Skip to main content

Advertisement

SpringerLink
Log in

Laboratory Diagnosis of Human Herpesvirus 8 Infection in Humans

  • Review
  • Published:
European Journal of Clinical Microbiology and Infectious Diseases Aims and scope Submit manuscript

Abstract.

Human herpesvirus 8 (HHV-8) is causally associated with Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. Serological and molecular biology assays are used to investigate the biology of this virus in different populations and diseases. Serological assays are mainly used to study the prevalence of the viral infection and to predict the diagnosis of Kaposi's sarcoma and other HHV-8-associated cancers. The appearance of antibodies against lytic antigens precedes the appearance of antibodies against latent antigens, probably explaining the lower sensitivity of assays based on latent HHV-8 antigens. The lack of international reference serum panels is presently the major bottleneck for further progress in the field of HHV-8 serology. Molecular biological assays are an absolute requirement for both the diagnosis and the follow-up of HHV-8 infection. Qualitative methods have been particularly useful to elucidate the mode of transmission and the causal association between HHV-8 and HHV-8-associated diseases. Quantitative methods have become an essential tool to monitor the progression of the infection and the effects of antiviral therapies. This review analyzes the performance of the different serological and molecular biological assays available at present. The main conclusion is that more research is needed to define the most useful laboratory tests for the diagnosis of HHV-8 infection and to establish the clinical role of such tests.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266:1865–1869

    CAS  PubMed  Google Scholar 

  2. Sarid R, Olsen SJ, Moore PS (1999) Kaposi's sarcoma-associated herpesvirus: epidemiology, virology, and molecular biology. Adv Virus Res 52:139–232

    CAS  PubMed  Google Scholar 

  3. Schulz TF (2000) Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8): epidemiology and pathogenesis. J Antimicrob Chemother 45, Topic T3:15–27

    Google Scholar 

  4. Boshoff C, Weiss RA (1998) Kaposi's sarcoma-associated herpesvirus. Adv Cancer Res 75:57–86

    CAS  PubMed  Google Scholar 

  5. Greensill J, Sheldon JA, Renwick NM, Beer BE, Norley S, Goudsmit J, Schulz TF (2000) Two distinct gamma-2 herpesviruses in African green monkeys: a second gamma-2 herpesvirus lineage among old world primates? J Virol 74:1572–1577

    Article  CAS  PubMed  Google Scholar 

  6. Cesarman E, Moore PS, Rao PH, Inghirami G, Knowles DM, Chang Y (1995) In vitro establishment and characterization of two acquired immunodeficiency syndrome-related lymphoma cell lines (BC-1 and BC-2) containing Kaposi's sarcoma-associated herpesvirus-like (KSHV) DNA sequences. Blood 86:2708–2714

    CAS  PubMed  Google Scholar 

  7. Arvanitakis L, Mesri EA, Nador RG, Said JW, Asch AS, Knowles DM, Cesarman E (1996) Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein-Barr virus. Blood 88:2648–2654

    CAS  PubMed  Google Scholar 

  8. Renne R, Zhong W, Herndier B, McGrath M, Abbey N, Kedes D, Ganem D (1996) Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nat Med 2:342–346

    CAS  PubMed  Google Scholar 

  9. Said JW, Tasaka T, Takeuchi S, Asou H, de Vos S, Cesarman E, Knowles DM, Koeffler HP (1996) Primary effusion lymphoma in women: report of two cases of Kaposi's sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women. Blood 88:3124–3128

    CAS  PubMed  Google Scholar 

  10. Gaidano G, Cechova K, Chang Y, Moore PS, Knowles DM, Dalla-Favera R (1996) Establishment of AIDS-related lymphoma cell lines from lymphomatous effusions. Leukemia 10:1237–1240

    CAS  PubMed  Google Scholar 

  11. Boshoff C, Gao SJ, Healy LE, Matthews S, Thomas AJ, Coignet L, Warnke RA, Strauchen JA, Matutes E, Kamel OW, Moore PS, Weiss RA, Chang Y (1998) Establishing a KSHV+ cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice. Blood 91:1671–1679

    CAS  PubMed  Google Scholar 

  12. Nealon K, Newcomb WW, Pray TR, Craik CS, Brown JC, Kedes DH (2001) Lytic replication of Kaposi's sarcoma-associated herpesvirus results in the formation of multiple capsid species: isolation and molecular characterization of A, B, and C capsids from a gammaherpesvirus. J Virol 75:2866–2878

    Article  CAS  PubMed  Google Scholar 

  13. Russo JJ, Bohenzky RA, Chien MC, Chen J, Yan M, Maddalena D, Parry JP, Peruzzi D, Edelman IS, Chang Y, Moore PS (1996) Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci USA 93:14862–14867

    Article  CAS  PubMed  Google Scholar 

  14. Neipel F, Albrecht JC, Fleckenstein B (1997) Cell-homologous genes in the Kaposi's sarcoma-associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity? J Virol 71:4187–4192

