 7:e1002169.[PubMed]
101. Wang D, Fang L, Wei D, Zhang H, Luo R, Chen H, Li K, Xiao S. 2014. Hepatitis A virus 3C protease cleaves NEMO to impair induction of beta interferon. J Virol 88:1025210258.[PubMed]
102. Kurane I, Binn LN, Bancroft WH, Ennis FA. 1985. Human lymphocyte responses to hepatitis A virus-infected cells: interferon production and lysis of infected cells. J Immunol 135:21402144.[PubMed]
103. Fleischer B, Fleischer S, Maier K, Wiedmann KH, Sacher M, Thaler H, Vallbracht A. 1990. Clonal analysis of infiltrating T lymphocytes in liver tissue in viral hepatitis A. Immunology 69:1419.[PubMed]
104. Maier K, Gabriel P, Koscielniak E, Stierhof YD, Wiedmann KH, Flehmig B, Vallbracht A. 1988. Human gamma interferon production by cytotoxic T lymphocytes sensitized during hepatitis A virus infection. J Virol 62:37563763.[PubMed]
105. Walker CM, Feng Z, Lemon SM. 2015. Reassessing immune control of hepatitis A virus. Curr Opin Virol 11:713.[PubMed]
106. Meyers JH, Chakravarti S, Schlesinger D, Illes Z, Waldner H, Umetsu SE, Kenny J, Zheng XX, Umetsu DT, DeKruyff RH, Strom TB, Kuchroo VK. 2005. TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation. Nat Immunol 6:455464.[PubMed]
107. McIntire JJ, Umetsu SE, Macaubas C, Hoyte EG, Cinnioglu C, Cavalli-Sforza LL, Barsh GS, Hallmayer JF, Underhill PA, Risch NJ, Freeman GJ, DeKruyff RH, Umetsu DT. 2003. Immunology: hepatitis A virus link to atopic disease. Nature 425:576.[PubMed]
108. Umetsu DT, McIntire JJ, Akbari O, Macaubas C, DeKruyff RH. 2002. Asthma: an epidemic of dysregulated immunity. Nat Immunol 3:715720.[PubMed]
109. Gabriel P, Vallbracht A, Flehmig B. 1986. Lack of complement-dependent cytolytic antibodies in hepatitis A virus infection. J Med Virol 20:2331.[PubMed]
110. Margolis HS, Nainan OV. 1990. Identification of virus components in circulating immune complexes isolated during hepatitis A virus infection. Hepatology 11:3137.[PubMed]
111. Lemon SM, Murphy PC, Provost PJ, Chalikonda I, Davide JP, Schofield TL, Nalin DR, Lewis JA. 1997. Immunoprecipitation and virus neutralization assays demonstrate qualitative differences between protective antibody responses to inactivated hepatitis A vaccine and passive immunization with immune globulin. J Infect Dis 176:919.[PubMed]
112. Lemon SM, Brown CD, Brooks DS, Simms TE, Bancroft WH. 1980. Specific immunoglobulin M response to hepatitis A virus determined by solid-phase radioimmunoassay. Infect Immun 28:927936.[PubMed]
113. Lemon SM. 1985. IgM neutralizing antibody to hepatitis A virus. J Infect Dis 152:13531354.[PubMed]
114. Stapleton JT, Lange DK, LeDuc JW, Binn LN, Jansen RW, Lemon SM. 1991. The role of secretory immunity in hepatitis A virus infection. J Infect Dis 163:711.[PubMed]
115. World Health Organization. 2012. WHO position paper on hepatitis A vaccines—June 2012. Wkly Epidemiol Rec 87:261276.[PubMed]
116. Bell BP. 2000. Global epidemiology of hepatitis A: implications for control strategies. 10th International Symposium on Viral Hepatitis and Liver Disease. 9–13 April, Atlanta, Georgia, USA. Abstract A008.
