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