    CAS  PubMed  Google Scholar 

  15. Dupin N, Fisher C, Kellam P, Ariad S, Tulliez M, Franck N, van Marck E, Salmon D, Gorin I, Escande JP, Weiss RA, Alitalo K, Boshoff C (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 96:4546–4551

    Article  CAS  PubMed  Google Scholar 

  16. Parravicini C, Chandran B, Corbellino M, Berti E, Paulli M, Moore PS, Chang Y (2000) Differential viral protein expression in Kaposi's sarcoma-associated herpesvirus-infected diseases: Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Am J Pathol 156:743–749

    CAS  PubMed  Google Scholar 

  17. Reedman BM, Klein G (1973) Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int J Cancer 11:499–520

    CAS  PubMed  Google Scholar 

  18. McGeoch DJ, Davison AJ (1999) The descent of human herpesvirus 8. Semin Cancer Biol 9:201–209

    Article  CAS  PubMed  Google Scholar 

  19. Nicholas J, Zong JC, Alcendor DJ, Ciufo DM, Poole LJ, Sarisky RT, Chiou CJ, Zhang X, Wan X, Guo HG, Reitz MS, Hayward GS (1998) Novel organizational features, captured cellular genes, and strain variability within the genome of KSHV/HHV8. J Natl Cancer Inst Monogr 23:79–88

    CAS  PubMed  Google Scholar 

  20. Chandran B, Bloomer C, Chan SR, Zhu L, Goldstein E, Horvat R (1998) Human herpesvirus-8 ORF K8.1 gene encodes immunogenic glycoproteins generated by spliced transcripts. Virology 249:140–149

    Article  CAS  PubMed  Google Scholar 

  21. Zhu L, Puri V, Chandran B (1999) Characterization of human herpesvirus-8 K8.1A/B glycoproteins by monoclonal antibodies. Virology 262:237–249

    Article  CAS  PubMed  Google Scholar 

  22. Lin SF, Sun R, Heston L, Gradoville L, Shedd D, Haglund K, Rigsby M, Miller G (1997) Identification, expression, and immunogenicity of Kaposi's sarcoma-associated herpesvirus-encoded small viral capsid antigen. J Virol 71:3069–3076

    CAS  PubMed  Google Scholar 

  23. Zong JC, Metroka C, Reitz MS, Nicholas J, Hayward GS (1997) Strain variability among Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genomes: evidence that a large cohort of United States AIDS patients may have been infected by a single common isolate. J Virol 71:2505–2511

    CAS  PubMed  Google Scholar 

  24. Zong JC, Ciufo DM, Alcendor DJ, Wan X, Nicholas J, Browning PJ, Rady PL, Tyring SK, Orenstein JM, Rabkin CS, Su IJ, Powell KF, Croxson M, Foreman KE, Nickoloff BJ, Alkan S, Hayward GS (1999) High-level variability in the ORF-K1 membrane protein gene at the left end of the Kaposi's sarcoma-associated herpesvirus genome defines four major virus subtypes and multiple variants or clades in different human populations. J Virol 73:4156–4170

    CAS  PubMed  Google Scholar 

  25. Cook PM, Whitby D, Calabro ML, Luppi M, Kakoola DN, Hjalgrim H, Ariyoshi K, Ensoli B, Davison AJ, Schulz TF (1999) Variability and evolution of Kaposi's sarcoma-associated herpesvirus in Europe and Africa. AIDS 13:1165–1176

    Article  CAS  PubMed  Google Scholar 

  26. Hayward GS (1999) KSHV strains: the origins and global spread of the virus. Semin Cancer Biol 9:187–199

    Article  CAS  PubMed  Google Scholar 

  27. Biggar RJ, Whitby D, Marshall V, Linhares AC, Black F (2000) Human herpesvirus 8 in Brazilian Amerindians: a hyperendemic population with a new subtype. J Infect Dis 181:1562–1568

    Google Scholar 

  28. Schulz TF (2000) KSHV (HHV8) infection. J Infect 41:125–129

    Article  CAS  PubMed  Google Scholar 

  29. Staskus KA, Zhong W, Gebhard K, Herndier B, Wang H, Renne R, Beneke J, Pudney J, Anderson DJ, Ganem D, Haase AT (1997) Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol 71:715–719

    CAS  PubMed  Google Scholar 

  30. Decker LL, Shankar P, Khan G, Freeman RB, Dezube BJ, Lieberman J, Thorley-Lawson DA (1996) The Kaposi sarcoma-associated herpesvirus (KSHV) is present as an intact latent genome in KS tissue but replicates in the peripheral blood mononuclear cells of KS patients. J Exp Med 184:283–288

