Abstract
Herpes simplex virus type 2 (HSV-2) is an incurable viral infection with severity ranging from asymptomatic to frequent recurrences. The viral shedding rate has been shown as a reproducible HSV-2 severity end point that correlates with lesion rates. We used a genome-wide association study (GWAS) to investigate the role of common human genetic variation in HSV-2 severity. We performed a GWAS on 223 HSV-2-positive participants of European ancestry. Severity was measured by viral shedding rate, as defined by the percent of days PCR+ for HSV-2 DNA over at least 30 days. Analyses were performed under linear regression models, adjusted for age, sex, and ancestry. There were no genome-wide significant (p < 5E-08) associations with HSV-2 viral shedding rate. The top nonsignificant SNP (rs75932292, p = 6.77E-08) associated with HSV-2 viral shedding was intergenic, with the nearest known biologically interesting gene (ABCA1) ~130 kbp downstream. Several other SNPs approaching significance were in or near genes with viral or neurological associations, including four SNPs in KIF1B. The current study is the first comprehensive genome-wide investigation of human genetic variation in virologic severity of established HSV-2 infection. However, no significant associations were observed with HSV-2 virologic severity, leaving the exact role of human variation in HSV-2 severity unclear.
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Acknowledgements
The authors would like to thank Dr. Amalia Magaret for her statistical input. This work was supported by NIH grants P01 AI030731 (AW and DMK) and R01 AI094019 (DMK).
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SEK, PRS, and ASA declare that they have no conflict of interest. DMK is a consultant to Glaxo SmithKline and has research grants or contracts from Immune Design Corporation, Admedus Vaccines, Merck, and Sanofi Pasteur. DMK and AW are co-inventors on patents owned by the University of Washington. AW receives research funding from Genocea and Vical and is a consultant for Aicuris. DBG receives research funding from Janssen, AstraZeneca, Gilead, Biogen, and UCB, is a consultant for AstraZeneca, and holds a patent for IL28B findings.
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Kleinstein, S.E., Shea, P.R., Allen, A.S. et al. Genome-wide association study (GWAS) of human host factors influencing viral severity of herpes simplex virus type 2 (HSV-2). Genes Immun 20, 112–120 (2019). https://doi.org/10.1038/s41435-018-0013-4
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DOI: https://doi.org/10.1038/s41435-018-0013-4
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