Chapter 28 : Human Herpesviruses 6, 7, and 8

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

Preview this chapter:
Zoom in

Human Herpesviruses 6, 7, and 8, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815974/9781555814625_Chap28-1.gif /docserver/preview/fulltext/10.1128/9781555815974/9781555814625_Chap28-2.gif


Human herpesvirus 6 (HHV-6), HHV-7, and HHV-8 (also known as Kaposi’s sarcoma [KS]-associated herpesvirus) were discovered between 1986 and 1994. HHV-8 is the etiologic agent of KS and has been closely associated with multicentric Castleman’s disease (MCD) and a form of body cavity lymphoma known as primary effusion lymphoma (PEL). The major applications of HHV-6 serology are for (i) discriminating primary HHV-6 infections from adverse vaccine reactions in young children and (ii) detecting temporal changes in serostatus as part of diagnosing possible HHV-6 involvement in an acute clinical event. In addition to the extensive antigenic cross-reactivity between the HHV-6 variants, the variants have sufficient cross-reactivity with HHV-7 to lead to occasional false-positive results unless antigen adsorptions are done or an immunoblot assay is used that is based on non-cross-reactive antigens. During the AIDS epidemic, the incidence of KS dramatically increased, and it is now the most common malignancy in all segments of the population. The major application of HHV-8 diagnostic tests is in research studies of epidemiology, transmission, and new disease associations. Reports of HHV-8 associations with sarcoidosis and angiosarcoma were followed by several reports of no involvement of HHV-8 with these diseases. Other disease associations for HHV-8 have been reported for various lymphomas, cutaneous neoplasms, encephalitis, and Bowen’s disease, but investigations have been too few or the diseases too rare to rigorously confirm or refute any involvement of HHV-8.

Citation: Pellett P, Dollard S. 2009. Human Herpesviruses 6, 7, and 8, p 494-522. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch28
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

HHV-6B (A) and HHV-7 (B) virions grown in cord blood lymphocytes. Virus particles are extracellular and mature. Culture material was provided by Jodi Black and Carlos Lopez, and electron microscopy and photography were by Cynthia Goldsmith, Centers for Disease Control and Prevention. Bars = 100 nm.

Citation: Pellett P, Dollard S. 2009. Human Herpesviruses 6, 7, and 8, p 494-522. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch28
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Immune response to HHV-6 showing the temporal relationship between viral load, the clinical signs and symptoms of infection (roseola), and the production of specific IgM and IgG antibodies.

Citation: Pellett P, Dollard S. 2009. Human Herpesviruses 6, 7, and 8, p 494-522. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch28
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

HHV-8 virions in BCBL-1 cells incubated with 0.3 mM sodium butyrate for 5 days. Boxed areas in panel B are shown at higher magnification in panels A, C, and D. (B) Induced cells show signs of lytic infection including condensed and marginated chromatin and numerous nuclear inclusions that contain maturing virus particles (A). Virions in membrane-bound vesicles associated with the nuclear (C) and cytoplasmic (D) membranes are shown. Culture material was provided by Margaret Offermann (Emory University) and Jodi Black (Centers for Disease Control and Prevention [CDC]) (Yu et al., 1999). Electron microscopy and photography were by Cynthia Goldsmith, CDC. Bars = 1 µm (B) and 100 nm (A, C, and D).

Citation: Pellett P, Dollard S. 2009. Human Herpesviruses 6, 7, and 8, p 494-522. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch28
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Relative HHV-8 antibody reactivity measured by enzyme-linked immunosorbent assay with recombinant ORF 65 protein among various groups: 1, patients with AIDS KS; 2, HIV-infected homosexual men without KS; 3, United Kingdom blood donors; 4, intravenous drug users; 5, hemophiliacs. O.D., optical density. Figure courtesy of Thomas Schulz, Hannover Medical School, and The Lancet Ltd. (Simpson et al., 1996). Reprinted with permission from Elsevier.

Citation: Pellett P, Dollard S. 2009. Human Herpesviruses 6, 7, and 8, p 494-522. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch28
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Ablashi, D. V.,, N. Balachandran,, S. F. Josephs,, C. L. Hung,, G. R. F. Krueger,, B. Kramarsky,, S. Z. Salahuddin, and, R. C. Gallo. 1991. Genomic polymorphism, growth properties, and immunologic variations in human herpesvirus-6 isolates. Virology 184: 545552.
2. Ablashi, D. V.,, L. G. Chatlynne,, J. E. Whitman, Jr., and, E. Cesarman. 2002. Spectrum of Kaposi’s sarcoma-associated herpesvirus, or human herpesvirus 8, diseases. Clin. Microbiol. Rev. 15: 439464.
3. Ablashi, D. V.,, M. Handy,, J. Bernbaum,, L. G. Chatlynne,, W. Lapps,, B. Kramarsky,, Z. N. Berneman,, A. L. Komaroff, and, J. E. Whitman. 1998. Propagation and characterization of human herpesvirus-7 (HHV-7) isolates in a continuous Tlymphoblastoid cell line (SupT1). J. Virol. Methods 73: 123140.
4. Ablashi, D. V.,, W. Lapps,, M. Kaplan,, J. E. Whitman,, J. R. Richert, and, G. R. Pearson. 1999. Human herpesvirus-6 (HHV-6) infection in multiple sclerosis: a preliminary report. Mult. Scler. 4: 490496.
5. Achour, A.,, D. Boutolleau,, A. Gautheret-Dejean, and, H. Agut. 2006. Is human herpesvirus-6 DNA in plasma the right marker for active infection? J. Infect. Dis. 194: 17951796.
6. Achour, A.,, D. Boutolleau,, A. Slim,, H. Agut, and, A. Gautheret-Dejean. 2007. Human herpesvirus-6 (HHV-6) DNA in plasma reflects the presence of infected blood cells rather than circulating viral particles. J. Clin. Virol. 38: 280285.
7. Akhyani, N.,, J. Fotheringham,, K. Yao,, F. Rashti, and, S. Jacobson. 2006. Efficacy of antiviral compounds in human herpesvirus-6-infected glial cells. J. Neurovirol. 12: 284293.
8. Alvarez-Lafuente, R.,, V. De Las Heras,, M. Bartolome,, M. Garcia-Montojo, and, R. Arroyo. 2006. Human herpesvirus 6 and multiple sclerosis: a one-year follow-up study. Brain Pathol. 16: 2027.
9. Andre-Garnier, E.,, N. Robillard,, M. Costa-Mattioli,, B. Besse,, S. Billaudel, and, B. M. Imbert-Marcille. 2003. A one-step RTPCR and a flow cytometry method as two specific tools for direct evaluation of human herpesvirus-6 replication. J. Virol. Methods 108: 213222.
10. Andreoni, M.,, D. Goletti,, P. Pezzotti,, A. Pozzetto,, P. Monini,, L. Sarmati,, F. Farchi,, G. Tisone,, A. Piazza,, F. Pisani,, M. Angelico,, P. Leone,, F. Citterio,, B. Ensoli, and, G. Rezza. 2001. Prevalence, incidence and correlates of HHV-8/KSHV infection and Kaposi’s sarcoma in renal and liver transplant recipients. J. Infect. 43: 195199.
11. Andreoni, M.,, L. Sarmati,, E. Nicastri,, G. El Sawaf,, M. El Zalabani,, I. Uccella,, R. Bugarini,, S. G. Parisi, and, G. Rezza. 2002. Primary human herpesvirus 8 infection in immunocompetent children. JAMA 287: 12951300.
12. Asada, H.,, V. Klaus-Kovtun,, H. Golding,, S. I. Katz, and, A. Blauvelt. 1999. Human herpesvirus 6 infects dendritic cells and suppresses human immunodeficiency virus type 1 replication in coinfected cultures. J. Virol. 73: 40194028.
13. Asano, Y.,, T. Nakashima,, T. Yoshikawa,, S. Suga, and, T. Yazaki. 1991a. Severity of human herpesvirus-6 viremia and clinical findings in infants with exanthem subitum. J. Pediatr. 118: 891895.
14. Asano, Y.,, T. Yoshikawa,, S. Suga,, T. Hata,, T. Yamazaki, and, T. Yazaki. 1991b. Simultaneous occurrence of human herpesvirus 6 infection and intussusception in three infants. Ped. Infect. Dis. J. 10: 335337.
