title: Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation.
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-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.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Prameet M
authors.initials: PM
authors.lastname: Sheth
authors.forename: Sherzana
authors.initials: S
authors.lastname: Sunderji
authors.forename: Lucy Y Y
authors.initials: LY
authors.lastname: Shin
authors.forename: Anuradha
authors.initials: A
authors.lastname: Rebbapragada
authors.forename: Sanja
authors.initials: S
authors.lastname: Huibner
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Macdonald
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ngugi
authors.forename: Job J
authors.initials: JJ
authors.lastname: Bwayo
authors.forename: Stephen
authors.initials: S
authors.lastname: Moses
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.forename: Mona
authors.initials: M
authors.lastname: Loutfy
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000914:Antibodies, Viral / Q000097:blood; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006558:Herpes Genitalis / Q000150:complications* / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008562:Membrane Glycoproteins; D007371:Interferon-gamma; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1