Chapter 93A
Human Herpes-virus 8
Main Menu   Table Of Contents



Taxonomically, Herpesviridae are divided into three subfamilies: Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae. There are eight human herpesviruses (HHV), including three that have been more recently discovered, HHV-6, HHV-7, and HHV-8.1–3 HHV include herpes simplex viruses (HSV) 1 and 2 and varicella zoster virus (VZV) (HHV-3), which belong to the alphaherpesvirus subfamily. This subfamily is characterized by its neurotropism and limited gene expression during latency. The beta subfamily of HHV is composed of cytomegalovirus (HHV-5) and HHV-6 and HHV-7. These viruses are distinguished from other herpesviruses by their limited host range and their cell type specificity. The newest member of the HHV family is HHV-8 (Kaposi's sarcoma [KS] herpesvirus), a member of the gammaherpesvirus subfamily. This subfamily also includes Epstein-Barr virus (EBV) (HHV-4) and is characterized by productive and latent infection of lymphocytes. Probably the most important characteristic of all herpesviruses is their ability to establish latent infections.
Back to Top
HHV-8 is a member of the gammaherpesvirus subfamily, showing greatest nucleotide homology to members of the genus Rhadinovirus. The existence of this virus was initially recognized by using representational difference analysis of nucleic acids from tissues of a KS patient. The deoxyribonucleic acid (DNA) fragments obtained by this procedure had regions of homology to late genes of other gammaherpesviruses.1 Since the initial discovery, HHV-8 has been found in all forms of KS: classic, endemic, and acquired immunodeficiency syndrome (AIDS) associated. Because of its association with KS, it is also known as Kaposi's sarcoma associated herpesvirus (KSHV). Similar to other herpesviruses, strain variations in HHV-8 have also been found. The strain variations are mainly due to variations in the gene products of KSHV open reading frame (ORF)-K1 and ORF-K15. Both of these seem to code for membrane-signaling proteins and may play a key role in the biology and disease manifestation associated with HHV-8.4 Three distinct strains of HHV-8 have been identified, which appear to be restricted in their geographic distribution: B and C are the most common in Africa, whereas A predominates in the Mediterranean region. Geographic strain variations in gene sequences have also been identified in virus isolated from Japan, Kuwait, Europe, Russia, Australia, South America, United States of America, and Saudi Arabia.5–9

HHV-8 does not readily infect most cell types. Thus far, no primary cell or cell line is permissive to HHV-8 infection and none can produce infectious virus. However, several investigators have shown the transmission of HHV-8 DNA from BC-1 cell line into Raji (EBV positive B-cell line), BJAB (EBV negative B-cell line), Molt-3, and owl monkey kidney (OMK) cell lines and cord blood mononuclear cells.10,11 HHV-8 from KS lesions has also been propagated in embryonic kidney 293 cells. In all these cells, active infection was not noticed and the viral DNA was not detected after a few passages.12 About 38 additional cell lines, including B cells, endothelial cells, and cells of fibroblastic origin were used as targets for transmission, but all failed.

Primary cultures of human monocytes/macrophages from patients with AIDS-associated KS can be infected with HHV-8, and treatment with cytokines seems to enhance viral production and allow the cells to maintain the virus for a longer period.13 Microvascular endothelial cells transformed with papilloma virus type 16 genes, E6 and E7, were also permissive to HHV-8 from BC-1 cell line.14 Untransformed primary fetal microvascular endothelial cells have also been successfully infected with HHV-8 from a primary effusion lymphoma (PEL) cell line.15,16

HHV-8 exhibits typical herpesvirus morphology of 100 to 150 nm-enveloped particles. The capsids are icosahedral with a diameter of 90 to 110 nm, which consists of 162 hexagonal capsomeres. The tegument is a protein-containing region between capsid and the envelope. Electron micrographs clearly indicated that the core is a complex of DNA and protein. About 35% of the virion is usually intact, and 65% is defective.17 The double-stranded linear DNA genome of the virus has been estimated to be 165 to 170 kilobase (kb).11 The genome of HHV-8 is similar to herpesvirus saimiri (HVS) found in squirrel monkeys. It has a single contiguous region, 140 to 145 kb, containing all the coding regions. The genome has repeats of 803 bp in length that are 85% guanine and cytosine. Each DNA molecule harbors about 35 to 45 repeat units.18,19