15. Asano, Y.,, T. Yoshikawa,, S. Suga,, I. Kobayashi,, T. Nakashima,, T. Yazaki,, Y. Kajita, and, T. Ozaki. 1994. Clinical features of infants with primary human herpesvirus 6 infection (exanthem subitum, roseola infantum). Pediatrics 93: 104108.
16. Atkinson, J. O.,, R. J. Biggar,, J. J. Goedert, and, E. A. Engels. 2004. The incidence of Kaposi sarcoma among injection drug users with AIDS in the United States. J. Acquir. Immune Defic. Syndr. 37: 12821287.
17. Aubin, J. T.,, H. Agut,, H. Collandre,, K. Yamanishi,, B. Chandran,, L. Montagnier, and, J. M. Huraux. 1993. Antigenic and genetic differentiation of the two putative types of human herpes virus 6. J. Virol. Methods 41: 223234.
18. Aubin, J. T.,, L. Poirel,, C. Robert,, J. M. Huraux, and, H. Agut. 1994. Identification of human herpesvirus 6 variants A and B by amplimer hybridization with variant-specific oligonucleotides and amplification with variant-specific primers. J. Clin. Microbiol. 32: 24342440.
19. Balachandra, K.,, P. Bowonkiratikachorn,, B. Poovijit,, A. Thattiyaphong,, C. Jayavasu,, C. Wasi,, M. Takahashi, and, K. Yamanishi. 1991. Human herpesvirus 6 (HHV-6) infection and exanthem subitum in Thailand. Acta Paediatr. Jpn. 33: 434439.
20. Ballestas, M. E.,, P. A. Chatis,, and K. M. Kaye. 1999. Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284: 641644.
21. Barozzi, B.,, M. Luppi,, F. Facchetti,, C. Mecucci,, M. Alu,, R. Sarid,, V. Rasini,, L. Ravazzini,, E. Rossi,, S. Festa,, B. Crescenzi,, D. Wolf,, T. Schulz, and, G. Torelli. 2003. Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors. Nat. Med. 9: 554561.
22. Bechtel, J.,, A. Grundhoff, and, D. Ganem. 2005. RNAs in the virion of Kaposi’s sarcoma-associated herpesvirus. J. Virol. 79: 1013810146.
23. Bechtel, J. T.,, Y. Liang,, J. Hvidding, and, D. Ganem. 2003. Host range of Kaposi’s sarcoma-associated herpesvirus in cultured cells. J. Virol. 77: 64746481.
24. Beral, V.,, T. A. Peterman,, R. L. Berkelman, and, H. W. Jaffe. 1990. Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 335: 123128.
25. Berenson, J. R.,, and R. A. Vescio. 1999. HHV-8 is present in multiple myeloma patients. Blood 93: 31573159.
26. Berneman, Z. N.,, D. V. Ablashi,, G. Li,, M. Eger-Fletcher,, M. S. Reitz, Jr.,, C. L. Hung,, I. Brus,, A. L. Komaroff, and, R. C. Gallo. 1992. Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human cytomegalovirus. Proc. Natl. Acad. Sci. USA 89: 1055210556.
27. Biggar, R. J.,, E. A. Engels,, D. Whitby,, D. H. Kedes, and, J. J. Goedert. 2003. Antibody reactivity to latent and lytic antigens to human herpesvirus-8 in longitudinally followed homosexual men. J Infect. Dis. 187: 1218.
28. Black, J. B.,, D. A. Burns,, C. S. Goldsmith,, P. M. Feorino,, K. Kite-Powell,, R. F. Schinazi,, P. W. Krug, and, P. E. Pellett. 1997. Biologic properties of human herpesvirus 7 strain SB. Virus Res. 52: 2541.
29. Black, J. B.,, E. Durigon,, K. Kite-Powell,, L. de Souza,, S. P. Curli,, A. M. S. Afonso,, M. Theobaldo, and, P. E. Pellett. 1996a. Seroconversion to human herpesvirus 6 and human herpesvirus 7 among Brazilian children with clinical diagnoses of measles or rubella. Clin. Infect. Dis. 23: 11561158.
30. Black, J. B.,, N. Inoue,, K. Kite-Powell,, S. Zaki, and, P. E. Pellett. 1993. Frequent isolation of human herpesvirus 7 from saliva. Virus Res. 29: 9198.
31. Black, J. B.,, K. C. Sanderlin,, C. S. Goldsmith,, H. E. Gary,, C. Lopez, and, P. E. Pellett. 1989. Growth properties of human herpesvirus-6 strain Z29. J. Virol. Methods 26: 133145.
32. Black, J. B.,, T. F. Schwarz,, J. L. Patton,, K. Kite-Powell,, P. E. Pellett,, S. Wiersbitzky,, R. Bruns,, C. Muller,, G. Jager, and, J. Stewart. 1996b. Evaluation of immunoassays for detection of antibodies to human herpesvirus 7. Clin. Diagn. Lab. Immunol. 3: 7983.
33. Blackbourn, D. J.,, E. Lennette,, B. Klencke,, A. Moses,, B. Chandran,, M. Weinstein,, R. G. Glogau,, M. H. Witte,, D. L. Way,, T. Kutzkey,, B. Herndier, and, J. A. Levy. 2000. The restricted cellular host range of human herpesvirus 8. AIDS 14: 11231133.
34. Blackbourn, D. J.,, E. T. Lennette,, J. Ambroziak,, D. V. Mourich, and, J. A. Levy. 1998. Human herpesvirus 8 detection in nasal secretions and saliva. J. Infect. Dis. 177: 213216.
35. Blackbourn, D. J.,, and J. A. Levy. 1997. Human herpesvirus 8 in semen and prostate. AIDS 11: 249250.
36. Blackbourn, D. J.,, D. Osmond,, J. A. Levy, and, E. T. Lennette. 1999. Increased human herpesvirus 8 seroprevalence in young homosexual men who have multiple sex contacts with different partners. J. Infect. Dis. 179: 237239.
37. Borghi, E.,, E. Pagani,, R. Mancuso,, S. Delbue,, M. Valli,, R. Mazziotti,, L. Giordano,, R. Micheli, and, P. Ferrante. 2005. Detection of herpesvirus-6A in a case of subacute cerebellitis and myoclonic dystonia. J. Med. Virol. 75: 427429.
38. Boshoff, C.,, T. F. Schultz,, M. M. Kennedy,, A. K. Graham,, C. Fisher,, A. Thomas,, J. O. McGee,, R. A. Weiss, and, J. J. O’Leary. 1995. Kaposi’s sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat. Med. 1: 12741278.
39. Bourboulia, D.,, D. Whitby,, C. Boshoff,, R. Newton,, V. Beral,, H. Carrara,, A. Lane, and, F. Sitas. 1998. Serologic evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus infection. JAMA 280: 3132.
40. Boutolleau, D.,, H. Agut, and, A. Gautheret-Dejean. 2006a. Human herpesvirus 6 genome integration: a possible cause of misdiagnosis of active viral infection? J. Infect. Dis. 194: 10191020.
41. Boutolleau, D.,, C. Duros,, P. Bonnafous,, D. Caiola,, A. Karras,, N. D. Castro,, M. Ouachee,, P. Narcy,, M. Gueudin,, H. Agut, and, A. Gautheret-Dejean. 2006b. Identification of human herpesvirus 6 variants A and B by primer-specific real-time PCR may help to revisit their respective role in pathology. J. Clin. Virol. 35: 257263.
42. Braun, D. K.,, G. Dominguez, and, P. E. Pellett. 1997. Human herpesvirus 6. Clin. Microbiol. Rev. 10: 521567.
43. Brayfield, B. P.,, C. Kankasa,, J. T. West,, J. Muyanga,, G. Bhat,, W. Klaskala,, C. D. Mitchell, and, C. Wood. 2004. Distribution of Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 in maternal saliva and breast milk in Zambia: implications for transmission. J. Infect. Dis. 189: 22602270.
44. Brayfield, B. P.,, S. Phiri,, C. Kankasa,, J. Muyanga,, H. Mantina,, G. Kwenda,, J. T. West,, G. Bhat,, D. B. Marx,, W. Klaskala,, C. D. Mitchell, and, C. Wood. 2003. Postnatal human herpes-virus 8 and human immunodeficiency virus type 1 infection in mothers and infants from Zambia. J. Infect. Dis. 187: 559568.
45. Bultmann, B. D.,, K. Klingel,, M. Nabauer,, D. Wallwiener, and, R. Kandolf. 2005. High prevalence of viral genomes and inflammation in peripartum cardiomyopathy. Am. J. Obstet. Gynecol. 193: 363365.
