Classical Kaposi’s Sarcoma (cKS) is a rare vascular tumor, which develops in subjects infected with Human Herpesvirus-8 (HHV-8). Beside the host predisposing factors, viral genetic variants might possibly be related to disease development. The aim of this study was to identify HHV-8 variants in patients with cKS or in HHV-8 infected subjects either asymptomatic or with cKS-unrelated cutaneous lymphoproliferative disorders. The VR1 and VR2 regions of the ORF K1 sequence were analyzed in samples (peripheral blood and/or lesional tissue) collected between 2000 and 2010 from 27 subjects with HHV-8 infection, established by the presence of anti-HHV-8 antibodies. On the basis of viral genotyping, a phylogenetic analysis and a time-scaled evaluation were performed. Two main clades of HHV-8, corresponding to A and C subtypes, were identified. Moreover, for each subtype, two main clusters were found distinctively associated to cKS or non-cKS subjects. Selective pressure analysis showed twelve sites of the K1 coding gene (VR1 and VR2 regions) under positive selective pressure and one site under negative pressure. Thus, present data suggest that HHV-8 genetic variants may influence the susceptibility to cKS in individuals with HHV-8 infection.

Three hundred seventy‐nine individuals [137 non‐injecting drug using (non‐IDU) heterosexuals, 130 homosexual men and 112 IDU] attending the human immunodeficiency virus (HIV) testing program of a sexually transmitted disease (STD) clinic in Rome were studied to estimate the prevalence and to identify the modalities of transmission of human herpesvirus‐8 (HHV‐8) infection. Serological analysis was performed by using an immunofluorescence assay able to detect anti‐latent and anti‐lytic HHV‐8 antibodies. Twelve acquired immunodeficiency syndrome (AIDS)‐Kaposi's sarcoma (KS) patients and 94 blood donors were tested as reference population groups. Anti‐lytic antibodies were detected in 185 (48.8%) individuals; 52 of them (13.7%) also had anti‐latent antibodies. Both anti‐lytic and anti‐latent antibody prevalence were higher among homosexual men (66.9% and 27.7%, respectively) than among IDU (49.1% and 8.0%, respectively) and non‐IDU heterosexuals (31.4% and 5.1%, respectively), and tended to increase with age. Anti‐lytic HHV‐8 antibodies were associated with syphilis [odds ratio (OR) = 3.81] but not with hepatitis C virus (HCV) seropositivity. HIV‐infected homosexual men were more likely to have HHV‐8 antibodies than those who were HIV‐negative. When using anti‐latent antibodies the direction of the OR remained the same, although the associations did not often reach statistical significance. Among AIDS‐KS patients, 83.3% had anti‐lytic and 66.6% had anti‐latent antibodies. Among blood donors, 28% had anti‐lytic antibodies and 2 of them (2.1%) also had anti‐latent antibodies. Our data indicate that HHV‐8 seroprevalence increases with age and is higher among homosexual men, particularly those infected with HIV. This is consistent with sexual transmission of HHV‐8 infection. In addition, the presence of HHV‐8 antibodies in HIV‐negative non‐IDU heterosexual contacts and in healthy blood donors is consistent with the high incidence of classic KS in Italy. Int. J. Cancer. 77:361–365, 1998.