Back to Top
When the envelope glycoproteins of HHV-8 bind proteoglycans on the surface of the host cells, penetration occurs by fusion of viral envelope with plasma membrane of the cell. Following insertion into the host genome, DNA replication and capsid assembly occur in the nucleus of the host cell.11,12

Infectious virus has been isolated from body cavity-based B-cell lymphoma cells.20 In some cell lines derived from these lymphomas, EBV is also present, and both viruses may be latent.21 HHV-8 in these cell lines can be reactivated to produce viral particles.20,22 Virus transcripts have also been detected in endothelial-derived spindle cells from tumors of KS.23 HHV-8 is transmissible to B cells and replicates in the peripheral blood mononuclear cells of KS patients.10,24

HHV-8 expresses unique polyadenylated (poly A) nuclear ribonucleic acid (RNA) that colocalizes with uracil (U) small nuclear RNA but not with polysomes, suggesting a regulatory role for the RNA.25 In the latently infected B-cell lymphoma cell lines and KS cells, the genome exists in a circular form, similar to that described for other herpesviruses during latency.26 In KS, transcription of viral genes is restricted; only two transcripts are detected: one for a possible membrane protein and the second the abundant, poly A-containing nuclear transcript.27

Back to Top
The exact nature of the steps involved in the DNA replication is unknown. The whole viral genome has been sequenced. Of the approximately 95 genes comprising the HHV-8 genome, nearly 25 encode novel proteins not found in other HHVs. HHV-8 contains regions encoding homologues of several cellular genes that have regulatory roles in the immune response.18,28 KSHV carries 11 ORFs that encode homologues to cellular proteins involved in signal transduction, cell cycle regulation, transformation, and/or inhibition of apoptosis.29–32

A homologue of bcl-2, an important inhibitor of apoptosis in lymphoid and other cell types, is produced by HHV-8 and can inhibit apoptosis induced by several stimuli, thereby leading to an extended survival of the infected cells.29,30 Homologues of the chemokines, macrophage inflammatory protein-1, macrophage inflammatory protein-11, and the cytokine IL-6 are also produced.33–35 HHV-8-associated malignancies such as KS have been found to express a unique protein called kaposin, coded by latent transcript (ORF-12). Kaposin gene product induces tumorigenic transformation in transfected rat cells. Kaposin has also been detected in PEL cell lines, which are persistently infected with HHV-8.31,32 The virus also encode a D-type cyclin that can associate with CDK6 and induce phosphorylation of retinoblastoma (Rb) protein and overcome Rb-mediated cell cycle arrest.36,37 LNA-1 (ORF-37), the most frequently identified protein in KS tumor cells, has also been tumorigenic. It transforms primary rat embryo cells that seem to act as a transcriptional cofactor and contributes to HHV-8 induced oncogenesis by the retinoblastoma E2F transcriptional regulatory pathway.38 The virus also encodes homologues of interferon regulatory factors, a neural cell adhesion molecule, and the IL-8 receptor.39–41 The roles of these molecules in modifying the environment in which the virus infected cell exists, including the impact on the immune response to the virus, remain to be elucidated.

Back to Top
Unlike most HHVs, HHV-8 is not spread universally among all human populations. The highest seroprevalences in healthy populations are found in sub-Saharan Africa where approximately 40% are positive for HHV-8 antibodies. In the areas around the Mediterranean Sea, the seroprevalence is about 10%. In North Europe, Southeast Asia, and the Caribbean, the seroprevalence is 2% to 4%. In the United States, prevalence has been measured in the 5% to 20% range. In HIV-1 infected populations, the prevalence of HHV-8 can rise to 20% to 50% above the healthy population.42

