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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Date
2010
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology
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-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.
Description
Keywords
HIV infections--Virology., HIV infections--Immunology.
Citation
Mlotshwa 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.