Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2

P>Natural killer (NK) cells bridge the interface between innate and adaptive immunity and are implicated in the control of herpes simplex virus 2 (HSV-2) infection. In subjects infected with human immunodeficiency virus 1 (HIV-1), the critical impact of the innate immune response on disease progression has recently come into focus. Higher numbers of NK cells are associated with lower HIV-1 plasma viraemia. Individuals with the compound genotype of killer cell immunoglobulin-like receptor (KIR) 3DS1 and human leucocyte antigen (HLA)-Bw4-80I, or who have alleles of KIR3DL1 that encode proteins highly expressed on the NK cell surface, have a significant delay in disease progression. We studied the effect of HSV-2 co-infection in HIV-1-infected subjects, and show that HSV-2 co-infection results in a pan-lymphocytosis, with elevated absolute numbers of CD4+ and CD8+ T cells, and NK cells. The NK cells in HSV-2 co-infected subjects functioned more efficiently, with an increase in degranulation after in vitro stimulation. The number of NK cells expressing the activating receptors NKp30 and NKp46, and expressing KIR3DL1 or KIR3DS1, was inversely correlated with HIV-1 plasma viral load in subjects mono-infected with HIV-1, but not in subjects co-infected with HSV-2. This suggests that HSV-2 infection mediates changes within the NK cell population that may affect immunity in HIV-1 infection.

National Institute of Allergies and Infectious Diseases[NIAID AI060379]

National Institute of Allergies and Infectious Diseases[AI052731]

National Institute of Allergies and Infectious Diseases[AI064520]

National Institute of Allergies and Infectious Diseases[AI64520]

National Institute of Allergies and Infectious Diseases[AI-066917]

National Institute of Allergies and Infectious Diseases[AI-076014]

Brazilian Program

Ministry of Health[914/BRA/3014 - UNESCO/Kallas]

Sao Paulo City Health Department[2004-0.168.922-7/Kallas]

FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[04/15 856-9/Kallas]

John E. Fogarty International Center (FIRCA/NIH)[D43 TW00003]

AIDS Research Institute of the AIDS Biology Program at UCSF

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazilian Ministry of Education