Host immunogenetics and control of human herpesvirus-8 infection

Background. Kaposi sarcoma (KS) is primarily caused by human herpesvirus (HHV)-8 infection, and the risk is increased with high HHV-8 lytic or latent antibody titers or the detection of HHV-8 DNA in peripheral blood mononuclear cells (PBMCs). Host genes important for control of HHV-8 infection are not well characterized. Methods. In 172 HHV-8 latent nuclear antigen ( LANA)-seropositive adults in Italy without KS, we examined correlations of common variants in host immune genes with the detection of HHV-8 DNA in PBMCs and with high lytic and latent antibody titers. Twenty-eight single-nucleotide polymorphisms in 14 genes were analyzed. We detected HHV-8 DNA in PBMCs with real-time amplification of the K6 gene, anti-K8.1 ( lytic) titers with enzyme-linked immunosorbent assay, and anti-LANA ( latent) titers with immunofluorescence. Results. Detection of HHV-8 DNA in PBMCs was not significantly related to any variant examined. In contrast, a 3-locus haplotype of IL4, which contains the -1098G allele ( rs2243248), was overrepresented among subjects with high lytic titers ( odds ratio [ OR], 2.8 [ 95% confidence interval {CI}, 1.1-6.7]), compared with those with low titers, as was the functional promoter variant of IL6, C-236C ( rs1800795) ( OR, 3.7 [ 95% CI, 1.1-12.8]). Compared with subjects with low HHV-8 latent antibody titers, analysis of inferred haplotypes for IL12A revealed an overrepresentation of -798T/277A in subjects with high HHV-8 latent antibody titers ( OR, 2.4 [ 95% CI, 1.1-5.2]). Conclusions. Our observations are the first to provide preliminary evidence suggesting that common variants in key host immune genes could influence the control of HHV-8 infection.