title: Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract.
abstract: OBJECTIVE
  There is substantial epidemiological evidence that infection by Herpes simplex virus type 2 (HSV2) enhances both HIV susceptibility and subsequent sexual transmission. Both infections are extremely common in female sex workers (FSWs) in sub-Saharan Africa, and up to 80% of new HIV infections in urban men in the region are acquired via transactional sex. The present study aimed to elucidate the mucosal immune interactions between HIV and HSV2 in the genital tract.
  
  
  METHODS
  Endocervical immune cell populations, cytokine/chemokine protein levels in cervico-vaginal secretions and cervical immune gene expression profiles were measured in a well-defined cohort of HIV-infected and uninfected Kenyan FSWs. Associations between the genital immune milieu and infection by and/or shedding of common genital co-pathogens were examined.
  
  
  RESULTS
  HIV-infected FSWs were much more likely to be infected by HSV2, and to shed HSV2 DNA in the genital tract. There was also a profound negative 'mucosal synergy' between these viruses. In HIV uninfected FSWs, HSV2 infection was associated with a ten-fold increase in cervical immature dendritic cells (iDC) expressing DC-SIGN, and a three-fold increase in cervical CD4+ T cells expressing CCR5. HIV infection was associated with iDC depletion in the cervix, and with increased HSV2 genital reactivation, which in turn was associated with HIV shedding levels.
  
  
  CONCLUSIONS
  The findings suggest a mucosal vicious circle in which HSV2 infection increases HIV target cells in the genital mucosa, subsequent HIV infection impairs HSV2 mucosal immune control, and local HSV2 reactivation enhances both HSV2 and HIV transmission.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada. anu.rebbapragada@utoronto.ca
authors.forename: Anuradha
authors.initials: A
authors.lastname: Rebbapragada
authors.forename: Charles
authors.initials: C
authors.lastname: Wachihi
authors.forename: Christopher
authors.initials: C
authors.lastname: Pettengell
authors.forename: Sherzana
authors.initials: S
authors.lastname: Sunderji
authors.forename: Sanja
authors.initials: S
authors.lastname: Huibner
authors.forename: Walter
authors.initials: W
authors.lastname: Jaoko
authors.forename: Blake
authors.initials: B
authors.lastname: Ball
authors.forename: Keith
authors.initials: K
authors.lastname: Fowke
authors.forename: Tony
authors.initials: T
authors.lastname: Mazzulli
authors.forename: Francis A
authors.initials: FA
authors.lastname: Plummer
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000328:Adult; D002584:Cervix Uteri / Q000276:immunology / Q000821:virology; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006558:Herpes Genitalis / Q000150:complications / Q000276:immunology* / Q000635:transmission / Q000821:virology; D006801:Humans; D018928:Immunity, Mucosal; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology; D011477:Sex Work; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014621:Vagina / Q000276:immunology / Q000821:virology; D017201:Virus Shedding / Q000276:immunology