Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1997 Mar;71(3):2505–2511. doi: 10.1128/jvi.71.3.2505-2511.1997

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 C Zong 1, C Metroka 1, M S Reitz 1, J Nicholas 1, G S Hayward 1
PMCID: PMC191364  PMID: 9032391

Abstract

Previous analysis of the majority of Kaposi's sarcoma (KS) tumors, in both AIDS and non-AIDS populations, has revealed the consistent presence of two small subsegments (open reading frame 25/26 [ORF25/26] and ORF75) of a novel human gamma class herpesvirus genome referred to as KSHV or HHV-8. We have carried out DNA sequence comparisons with DNAs encompassing a total of 2,500 bp each over three separate PCR-amplified fragments from KS lesions and body cavity-based lymphoma (BCBL) samples from 12 distinct patients, including four African and two classical or endemic non-AIDS KS samples. The results revealed differences at 37 of 2,500 nucleotide positions (i.e., 1.5% overall variation). However, the 12 HHV-8 genomes examined fell into three distinct but very narrow subgroupings (A, B, and C strains). All A strain isolates differed from B strain isolates at 16 positions, but of the eight U.S. samples tested, six were A strains, and these differed at no more than two positions among them. Similarly, three of the four African samples were B strains, which differed from each other at only one position. The two C strain genomes also displayed only one nucleotide variation, but they differed from all A strains at 26 positions and from all B strains at 20 positions. One C strain genome was present in all six independent lesions from an AIDS KS patient with disseminated disease, and the other represented a mosaic A/C recombinant genome from the HBL6 cell line derived from a BCBL tumor. Evaluation of previous data suggests that B and C strains may predominate in Africa and that A strains predominate in classical Mediterranean samples. Although both B and C strains are represented in U.S. AIDS patients, the majority (70 to 80%) of samples from the mid-East Coast region at least appear to be virtually identical, supporting the concept that they may all derive from the spread during the AIDS epidemic of a single recently transmitted infectious agent.