    CAS  PubMed  Google Scholar 

  31. Grandadam M, Dupin N, Calvez V, Gorin I, Blum L, Kernbaum S, Sicard D, Buisson Y, Agut H, Escande JP, Huraux JM (1997) Exacerbations of clinical symptoms in human immunodeficiency virus type 1-infected patients with multicentric Castleman's disease are associated with a high increase in Kaposi's sarcoma herpesvirus DNA load in peripheral blood mononuclear cells. J Infect Dis 175:1198–1201

    Google Scholar 

  32. Bigoni B, Dolcetti R, de Lellis L, Carbone A, Boiocchi M, Cassai E, Di Luca D (1996) Human herpesvirus 8 is present in the lymphoid system of healthy persons and can reactivate in the course of AIDS. J Infect Dis 173:542–549

    Google Scholar 

  33. Whitby D, Howard MR, Tenant-Flowers M, Brink NS, Copas A, Boshoff C, Hatzioannou T, Suggett FE, Aldam DM, Denton AS, et al (1995) Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma. Lancet 346:799–802

    CAS  PubMed  Google Scholar 

  34. Gao SJ, Kingsley L, Hoover DR, Spira TJ, Rinaldo CR, Saah A, Phair J, Detels R, Parry P, Chang Y, Moore PS (1996) Seroconversion to antibodies against Kaposi's sarcoma-associated herpesvirus-related latent nuclear antigens before the development of Kaposi's sarcoma. N Engl J Med 335:233–241

    Article  CAS  PubMed  Google Scholar 

  35. Martin JN, Ganem DE, Osmond DH, Page-Shafer KA, Macrae D, Kedes DH (1998) Sexual transmission and the natural history of human herpesvirus 8 infection. N Engl J Med 338:948–954

    Article  CAS  PubMed  Google Scholar 

  36. Smith NA, Sabin CA, Gopal R, Bourboulia D, Labbet W, Boshoff C, Barlow D, Band B, Peters BS, de Ruiter A, Brown DW, Weiss RA, Best JM, Whitby D (1999) Serologic evidence of human herpesvirus 8 transmission by homosexual but not heterosexual sex. J Infect Dis 180:600–606

    Google Scholar 

  37. Rezza G, Capobianchi M, Serraino D, Peroni M, Piselli P, Calcaterra S, Pavia C, Zaniratti S, Ippolito G (2001) HHV-8 shedding among HIV-infected women. J Acquir Immune Defic Syndr 28:103–104

    CAS  PubMed  Google Scholar 

  38. Tedeschi R, Caggiari L, Silins I, Kallings I, Andersson-Ellstrom A, De Paoli P, Dillner J (2000) Seropositivity to human herpesvirus 8 in relation to sexual history and risk of sexually transmitted infections among women. Int J Cancer 87:232–235

    Article  CAS  PubMed  Google Scholar 

  39. Simpson GR, Schulz TF, Whitby D, Cook PM, Boshoff C, Rainbow L, Howard MR, Gao SJ, Bohenzky RA, Simmonds P, Lee C, de Ruiter A, Hatzakis A, Tedder RS, Weller IV, Weiss RA, Moore PS (1996) Prevalence of Kaposi's sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen. Lancet 348:1133–1138

    Article  CAS  PubMed  Google Scholar 

  40. Calabro ML, Sheldon J, Favero A, Simpson GR, Fiore JR, Gomes E, Angarano G, Chieco-Bianchi L, Schulz TF (1998) Seroprevalence of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 in several regions of Italy. J Human Virol 1:207–213

    CAS  Google Scholar 

  41. Bourboulia D, Whitby D, Boshoff C, Newton R, Beral V, Carrara H, Lane A, Sitas F (1998) Serologic evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus infection. JAMA 280:31–32

    CAS  Google Scholar 

  42. Koelle DM, Huang ML, Chandran B, Vieira J, Piepkorn M, Corey L (1997) Frequent detection of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) DNA in saliva of human immunodeficiency virus-infected men: clinical and immunologic correlates. J Infect Dis 176:94–102

    Google Scholar 

  43. Calabro ML, Gasperini P, Barbierato M, Ometto L, Zanchetta M, De Rossi A, Chieco-Bianchi L (2000) A search for human herpesvirus 8 (HHV-8) in HIV-1 infected mothers and their infants does not suggest vertical transmission of HHV-8. Int J Cancer 85:296–297

    Article  CAS  PubMed  Google Scholar 

  44. Serraino D, Tedeschi RM, Songini M, Cepulic M, Caggiari L, Locatelli M, Bonevski A, Ippolito G, Franceschi S (2000) Prevalence of antibodies to human herpesvirus 8 in children from Sardinia and Croatia. Infection 28:336–338

    Article  CAS  PubMed  Google Scholar 

  45. Mayama S, Cuevas LE, Sheldon J, Omar OH, Smith DH, Okong P, Silvel B, Hart CA, Schulz TF (1998) Prevalence and transmission of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in Ugandan children and adolescents. Int J Cancer 77:817–820