46. Cacheux, W.,, N. Carbonell,, O. Rosmorduc,, D. Wendum,, F. Paye,, R. Poupon,, O. Chazouilleres, and, J. Gozlan. 2005. HHV-6-related acute liver failure in two immunocompetent adults: favourable outcome after liver transplantation and/or ganciclovir therapy. J. Intern. Med. 258: 573578.
47. Calabro, M. L.,, J. R. Fiore,, A. Favero,, A. Lepera,, A. Saracino,, G. Angarano,, T. F. Schulz, and, L. Chieco-Bianchi. 1999. Detection of human herpesvirus 8 in cervicovaginal secretions and seroprevalence in human immunodeficiency virus type 1-seropositive and -seronegative women. J. Infect. Dis. 179: 15341537.
48. Campadelli-Fiume, G.,, S. Guerrini,, X. Liu, and, L. Foa-Tomasi. 1993. Monoclonal antibodies to glycoprotein B differentiate human herpesvirus 6 into two clusters, variants A and B. J. Gen. Virol. 74: 22572262.
49. Campadelli-Fiume, G.,, P. Mirandola, and, L. Menotti. 1999. Human herpesvirus 6: an emerging pathogen. Emerg. Infect. Dis. 5: 353366.
50. Campbell, T. B.,, M. Borok,, L. Gwanzura,, S. MaWhinney,, I. E. White,, B. Ndemera,, I. Gudza,, L. Fitzpatrick, and, R. T. Schooley. 2000. Relationship of human herpesvirus 8 peripheral blood virus load and Kaposi’s sarcoma clinical stage. AIDS 14: 21092116.
51. Cannon, M. J.,, S. C. Dollard,, J. B. Black,, B. R. Edlin,, C. Hannah,, S. E. Hogan,, M. M. Patel,, H. W. Jaffe,, M. K. Offermann,, T. J. Spira,, P. E. Pellett, and, C. J. Gunthel. 2003. Risk factors for Kaposi’s sarcoma in men seropositive for both human herpesvirus 8 and human immunodeficiency virus. AIDS 17: 215222.
52. Cannon, M. J.,, S. C. Dollard,, D. K. Smith,, R. S. Klein,, P. Schuman,, J. D. Rich,, D. Vlahov, and, P. E. Pellett for the HIV Epidemiology Research Study Group. 2001. Blood-borne and sexual transmission of human herpesvirus 8 in women with or at risk for human immunodeficiency virus infection. N. Engl. J. Med. 344: 637643.
53. Capouya, J. D.,, D. M. Berman, and, J. A. Dumois. 2006. Mollaret’s meningitis due to human herpesvirus 6 in an adolescent. Clin. Pediatr. (Philadelphia) 45: 861863.
54. Carrigan, D. R.,, and K. K. Knox. 1994. Human herpesvirus 6 (HHV-6) isolation from bone marrow: HHV-6-associated bone marrow suppression in bone marrow transplant patients. Blood 84: 33073310.
55. Caserta, M. T.,, C. B. Hall,, K. Schnabel,, G. Lofthus, and, M. P. McDermott. 2007. Human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) infections of pregnant women. J. Infect. Dis. 196: 12961303.
56. Caserta, M. T.,, C. B. Hall,, K. Schnabel,, C. E. Long, and, N. D’Heron. 1998. Primary human herpesvirus 7 infection: a comparison of human herpesvirus 7 and human herpesvirus 6 infections in children. J. Pediatr. 133: 386389.
57. Caserta, M. T.,, C. B. Hall,, K. Schnabel,, K. McIntyre,, C. Long,, M. Costanzo,, S. Dewhurst,, R. Insel, and, L. G. Epstein. 1994. Neuroinvasion and persistence of human herpesvirus 6 in children. J. Infect. Dis. 170: 15861589.
58. Caserta, M. T.,, M. P. McDermott,, S. Dewhurst,, K. Schnabel,, J. A. Carnahan,, L. Gilbert,, G. Lathan,, G. K. Lofthus, and, C. B. Hall. 2004. Human herpesvirus 6 (HHV6) DNA persistence and reactivation in healthy children. J. Pediatr. 145: 478484.
59. Cattelan, A. M.,, M. L. Calabro,, P. Gasperini,, S. M. Aversa,, M. Zanchetta,, F. Meneghetti,, A. De Rossi, and, L. Chieco-Bianchi. 2001. Acquired immunodeficiency syndrome-related Kaposi’s sarcoma regression after highly active antiretroviral therapy: biologic correlates of clinical outcome. J. Natl. Cancer Inst. Monogr. 2001: 4449.
60. Centers for Disease Control and Prevention. 1999. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. MMWR Recommed. Rep. 48 (RR-10): 166.
61. Cermelli, C.,, P. Pietrosemoli,, M. Meacci,, M. Pecorari,, A. M. Sabbatini,, B. Colombari, and, M. Portolani. 1997. SupT-1: a cell system suitable for an efficient propagation of both HHV-7 and HHV-6 variants A and B. New Microbiol. 20: 187196.
62. Cesarman, E.,, Y. Chang,, P. S. Moore,, J. W. Said, and, D. M. Knowles. 1995. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body cavity-based lymphomas. N. Engl. J. Med. 332: 11861191.
63. Cesarman, E.,, and D. M. Knowles. 1999. The role of Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) in lymphoproliferative diseases. Semin. Cancer Biol. 9: 165174.
64. Challoner, P. B.,, K. T. Smith,, J. D. Parker,, D. L. MacLeod,, S. N. Coulter,, T. M. Rose,, E. R. Schultz,, J. L. Bennett,, R. L. Garber,, M. Chang,, P. A. Schad,, P. M. Stewart,, R. C. Nowinski,, J. P. Brown, and, G. C. Burmer. 1995. Plaque-associated expression of human herpesvirus 6 in multiple sclerosis. Proc. Natl. Acad. Sci. USA 92: 74407444.
65. Chan, P. K.,, C. K. Li,, K. W. Chik,, V. Lee,, M. M. Shing,, K. C. Ng,, J. L. Cheung,, T. F. Fok, and, A. F. Cheng. 2004. Risk factors and clinical consequences of human herpesvirus 7 infection in paediatric haematopoietic stem cell transplant recipients. J. Med. Virol. 72: 668674.
66. Chandran, B.,, M. S. Smith,, D. M. Koelle,, L. Corey,, R. Horvat, and, E. Goldstein. 1998. Reactivities of human sera with human herpesvirus-8-infected BCBL-1 cells and identification of HHV-8-specific proteins and glycoproteins and the encoding cDNAs. Virology 243: 208217.
67. Chandran, B.,, S. Tirawatnapong,, B. Pfeiffer, and, D. V. Ablashi. 1992. Antigenic relationships among human herpesvirus-6 isolates. J. Med. Virol. 37: 247254.
68. Chang, Y.,, E. Cesarman,, M. S. Pessin,, F. Lee,, J. Culpepper,, D. M. Knowles, and, P. S. Moore. 1994. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266: 18651869.
69. Chapenko, S.,, I. Folkmane,, V. Tomsone,, S. Kozireva,, J. Bicans,, D. Amerika,, R. Rozentals, and, M. Murovska. 2001. Infection of beta-herpesviruses (CMV, HHV-6, HHV-7): role in post-renal transplantation complications. Transplant. Proc. 33: 24632464.
70. Chatlynne, L. G.,, W. Lapps,, M. Handy,, Y. Q. Huang,, R. Masood,, A. S. Hamilton,, J. W. Said,, H. P. Koeffler,, M. H. Kaplan,, A. Friedman-Kien,, P. S. Gill,, J. E. Whitman, and, D. V. Ablashi. 1998. Detection and titration of human herpesvirus-8-specific antibodies in sera from blood donors, acquired immunodeficiency syndrome patients, and Kaposi’s sarcoma patients using a whole virus enzyme-linked immunosorbent assay. Blood 92: 5358.
71. Cheuk, W.,, K. O. Wong,, C. S. Wong,, J. E. Dinkel,, D. Ben Dor, and, J. K. Chan. 2004. Immunostaining for human herpes-virus 8 latent nuclear antigen-1 helps distinguish Kaposi sarcoma from its mimickers. Am. J. Clin. Pathol. 121: 335342.
