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Abstract

Title: Host Immunogenetics and Control of Human Herpesvirus-8 Infection.
Author: Brown EE, Fallin MD, Goedert JJ, Hutchinson A, Vitale F, Lauria C, Giuliani M, Marshall V, Mbisa G, Serraino D, Messina A, Durum S, Whitby D, Chanock SJ
Journal: J Infect Dis 193(8):1054-1062
Year: 2006
Month: April

Abstract: 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.