Polymorphisms in Toll-like receptor 3 confer natural resistance to human herpes simplex virus type 2 infection

• Published in: Journal of general virology Vol. 93; no. 8; pp. 1717 - 1724
• Main Authors: Svensson, Alexandra, Tunbäck, Petra, Nordström, Inger, Padyukov, Leonid, Eriksson, Kristina
• Format: Journal Article
• Language: English
• Published: Reading Society for General Microbiology 01.08.2012
• Subjects: Adult; Aged; Alleles; Biological and medical sciences; Case-Control Studies; Dermatologi och venereologi; Dermatology and Venereal Diseases; DNA; DNA - genetics; epidemiology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Gene Expression Regulation - immunology; Genetic; Genetic Predisposition to Disease; genetics; Genotype; Herpes Genitalis; Herpes Genitalis - epidemiology; Herpes Genitalis - genetics; Herpes Genitalis - immunology; Herpes simplex virus 1; Herpes simplex virus 2; Herpesvirus 2; Herpesvirus 2, Human - immunology; Homozygote; Human; Human herpesvirus 1; Humans; immunology; Male; Messenger; metabolism; Microbiology; Middle Aged; Miscellaneous; Polymorphism; Polymorphism, Genetic; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sweden; Sweden - epidemiology; Toll-Like Receptor 3; Toll-Like Receptor 3 - genetics; Toll-Like Receptor 3 - metabolism; Virology; Young Adult; Sweden; Virus; Human; Resistance; Toll like receptor 3; Herpesviridae; Alphaherpesvirinae; Human herpesvirus 2; Polymorphism
• ISSN: 0022-1317; 1465-2099; 1465-2099
• DOI: 10.1099/vir.0.042572-0

Lack of Toll-like receptor 3 (TLR3) functional activity predisposes children to human herpesvirus 1 (HSV-1) encephalitis. In this study, we have investigated whether there is any link between TLR3 and adult HSV-2 infection by studying genetic variations in TLR3. The frequency of four single-nucleotide polymorphisms (SNPs) in the TLR3 gene in 239 patients with genital HSV-2 infection and 162 healthy controls, as well as the impact of these variants on TLR3 gene-expression levels, were compared. Two SNPs in the TLR3 gene (rs13126816 and rs3775291) were associated with a reduced incidence of HSV-2 infection. The minor allelic variants at both rs13126816 and rs3775291 were more common among healthy HSV-2-seronegative subjects than among HSV-2-infected individuals. This was even more apparent in HSV-1-seronegative individuals. There was, however, no association between any of the four TLR3 SNPs and HSV-2 disease severity, as they were expressed at similar proportions in asymptomatic and symptomatic HSV-2-infected patients alike. Furthermore, when assessing TLR3 mRNA expression in a limited number of HSV-2-infected individuals, we found that individuals carrying the homozygous genotypes for the minor alleles had significantly higher levels of TLR3 mRNA expression in peripheral blood mononuclear cells in response to HSV-2 stimulation than individuals that were homozygous for the major allele variants. Taken together, these results suggest that genetic variations in TLR3 may affect the susceptibility to HSV-2 infection in humans.