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Fluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression.

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dc.contributor.authorMlotshwa, Mandla.
dc.contributor.authorRiou, Catherine.
dc.contributor.authorChopera, Denis Rutendo.
dc.contributor.authorde Assis Rosa, Debra.
dc.contributor.authorNtale, Roman.
dc.contributor.authorTreurnicht, Florette K.
dc.contributor.authorWoodman, Zenda.
dc.contributor.authorWerner, Lise.
dc.contributor.authorvan Loggerenberg, Francois.
dc.contributor.authorMlisana, Koleka Patience.
dc.contributor.authorWilliamson, Carolyn.
dc.contributor.authorGray, Clive M.
dc.contributor.authorAbdool Karim, Salim Safurdeen.
dc.date.accessioned2012-11-12T13:19:01Z
dc.date.available2012-11-12T13:19:01Z
dc.date.created2010
dc.date.issued2010
dc.description.abstractDeciphering 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-y) 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-y-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.en
dc.identifier.citationMlotshwa M., Riou C., Chopera D., et al. Fluidity of HIV-1-specific T-cell responses during acute and early subtype C HIV-1 infection and associations with early disease progression. J Virol. 2010;84(22):12018–12029.en
dc.identifier.issn0022-538X
dc.identifier.urihttp://dx.doi.org/10.1128/JVI.01472-10en
dc.identifier.urihttp://hdl.handle.net/10413/7835
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.subjectHIV infections--Virology.en
dc.subjectHIV infections--Immunology.en
dc.titleFluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression.en
dc.typePeer reviewed journal articleen

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