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.
From the aDepartment of Medicine, Canada
bMcLaughlin Institute of Molecular Medicine, University of Toronto, Toronto, Ontario, Canada
cDepartment of Medical Microbiology, University of Nairobi, Nairobi, Kenya
dDepartment of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba
eDepartment of Microbiology, Mount Sinai Hospital, Toronto, Ontario, Canada.
fDepartment of Medicine, University Health Network, Toronto, Ontario, Canada.
Received 7 August, 2006
Revised 10 September, 2006
Accepted 30 October, 2006
Correspondence to Anu Rebbapragada, Clinical Science Division, Medical Sciences Building #6356, University of Toronto, Toronto, Ontario, Canada, M5S1A8. E-mail: firstname.lastname@example.org