Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition.
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.
Zhu
Jia
J
Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Hladik
Florian
F
Woodward
Amanda
A
Klock
Alexis
A
Peng
Tao
T
Johnston
Christine
C
Remington
Michael
M
Magaret
Amalia
A
Koelle
David M
DM
Wald
Anna
A
Corey
Lawrence
L
D000212:Acyclovir / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D002470:Cell Survival; D005260:Female; D005835:Genitalia / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology*; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism*; D012867:Skin / Q000276:immunology; D019562:Viral Load; D014775:Virus Activation / Q000276:immunology*
D019380:Anti-HIV Agents; D019713:Receptors, CCR5; D000212:Acyclovir