The seroepidemiology of HHV-8 in HIV-1 positive patients (the patient population in the United States in which KS is most common) suggests that HHV-8 is sexually transmitted.43 The geographic distribution of KS and of seropositivity to HHV-8 vary in a coordinated way. In one study, the incidence of seropositivity to HHV-8 was compared in Uganda, where the rate of KS is among the world's highest; Italy, which has a moderate rate of KS; and the United States, which before the occurrence of AIDS had a low rate of KS. It was found that in Uganda, 50% to 60% of HIV-1 negative individuals without KS had antibody to HHV-8. In Italy, only 4% of blood donors were seropositive; in the United States, none of the blood donor samples tested had antibody to HHV-8.44 Most cases of KS in AIDS patients seen in the central east coast of the United States are essentially identical in a DNA sequence that was used for characterization in one study, suggesting that all of these U.S. cases may have a single recent origin.45 In patients with one of the diseases associated with HHV-8, such as KS, primary effusion lymphomas, and multicentric Castleman's disease, the seroprevalence rates rise to 100%.46 The transmission of HHV-8 most frequently occurs via saliva and sexual contacts.47,48 High correlations of seropositivity were also found between mother and child and among siblings.49

The virus has been cultured from a rare form of B-cell lymphoma, primary effusion lymphoma, multicentric Castleman's disease, and KS. The classic form of KS is a multifocal pigmented sarcoma found in older adult men. This type of sarcoma affects mostly older men of Mediterranean and Eastern European ancestry.50 Since its initial description, three more forms of KS have been identified. The second type, “endemic African” KS is more aggressive than the classic form and involves lymph nodes and skin. It often affects HIV-1 negative hosts and children. A third form of KS occurs after organ transplants in patients on immunosuppressive drugs. This form is also common in individuals of Mediterranean ancestry. The fourth form, which is one of the most aggressive types of KS, is often described in healthy homosexual men. It not only involves skin and lymph nodes but also often disseminates to the lungs, gastrointestinal track, liver, and spleen. Often this type of KS is also refers to as AIDS-associated KS.51–53 HHV-8 has been found in all forms of KS.54

Viral DNA has been specifically localized to tumor cells in KS and B-cell lymphoma by in situ PCR.55 In KS sarcoma patients, in situ hybridization has shown that viral DNA is restricted in its tissue distribution to cells of the lesions. Even in early lesions, the virus is present in spindle cells of KS.23 Using PCR analysis, HHV-8 DNA has also been detected in peripheral blood mononuclear cells from patients at the time of and years before development of KS, in lymphoid tissues, in bronchoalveolar lavage fluid from patients with pulmonary KS, in KS lesions from HIV-1 negative patients, and in saliva from people with KS.56–60 In situ hybridization studies have also demonstrated the virus in prostate tissue and semen of healthy men in Italy, but other studies failed to detect viral DNA in semen or urogenital or prostate tissue.56,60–62 The association between HHV-8 and KS is evident from numerous studies, but it remains unclear whether HHV-8 causes KS or KS creates an environment in patients that is conducive to HHV-8 infection or growth.

In multicentric Castleman's disease, a disease characterized by a typical lymphoid proliferation, HHV-8 DNA is detectable, and increases in viral load correlates with increases in clinical measures of disease.63 The presence of the virus has been reported in non-Hodgkin's AIDS-associated body cavity-based lymphomas (primary effusion lymphomas) and some skin cancers and other tissues in HIV-1 infected individuals; however, it is not present in peripheral blood mononuclear cells of family members of sporadic KS patients. Although KS of eyelid or conjunctiva occurs in 20% to 25% of AIDS patients, detection of virus or viral DNA from these lesions has not yet been reported.64,65

Glucocorticoids are known to augment growth of KS tumors and have been shown to enhance replication of HHV-8 infected cells in culture. KS tumor cells produce transforming growth factor-β, an inhibitor of replication of some hematopoietic and endothelial cells that can act in an autocrine manner to reduce cell growth. Glucocorticoids do not inhibit transforming growth factor-β synthesis but block activation to an active form, thereby allowing increased cell proliferation.66 The sensitivity of HHV-8 to antiviral agents has been assessed in HHV-8-carrying B-cell lymphoma cells in culture. The virus appears to be insensitive to acyclovir but sensitive to antiviral agents used for anti-human cytomegalovirus (HCMV) therapy, including ganciclovir, foscarnet, and cidofovir.24,67 These results from cell cultures are consistent with findings from clinical use of antiviral drugs in AIDS patients. Both ganciclovir and foscarnet (but not acyclovir) reduced the risk of development of KS in this patient population.68