117. Jacobsen KH, Wiersma ST. 2010. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005. Vaccine 28:66536657.[PubMed]
118. Franco E, Meleleo C, Serino L, Sorbara D, Zaratti L. 2012. Hepatitis A: epidemiology and prevention in developing countries. World J Hepatol 4:6873.[PubMed]
119. Lee H, Jeong H, Yun H, Kim K, Kim JH, Yang JM, Cheon DS. 2012. Genetic analysis of hepatitis A virus strains that induced epidemics in Korea during 2007–2009. J Clin Microbiol 50:12521257.[PubMed]
120. Cervio G, Trentadue J, D'Agostino D, Luque C, Giorgi M, Armoni J, Debbag R. 2011. Decline in HAV-associated fulminant hepatic failure and liver transplant in children in Argentina after the introduction of a universal hepatitis A vaccination program. Hepat Med 3:99106.[PubMed]
121. Armstrong GL, Bell BP. 2002. Hepatitis A virus infections in the United States: model-based estimates and implications for childhood immunization. Pediatrics 109:839845.[PubMed]
122. Daniels D, Grytdal S, Wasley A Centers for Disease Control and Prevention (CDC). 2009. Surveillance for acute viral hepatitis—United States, 2007. MMWR Surveill Summ 58:127.[PubMed]
123. Bell BP, Kruszon-Moran D, Shapiro CN, Lambert SB, McQuillan GM, Margolis HS. 2005. Hepatitis A virus infection in the United States: serologic results from the Third National Health and Nutrition Examination Survey. Vaccine 23:57985806.[PubMed]
124. Bell BP, Shapiro CN, Alter MJ, Moyer LA, Judson FN, Mottram K, Fleenor M, Ryder PL, Margolis HS. 1998. The diverse patterns of hepatitis A epidemiology in the United States-implications for vaccination strategies. J Infect Dis 178:15791584.[PubMed]
125. Centers for Disease Control (CDC). 1992. Hepatitis A among homosexual men—United States, Canada, and Australia. MMWR Morb Mortal Wkly Rep 41:155155, 161–164.[PubMed]
126. Samandari T, Bell BP, Armstrong GL. 2004. Quantifying the impact of hepatitis A immunization in the United States, 1995–2001. Vaccine 22:43424350.[PubMed]
127. Wasley A, Samandari T, Bell BP. 2005. Incidence of hepatitis A in the United States in the era of vaccination. JAMA 294:194201.[PubMed]
128. Fiore AE, Wasley A, Bell BP Advisory Committee on Immunization Practices (ACIP). 2006. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 55(RR-7):123.[PubMed]
129. Bialek SR, Thoroughman DA, Hu D, Simard EP, Chattin J, Cheek J, Bell BP. 2004. Hepatitis A incidence and hepatitis A vaccination among American Indians and Alaska Natives, 1990–2001. Am J Public Health 94:9961001.[PubMed]
130. Wasley A, Miller JT, Finelli L Centers for Disease Control and Prevention (CDC). 2007. Surveillance for acute viral hepatitis—United States, 2005. MMWR Surveill Summ 56:124.[PubMed]
131. Ly KN, Klevens RM. 2015. Trends in disease and complications of hepatitis A virus infection in the United States, 1999–2011: a new concern for adults. J Infect Dis 212:176182.[PubMed]
132. Klevens RM, Denniston MM, Jiles-Chapman RB, Murphy TV. 2015. Decreasing immunity to hepatitis A virus infection among US adults: findings from the National Health and Nutrition Examination Survey (NHANES), 1999–2012. Vaccine 33:61926198.[PubMed]
133. Collier MG, Khudyakov YE, Selvage D, Adams-Cameron M, Epson E, Cronquist A, Jervis RH, Lamba K, Kimura AC, Sowadsky R, Hassan R, Park SY, Garza E, Elliott AJ, Rotstein DS, Beal J, Kuntz T, Lance SE, Dreisch R, Wise ME, Nelson NP, Suryaprasad A, Drobeniuc J, Holmberg SD, Xu F Hepatitis A Outbreak Investigation Team. 2014. Outbreak of hepatitis A in the USA associated with frozen pomegranate arils imported from Turkey: an epidemiological case study. Lancet Infect Dis 14:976981.[PubMed]
134. Centers for Disease Control and Prevention, Department of Health and Human Services. 2013. Surveillance for acute viral hepatitis—United States, 2013. Centers for Disease Control and Prevention, Atlanta, GA.