72. Chiu, S. S.,, C. Y. Cheung,, C. Y. Tse, and, M. Peiris. 1998. Early diagnosis of primary human herpesvirus 6 infection in childhood: serology, polymerase chain reaction, and virus load. J. Infect. Dis. 178: 12501256.
73. Chokephaibulkit, K.,, P. A. Brunell,, V. Vimal,, C. Long,, K. Schnabel, and, C. B. Hall. 1997. Enzyme-linked immunosorbent assay for detection of antibody to human herpesvirus 6. Clin. Diagn. Lab. Immunol. 4: 687691.
74. Chou, S.,, and G. I. Marousek. 1994. Analysis of interstrain variation in a putative immediate-early region of human herpesvirus 6 DNA and definition of variant-specific sequences. Virology 198: 370376.
75. Clark, D. A.,, M. Ait-Khaled,, A. C. Wheeler,, I. M. Kidd,, J. E. McLaughlin,, M. A. Johnson,, P. D. Griffiths, and, V. C. Emery. 1996. Quantification of human herpesvirus 6 in immunocompetent persons and post-mortem tissues from AIDS patients by PCR. J. Gen. Virol. 77: 22712275.
76. Clark, D. A.,, M. L. Freeland,, L. K. Mackie,, R. F. Jarrett, and, D. E. Onions. 1993. Prevalence of antibody to human herpes-virus 7 by age. J. Infect. Dis. 168: 251252.
77. Clark, D. A.,, I. M. Kidd,, K. E. Collingham,, M. Tarlow,, T. Aueni,, A. Riordan,, P. D. Griffiths,, V. C. Emery, and, D. Pillay. 1997. Diagnosis of primary human herpesvirus 6 and 7 infections in febrile infants by polymerase chain reaction. Arch. Dis. Child. 77: 4245.
78. Clark, D. A.,, E. P. Nacheva,, H. N. Leong,, D. Brazma,, Y. T. Li,, E. H. Tsao,, H. C. Buyck,, C. E. Atkinson,, H. M. Lawson,, M. N. Potter, and, P. D. Griffiths. 2006a. Transmission of integrated human herpesvirus 6 through stem cell transplantation: implications for laboratory diagnosis. J. Infect. Dis. 193: 912916.
79. Clark, D. A.,, E. H. Tsao,, H. N. Leong,, K. N. Ward,, E. P. Nacheva, and, P. D. Griffiths. 2006b. Human herpesvirus 6 genome integration: a possible cause of misdiagnosis of active viral infection? J. Infect. Dis. 194: 10211023.
80. Cohen, A.,, D. G. Wolf,, E. Guttman-Yassky, and, R. Sarid. 2005. Kaposi’s sarcoma-associated herpesvirus: clinical, diagnostic, and epidemiological aspects. Crit. Rev. Clin. Lab. Sci. 42: 101153.
81. Collot, S.,, B. Petit,, D. Bordessoule,, S. Alain,, M. Touati,, F. Denis, and, S. Ranger-Rogez. 2002. Real-time PCR for quantification of human herpesvirus 6 DNA from lymph nodes and saliva. J. Clin. Microbiol. 40: 24452451.
82. Cone, R. W.,, M. L. Huang,, L. Corey,, J. Zeh,, R. Ashley, and, R. Bowden. 1999. Human herpesvirus 6 infections after bone marrow transplantation: clinical and virologic manifestations. J. Infect. Dis. 179: 311318.
83. Cone, R. W.,, M. L. Huang,, R. C. Hackman, and, L. Corey. 1996. Coinfection with human herpesvirus 6 variants A and B in lung tissue. J. Clin. Microbiol. 34: 877881.
84. Cook, P. M.,, D. Whitby,, M. L. Calabro,, M. Luppi,, D. N. Kakoola,, H. Hjalgrim,, K. Ariyoshi,, B. Ensoli,, A. J. Davison,, T. F. Schulz, and the International Collaborative Group. 1999. Variability and evolution of Kaposi’s sarcoma-associated herpesvirus in Europe and Africa. AIDS 13: 11651176.
85. Cool, C. D.,, P. R. Rai,, M. E. Yeager,, D. Hernandez-Saavedra,, A. E. Serls,, T. M. Bull,, M. W. Geraci,, K. K. Brown,, J. M. Routes,, R. M. Tuder, and, N. F. Voelkel. 2003. Expression of human herpesvirus 8 in primary pulmonary hypertension. N. Engl. J. Med. 349: 11131122.
86. Cordero, E.,, L. F. Lopez-Cortes,, P. Viciana,, A. Alarcon, and, J. Pachon. 1997. Foscarnet and AIDS-associated Kaposi’s sarcoma. AIDS 11: 17871788.
87. Costagliola, D.,, M. Mary-Krause, et al. 1995. Can antiviral agents decrease the occurrence of Kaposi’s sarcoma? Lancet 346: 578.
88. Couillard, M.,, J. R. Joly,, L. Deschenes, and, G. Richer. 1992. Evaluation of variables in immunofluorescence procedures for the detection of antibodies against human herpesvirus 6 (HHV-6). Diagn. Microbiol. Infect. Dis. 15: 313320.
89. Coyle, P. V.,, M. Briggs,, R. S. Tedder, and, J. D. Fox. 1992. Comparison of three immunoassays for the detection of anti-HHV6. J. Virol. Methods 38: 283295.
90. Daibata, M.,, I. Miyoshi,, H. Taguchi,, H. Matsubara,, H. Date,, N. Shimizu, and, Y. Ohtsuki. 2004. Absence of human herpesvirus 8 in lung tissues from Japanese patients with primary pulmonary hypertension. Respir. Med. 98: 12311232.
91. Daibata, M.,, T. Taguchi,, T. Sawada,, H. Taguchi, and, I. Miyoshi. 1998. Chromosomal transmission of human herpesvirus 6 DNA in acute lymphoblastic leukaemia. Lancet 352: 543544.
92. Davidkin, I.,, S. Jokinen,, A. Paananen,, P. Leinikki, and, H. Peltola. 2005. Etiology of mumps-like illnesses in children and adolescents vaccinated for measles, mumps, and rubella. J. Infect. Dis. 191: 719723.
93. De Bolle, L.,, D. Michel,, T. Mertens,, C. Manichanh,, H. Agut,, E. De Clercq, and, L. Naesens. 2002. Role of the human herpesvirus 6 u69-encoded kinase in the phosphorylation of ganciclovir. Mol. Pharmacol. 62: 714721.
94. De Bolle, L.,, L. Naesens, and, E. De Clercq. 2005. Update on human herpesvirus 6 biology, clinical features, and therapy. Clin. Microbiol. Rev. 18: 217245.
95. Delbridge, M. S.,, M. S. Karim,, B. M. Shrestha, and, W. McKane. 2006. Colitis in a renal transplant patient with human herpes-virus-6 infection. Transpl. Infect. Dis. 8: 226228.
96. Derfuss, T.,, R. Hohlfeld, and, E. Meinl. 2005. Intrathecal antibody (IgG) production against human herpesvirus type 6 occurs in about 20% of multiple sclerosis patients and might be linked to a polyspecific B-cell response. J. Neurol. 252: 968971.
97. de Sanjose, S.,, V. Marshall,, J. Sola,, V. Palacio,, R. Almirall,, J. J. Goedert,, F. X. Bosch, and, D. Whitby. 2002. Prevalence of Kaposi’s sarcoma-associated herpesvirus infection in sex workers and women from the general population in Spain. Int. J. Cancer 98: 155158.
98. DesJardin, J. A.,, L. Gibbons,, E. Cho,, S. E. Supran,, M. E. Falagas,, B. G. Werner, and, D. R. Snydman. 1998. Human herpesvirus 6 reactivation is associated with cytomegalovirus infection and syndromes in kidney transplant recipients at risk for primary cytomegalovirus infection. J. Infect. Dis. 178: 17831786.
99. Dewhurst, S. 2004. Human herpesvirus type 6 and human herpesvirus type 7 infections of the central nervous system. Herpes 11 (Suppl. 2): 105A111A.
100. Dewhurst, S.,, B. Chandran,, K. McIntyre,, K. Schnabel, and, C. B. Hall. 1992. Phenotypic and genetic polymorphisms among human herpesvirus-6 isolates from North American infants. Virology 190: 490493.
101. Di Lorenzo, G.,, P. A. Konstantinopoulos,, L. Pantanowitz,, R. Di Trolio,, S. De Placido, and, B. J. Dezube. 2007. Management of AIDS-related Kaposi’s sarcoma. Lancet Oncol. 8: 167176.