Antiviral therapy of HIV-1 has a beneficial effect on AIDS-associated KS patients. Topical treatment with 10% docosanol cream has reduced KS lesions by 20% as compared with untreated patients. The drug has inhibitory effects on several enveloped viruses in vitro including HSV-1, HSV-2, HCMV, HHV-6, and HIV-1.69

Back to Top

1. Chang Y, Cesarman E, Pessin MS et al: Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 265:1865, 1994

2. Pellet E, Black JB: Human herpesvirus-6. In Fields BW, Knipe DM, Howley PM et al. (eds): Virology. 3rd ed. Philadelphia, Lippincott-Raven, 1996, p 2587

3. Joseph SF, Salahuddin SA, Ablashi DV et al: Genomic analysis of the human B-lympho-tropic virus (HBLV). Science 234:601, 1986

4. Hayward GS: KSHV strains: The origin and global spread of the virus. Semin Cancer Biol 9:187, 1999

5. Meng YX, Spira TJ, Bhat GJ et al: Individuals from North America, Australia, and Africa are infected with four different gene types of human herpesvirus 8. Virology 261:106, 1999

6. Lacoste VE, Kadyrova J, Chistiakova V et al: Molecular characterization of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 strains from Russia. J Gen Virol 81:1217, 2000

7. Fouchard NV, Lacoste P, Couppie M et al: Detection and genetic polymorphism of human herpesvirus type 8 in endemic or epidemic Kaposi's sarcoma from West and Central Africa, and South America. Int J Cancer 85:166, 2000

8. Zhang YJ, Davis TL, Wang XP et al: Distinct distribution of rare US gene types of Kaposi's sarcoma-associated herpesvirus (KSHV) in south Texas for KSHV epidemiology. J Infect Dis 183:125, 2001

9. Meng YX, Sata T, Stamey FR et al: Molecular characterization of strains of human herpesvirus 8 from Japan, Argentina, and Kuwait. J Gen Virol 82:499, 2001

10. Mesri EA, Cesarman E, Arvanitatis L et al: Human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus is a new transmissible virus that infects B-cells. J Exp Med 183:2385, 1996

11. Moore PS, Gao JS, Dominguez G et al: Primary characterization of a herpesvirus-like agent associated with Kaposi's sarcoma. J Virol 70:549, 1996

12. Foreman KE, Friborg J, Kong WP et al: Propagation of human herpesvirus from AIDS-associated Kaposi's sarcoma. N Engl J Med 336:163, 1997

13. Biberfeld PB, Ensoli M, Schulz TF: Kaposi's sarcoma associated herpesvirus/human herpesvirus 8, cytokines, growth factors, and HIV in pathogenesis of Kaposi's sarcoma. Curr Opin Infect Dis 11:97, 1998

14. Moses AV, Fish KN, Ruhl P et al: Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8. J Virol 73:6892, 1999

15. Cannon JS, Ciufo D, Hawkins AL et al: A new primary effusion lymphoma-derived cell line yields a highly infectious Kaposi's sarcoma herpesvirus-containing supernatant. J Virol 74:10187, 2000

16. Wu FY, Ahn JA, Alcendor DJ et al: Origin independent assembly of Kaposi's sarcoma-associated herpesvirus DNA replication compartments in transient cotransfection assays and association with ORF-K8 protein and cellular PML. J Virol 75:1487, 2001

17. Wu LP, Lox, Yu JK et al: Three dimensional structure of the human herpesvirus 8 capsid. J Virol 74:9646, 2000

18. Russo JJ, Bohenzky RA, Chien MC et al: Nucleotide sequence of the Kaposi's sarcoma-associated herpesvirus (HHV-8). Proc Natl Acad Sci U S A 93:14862, 1996

19. Langunoff M, Ganem D: The structure and coding organization of the genomic termini of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8). Virology 236:147, 1997

20. Cesarman E, Chang Y, Moore PS et al: Kaposi's sarcoma-associated herpesvirus-like DNA sequences are present in AIDS-related body cavity based lymphomas. N Engl J Med 332:1186, 1995