    Article  CAS  PubMed  Google Scholar 

  46. LaDuca JR, Love JL, Abbott LZ, Dube S, Freidman-Kien AE, Poiesz BJ (1998) Detection of human herpesvirus 8 DNA sequences in tissues and bodily fluids. J Infect Dis 178:1610–1615

    Google Scholar 

  47. Blackbourn DJ, Ambroziak J, Lennette E, Adams M, Ramachandran B, Levy JA (1997) Infectious human herpesvirus 8 in a healthy North American blood donor. Lancet 349:609–611

    Article  CAS  PubMed  Google Scholar 

  48. Parravicini C, Olsen SJ, Capra M, Poli F, Sirchia G, Gao SJ, Berti E, Nocera A, Rossi E, Bestetti G, Pizzuto M, Galli M, Moroni M, Moore PS, Corbellino M (1997) Risk of Kaposi's sarcoma-associated herpes virus transmission from donor allografts among Italian posttransplant Kaposi's sarcoma patients. Blood 90:2826–2829

    CAS  PubMed  Google Scholar 

  49. Cannon MJ, Dollard SC, Smith DK, Klein RS, Schuman P, Rich JD, Vlahov D, Pellett PE (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 344:637–643

    Article  CAS  PubMed  Google Scholar 

  50. Farge D, Lebbe C, Marjanovic Z, Tuppin P, Mouquet C, Peraldi MN, Lang P, Hiesse C, Antoine C, Legendre C, Bedrossian J, Gagnadoux MF, Loirat C, Pellet C, Sheldon J, Golmard JL, Agbalika F, Schulz TF (1999) Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Transplantation 67:1236–1242

    CAS  PubMed  Google Scholar 

  51. Cattani P, Capuano M, Graffeo R, Ricci R, Cerimele F, Cerimele D, Nanni G, Fadda G (2001) Kaposi's sarcoma associated with previous human herpesvirus 8 infection in kidney transplant recipients. J Clin Microbiol 39:506–508

    Article  CAS  PubMed  Google Scholar 

  52. Schulz TF (1999) Epidemiology of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8. Adv Cancer Res 76:121–160

    CAS  PubMed  Google Scholar 

  53. Blackbourn DJ, Levy JA (1997) Human herpesvirus 8 in semen and prostate. AIDS 11:249–250

    CAS  PubMed  Google Scholar 

  54. Pellett PE, Spira TJ, Bagasra O, Boshoff C, Corey L, de Lellis L, Huang ML, Lin JC, Matthews S, Monini P, Rimessi P, Sosa C, Wood C, Stewart JA (1999) Multicenter comparison of PCR assays for detection of human herpesvirus 8 DNA in semen. J Clin Microbiol 37:1298–1301

    CAS  PubMed  Google Scholar 

  55. Howard MR, Whitby D, Bahadur G, Suggett F, Boshoff C, Tenant-Flowers M, Schulz TF, Kirk S, Matthews S, Weller IV, Tedder RS, Weiss RA (1997) Detection of human herpesvirus 8 DNA in semen from HIV-infected individuals but not healthy semen donors. AIDS 11:F15–19

    CAS  PubMed  Google Scholar 

  56. Whitby D, Luppi M, Barozzi P, Boshoff C, Weiss RA, Torelli G (1998) Human herpesvirus 8 seroprevalence in blood donors and lymphoma patients from different regions of Italy. J Natl Cancer Inst 90:395–397

    Article  CAS  PubMed  Google Scholar 

  57. Lebbe C, Agbalika F, de Cremoux P, Deplanche M, Rybojad M, Masgrau E, Morel P, Calvo F (1997) Detection of human herpesvirus 8 and human T-cell lymphotropic virus type 1 sequences in Kaposi sarcoma. Arch Dermatol 133:25–30

    CAS  PubMed  Google Scholar 

  58. Viviano E, Vitale F, Ajello F, Perna AM, Villafrate MR, Bonura F, Arico M, Mazzola G, Romano N (1997) Human herpesvirus type 8 DNA sequences in biological samples of HIV-positive and negative individuals in Sicily. AIDS 11:607–612

    CAS  PubMed  Google Scholar 

  59. Ariyoshi K, Schim van der Loeff M, Cook P, Whitby D, Corrah T, Jaffar S, Cham F, Sabally S, O'Donovan D, Weiss RA, Schulz TF, Whittle H (1998) Kaposi's sarcoma in the Gambia, West Africa is less frequent in human immunodeficiency virus type 2 than in human immunodeficiency virus type 1 infection despite a high prevalence of human herpesvirus 8. J Human Virol 1:193–199

    CAS  Google Scholar 

  60. Gao SJ, Kingsley L, Li M, Zheng W, Parravicini C, Ziegler J, Newton R, Rinaldo CR, Saah A, Phair J, Detels R, Chang Y, Moore PS (1996) KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med 2:925–928