102. Di Luca, D.,, P. Mirandola,, T. Ravaioli,, B. Bigoni, and, E. Cassai. 1996. Distribution of HHV-6 variants in human tissues. Infect. Agents Dis. 5: 203214.
103. Di Luca, D.,, P. Mirandola,, T. Ravaioli,, R. Dolcetti,, A. Frigatti,, P. Bovenzi,, L. Sighinolfi,, P. Monini, and, E. Cassai. 1995. Human herpesviruses 6 and 7 in salivary glands and shedding in saliva of healthy and human immunodeficiency virus positive individuals. J. Med. Virol. 45: 462468.
104. Dockrell, D. H.,, J. C. Mendez,, M. Jones,, W. S. Harmsen,, D. M. Ilstrup,, T. F. Smith,, R. H. Wiesner,, R. A. Krom, and, C. V. Paya. 1999. Human herpesvirus 6 seronegativity before transplantation predicts the occurrence of fungal infection in liver transplant recipients. Transplantation 67: 399403.
105. Dollard, S. C.,, K. E. Nelson,, P. M. Ness,, V. Stambolis,, M. J. Kuehnert,, P. E. Pellett, and, M. J. Cannon. 2005. Possible transmission of human herpesvirus-8 by blood transfusion in a historical United States cohort. Transfusion (Paris) 45: 500503.
106. Dollard, S. C.,, and P. E. Pellett. 2000. Human herpesviruses 6, 7 and 8. Rev. Med. Microbiol. 11: 113.
107. Dominguez, G.,, T. R. Dambaugh,, F. R. Stamey,, S. Dewhurst,, N. Inoue, and, P. E. Pellett. 1999. Human herpesvirus 6B genome sequence: coding content and comparison with human herpesvirus 6A. J. Virol. 73: 80408052.
108. Drobyski, W. R.,, M. Eberle,, D. Majewski, and, L. A. Baxter-Lowe. 1993. Prevalence of human herpesvirus 6 variant A and B infections in bone marrow transplant recipients as determined by polymerase chain reaction and sequence-specific oligonucleotide probe hybridization. J. Clin. Microbiol. 31: 15151520.
109. Dupin, N.,, C. Fisher,, P. Kellam,, S. Ariad,, M. Tulliez,, N. Franck,, E. van Marck,, D. Salmon,, I. Gorin,, J. P. Escande,, R. A. Weiss,, K. Alitalo, and, C. Boshoff. 1999. Distribution of human herpesvirus-8 latently infected cells in Kaposi’s sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma. Proc. Natl. Acad. Sci. USA 96: 45464551.
110. Emery, V. C.,, M. C. Atkins,, E. F. Bowen,, D. A. Clark,, M. A. Johnson,, I. M. Kidd,, J. E. McLaughlin,, A. N. Phillips,, P. M. Strappe, and, P. D. Griffiths. 1999. Interactions between beta-herpesviruses and human immunodeficiency virus in vivo: evidence for increased human immunodeficiency viral load in the presence of human herpesvirus 6. J. Med. Virol. 57: 278282.
111. Enbom, M.,, C. Martin,, S. Fredrikson,, L. Jagdahl,, H. Dahl, and, A. Linde. 1997. Intrathecal antibody production to lymphotropic herpesviruses in patients with multiple sclerosis. Neurol. Infect. Epidemiol. 2: 107111.
112. Enbom, M.,, J. Sheldon,, E. Lennette,, T. Schulz,, D. V. Ablashi,, F. Neipel,, P. Biberfeld,, H. Carlberg,, P. Ljungman,, A. Nilsson,, T. Soderstrom,, J. Wadstrom, and, A. Linde. 2000. Antibodies to human herpesvirus 8 latent and lytic antigens in blood donors and potential high-risk groups in Sweden: variable frequencies found in a multicenter serological study. J. Med. Virol. 62: 498504.
113. Engels, E. A.,, J. O. Atkinson,, B. I. Graubard,, G. M. McQuillan,, C. Gamache,, G. Mbisa,, S. Cohn,, D. Whitby, and, J. J. Goedert. 2007. Risk factors for human herpesvirus 8 infection among adults in the United States and evidence for sexual transmission. J. Infect. Dis. 196: 199207.
114. Engels, E. A.,, R. J. Biggar,, V. A. Marshall,, M. A. Walters,, C. J. Gamache,, D. Whitby, and, J. J. Goedert. 2003. Detection and quantification of Kaposi’s sarcoma-associated herpesvirus to predict AIDS-associated Kaposi’s sarcoma. AIDS 17: 18471851.
115. Engels, E. A.,, R. M. Pfeiffer,, J. J. Goedert,, P. Virgo,, T. S. McNeel,, S. M. Scoppa, and, R. J. Biggar. 2006. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS 20: 16451654.
116. Engels, E. A.,, D. Whitby,, P. B. Goebel,, A. Stossel,, D. Waters,, A. Pintus,, L. Contu,, R. J. Biggar, and, J. J. Goedert. 2000. Identifying human herpesvirus 8 infection: performance characteristics of serologic assays. J. Acquir. Immune Defic. Syndr. 23: 346354.
117. Feldstein, A. E.,, R. R. Razonable,, T. G. Boyce,, D. K. Freese,, M. El Youssef,, J. Perrault,, C. V. Paya, and, M. B. Ishitani. 2003. Prevalence and clinical significance of human herpesviruses 6 and 7 active infection in pediatric liver transplant patients. Pediatr. Transplant. 7: 125129.
118. Fernandez, F.,, J. Gutierrez,, A. Sorlozano,, J. M. Romero,, M. J. Soto, and, F. Ruiz-Cabello. 2006. Comparison of the SYBR Green and the hybridization probe format for real-time PCR detection of HHV-6. Microbiol. Res. 161: 158163.
119. Fillet, A. M.,, P. Lozeron,, H. Agut,, O. Lyon-Caen, and, R. Liblau. 1998. HHV-6 and multiple sclerosis. Nat. Med. 4: 537.
120. Foa-Tomasi, L.,, E. Avitabile, and, G. Campadelli-Fiume. 1995. Selection of a monoclonal antibody specific for variant B human herpesvirus 6-infected mononuclear cells. J. Virol. Methods 51: 289296.
121. Foa-Tomasi, L.,, E. Avitabile,, L. Ke, and, G. Campadelli-Fiume. 1994. Polyvalent and monoclonal antibodies identify major immunogenic proteins specific for human herpesvirus 7-infected cells and have weak cross-reactivity with human herpesvirus 6. J. Gen. Virol. 75: 27192727.
122. Foa-Tomasi, L.,, M. P. Fiorilli,, E. Avitabile, and, G. Campadelli-Fiume. 1996. Identification of an 85 kDa phosphoprotein as an immunodominant protein specific for human herpesvirus 7-infected cells. J. Gen. Virol. 77: 511518.
123. Fogdell-Hahn, A.,, S. S. Soldan,, S. Shue,, N. Akhyani,, H. Refai,, J. Ahlqvist, and, S. Jacobson. 2005. Co-purification of soluble membrane cofactor protein (CD46) and human herpesvirus 6 variant A genome in serum from multiple sclerosis patients. Virus Res. 110: 5763.
124. Fotheringham, J.,, N. Akhyani,, A. Vortmeyer,, D. Donati,, E. Williams,, U. Oh,, M. Bishop,, J. Barrett,, J. Gea-Banacloche, and, S. Jacobson. 2007a. Detection of active human herpesvirus-6 infection in the brain: correlation with polymerase chain reaction detection in cerebrospinal fluid. J. Infect. Dis. 195: 450454.
125. Fotheringham, J.,, D. Donati,, N. Akhyani,, A. Fogdell-Hahn,, A. Vortmeyer,, J. D. Heiss,, E. Williams,, S. Weinstein,, D. A. Bruce,, W. D. Gaillard,, S. Sato,, W. H. Theodore, and, S. Jacobson. 2007b. Association of human herpesvirus-6B with mesial temporal lobe epilepsy. PLoS Med. 4: e180.
126. Frances, C.,, C. Mouquet,, A. G. Marcelin,, S. Barete,, R. Agher,, D. Charron,, H. Benalia,, N. Dupin,, J. C. Piette,, M. O. Bitker, and, V. Calvez. 2000. Outcome of kidney transplant recipients with previous human herpesvirus-8 infection. Transplantation 69: 17761779.