21. Miller G, Heston L, Grogan E et al: Selective switch between latency and lytic replication of Kaposi's sarcoma herpesvirus and Epstein-Barr virus in dually infected body cavity lymphoma cells. J Virol 71:314, 1997

22. Renne R, Zhong W, Herndier B et al: Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nat Med 2:342, 1996

23. Staskus KA, Zhong W, Gebhard K et al: Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol 71:715, 1997

24. Renne R, Blackbourn D, Whitby D et al: Limited transmission of Kaposi's sarcoma-associated herpesvirus in cultured cells. J Virol 72:5182, 1998

25. Sun R, Lin S-F, Gradoville L et al: Polyadenylated nuclear RNA encoded by Kaposi sarcoma-associated herpesvirus. Proc Natl Acad Sci U S A 93:11883, 1996

26. Decker KK, Shankera P, Khan G et al: The Kaposi sarcoma-associated herpesvirus (KSHV) is present as an intact latent genome KS tissue but replicates in the peripheral blood mononuclear cells of KS patients. J Exp Med 184:283, 1996

27. Zhong W, Wang H, Herndier B et al: Restricted expression of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma. Proc Natl Acad Sci U S A 93:6641, 1996

28. Bosch ML, Strand KB, Rose TM: The gamma herpesvirus sequence comparison. J Virol 72:8458, 1998

29. Sarid R, Sato T, Bohenzky RA et al: Kaposi's sarcoma-associated herpesvirus encodes a functional bcl-2 homologue. Nat Med 3:293, 1997

30. Cheng EH-Y, Nicholas J, Bellows DS et al: A bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with bax or bak. Pro Natl Acad Sci U S A 94:60, 1997

31. Muralidhar S, Pumfrery AM, Hassani M et al: Identification of kaposin (open reading from K12) as a human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) transforming gene. J Virol 72:4980, 1998

32. Muralidhar S, Pumfrery AM, Hassani M et al: Identification of kaposin (ORF K12) as a human herpesvirus 8 (Kaposi's sarcoma associated herpesvirus) oncogene. J Acquir Immune Defic Syndr Hum Retrovirol 17:A27, 1998

33. Moore PS, Boshoff C, Weiss RA et al: Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science 274:1739, 1996

34. Neipel F, Albrecht J-C, Ensser A et al: Human herpesvirus 8 encodes a homolog of interleukin-6. J Virol 71:839, 1997

35. Nicholas J, Ruvolo VR, Burns WH et al: Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein- and interleukin-6. Nat Med 3:287, 1997

36. Chang Y, Moore PS, Tabol SJ et al: Cyclin encoded by KS herpesvirus [Scientific correspondence]. Nature 382:410, 1996

37. Li M, Lee H, Yoon DW et al: Kaposi's sarcoma-associated herpesvirus encodes a functional cyclin. J Virol 71:1984, 1997

38. Radkov SA, Kellam P, Boshoff C: The latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene Hras transforms primary rat cells. Nat Med 6:1121, 2000

39. Li M, Lee H, Guo J et al: Kaposi's sarcoma-associated viral interferon regulatory factor. J Virol 72:5433, 1998

40. Godden-Kent D, Talbot SJ, Boshoff C et al: The cyclin encoded by Kaposi's sarcoma-associated herpesvirus stimulates cdk6 to phosphorylate the retinoblastoma protein and histone H1. J Virol 71:4193, 1997

41. Guo HG, Browning P, Nicholas J et al: Characterization of a chemokine receptor-related genes in human herpesvirus 8 and its expression in Kaposi's sarcoma. Virology 228:371, 1997

42. Ablashi DV, Chatlynne LG, Cooper HC et al: Seroprevalence of human herpesvirus 8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa. Br J Cancer 81:893, 1999

43. Kedes DH, Operskalski E, Busch M et al: 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, 1996

44. Gao S-J, Kingsley L, Li M et al: KSHV antibodies among Americans, Italians, and Ugandans with and without Kaposi's sarcoma. Nat Med 2:925, 1996

45. Zong J-C, Metroka C, Reitz M et al: Strain variability among Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genome: Evidence that a large cohort of United States AIDS patients may have been infected by a single common isolate. J Virol 71:2505, 1997

