Article abstract
Nature Medicine 15, 886 - 892 (2009)
Published online: 2 August 2009 | doi:10.1038/nm.2006
Persistence of HIV-1 receptor–positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition
Jia Zhu1,2, Florian Hladik1,3,4,6, Amanda Woodward1,3,6, Alexis Klock1,2, Tao Peng1,2, Christine Johnston1,3, Michael Remington2, Amalia Magaret1,2, David M Koelle1,2,3, Anna Wald1,2,3,5 & Lawrence Corey1,2,3,5
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.
- Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
- Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
- Department of Medicine, University of Washington, Seattle, Washington, USA.
- Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, USA.
- Department of Epidemiology, University of Washington, Seattle, Washington, USA.
- These authors contributed equally to this work.
Correspondence to: Lawrence Corey1,2,3,5 e-mail: lcorey@fhcrc.org
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