    CAS  PubMed  Google Scholar 

  61. Kasolo FC, Mpabalwani E, Gompels UA (1997) Infection with AIDS-related herpesviruses in human immunodeficiency virus-negative infants and endemic childhood Kaposi's sarcoma in Africa. J Gen Virol 78:847–855

    CAS  PubMed  Google Scholar 

  62. Gessain A, Mauclere P, van Beveren M, Plancoulaine S, Ayouba A, Essame-Oyono JL, Martin PM, de The G (1999) Human herpesvirus 8 primary infection occurs during childhood in Cameroon, Central Africa. Int J Cancer 81:189–192

    Article  CAS  PubMed  Google Scholar 

  63. Mendez JC, Procop GW, Espy MJ, Paya CV, Smith TF (1998) Detection and semiquantitative analysis of human herpesvirus 8 DNA in specimens from patients with Kaposi's sarcoma. J Clin Microbiol 36:2220–2222

    CAS  PubMed  Google Scholar 

  64. Boshoff C, Whitby D, Hatziioannou T, Fisher C, van der Walt J, Hatzakis A, Weiss R, Schulz T (1995) Kaposi's-sarcoma-associated herpesvirus in HIV-negative Kaposi's sarcoma. Lancet 345:1043–1044

    CAS  Google Scholar 

  65. Moore PS, Kingsley LA, Holmberg SD, Spira T, Gupta P, Hoover DR, Parry JP, Conley LJ, Jaffe HW, Chang Y (1996) Kaposi's sarcoma-associated herpesvirus infection prior to onset of Kaposi's sarcoma. AIDS 10:175–180

    CAS  PubMed  Google Scholar 

  66. Komanduri KV, Luce JA, McGrath MS, Herndier BG, Ng VL (1996) The natural history and molecular heterogeneity of IV-associated primary malignant lymphomatous effusions. J Acquir Immune Defic Syndr Hum Retrovirol 13:215–226

    CAS  PubMed  Google Scholar 

  67. Schulz TF (2001) KSHV/HHV8-associated lymphoproliferations in the AIDS setting. Eur J Cancer 37:1217–1226

    Article  CAS  PubMed  Google Scholar 

  68. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM (1995) Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 332:1186–1191

    Article  CAS  PubMed  Google Scholar 

  69. Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, Babinet P, d'Agay MF, Clauvel JP, Raphael M, Degos L, et al (1995) Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 86:1276–1280

    CAS  PubMed  Google Scholar 

  70. Oksenhendler E, Boulanger E, Galicier L, Du MQ, Dupin N, Diss TC, Hamoudi R, Daniel MT, Agbalika F, Boshoff C, Clauvel JP, Isaacson PG, Meignin V (2002) High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease. Blood 99:2331–2336

    Article  CAS  PubMed  Google Scholar 

  71. Luppi M, Barozzi P, Schulz TF, Trovato R, Donelli A, Narni F, Sheldon J, Marasca R, Torelli G (2000) Nonmalignant disease associated with human herpesvirus 8 reactivation in patients who have undergone autologous peripheral blood stem cell transplantation. Blood 96:2355–2367

    CAS  PubMed  Google Scholar 

  72. Rettig MB, Ma HJ, Vescio RA, Pold M, Schiller G, Belson D, Savage A, Nishikubo C, Wu C, Fraser J, Said JW, Berenson JR (1997) Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients. Science 276:1851–1854

    CAS  PubMed  Google Scholar 

  73. Berenson JR, Vescio RA (1999) HHV-8 is present in multiple myeloma patients. Blood 93:3157–3159 and 3164–3166

    CAS  PubMed  Google Scholar 

  74. Tarte K, Chang Y, Klein B (1999) Kaposi's sarcoma-associated herpesvirus and multiple myeloma: lack of criteria for causality. Blood 93:3159–3164

    CAS  PubMed  Google Scholar 

  75. Hjalgrim H, Frisch M, Melbye M (1998) Incidence rates of classical Kaposi's sarcoma and multiple myeloma do not correlate. Br J Cancer 78:419–420

    CAS  PubMed  Google Scholar 

  76. Masood R, Zheng T, Tupule A, Arora N, Chatlynne L, Handy M, Whitman J Jr (1997) Kaposi's sarcoma-associated herpesvirus infection and multiple myeloma. Science 278:1970–1973

    CAS  PubMed  Google Scholar 

  77. Tedeschi R, Kvarnung M, Knekt P, Schulz TF, Szekely L, De Paoli PD, Aromaa A, Teppo L, Dillner J (2001) A prospective seroepidemiological study of human herpesvirus-8 infection and the risk of multiple myeloma. Br J Cancer 84:122–125

    CAS  PubMed  Google Scholar 

  78. Miller G, Rigsby MO, Heston L, Grogan E, Sun R, Metroka C, Levy JA, Gao SJ, Chang Y, Moore P (1996) Antibodies to butyrate-inducible antigens of Kaposi's sarcoma-associated herpesvirus in patients with HIV-1 infection. N Engl J Med 334:1292–1297

    Article  CAS  PubMed  Google Scholar 

  79. Lennette ET, Blackbourn DJ, Levy JA (1996) Antibodies to human herpesvirus type 8 in the general population and in Kaposi's sarcoma patients. Lancet 348:858–861

    Article  CAS  PubMed  Google Scholar 

  80. Smith MS, Bloomer C, Horvat R, Goldstein E, Casparian JM, Chandran B (1997) Detection of human herpesvirus 8 DNA in Kaposi's sarcoma lesions and peripheral blood of human immunodeficiency virus-positive patients and correlation with serologic measurements. J Infect Dis 176:84–93

    Google Scholar 

  81. Kedes DH, Operskalski E, Busch M, Kohn R, Flood J, Ganem D (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 2:918–924

    CAS  PubMed  Google Scholar 

  82. Edelman DC, Ketema F, Saville RD, Herman J, Sill AM, Gill PS, Blattner WA, Constantine NT (2000) Specifics on the refinement and application of two serological assays for the detection of antibodies to HHV-8. J Clin Virol 16:225–237

    Article  CAS  PubMed  Google Scholar 

  83. Chatlynne LG, Ablashi DV (1999) Seroepidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV). Semin Cancer Biol 9:175–185

    Article  CAS  PubMed  Google Scholar 

  84. Enbom M, Tolfvenstam T, Ghebrekidan H, Ruden U, Grandien M, Wahren B, Linde A (1999) Seroprevalence of human herpes virus 8 in different Eritrean population groups. J Clin Virol 14:167–172

    Article  CAS  PubMed  Google Scholar 

  85. Inoue N, Mar EC, Dollard SC, Pau CP, Zheng Q, Pellett PE (2000) New immunofluorescence assays for detection of human herpesvirus 8-specific antibodies. Clin Diagn Lab Immunol 7:427–435

    Article  CAS  PubMed  Google Scholar 

  86. Chandran B, Smith MS, Koelle DM, Corey L, Horvat R, Goldstein E (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 243:208–217

    Article  CAS  PubMed  Google Scholar 

  87. Rainbow L, Platt GM, Simpson GR, Sarid R, Gao SJ, Stoiber H, Herrington CS, Moore PS, Schulz TF (1997) The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen. J Virol 71:5915–5921

    CAS  PubMed  Google Scholar 

  88. Lang D, Hinderer W, Rothe M, Sonneborn HH, Neipel F, Raab M, Rabenau H, Masquelier B, Fleury H (1999) Comparison of the immunoglobulin-G-specific seroreactivity of different recombinant antigens of the human herpesvirus 8. Virology 260:47–54

    Article  CAS  PubMed  Google Scholar 

  89. Lam LL, Pau CP, Dollard SC, Pellett PE, Spira TJ (2002) Highly sensitive assay for human herpesvirus 8 antibodies that uses a multiple antigenic peptide derived from open reading frame k8.1. J Clin Microbiol 40:325–329

    Article  CAS  PubMed  Google Scholar 

  90. Li M, MacKey J, Czajak SC, Desrosiers RC, Lackner AA, Jung JU (1999) Identification and characterization of Kaposi's sarcoma-associated herpesvirus K8.1 virion glycoprotein. J Virol 73:1341–1349

    CAS  PubMed  Google Scholar 

  91. Katano H, Iwasaki T, Baba N, Terai M, Mori S, Iwamoto A, Kurata T, Sata T (2000) Identification of antigenic proteins encoded by human herpesvirus 8 and seroprevalence in the general population and among patients with and without Kaposi's sarcoma. J Virol 74:3478–3485

    Article  CAS  PubMed  Google Scholar 

  92. Pau CP, Lam LL, Spira TJ, Black JB, Stewart JA, Pellett PE, Respess RA (1998) Mapping and serodiagnostic application of a dominant epitope within the human herpesvirus 8 ORF 65-encoded protein. J Clin Microbiol 36:1574–1577

    CAS  PubMed  Google Scholar 

  93. Tedeschi R, De Paoli P, Schulz TF, Dillner J (1999) Human serum antibodies to a major defined epitope of human herpesvirus 8 small viral capsid antigen. J Infect Dis 179:1016–1020

    Google Scholar 

  94. Chatlynne LG, Lapps W, Handy M, Huang YQ, Masood R, Hamilton AS, Said JW, Koeffler HP, Kaplan MH, Friedman-Kien A, Gill PS, Whitman JE, Ablashi DV (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 92:53–58

    CAS  PubMed  Google Scholar 

  95. Martin JN, Amad Z, Cossen C, Lam PK, Kedes DH, Page-Shafer KA, Osmond DH, Forghani B (2000) Use of epidemiologically well-defined subjects and existing immunofluorescence assays to calibrate a new enzyme immunoassay for human herpesvirus 8 antibodies. J Clin Microbiol 38:696–701