46. Gompels UA, Kasolo FC: HHV-8 serology and Kaposi's sarcoma. Lancet 348:1587, 1996

47. Koelle DM, Huang ML, Chandran B et al: 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 176:94, 1997

48. Grulich AE, Olsen SJ, Luo K et al: Kaposi's sarcoma-associated herpesvirus: Sexually transmissible infection. J. AIDS Hum Retrovirol 20:387, 1999

49. Bourboulia DD, Whitby D, Boshoff C et al: Serologic evidence for mother-to-child transmission of Kaposi's sarcoma-associated herpesvirus infection. J Am Med 280:31, 1998

50. Kaposi M: Idiopatisches multiples Pigmentsarkom der Haut. Arch Dermatol Syphilis 4:265, 1872

51. Franceschi S, Geddes M: Epidemiology of classic Kaposi's sarcoma, with special reference to Mediterranean population. Tumor 81:308, 1995

52. Friedman-Kien AE: Disseminated Kaposi's sarcoma syndrome in young homosexual men. J Am Acad Dermatol 5:468, 1981

53. Ziegler JL, Katongole-Mbiddle E: Kaposi's sarcoma in childhood: An analysis of 100 cases from Uganda and relationship to HIV infection. Int J Cancer 65:200, 1996

54. Li SJ, Huang YQ, Cockerell CJ: Localization of human herpesvirus type 8 in vascular endothelial and perivascular spindle-shaped cells of Kaposi's sarcoma lesions by in situ hybridization. Am J Pathol 148:1714, 1996

55. Foreman KE, Bacon PE, His Ed et al: In situ polymerase chain reaction-based localization studies support role of human herpesvirus-8 as the cause of two AIDS-related neoplasms: Kaposi's sarcoma and body cavity lymphoma. J Clin Invest 99:2971, 1997

56. Corbellino M, Poirel L, Bestetti G et al: Restricted tissue distribution of extralesional Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS patients with Kaposi's sarcoma. AIDS Res Hum Retrovir 12:651, 1996

57. Lefrere JJ, Meyohas MC, Mariotti M et al: 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, 1996

58. Cathomas G, Tamm M, Mcgandy CE et al: Detection of herpesvirus-like DNA in the bronchoalveolar lavage fluid of patients with pulmonary Kaposi's sarcoma. Eur Respir J 9:1743, 1996

59. Chuck S, Grant RM, Katongole-Mbiddle E et al: Frequent presence of a novel herpesvirus genome in lesions of human immunodeficiency virus-negative Kaposi's sarcoma. J Infect Dis 173:248, 1996

60. Koelle DM, Huang ML, Chandran B et al: 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, 1997

61. Monini P, deLellis L, Fabris M et al: Kaposi's sarcoma-associated herpesvirus DNA sequences in prostate tissue and human semen. N Engl J Med 334:1168, 1996

62. Tasaka T, Said JW, Morosetti R et al: Is Kaposi's sarcoma-associated herpesvirus ubiquitous in urogenital and prostate tissue? Blood 89:1686, 1997

63. Grandadam M, Dupin N, Calvez V et al: 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, 1997

64. Guembel HO, Ohrloff C: Opportunistic infections of the eye in immunocompromised patients. Ophthalmologica 211:53, 1997

65. Maclean H, Hall AJ, McCombe MF et al: AIDS and the eye. A 10-year experience. Aust N Z J Ophthalmol 24:61, 1996

66. Cai J, Zheng T, Lotz M et al: Glucocorticoids induce Kaposi's sarcoma cell proliferation through the regulation of transforming growth factor-beta. Blood 89:1491, 1997

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

68. Glesby MJ, Hoover DR, Weng S et al: Use of antiherpes drugs and the risk of Kaposi's sarcoma: Data from the multicenter AIDS cohort study. J Infect Dis 173:1477, 1996

69. Scolaro MJ, Gunnill LB, Pope LE et al: The antiviral drug docosanol as a treatment for Kaposi's sarcoma lesions in HIV Type 1 infected patients: A pilot clinical study. AIDS Res Hum Retrovirol 17:35, 2001

Back to Top