https://orcid.org/0000-0001-8332-8578
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Amanda M Casto, Hoseung Song, Hong Xie, Stacy Selke, Pavitra Roychoudhury, Michael C Wu, Anna Wald, Alexander L Greninger, Christine Johnston, Viral Genomic Variation and the Severity of Genital Herpes Simplex Virus-2 Infection as Quantified by Shedding Rate: A Viral Genome-Wide Association Study, The Journal of Infectious Diseases, 2024;, jiae283, https://doi.org/10.1093/infdis/jiae283
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Abstract
The clinical severity of genital herpes simplex virus-2 (HSV-2) infection varies widely among infected persons with some experiencing frequent genital lesions while others are asymptomatic. The viral genital shedding rate is closely associated with, and has been established as, a surrogate marker of clinical severity.
To assess the relationship between viral genetics and shedding, we assembled a set of 145 persons who had the severity of their genital herpes quantified through determination of their HSV genital shedding rate. An HSV-2 sample from each person was sequenced and biallelic variants among these genomes were identified.
We found no association between metrics of genome-wide variation in HSV-2 and shedding rate. A viral genome-wide association study identified the minor alleles of 3 individual unlinked variants as significantly associated with higher shedding rate (P < 8.4 × 10−5): C44973T (A512T), a nonsynonymous variant in UL22 (glycoprotein H); A74534G, a synonymous variant in UL36 (large tegument protein); and T119283C, an intergenic variant. We also found an association between the total number of minor alleles for the significant variants and shedding rate (P = 6.6 × 10−7).
These results add to a growing body of literature for HSV suggesting a connection between viral genetic variation and clinically important phenotypes of infection.
