Coinfection with Herpes Simplex Virus Type 2 Is Associated with Reduced HIV-Specific T Cell Responses and Systemic Immune Activation

• Published in: The Journal of infectious diseases Vol. 197; no. 10; pp. 1394 - 1401
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.05.2008; University of Chicago Press
• Subjects: ADP-ribosyl Cyclase 1 - analysis; AIDS; Antibodies, Viral - blood; Biological and medical sciences; Blood; Blood plasma; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Coinfection; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Epitopes, T-Lymphocyte - immunology; Female; Flow Cytometry; Forkhead Transcription Factors - analysis; Fundamental and applied biological sciences. Psychology; Herpes Genitalis - complications; Herpes Genitalis - immunology; Herpes simplex virus 2; HIV; HIV 1; HIV Infections - complications; HIV Infections - immunology; HIV/AIDS; Human herpesvirus 2; Human immunodeficiency virus; Human immunodeficiency virus 2; Humans; Infections; Infectious diseases; Interferon-gamma - biosynthesis; Lymphocyte Activation; Male; Medical sciences; Membrane Glycoproteins - analysis; Microbiology; Miscellaneous; T lymphocytes; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology; Viral Load; Virology; Virus; Mixed infection; Microbiology; Herpesviridae; Alphaherpesvirinae; Retroviridae; Human herpesvirus 2; Cellular immunity; Human immunodeficiency virus; Lentivirus
• ISSN: 0022-1899; 1537-6613
• 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-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.