135. Tjon GM, Coutinho RA, van den Hoek A, Esman S, Wijkmans CJ, Hoebe CJ, Wolters B, Swaan C, Geskus RB, Dukers N, Bruisten SM. 2006. High and persistent excretion of hepatitis A virus in immunocompetent patients. J Med Virol 78:13981405.[PubMed]
136. Steffen R, Kane MA, Shapiro CN, Billo N, Schoellhorn KJ, van Damme P. 1994. Epidemiology and prevention of hepatitis A in travelers. JAMA 272:885889.[PubMed]
137. Weinberg M, Hopkins J, Farrington L, Gresham L, Ginsberg M, Bell BP. 2004. Hepatitis A in Hispanic children who live along the United States-Mexico border: the role of international travel and food-borne exposures. Pediatrics 114:e68e73.[PubMed]
138. Villano SA, Nelson KE, Vlahov D, Purcell RH, Saah AJ, Thomas DL. 1997. Hepatitis A among homosexual men and injection drug users: more evidence for vaccination. Clin Infect Dis 25:726728.[PubMed]
139. Hutin YJ, Sabin KM, Hutwagner LC, Schaben L, Shipp GM, Lord DM, Conner JS, Quinlisk MP, Shapiro CN, Bell BP. 2000. Multiple modes of hepatitis A virus transmission among methamphetamine users. Am J Epidemiol 152:186192.[PubMed]
140. Mannucci PM, Gdovin S, Gringeri A, Colombo M, Mele A, Schinaia N, Ciavarella N, Emerson SU, Purcell RH Italian Collaborative Group. 1994. Transmission of hepatitis A to patients with hemophilia by factor VIII concentrates treated with organic solvent and detergent to inactivate viruses. Ann Intern Med 120:17.[PubMed]
141. Franco E, Giambi C, Ialacci R, Coppola RC, Zanetti AR. 2003. Risk groups for hepatitis A virus infection. Vaccine 21:22242233.[PubMed]
142. Fiore AE. 2004. Hepatitis A transmitted by food. Clin Infect Dis 38:705715.[PubMed]
143. Sane J, MacDonald E, Vold L, Gossner C, Severi E Outbreak Investigation Team. 2015. Multistate foodborne hepatitis A outbreak among European tourists returning from Egyptneed for reinforced vaccination recommendations, November 2012 to April 2013. Euro Surveill 20:Article 21018.[PubMed]
144. Hadler SC, Webster HM, Erben JJ, Swanson JE, Maynard JE. 1980. Hepatitis A in day-care centers. A community-wide assessment. N Engl J Med 302:12221227.[PubMed]
145. Goodman RA. 1985. Nosocomial hepatitis A. Ann Intern Med 103:452454.[PubMed]
146. Trout D, Mueller C, Venczel L, Krake A. 2000. Evaluation of occupational transmission of hepatitis A virus among wastewater workers. J Occup Environ Med 42:8387.[PubMed]
147. Yao G,. 1991. Clinical spectrum and natural history of viral hepatitis A in a 1988 Shanghai epidemic, p 7678. In Hollinger FB, Lemon SM, Margolis HS (ed), Viral Hepatitis and Liver Diseases. Williams and Wilkens, Baltimore.
148. Tong MJ, Thursby M, Rakela J, McPeak C, Edwards VM, Mosley JW. 1981. Studies on the maternal-infant transmission of the viruses which cause acute hepatitis. Gastroenterology 80:9991004.[PubMed]
149. Schiff ER. 1992. Atypical clinical manifestations of hepatitis A. Vaccine 10(Suppl 1):S18S20.[PubMed]
150. Jung YM, Park SJ, Kim JS, Jang JH, Lee SH, Kim JW, Park YM, Hwang SG, Rim KS, Kang SK, Lee HS, Yun HS, Jee YM, Jeong SH. 2010. Atypical manifestations of hepatitis A infection: a prospective, multicenter study in Korea. J Med Virol 82:13181326.[PubMed]
151. Bornstein JD, Byrd DE, Trotter JF. 1999. Relapsing hepatitis A: a case report and review of the literature. J Clin Gastroenterol 28:355356.[PubMed]
152. Sjogren MH, Tanno H, Fay O, Sileoni S, Cohen BD, Burke DS, Feighny RJ. 1987. Hepatitis A virus in stool during clinical relapse. Ann Intern Med 106:221226.[PubMed]
153. Taylor RM, Davern T, Munoz S, Han SH, McGuire B, Larson AM, Hynan L, Lee WM, Fontana RJ US Acute Liver Failure Study Group. 2006. Fulminant hepatitis A virus infection in the United States: incidence, prognosis, and outcomes. Hepatology 44:15891597.[PubMed]
