Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation

J Infect Dis. 2008 May 15;197(10):1394-401. doi: 10.1086/587697.


Background: Chronic coinfection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) has been associated with an increased HIV viral load and more rapid disease progression, perhaps related to HSV-2-associated alterations in host immunity.

Methods: Studies were nested within (1) a cross-sectional study of men coinfected with HIV and HSV-2 and (2) women not infected with HIV, both before and after HSV-2 acquisition. HSV-2 infection status was determined by ELISA. HIV-specific CD8(+) T cell epitopes were mapped, and proliferation of HIV-specific cells was also assessed. Systemic inflammatory and regulatory T cell populations were assayed by flow cytometry.

Results: The breadth of both the HIV-specific CD8(+) T cell interferon-gamma and proliferative responses was reduced in participants coinfected with HIV and HSV-2, independent of the HIV plasma viral load and CD4(+) T cell count, and the magnitude of the responses was also reduced. HSV-2 infection in this group was associated with increased T cell CD38 expression but not with differences in the proportion of CD4(+) FoxP3(+) regulatory T cells. However, in women not infected with HIV, acquisition of HSV-2 was associated with an increase in the proportion of regulatory T cells.

Conclusions: HSV-2 coinfection was associated with reduced HIV-specific T cell responses and systemic inflammation. The immune effects of HSV-2 may underlie the negative impact that this coinfection has on the clinical course of HIV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / analysis
  • Antibodies, Viral / blood
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Enzyme-Linked Immunosorbent Assay
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / analysis
  • HIV Infections / complications*
  • HIV Infections / immunology*
  • Herpes Genitalis / complications*
  • Herpes Genitalis / immunology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins / analysis
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Viral Load


  • Antibodies, Viral
  • Epitopes, T-Lymphocyte
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Membrane Glycoproteins
  • Interferon-gamma
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1