背景:生殖器HSV-2感染的临床严重程度在感染者中差异很大,有些人经历频繁的生殖器病变,而另一些人则无症状。病毒生殖器脱落率与临床严重程度的替代指标密切相关,并已被确立为临床严重程度的替代指标。
方法:为了评估病毒遗传学和脱落之间的关系,我们收集了一组145人,他们通过测定他们的HSV生殖器脱落率对生殖器疱疹的严重程度进行了量化.对来自每个人的HSV-2样品进行测序,并鉴定这些基因组中的双等位基因变体。
结果:我们发现HSV-2全基因组变异指标与脱落率之间没有关联。一项病毒全基因组关联研究(vGWAS)确定了三个个体未连锁变体的次要等位基因与较高的脱落率显着相关(p<8.4x10-5):C44973T(A512T),UL22(糖蛋白H)中的非同义变体;A74534G,UL36(大皮蛋白)的同义变体;和T119283C,基因间变异。我们还发现显著变体的次要等位基因总数与脱落率之间存在关联(p=6.6x10-7)。
结论:这些结果增加了越来越多的HSV文献,提示病毒遗传变异与临床上重要的感染表型之间存在联系。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: These results add to a growing body of literature for HSV suggesting a connection between viral genetic variation and clinically important phenotypes of infection.