127. Frenkel, N.,, E. C. Schirmer,, L. S. Wyatt,, G. Katsafanas,, E. Roffman,, R. M. Danovich, and, C. H. June. 1990. Isolation of a new herpesvirus from CD4+ T cells. Proc. Natl. Acad. Sci. USA 87: 748752.
128. Friedman, J. E.,, J. B. Zabriskie,, C. Plank,, D. Ablashi,, J. Whitman,, B. Shahan,, R. Edgell,, M. Shieh,, O. Rapalino,, R. Zimmerman, and, D. Sheng. 2005. A randomized clinical trial of valacyclovir in multiple sclerosis. Mult. Scler. 11: 286295.
129. Fujimaki, K.,, T. Mori,, A. Kida,, M. Tanaka,, N. Kawai,, T. Matsushima,, K. Kishi,, S. Fujisawa,, T. Sakura,, A. Yokota,, Y. Kanda,, J. Taguchi,, H. Akiyama,, H. Kanamori,, A. Maruta,, S. Okamoto, and, H. Sakamaki. 2006. Human herpesvirus 6 meningoencephalitis in allogeneic hematopoietic stem cell transplant recipients. Int. J. Hematol. 84: 432437.
130. Fujisaki, H.,, K. Tanaka-Taya,, H. Tanabe,, T. Hara,, H. Miyoshi,, S. Okada, and, K. Yamanishi. 1998. Detection of human herpesvirus 7 (HHV-7) DNA in breast milk by polymerase chain reaction and prevalence of HHV-7 antibody in breast-fed and bottle-fed children. J. Med. Virol. 56: 275279.
131. Gautheret, A.,, J. T. Aubin,, L. Poirel,, S. Chopineau,, H. Agut, and, E. Dussaix. 1996. Detection and variant identification of HHV-6 by a non-radioactive hybridization microplate assay for amplimers detection. J. Virol. Methods 58: 3340.
132. Gautheret-Dejean, A.,, C. Manichanh,, F. Thien-Ah-Koon,, A. M. Fillet,, N. Mangeney,, M. Vidaud,, N. Dhedin,, J. P. Vernant, and, H. Agut. 2002. Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. J. Virol. Methods 100: 2735.
133. Gessain, A.,, P. Mauclere,, M. van Beveren,, S. Plancoulaine,, A. Ayouba,, J. L. Essame-Oyono,, P. M. Martin, and, G. de The. 1999. Human herpesvirus 8 primary infection occurs during childhood in Cameroon, Central Africa. Int. J. Cancer. 81: 189192.
134. Giraldo, G.,, E. Beth, and, F. Haguenau. 1972. Herpes-type virus particles in tissue culture of Kaposi’s sarcoma from different geographic regions. J. Natl. Cancer Inst. 49: 15091526.
135. Glesby, M. J.,, D. R. Hoover,, S. Weng,, N. M. H. Graham,, J. P. Phair,, R. Detels,, M. Ho, and, A. J. Saah. 1996. Use of antiherpes drugs and the risk of Kaposi’s sarcoma: data from the Multicenter AIDS Cohort Study. J. Infect. Dis. 173: 14771480.
136. Gompels, U. A.,, D. R. Carrigan,, A. L. Carss, and, J. Arno. 1993. Two groups of human herpesvirus 6 identified by sequence analyses of laboratory strains and variants from Hodgkin’s lymphoma and bone marrow transplant patients. J. Gen. Virol. 74: 613622.
137. Gorniak, R. J.,, G. S. Young,, D. E. Wiese,, F. M. Marty, and, R. B. Schwartz. 2006. MR imaging of human herpesvirus-6-associated encephalitis in 4 patients with anterograde amnesia after allogeneic hematopoietic stem-cell transplantation. AJNR Am. J. Neuroradiol. 27: 887891.
138. Grulich, A. E.,, S. J. Olsen,, K. Luo,, O. Hendry,, P. Cunningham,, D. A. Cooper,, S. J. Gao,, Y. Chang,, P. S. Moore, and, J. M. Kaldor. 1999. Kaposi’s sarcoma-associated herpesvirus: a sexually transmissible infection? J. Acquir. Immune. Defic. Syndr. 20: 387393.
139. Hall, C. B.,, M. T. Caserta,, K. C. Schnabel,, M. P. McDermott,, G. K. Lofthus,, J. A. Carnahan,, L. M. Gilbert, and, S. Dewhurst. 2006. Characteristics and acquisition of human herpesvirus (HHV) 7 infections in relation to infection with HHV-6. J. Infect. Dis. 193: 10631069.
140. Hall, C. B.,, C. E. Long,, K. C. Schnabel,, M. T. Caserta,, K. M. McIntyre,, M. A. Costanzo,, A. Knott,, S. Dewhurst,, R. A. Insel, and, L. G. Epstein. 1994. Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N. Engl. J. Med. 331: 432438.
141. Hammock, L.,, A. Reisenauer,, W. Wang,, C. Cohen,, G. Birdsong, and, A. L. Folpe. 2005. Latency-associated nuclear antigen expression and human herpesvirus-8 polymerase chain reaction in the evaluation of Kaposi sarcoma and other vascular tumors in HIV-positive patients. Mod. Pathol. 18: 463468.
142. Harma, M.,, K. Hockerstedt,, L. Krogerus, and, I. Lautenschlager. 2006a. Pretransplant human herpesvirus 6 infection of patients with acute liver failure is a risk factor for posttransplant human herpesvirus 6 infection of the liver. Transplantation 81: 367372.
143. Harma, M.,, K. Hockerstedt,, O. Lyytikainen, and, I. Lautenschlager. 2006b. HHV-6 and HHV-7 antigenemia related to CMV infection after liver transplantation. J. Med. Virol. 78: 800805.
144. Hayward, G. S. 1999. KSHV strains: the origins and global spread of the virus. Semin. Cancer Biol. 9: 187199.
145. Henke-Gendo, C.,, T. F. Schulz, and, M. M. Hoeper. 2004. HHV-8 in pulmonary hypertension. N. Engl. J. Med. 350: 194195.
146. Hidaka, Y.,, Y. Liu,, M. Yamamoto,, R. Mori,, C. Miyazaki,, K. Kusuhara,, K. Okada, and, K. Ueda. 1993. Frequent isolation of human herpesvirus 7 from saliva samples. J. Med. Virol. 40: 343346.
147. Hladik, W.,, S. C. Dollard,, J. Mermin,, A. L. Fowlkes,, R. Downing,, M. M. Amin,, F. Banage,, E. Nzaro,, P. Kataaha,, T. J. Dondero,, P. E. Pellett, and, E. M. Lackritz. 2006. Transmission of human herpesvirus 8 by blood transfusion. N. Engl. J. Med. 355: 13311338.
148. Hoang, M. P.,, K. F. Ross,, D. B. Dawson,, R. H. Scheuermann, and, B. B. Rogers. 1999. Human herpesvirus-6 and sudden death in infancy: report of a case and review of the literature. J. Forensic Sci. 44: 432437.
149. Hollsberg, P.,, M. Kusk,, E. Bech,, H. J. Hansen,, J. Jakobsen, and, S. Haahr. 2005. Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis patients: associations with disease activity. Acta Neurol. Scand. 112: 395402.
150. Huang, H.,, M. Kamijima,, H. Wang,, S. Li,, T. Yoshikawa,, G. Lai,, Z. Huang,, H. Liu,, J. Chen,, Y. Takeuchi,, T. Nakajima, and, L. Li. 2006. Human herpesvirus 6 reactivation in trichloroethylene-exposed workers suffering from generalized skin disorders accompanied by hepatic dysfunction. J. Occup. Health 48: 417423.
151. Huang, L. M.,, C. Y. Lee,, M. Y. Liu, and, P. I. Lee. 1997. Primary infections of human herpesvirus-7 and human herpesvirus-6: a comparative, longitudinal study up to 6 years of age. Acta Paediatr. 86: 604608.
152. Hymas, W.,, J. Stevenson,, E. W. Taggart, and, D. Hillyard. 2005. Use of lyophilized standards for the calibration of a newly developed real time PCR assay for human herpes type six (HHV6) variants A and B. J. Virol. Methods 128: 143150.
153. Ihira, M.,, S. Akimoto,, F. Miyake,, A. Fujita,, K. Sugata,, S. Suga,, M. Ohashi,, N. Nishimura,, T. Ozaki,, Y. Asano, and, T. Yoshikawa. 2007. Direct detection of human herpesvirus 6 DNA in serum by the loop-mediated isothermal amplification method. J. Clin. Virol. 39: 2226.
