title: Fluidity of HIV-1-specific T-cell responses during acute and early subtype C HIV-1 infection and associations with early disease progression.
abstract: Deciphering immune events during early stages of human immunodeficiency virus type 1 (HIV-1) infection is critical for understanding the course of disease. We characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C infection in 53 individuals and associated temporal patterns of responses with disease progression in the first 12 months. There was a diverse pattern of T-cell recognition across the proteome, with the recognition of Nef being immunodominant as early as 3 weeks postinfection. Over the first 6 months, we found that there was a 23% chance of an increased response to Nef for every week postinfection (P = 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%). Responses to Env and regulatory proteins appeared to remain stable. Three temporal patterns of HIV-specific T-cell responses could be distinguished: persistent, lost, or new. The proportion of persistent T-cell responses was significantly lower (P = 0.0037) in individuals defined as rapid progressors than in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell responses were coincidental with autologous viral epitope escape. Regression analysis between the time to fixed viral escape and lost T-cell responses (r = 0.61; P = 0.019) showed a mean delay of 14 weeks after viral escape. Collectively, T-cell epitope recognition is not a static event, and temporal patterns of IFN-γ-based responses exist. This is due partly to viral sequence variation but also to the recognition of invariant viral epitopes that leads to waves of persistent T-cell immunity, which appears to associate with slower disease progression in the first year of infection.
authors.affiliation: National Institute for Communicable Diseases, Johannesburg 2131, South Africa.
authors.forename: Mandla
authors.initials: M
authors.lastname: Mlotshwa
authors.forename: Catherine
authors.initials: C
authors.lastname: Riou
authors.forename: Denis
authors.initials: D
authors.lastname: Chopera
authors.forename: Debra
authors.initials: D
authors.lastname: de Assis Rosa
authors.forename: Roman
authors.initials: R
authors.lastname: Ntale
authors.forename: Florette
authors.initials: F
authors.lastname: Treunicht
authors.forename: Zenda
authors.initials: Z
authors.lastname: Woodman
authors.forename: Lise
authors.initials: L
authors.lastname: Werner
authors.forename: Francois
authors.initials: F
authors.lastname: van Loggerenberg
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.forename: Salim
authors.initials: S
authors.lastname: Abdool Karim
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: Clive M
authors.initials: CM
authors.lastname: Gray
mesh_terms: D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D007371:Interferon-gamma
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