154. Masada CT, Shaw BW Jr, Zetterman RK, Kaufman SS, Markin RS. 1993. Fulminant hepatic failure with massive necrosis as a result of hepatitis A infection. J Clin Gastroenterol 17:158162.[PubMed]
155. Vento S, Garofano T, Renzini C, Cainelli F, Casali F, Ghironzi G, Ferraro T, Concia E. 1998. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N Engl J Med 338:286290.[PubMed]
156. Wiedmann M, Boehm S, Schumacher W, Swysen C, Zauke M. 2003. Evaluation of three commercial assays for the detection of hepatitis Avirus. Eur J Clin Microbiol Infect Dis 22:129130.[PubMed]
157. Centers for Disease Control and Prevention (CDC). 2005. Positive test results for acute hepatitis A virus infection among persons with no recent history of acute hepatitis—United States, 2002–2004. MMWR Morb Mortal Wkly Rep 54:453456.[PubMed]
158. Nainan OV, Xia G, Vaughan G, Margolis HS. 2006. Diagnosis of hepatitis A virus infection: a molecular approach. Clin Microbiol Rev 19:6379.[PubMed]
159. Nainan OV, Armstrong GL, Han XH, Williams I, Bell BP, Margolis HS. 2005. Hepatitis A molecular epidemiology in the United States, 1996–1997: sources of infection and implications of vaccination policy. J Infect Dis 191:957963.[PubMed]
160. Koopmans M, von Bonsdorff CH, Vinjé J, de Medici D, Monroe S. 2002. Foodborne viruses. FEMS Microbiol Rev 26:187205.[PubMed]
161. Mbithi JN, Springthorpe VS, Boulet JR, Sattar SA. 1992. Survival of hepatitis A virus on human hands and its transfer on contact with animate and inanimate surfaces. J Clin Microbiol 30:757763.[PubMed]
162. Garner JS Hospital Infection Control Practices Advisory Committee. 1996. Guideline for isolation precautions in hospitals. Infect Control Hosp Epidemiol 17:5480.[PubMed]
163. Winokur PL, Stapleton JT. 1992. Immunoglobulin prophylaxis for hepatitis A. Clin Infect Dis 14:580586.[PubMed]
164. Cohn EJ, Oncley JL, Strong LE, Hughes WL Jr, Armstrong SH Jr. 1944. Chemical, clinical, and immunological studies on the products of human plasma fractionation. I. The characterization of the protein fractions of human plasma. J Clin Invest 23:417432.[PubMed]
165. Conrad ME, Lemon SM. 1987. Prevention of endemic icteric viral hepatitis by administration of immune serum gamma globulin. J Infect Dis 156:5663.[PubMed]
166. Ellerbeck EF, Lewis JA, Nalin D, Gershman K, Miller WJ, Armstrong ME, Davide JP, Rhoad AE, McGuire B, Calandra G, Provost PJ, Midthun K. 1992. Safety profile and immunogenicity of an inactivated vaccine derived from an attenuated strain of hepatitis A. Vaccine 10:668672.[PubMed]
167. Midthun K, Ellerbeck E, Gershman K, Calandra G, Krah D, McCaughtry M, Nalin D, Provost P. 1991. Safety and immunogenicity of a live attenuated hepatitis A virus vaccine in seronegative volunteers. J Infect Dis 163:735739.[PubMed]
168. Bruguera M, Bayas J-M, Vilella A, Tural C, González A, Vidal J, Dal-Ré R, Salleras L. 1996. Immunogenicity and reactogenicity of a combined hepatitis A and B vaccine in young adults. Vaccine 14:14071411.[PubMed]
169. Innis BL, Snitbhan R, Kunasol P, Laorakpongse T, Poopatanakool W, Kozik CA, Suntayakorn S, Suknuntapong T, Safary A, Tang DB, Boslego JW. 1994. Protection against hepatitis A by an inactivated vaccine. JAMA 271:13281334.
170. Mao JS, Chai SA, Xie RY, Chen NL, Jiang Q, Zhu XZ, Zhang SY, Huang HY, Mao HW, Bao XN, Liu CJ. 1997. Further evaluation of the safety and protective efficacy of live attenuated hepatitis A vaccine (H2-strain) in humans. Vaccine 15:944947.[PubMed]