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.
Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Center for Cancer Research, National Cancer Institute, Rockville 20852, Maryland, USA. brownbe@mail.nih.gov
Elizabeth E
EE
Brown
M Daniele
MD
Fallin
James J
JJ
Goedert
Amy
A
Hutchinson
Francesco
F
Vitale
Carmela
C
Lauria
Massimo
M
Giuliani
Vickie
V
Marshall
Georgina
G
Mbisa
Diego
D
Serraino
Angelo
A
Messina
Scott
S
Durum
Denise
D
Whitby
Stephen J
SJ
Chanock
D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000235:genetics*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006239:Haplotypes; D006566:Herpesviridae Infections / Q000453:epidemiology / Q000276:immunology*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D000914:Antibodies, Viral; D016207:Cytokines; D004279:DNA, Viral; D042461:Vascular Endothelial Growth Factor A