154. Isegawa, Y.,, M. Takemoto,, K. Yamanishi,, A. Ohshima, and, N. Sugimoto. 2007. Real-time PCR determination of human herpesvirus 6 antiviral drug susceptibility. J. Virol. Methods 140: 2531.
155. Jacobson, L. P.,, F. J. Jenkins,, G. Springer,, A. Munoz,, K. V. Shah,, J. Phair,, Z. Zhang, and, H. Armenian. 2000. Interaction of human immunodeficiency virus type 1 and human herpesvirus type 8 infections on the incidence of Kaposi’s sarcoma. J. Infect. Dis. 181: 19401949.
156. Jenner, R. G.,, M. M. Alba,, C. Boshoff, and, P. Kellam. 2001. Kaposi’s sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J. Virol. 75: 891902.
157. Jones, J. L.,, D. L. Hanson,, S. Y. Chu,, J. W. Ward, and, H. W. Jaffe. 1995. AIDS-associated Kaposi’s sarcoma. Science 267: 10781079.
158. Jones, J. L.,, D. L. Hanson,, M. S. Dworkin,, D. L. Alderton,, P. L. Fleming,, J. E. Kaplan, and, J. Ward. 1999. Surveillance for AIDS-defining opportunistic illness, 1992-1997. MMWR Surveill. Summ. 48 (SS-2) : 122.
159. Jones, J. L.,, D. L. Hanson,, M. S. Dworkin, and, H. W. Jaffe. 2000. Incidence and trends in Kaposi’s sarcoma in the era of effective antiretroviral therapy. J. Acquir. Immune. Defic. Syndr. 24: 270274.
160. Kagialis-Girard, S.,, B. Durand,, V. Mialou,, M. P. Pages,, C. Galambrun,, Y. Bertrand, and, C. Negrier. 2006. Human herpesvirus 6 infection and transient acquired myelodysplasia in children. Pediatr. Blood Cancer 47: 543548.
161. Katano, H.,, K. Ito,, K. Shibuya,, T. Saji,, Y. Sato, and, T. Sata. 2005. Lack of human herpesvirus 8 infection in lungs of Japanese patients with primary pulmonary hypertension. J. Infect. Dis. 191: 743745.
162. Katano, H.,, Y. Sato,, T. Kurata,, S. Mori, and, T. Sata. 2000. Expression and localization of human herpesvirus 8-encoded proteins in primary effusion lymphoma, Kaposi’s sarcoma, and multicentric Castleman’s disease. Virology 269: 335344.
163. Katsafanas, G. C.,, E. C. Schirmer,, L. S. Wyatt, and, N. Frenkel. 1996. In vitro activation of human herpesviruses 6 and 7 from latency. Proc. Natl. Acad. Sci. USA 93: 97889792.
164. Kedes, D. H.,, and D. Ganem. 1997. Sensitivity of Kaposi’s sarcoma-associated herpesvirus replication to antiviral drugs. Implications for potential therapy. J. Clin. Investig. 99: 20822086.
165. Kedes, D. H.,, E. Operskalski,, M. Busch,, R. Kohn,, J. Flood, and, D. Ganem. 1996. The seroepidemiology of human herpesvirus 8 (Kaposi’s sarcoma-associated herpesvirus): distribution of infection in KS risk groups and evidence for sexual transmission. Nat. Med. 2: 918924.
166. Kempf, W.,, and G. Burg. 2000. Pityriasis rosea--a virusinduced skin disease? An update. Arch. Virol. 145: 15091520.
167. Kidd, I. M.,, D. A. Clark,, M. Ait-Khaled,, P. D. Griffiths, and, V. C. Emery. 1996. Measurement of human herpesvirus 7 load in peripheral blood and saliva of healthy subjects by quantitative polymerase chain reaction. J. Infect. Dis. 174: 396v 401.
168. Kidd, I. M.,, D. A. Clark,, J. A. Bremner,, D. Pillay,, P. D. Griffiths, and, V. C. Emery. 1998. A multiplex PCR assay for the simultaneous detection of human herpesvirus 6 and human herpesvirus 7, with typing of HHV-6 by enzyme cleavage of PCR products. J. Virol. Methods 70: 2936.
169. Kidd, I. M.,, D. A. Clark,, C. A. Sabin,, D. Andrew,, A. F. Hassan-Walker,, P. Sweny,, P. D. Griffiths, and, V. C. Emery. 2000. Prospective study of human betaherpesviruses after renal transplantation: association of human herpesvirus 7 and cytomegalovirus co-infection with cytomegalovirus disease and increased rejection. Transplantation 69: 24002404.
170. Kikuta, H.,, H. Lu,, K. Tomizawa, and, S. Matsumoto. 1990. Enhancement of human herpesvirus 6 replication in adult human lymphocytes by monoclonal antibody to CD3. J. Infect. Dis. 161: 10851087.
171. Kirova, Y. M.,, E. Belembaogo,, H. Frikha,, E. Haddad,, E. Calitchi,, E. Levy,, P. Piedbois, and, J. P. Le Bourgeois. 1998. Radiotherapy in the management of epidemic Kaposi’s sarcoma: a retrospective study of 643 cases. Radiother. Oncol. 46: 1922.
172. Koelle, D. M.,, M. L. Huang,, B. Chandran,, J. Vieira,, M. Piepkorn, and, L. Corey. 1997. Frequent detection of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in saliva of human immunodeficiency virus-infected men: clinical and immunologic correlates. J. Infect. Dis. 176: 94102.
173. Kolski, H.,, E. L. Ford-Jones,, S. Richardson,, M. Petric,, S. Nelson,, F. Jamieson,, S. Blaser,, R. Gold,, H. Otsubo,, H. Heurter, and, D. MacGregor. 1998. Etiology of acute childhood encephalitis at The Hospital for Sick Children, Toronto, 1994-1995. Clin. Infect. Dis. 26: 398409.
174. Kondo, K.,, T. Kondo,, T. Okuno,, M. Takahashi, and, K. Yamanishi. 1991. Latent human herpesvirus 6 infection of human monocytes/macrophages. J. Gen. Virol. 72: 14011408.
175. Kondo, K.,, T. Kondo,, K. Shimada,, K. Amo,, H. Miyagawa, and, K. Yamanishi. 2002. Strong interaction between human herpesvirus 6 and peripheral blood monocytes/macrophages during acute infection. J. Med. Virol. 67: 364369.
176. Kondo, K.,, J. Sashihara,, K. Shimada,, M. Takemoto,, K. Amo,, H. Miyagawa, and, K. Yamanishi. 2003. Recognition of a novel stage of betaherpesvirus latency in human herpesvirus 6. J. Virol. 77: 22582264.
177. Kositanont, U.,, C. Wasi,, N. Wanprapar,, P. Bowonkiratikachorn,, K. Chokephaibulkit,, S. Chearskul,, K. Chimabutra,, R. Sutthent,, S. Foongladda,, R. Inagi,, T. Kurata, and, K. Yamanishi. 1999. Primary infection of human herpesvirus 6 in children with vertical infection of human immunodeficicncy virus type 1. J. Infect. Dis. 180: 5055.
178. Kuhl, U.,, M. Pauschinger,, B. Seeberg,, D. Lassner,, M. Noutsias,, W. Poller, and, H. P. Schultheiss. 2005. Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation 112: 19651970.
179. Kumagai, T.,, T. Yoshikawa,, M. Yoshida,, T. Okui,, M. Ihira,, N. Nagata,, S. Yano,, K. Shiraki,, M. Yamada,, K. Ichihara, and, Y. Asano. 2006. Time course characteristics of human herpesvirus 6 specific cellular immune response and natural killer cell activity in patients with exanthema subitum. J. Med. Virol. 78: 792799.
180. Laney, A. S.,, M. J. Cannon,, H. W. Jaffe,, M. K. Offermann,, C. Y. Ou,, K. W. Radford,, M. M. Patel,, T. J. Spira,, C. J. Gunthel,, P. E. Pellett, and, S. C. Dollard. 2007. Human herpesvirus 8 presence and viral load are associated with the progression of AIDS-associated Kaposi’s sarcoma. AIDS 21: 15411545.
