Host Immunogenetics and Control of Human Herpesvirus–8 Infection

• Published in: The Journal of infectious diseases 2006-04, Vol.193 (8), p.1054-1062
• Main Authors: Brown, Elizabeth E., Fallin, M. Daniele, Goedert, James J., Hutchinson, Amy, Vitale, Francesco, Lauria, Carmela, Giuliani, Massimo, Marshall, Vickie, Mbisa, Georgina, Serraino, Diego, Messina, Angelo, Durum, Scott, Whitby, Denise, Chanock, Stephen J.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies; Antibodies, Viral - blood; Cytokines; Cytokines - genetics; DNA; DNA, Viral - blood; Female; Genotypes; Haplotypes; Herpesviridae; Herpesviridae Infections - epidemiology; Herpesviridae Infections - immunology; Herpesvirus 8, Human - genetics; Herpesvirus 8, Human - immunology; Human herpesvirus; Human herpesvirus 8; Humans; Infections; Kaposi sarcoma; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - virology; Male; Middle Aged; Risk Factors; T lymphocytes; Vascular Endothelial Growth Factor A - genetics; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/501470

BackgroundKaposi 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 MethodsIn 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 ResultsDetection 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]) ConclusionsOur 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