Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition.

Publication Type:

Journal Article

Source:

Nature medicine, Volume 15, Issue 8, p.886-92 (2009)

Keywords:

2009, Acyclovir, Adult, Anti-HIV Agents, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Survival, Female, Genitalia, Herpesvirus 2, Human, HIV Infections, HIV-1, Humans, Immunologic Memory, Male, Middle Aged, Receptors, CCR5, Skin, Vaccine and Infectious Disease Institute, Viral Load, Virus Activation

Abstract:

To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition, we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy. CD4(+) and CD8(+) T cells and a mixed population of plasmacytoid and myeloid dendritic cells (DCs), including cells expressing the C-type lectin receptor DC-SIGN, persisted at sites of HSV-2 reactivation for months after healing, even with daily antiviral therapy. The CD4(+) T cells that persisted reacted to HSV-2 antigen, were enriched for expression of the chemokine receptor CCR5, and were contiguous to DCs expressing the interleukin-3 receptor CD123 or DC-SIGN. Ex vivo infection with a CCR5-tropic strain of HIV-1 revealed greater concentrations of integrated HIV-1 DNA in cells derived from healed genital lesion biopsies than in cells from control skin biopsies. The persistence and enrichment of HIV receptor-positive inflammatory cells in the genitalia help explain the inability of anti-HSV-2 therapy to reduce HIV acquisition.