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

47 Citations (Scopus)

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

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Human Herpesvirus 2
Coinfection
HIV
T-Lymphocytes
Virus Diseases
Regulatory T-Lymphocytes
Viral Load
T-Lymphocyte Epitopes
CD4 Lymphocyte Count
Interferons
Disease Progression
Immunity
Flow Cytometry
Cross-Sectional Studies
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation. / Sheth, Prameet M.; Sunderji, Sherzana; Shin, Lucy Y Y; Rebbapragada, Anuradha; Huibner, Sanja; Kimani, Joshua; MacDonald, Kelly S.; Ngugi, Elizabeth; Bwayo, Job J.; Moses, Stephen; Kovacs, Colin; Loutfy, Mona; Kaul, Rupert.

In: Journal of Infectious Diseases, Vol. 197, No. 10, 15.05.2008, p. 1394-1401.

Research output: Contribution to journalArticle

Sheth, PM, Sunderji, S, Shin, LYY, Rebbapragada, A, Huibner, S, Kimani, J, MacDonald, KS, Ngugi, E, Bwayo, JJ, 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, vol. 197, no. 10, pp. 1394-1401. https://doi.org/10.1086/587697
Sheth, Prameet M. ; Sunderji, Sherzana ; Shin, Lucy Y Y ; Rebbapragada, Anuradha ; Huibner, Sanja ; Kimani, Joshua ; MacDonald, Kelly S. ; Ngugi, Elizabeth ; Bwayo, Job J. ; Moses, Stephen ; Kovacs, Colin ; Loutfy, Mona ; Kaul, Rupert. / Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation. In: Journal of Infectious Diseases. 2008 ; Vol. 197, No. 10. pp. 1394-1401.
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AU - Sunderji, Sherzana

AU - Shin, Lucy Y Y

AU - Rebbapragada, Anuradha

AU - Huibner, Sanja

AU - Kimani, Joshua

AU - MacDonald, Kelly S.

AU - Ngugi, Elizabeth

AU - Bwayo, Job J.

AU - Moses, Stephen

AU - Kovacs, Colin

AU - Loutfy, Mona

AU - Kaul, Rupert

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N2 - 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.

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