Variability of human immunodeficiency virus-1 in the female genital reservoir during genital reactivation of herpes simplex virus type 2

Clin Microbiol Infect. 2015 Sep;21(9):873.e1-9. doi: 10.1016/j.cmi.2015.05.014. Epub 2015 May 21.


Clinical and subclinical genital herpes simplex virus type 2 (HSV-2) reactivations have been associated with increases in human immunodeficiency virus (HIV)-1 genital shedding. Whether HSV-2 shedding contributes to the selection of specific genital HIV-1 variants remains unknown. We evaluated the genetic diversity of genital and blood HIV-1 RNA and DNA in 14 HIV-1/HSV-2-co-infected women, including seven with HSV-2 genital reactivation, and seven without as controls. HIV-1 DNA and HIV-1 RNA env V1-V3 sequences in paired blood and genital samples were compared. The HSV-2 selection pressure on HIV was estimated according to the number of synonymous substitutions (dS), the number of non-synonymous substitutions (dN) and the dS/dN ratio within HIV quasi-species. HIV-1 RNA levels in cervicovaginal secretions were higher in women with HSV-2 replication than in controls (p0.02). Plasma HIV-1 RNA and genital HIV-1 RNA and DNA were genetically compartmentalized. No differences in dS, dN and the dS/dN ratio were observed between the study groups for either genital HIV-1 RNA or plasma HIV-1 RNA. In contrast, dS and dN in genital HIV-1 DNA were significantly higher in patients with HSV-2 genital reactivation (p <0.01 and p <0.05, respectively). The mean of the dS/dN ratio in genital HIV-1 DNA was slightly higher in patients with HSV-2 genital replication, indicating a trend for purifying selection (p 0.056). HSV-2 increased the genetic diversity of genital HIV-1 DNA. These observations confirm molecular interactions between HSV-2 and HIV-1 at the genital tract level.

Keywords: Africa; HIV-1; HSV-2; Herpes simplex virus; genital herpes; phylogeny; variability.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood / virology
  • DNA, Viral / genetics
  • Exudates and Transudates / virology
  • Female
  • Genetic Variation*
  • Genitalia, Female / virology*
  • HIV Infections / complications*
  • HIV Infections / virology*
  • HIV-1 / classification*
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Herpes Genitalis / complications*
  • Herpesvirus 2, Human / physiology*
  • Humans
  • Mutation Rate
  • RNA, Viral / genetics
  • Selection, Genetic
  • Sequence Analysis, DNA
  • Viral Load
  • Virus Activation
  • env Gene Products, Human Immunodeficiency Virus / genetics


  • DNA, Viral
  • RNA, Viral
  • env Gene Products, Human Immunodeficiency Virus