Full Text

The Full Text of this article is available as a PDF (154.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams V., Kempf W., Schmid M., Müller B., Briner J., Burg G. Absence of herpesvirus-like DNA sequences in skin cancers of non-immunosuppressed patients. Lancet. 1995 Dec 23;346(8991-8992):1715–1716. doi: 10.1016/s0140-6736(95)92887-1. [DOI] [PubMed] [Google Scholar]
  2. Ambinder R. F., Newman C., Hayward G. S., Biggar R., Melbye M., Kestens L., Van Marck E., Piot P., Gigase P., Wright P. B. Lack of association of cytomegalovirus with endemic African Kaposi's sarcoma. J Infect Dis. 1987 Jul;156(1):193–197. doi: 10.1093/infdis/156.1.193. [DOI] [PubMed] [Google Scholar]
  3. Ambroziak J. A., Blackbourn D. J., Herndier B. G., Glogau R. G., Gullett J. H., McDonald A. R., Lennette E. T., Levy J. A. Herpes-like sequences in HIV-infected and uninfected Kaposi's sarcoma patients. Science. 1995 Apr 28;268(5210):582–583. doi: 10.1126/science.7725108. [DOI] [PubMed] [Google Scholar]
  4. Beral V. Epidemiology of Kaposi's sarcoma. Cancer Surv. 1991;10:5–22. [PubMed] [Google Scholar]
  5. Beral V., Peterman T. A., Berkelman R. L., Jaffe H. W. Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection? Lancet. 1990 Jan 20;335(8682):123–128. doi: 10.1016/0140-6736(90)90001-l. [DOI] [PubMed] [Google Scholar]
  6. Boldogh I., Beth E., Huang E. S., Kyalwazi S. K., Giraldo G. Kaposi's sarcoma. IV. Detection of CMV DNA, CMV RNA and CMNA in tumor biopsies. Int J Cancer. 1981 Oct 15;28(4):469–474. doi: 10.1002/ijc.2910280412. [DOI] [PubMed] [Google Scholar]
  7. Boshoff C., Schulz T. F., Kennedy M. M., Graham A. K., Fisher C., Thomas A., McGee J. O., Weiss R. A., O'Leary J. J. Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med. 1995 Dec;1(12):1274–1278. doi: 10.1038/nm1295-1274. [DOI] [PubMed] [Google Scholar]
  8. Boshoff C., Talbot S., Kennedy M., O'Leary J., Schulz T., Chang Y. HHV8 and skin cancers in immunosuppressed patients. Lancet. 1996 Feb 3;347(8997):338–339. doi: 10.1016/s0140-6736(96)90524-3. [DOI] [PubMed] [Google Scholar]
  9. Boshoff C., Whitby D., Hatziioannou T., Fisher C., van der Walt J., Hatzakis A., Weiss R., Schulz T. Kaposi's-sarcoma-associated herpesvirus in HIV-negative Kaposi's sarcoma. Lancet. 1995 Apr 22;345(8956):1043–1044. doi: 10.1016/s0140-6736(95)90780-7. [DOI] [PubMed] [Google Scholar]
  10. Cesarman E., Chang Y., Moore P. S., Said J. W., Knowles D. M. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med. 1995 May 4;332(18):1186–1191. doi: 10.1056/NEJM199505043321802. [DOI] [PubMed] [Google Scholar]
  11. Cesarman E., Moore P. S., Rao P. H., Inghirami G., Knowles D. M., Chang Y. 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. 1995 Oct 1;86(7):2708–2714. [PubMed] [Google Scholar]
  12. Chang Y., Cesarman E., Pessin M. S., Lee F., Culpepper J., Knowles D. M., Moore P. S. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865–1869. doi: 10.1126/science.7997879. [DOI] [PubMed] [Google Scholar]
  13. Collandre H., Ferris S., Grau O., Montagnier L., Blanchard A. Kaposi's sarcoma and new herpesvirus. Lancet. 1995 Apr 22;345(8956):1043–1043. doi: 10.1016/s0140-6736(95)90779-3. [DOI] [PubMed] [Google Scholar]
  14. Dambaugh T., Hennessy K., Chamnankit L., Kieff E. U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7632–7636. doi: 10.1073/pnas.81.23.7632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dupin N., Grandadam M., Calvez V., Gorin I., Aubin J. T., Havard S., Lamy F., Leibowitch M., Huraux J. M., Escande J. P. Herpesvirus-like DNA sequences in patients with Mediterranean Kaposi's sarcoma. Lancet. 1995 Mar 25;345(8952):761–762. doi: 10.1016/s0140-6736(95)90642-8. [DOI] [PubMed] [Google Scholar]
  16. Gao S. J., Kingsley L., Li M., Zheng W., Parravicini C., Ziegler J., Newton R., Rinaldo C. R., Saah A., Phair J. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med. 1996 Aug;2(8):925–928. doi: 10.1038/nm0896-925. [DOI] [PubMed] [Google Scholar]
  17. Giraldo G., Beth E., Huang E. S. Kaposi's sarcoma and its relationship to cytomegalovirus (CMNV). III. CMV DNA and CMV early antigens in Kaposi's sarcoma. Int J Cancer. 1980 Jul 15;26(1):23–29. doi: 10.1002/ijc.2910260105. [DOI] [PubMed] [Google Scholar]
  18. Gompels U. A., Nicholas J., Lawrence G., Jones M., Thomson B. J., Martin M. E., Efstathiou S., Craxton M., Macaulay H. A. The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution. Virology. 1995 May 10;209(1):29–51. doi: 10.1006/viro.1995.1228. [DOI] [PubMed] [Google Scholar]
  19. Huang Y. Q., Li J. J., Kaplan M. H., Poiesz B., Katabira E., Zhang W. C., Feiner D., Friedman-Kien A. E. Human herpesvirus-like nucleic acid in various forms of Kaposi's sarcoma. Lancet. 1995 Mar 25;345(8952):759–761. doi: 10.1016/s0140-6736(95)90641-x. [DOI] [PubMed] [Google Scholar]
  20. Kedes D. H., Operskalski E., Busch M., Kohn R., Flood J., Ganem D. 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. 1996 Aug;2(8):918–924. doi: 10.1038/nm0896-918. [DOI] [PubMed] [Google Scholar]