    CAS  PubMed  Google Scholar 

  96. Schatz O, Monini P, Bugarini R, Neipel F, Schulz TF, Andreoni M, Erb P, Eggers M, Haas J, Butto S, Lukwiya M, Bogner JR, Yaguboglu S, Sheldon J, Sarmati L, Goebel FD, Hintermaier R, Enders G, Regamey N, Wernli M, Sturzl M, Rezza G, Ensoli B (2001) Kaposi's sarcoma-associated herpesvirus serology in Europe and Uganda: multicentre study with multiple and novel assays. J Med Virol 65:123–132

    Article  CAS  PubMed  Google Scholar 

  97. Rabkin CS, Schulz TF, Whitby D, Lennette ET, Magpantay LI, Chatlynne L, Biggar RJ (1998) Interassay correlation of human herpesvirus 8 serologic tests. J Infect Dis 178:304–309

    Google Scholar 

  98. Engels EA, Whitby D, Goebel PB, Stossel A, Waters D, Pintus A, Contu L, Biggar RJ, Goedert JJ (2000) Identifying human herpesvirus 8 infection: performance characteristics of serologic assays. J Acquir Immune Defic Syndr 23:346–354

    CAS  PubMed  Google Scholar 

  99. Spira TJ, Lam L, Dollard SC, Meng YX, Pau CP, Black JB, Burns D, Cooper B, Hamid M, Huong J, Kite-Powell K, Pellett PE (2000) Comparison of serologic assays and PCR for diagnosis of human herpesvirus 8 infection. J Clin Microbiol 38:2174–2180

    CAS  PubMed  Google Scholar 

  100. Corchero JL, Mar EC, Spira TJ, Pellett PE, Inoue N (2001) Comparison of serologic assays for detection of antibodies against human herpesvirus 8. Clin Diagn Lab Immunol 8:913–921

    Article  CAS  PubMed  Google Scholar 

  101. Nolte FS (2000) Quantitative molecular techniques. In: Specter S, Hodinka RL, Young SA (eds) Clinical virology manual. American Society for Microbiology, Washington DC, pp 198–210

  102. Tedeschi R, Enbom M, Bidoli E, Linde A, De Paoli P, Dillner J (2001) Viral load of human herpesvirus 8 in peripheral blood of human immunodeficiency virus-infected patients with Kaposi's sarcoma. J Clin Microbiol 39:4269–4273

    Article  CAS  PubMed  Google Scholar 

  103. Pan L, Milligan L, Michaeli J, Cesarman E, Knowles DM (2001) Polymerase chain reaction detection of Kaposi's sarcoma-associated herpesvirus-optimized protocols and their application to myeloma. J Mol Diagn 3:32–38

    CAS  PubMed  Google Scholar 

  104. Tisdale JF, Stewart AK, Dickstein B, Little RF, Dube I, Cappe D, Dunbar CE, Brown KE (1998) Molecular and serological examination of the relationship of human herpesvirus 8 to multiple myeloma: orf 26 sequences in bone marrow stroma are not restricted to myeloma patients and other regions of the genome are not detected. Blood 92:2681–2687

    CAS  PubMed  Google Scholar 

  105. Monini P, De Lellis L, Fabris M, Rigolin F, Cassai E (1996) Kaposi's sarcoma-associated herpesvirus DNA sequences in prostate tissue and human semen. N Engl J Med 334:1168–1172

    Article  CAS  PubMed  Google Scholar 

  106. Tasaka T, Said JW, Morosetti R, Park D, Verbeek W, Nagai M, Takahara J, Koeffler HP (1997) Is Kaposi's sarcoma-associated herpesvirus ubiquitous in urogenital and prostate tissues? Blood 89:1686–1689

    CAS  PubMed  Google Scholar 

  107. Lefrere JJ, Meyohas MC, Mariotti M, Meynard JL, Thauvin M, Frottier J (1996) Detection of human herpesvirus 8 DNA sequences before the appearance of Kaposi's sarcoma in human immunodeficiency virus (HIV)-positive subjects with a known date of HIV seroconversion. J Infect Dis 174:283–287

    Google Scholar 

  108. Lallemand F, Desire N, Rozenbaum W, Nicolas JC, Marechal V (2000) Quantitative analysis of human herpesvirus 8 viral load using a real-time PCR assay. J Clin Microbiol 38:1404–1408

    CAS  PubMed  Google Scholar 

  109. Campbell TB, Borok M, Gwanzura L, MaWhinney S, White IE, Ndemera B, Gudza I, Fitzpatrick L, Schooley RT (2000) Relationship of human herpesvirus 8 peripheral blood virus load and Kaposi's sarcoma clinical stage. AIDS 14:2109–2116

    Article  CAS  PubMed  Google Scholar 

  110. Clementi M (2000) Quantitative molecular analysis of virus expression and replication. J Clin Microbiol 38:2030–2036

