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

Prameet M. Sheth, Sherzana Sunderji, Lucy Y Y Shin, Anuradha Rebbapragada, Sanja Huibner, Joshua Kimani, Kelly S. MacDonald, Elizabeth Ngugi, Job J. Bwayo, Stephen Moses, Colin Kovacs, Mona Loutfy, Rupert Kaul

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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-γ 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.

Original languageEnglish (US)
Pages (from-to)1394-1401
Number of pages8
JournalJournal of Infectious Diseases
Volume197
Issue number10
DOIs
StatePublished - May 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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    Sheth, P. M., Sunderji, S., Shin, L. Y. Y., Rebbapragada, A., Huibner, S., Kimani, J., MacDonald, K. S., Ngugi, E., Bwayo, J. J., Moses, S., Kovacs, C., Loutfy, M., & Kaul, R. (2008). Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation. Journal of Infectious Diseases, 197(10), 1394-1401. https://doi.org/10.1086/587697