181. Laney, A. S.,, T. De Marco,, J. S. Peters,, M. Malloy,, C. Teehankee,, P. S. Moore, and, Y. Chang. 2005. Kaposi sarcomaassociated herpesvirus and primary and secondary pulmonary hypertension. Chest 127: 762767.
182. Lautenschlager, I.,, K. Linnavuori, and, K. Hockerstedt. 2000. Human herpesvirus-6 antigenemia after liver transplantation. Transplantation 69: 25612566.
183. Lee, H.,, R. Veazey,, K. Williams,, M. Li,, J. Guo,, F. Neipel,, B. Fleckenstein,, A. Lackner,, R. C. Desrosiers, and, J. U. Jung. 1998. Deregulation of cell growth by the K1 gene of Kaposi’s sarcoma-associated herpesvirus. Nat. Med. 4: 435440.
184. Lehto, J. T.,, M. Halme,, P. Tukiainen,, A. Harjula,, J. Sipponen, and, I. Lautenschlager. 2007. Human herpesvirus-6 and -7 after lung and heart-lung transplantation. J. Heart Lung Transplant. 26: 4147.
185. Leite, J. L.,, J. A. Manfrinatto,, M. Mazzali, and, L. S. Ward. 2006. Polymorphisms at exon 4 of p53 and the susceptibility to herpesvirus types 6 and 1 infection in renal transplant recipients. Transpl. Int. 19: 732737.
186. Lennette, E. T.,, D. J. Blackbourn, and, J. A. Levy. 1996. Antibodies to human herpesvirus type 8 in the general population and in Kaposi’s sarcoma patients. Lancet 348: 858861.
187. Leong, H. N.,, P. W. Tuke,, R. S. Tedder,, A. B. Khanom,, R. P. Eglin,, C. E. Atkinson,, K. N. Ward,, P. D. Griffiths, and, D. A. Clark. 2007. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J. Med. Virol. 79: 4551.
188. Li, J. J.,, Y. Q. Huang,, C. J. Cockerell, and, A. E. Friedman-Kien. 1996. Localization of human herpes-like virus type 8 in vascular endothelial cells and perivascular spindle-shaped cells of Kaposi’s sarcoma lesions by in situ hybridization. Am. J. Pathol. 148: 17411748.
189. Lichterfeld, M.,, N. Qurishi,, C. Hoffmann,, B. Hochdorfer,, N. H. Brockmeyer,, K. Arasteh,, S. Mauss, and, J. K. Rockstroh. 2005. Treatment of HIV-1-associated Kaposi’s sarcoma with pegylated liposomal doxorubicin and HAART simultaneously induces effective tumor remission and CD4+ T cell recovery. Infection 33: 140147.
190. Little, R. F.,, F. Merced-Galindez,, K. Staskus,, D. Whitby,, Y. Aoki,, R. Humphrey,, J. M. Pluda,, V. Marshall,, M. Walters,, L. Welles,, I. R. Rodriguez-Chavez,, S. Pittaluga,, G. Tosato, and, R. Yarchoan. 2003. A pilot study of cidofovir in patients with kaposi sarcoma. J. Infect. Dis. 187: 149153.
191. Ljungman, P.,, H. Dahl,, Y. H. Xu,, K. Larsson,, M. Brytting, and, A. Linde. 2007. Effectiveness of ganciclovir against human herpesvirus-6 excreted in saliva in stem cell transplant recipients. Bone Marrow Transplant. 39: 497499.
192. Ljungman, P.,, and N. Singh. 2006. Human herpesvirus-6 infection in solid organ and stem cell transplant recipients. J. Clin. Virol. 37 (Suppl. 1) : S87S91.
193. Luppi, M.,, P. Barozzi,, R. Bosco,, D. Vallerini,, L. Potenza,, F. Forghieri, and, G. Torelli. 2006. Human herpesvirus 6 latency characterized by high viral load: chromosomal integration in many, but not all, cells. J. Infect. Dis. 194: 10201021.
194. Luppi, M.,, P. Barozzi,, A. Maiorana,, R. Marasca, and, G. Torelli. 1994. Human herpesvirus 6 infection in normal human brain tissue. J. Infect. Dis. 169: 943944.
195. Luppi, M.,, P. Barozzi,, C. Morris,, A. Maiorana,, R. Garber,, G. Bonacorsi,, A. Donelli,, R. Marasca,, A. Tabilio, and, G. Torelli. 1999. Human herpesvirus 6 latently infects early bone marrow progenitors in vivo. J. Virol. 73: 754759.
196. Luppi, M.,, P. Barozzi,, V. Rasini,, G. Riva,, A. Re,, G. Rossi,, G. Setti,, S. Sandrini,, F. Facchetti, and, G. Torelli. 2002. Severe pancytopenia and hemophagocytosis after HHV-8 primary infection in a renal transplant patient successfully treated with foscarnet. Transplantation 74: 131132.
197. Lusso, P.,, P. Secchiero,, R. W. Crowley,, A. Garzino-Demo,, Z. N. Berneman, and, R. C. Gallo. 1994. CD4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 91: 38723876.
198. Maeda, Y.,, T. Teshima,, M. Yamada,, K. Shinagawa,, S. Nakao,, Y. Ohno,, K. Kojima,, M. Hara,, K. Nagafuji,, S. Hayashi,, S. Fukuda,, H. Sawada,, K. Matsue,, K. Takenaka,, F. Ishimaru,, K. Ikeda,, K. Niiya, and, M. Harada. 1999. Monitoring of human herpesviruses after allogeneic peripheral blood stem cell transplantation and bone marrow transplantation. Br. J. Haematol. 105: 295302.
199. Mahrholdt, H.,, A. Wagner,, C. C. Deluigi,, E. Kispert,, S. Hager,, G. Meinhardt,, H. Vogelsberg,, P. Fritz,, J. Dippon,, C. T. Bock,, K. Klingel,, R. Kandolf, and, U. Sechtem. 2006. Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation 114: 15811590.
200. Manichanh, C.,, C. Olivier-Aubron,, J. P. Lagarde,, J. T. Aubin,, P. Bossi,, A. Gautheret-Dejean,, J. M. Huraux, and, H. Agut. 2001. Selection of the same mutation in the U69 protein kinase gene of human herpesvirus-6 after prolonged exposure to ganciclovir in vitro and in vivo. J. Gen. Virol. 82: 27672776.
201. Martin, C.,, M. Enbom,, M. Soderstrom,, S. Fredrikson,, H. Dahl,, J. Lycke,, T. Bergstrom, and, A. Linde. 1997. Absence of seven human herpesviruses, including HHV-6, by polymerase chain reaction in CSF and blood from patients with multiple sclerosis and optic neuritis. Acta Neurol. Scand. 95: 280283.
202. Martin, J. N.,, D. E. Ganem,, D. H. Osmond,, K. A. Page-Shafer,, D. Macrae, and, D. H. Kedes. 1998. Sexual transmission and the natural history of human herpesvirus 8 infection. N. Engl. J. Med. 338: 948954.
203. Matsuda, K.,, T. Ohnuma,, M. Fukuta,, M. Kawai,, T. Suzuki,, H. Ogawa, and, H. Arai. 2006. Case reports and literature review: the association between reactivation of human herpes virus-6 and peripheral white blood cell count in patients with carbamazepine-induced hypersensitivity syndrome. Prog. Neuropsychopharmacol. Biol. Psychiatry 30: 751754.
204. Mayama, S.,, L. E. Cuevas,, J. Sheldon,, O. H. Omar,, D. H. Smith,, P. Okong,, B. Silvel,, C. A. Hart, and, T. F. Schulz. 1998. Prevalence and transmission of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in Ugandan children and adolescents. Int. J. Cancer 77: 817820.
205. McCullers, J. A.,, F. D. Lakeman, and, R. J. Whitley. 1995. Human herpesvirus 6 is associated with focal encephalitis. Clin. Infect. Dis. 21: 571576.
206. Medveczky, M. M.,, E. Horvath,, T. Lund, and, P. G. Medveczky. 1997. “In vitro” antiviral drug sensitivity of the Kaposi’s sarcoma-associated herpesvirus. AIDS 11: 13271332.
207. Melbye, M.,, P. M. Cook,, H. Hjalgrim,, K. Begtrup,, G. R. Simpson,, R. J. Biggar,, P. Ebbesen, and, T. F. Schulz. 1998. Risk factors for Kaposi’s-sarcoma-associated herpesvirus (KSHV/HHV-8) seropositivity in a cohort of homosexual men, 1981-1996. Int. J. Cancer.