    CAS  PubMed  Google Scholar 

  111. Heid CA, Stevens J, Livak KJ, Williams PM (1996) Real time quantitative PCR. Genome Res 6:986–994

    CAS  PubMed  Google Scholar 

  112. Jordan JA (2000) Real time detection of PCR products and microbiology. New technologies for the life sciences: a Trends Guide. Elsevier, London, pp 61–66

  113. Stamey FR, Patel MM, Holloway BP, Pellett PE (2001) Quantitative, fluorogenic probe PCR assay for detection of human herpesvirus 8 DNA in clinical specimens. J Clin Microbiol 39:3537–3540

    Article  CAS  PubMed  Google Scholar 

  114. Lock MJ, Griffiths PD, Emery VC (1997) Development of a quantitative competitive polymerase chain reaction for human herpesvirus 8. J Virol Methods 64:19–26

    Article  CAS  PubMed  Google Scholar 

  115. Boivin G, Gaudreau A, Toma E, Lalonde R, Routy JP, Murray G, Handfield J, Bergeron MG (1999) Human herpesvirus 8 DNA load in leukocytes of human immunodeficiency virus-infected subjects: correlation with the presence of Kaposi's sarcoma and response to anticytomegalovirus therapy. Antimicrob Agents Chemother 43:377–380

    CAS  PubMed  Google Scholar 

  116. White IE, Campbell TB (2000) Quantitation of cell-free and cell-associated Kaposi's sarcoma-associated herpesvirus DNA by real-time PCR. J Clin Microbiol 38:1992–1995

    CAS  PubMed  Google Scholar 

  117. Zoeteweij JP, Eyes ST, Orenstein JM, Kawamura T, Wu L, Chandran B, Forghani B, Blauvelt A (1999) Identification and rapid quantification of early- and late-lytic human herpesvirus 8 infection in single cells by flow cytometric analysis: characterization of antiherpesvirus agents. J Virol 73:5894–5902

    CAS  PubMed  Google Scholar 

  118. Kedes DH, Ganem D (1997) Sensitivity of Kaposi's sarcoma-associated herpesvirus replication to antiviral drugs. Implications for potential therapy. J Clin Invest 99:2082–2086

    CAS  PubMed  Google Scholar 

  119. Moore PS, Gao SJ, Dominguez G, Cesarman E, Lungu O, Knowles DM, Garber R, Pellett PE, McGeoch DJ, Chang Y (1996) Primary characterization of a herpesvirus agent associated with Kaposi's sarcoma. J Virol 70:549–558

    CAS  PubMed  Google Scholar 

  120. Rezza G, Lennette ET, Giuliani M, Pezzotti P, Caprilli F, Monini P, Butto S, Lodi G, Di Carlo A, Levy JA, Ensoli B (1998) Prevalence and determinants of anti-lytic and anti-latent antibodies to human herpesvirus-8 among Italian individuals at risk of sexually and parenterally transmitted infections. Int J Cancer 77:361–365

    Article  CAS  PubMed  Google Scholar 

  121. Andre S, Schatz O, Bogner JR, Zeichhardt H, Stoffler-Meilicke M, Jahn HU, Ullrich R, Sonntag AK, Kehm R, Haas J (1997) Detection of antibodies against viral capsid proteins of human herpesvirus 8 in AIDS-associated Kaposi's sarcoma. J Mol Med 75:145–152

    Article  CAS  PubMed  Google Scholar 

  122. Raab MS, Albrecht JC, Birkmann A, Yaguboglu S, Lang D, Fleckenstein B, Neipel F (1998) The immunogenic glycoprotein gp35–37 of human herpesvirus 8 is encoded by open reading frame K8.1. J Virol 72:6725–6731

    CAS  PubMed  Google Scholar 

  123. Pauk J, Huang ML, Brodie SJ, Wald A, Koelle DM, Schacker T, Celum C, Selke S, Corey L (2000) Mucosal shedding of human herpesvirus 8 in men. N Engl J Med 343:1369–1377

    Article  CAS  PubMed  Google Scholar 

  124. Hudnall SD, Rady PL, Tyring SK, Fish JC (1998) Serologic and molecular evidence of human herpesvirus 8 activation in renal transplant recipients. J Infect Dis 178:1791–1794

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Microbiology-Immunology and Virology Department, Centro di Riferimento Oncologico, IRCCS, via Pedemontana Occ. 12, 33081 Aviano, Italy

    R. Tedeschi & P. De Paoli

  2. Department of Medical Microbiology, MAS University Hospital, Entrance 78, 20502 Malmö, Sweden

    J. Dillner

Authors
  1. R. Tedeschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Dillner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. De Paoli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. De Paoli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tedeschi, R., Dillner, J. & De Paoli, P. Laboratory Diagnosis of Human Herpesvirus 8 Infection in Humans. Eur J Clin Microbiol Infect Dis 21, 831–844 (2002). https://doi.org/10.1007/s10096-002-0836-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-002-0836-8

Keywords

Search

Navigation