  21. Kemény L., Kiss M., Gyulai R., Dobozy A., Adám E., Nagy F. Herpesvirus-like nucleic acid sequences in patients with Eastern European sporadic Kaposi's Sarcoma. J Invest Dermatol. 1996 Feb;106(2):381–381. doi: 10.1111/1523-1747.ep12343185. [DOI] [PubMed] [Google Scholar]
  22. Knowles D. M., Inghirami G., Ubriaco A., Dalla-Favera R. Molecular genetic analysis of three AIDS-associated neoplasms of uncertain lineage demonstrates their B-cell derivation and the possible pathogenetic role of the Epstein-Barr virus. Blood. 1989 Feb 15;73(3):792–799. [PubMed] [Google Scholar]
  23. Lebbé C., de Crémoux P., Rybojad M., Costa da Cunha C., Morel P., Calvo F. Kaposi's sarcoma and new herpesvirus. Lancet. 1995 May 6;345(8958):1180–1180. doi: 10.1016/s0140-6736(95)91011-5. [DOI] [PubMed] [Google Scholar]
  24. Ling P. D., Ryon J. J., Hayward S. D. EBNA-2 of herpesvirus papio diverges significantly from the type A and type B EBNA-2 proteins of Epstein-Barr virus but retains an efficient transactivation domain with a conserved hydrophobic motif. J Virol. 1993 Jun;67(6):2990–3003. doi: 10.1128/jvi.67.6.2990-3003.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lisitsyn N., Lisitsyn N., Wigler M. Cloning the differences between two complex genomes. Science. 1993 Feb 12;259(5097):946–951. doi: 10.1126/science.8438152. [DOI] [PubMed] [Google Scholar]
  26. Lunardi-Iskandar Y., Bryant J. L., Zeman R. A., Lam V. H., Samaniego F., Besnier J. M., Hermans P., Thierry A. R., Gill P., Gallo R. C. Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in immunodeficient mice blocked by a human pregnancy hormone. Nature. 1995 May 4;375(6526):64–68. doi: 10.1038/375064a0. [DOI] [PubMed] [Google Scholar]
  27. Lundgren J. D., Melbye M., Pedersen C., Rosenberg P. S., Gerstoft J. Changing patterns of Kaposi's sarcoma in Danish acquired immunodeficiency syndrome patients with complete follow-up. The Danish Study Group for HIV Infection (DASHI). Am J Epidemiol. 1995 Apr 1;141(7):652–658. doi: 10.1093/oxfordjournals.aje.a117481. [DOI] [PubMed] [Google Scholar]
  28. McGeoch D. J., Cook S., Dolan A., Jamieson F. E., Telford E. A. Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses. J Mol Biol. 1995 Mar 31;247(3):443–458. doi: 10.1006/jmbi.1995.0152. [DOI] [PubMed] [Google Scholar]
  29. McGeoch D. J., Cook S. Molecular phylogeny of the alphaherpesvirinae subfamily and a proposed evolutionary timescale. J Mol Biol. 1994 Apr 22;238(1):9–22. doi: 10.1006/jmbi.1994.1264. [DOI] [PubMed] [Google Scholar]
  30. Miles S. A. Pathogenesis of HIV-related Kaposi's sarcoma. Curr Opin Oncol. 1994 Sep;6(5):497–502. doi: 10.1097/00001622-199409000-00009. [DOI] [PubMed] [Google Scholar]
  31. Moore P. S., Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and without HIV infection. N Engl J Med. 1995 May 4;332(18):1181–1185. doi: 10.1056/NEJM199505043321801. [DOI] [PubMed] [Google Scholar]
  32. Nicholas J., Ruvolo V., Zong J., Ciufo D., Guo H. G., Reitz M. S., Hayward G. S. A single 13-kilobase divergent locus in the Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genome contains nine open reading frames that are homologous to or related to cellular proteins. J Virol. 1997 Mar;71(3):1963–1974. doi: 10.1128/jvi.71.3.1963-1974.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Raab-Traub N., Flynn K. The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation. Cell. 1986 Dec 26;47(6):883–889. doi: 10.1016/0092-8674(86)90803-2. [DOI] [PubMed] [Google Scholar]
  34. Rady P. L., Yen A., Rollefson J. L., Orengo I., Bruce S., Hughes T. K., Tyring S. K. Herpesvirus-like DNA sequences in non-Kaposi's sarcoma skin lesions of transplant patients. Lancet. 1995 May 27;345(8961):1339–1340. doi: 10.1016/s0140-6736(95)92538-4. [DOI] [PubMed] [Google Scholar]
  35. Renne R., Zhong W., Herndier B., McGrath M., Abbey N., Kedes D., Ganem D. Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nat Med. 1996 Mar;2(3):342–346. doi: 10.1038/nm0396-342. [DOI] [PubMed] [Google Scholar]
  36. Soulier J., Grollet L., Oksenhendler E., Cacoub P., Cazals-Hatem D., Babinet P., d'Agay M. F., Clauvel J. P., Raphael M., Degos L. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood. 1995 Aug 15;86(4):1276–1280. [PubMed] [Google Scholar]
  37. Whitby D., Howard M. R., Tenant-Flowers M., Brink N. S., Copas A., Boshoff C., Hatzioannou T., Suggett F. E., Aldam D. M., Denton A. S. Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma. Lancet. 1995 Sep 23;346(8978):799–802. doi: 10.1016/s0140-6736(95)91619-9. [DOI] [PubMed] [Google Scholar]
  38. Wrightham M. N., Stewart J. P., Janjua N. J., Pepper S. D., Sample C., Rooney C. M., Arrand J. R. Antigenic and sequence variation in the C-terminal unique domain of the Epstein-Barr virus nuclear antigen EBNA-1. Virology. 1995 Apr 20;208(2):521–530. doi: 10.1006/viro.1995.1183. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES