%0 Journal Article
%T Viral genomic variation and the severity of genital HSV-2 infection as quantified by shedding rate: a viral genome-wide association study.
%A Casto AM
%A Song H
%A Xie H
%A Selke S
%A Roychoudhury P
%A Wu MC
%A Wald A
%A Greninger AL
%A Johnston C
%J J Infect Dis
%V 0
%N 0
%D 2024 May 28
%M 38805234
%F 7.759
%R 10.1093/infdis/jiae283
%X <B>BACKGROUND: </B>The clinical severity of genital 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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>We found no association between metrics of genome-wide variation in HSV-2 and shedding rate. A viral genome-wide association study (vGWAS) identified the minor alleles of three individual unlinked variants as significantly associated with higher shedding rate (p<8.4x10-5): C44973T (A512T), a non-synonymous 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=6.6x10-7).<BR><B>CONCLUSIONS: </B>These results add to a growing body of literature for HSV suggesting a connection between viral genetic variation and clinically important phenotypes of infection.