Escape is a more common mechanism than avidity reduction for evasion of CD8+ T cell responses in primary human immunodeficiency virus type 1 infection.

Turnbull, E; Baalwa, J; Conrod, K; Wang, S; Wei, X; Wong, M; Turner, J; Pellegrino, P; Williams, I; Shaw, G; Borrow, P

Journal article

Escape is a more common mechanism than avidity reduction for evasion of CD8+ T cell responses in primary human immunodeficiency virus type 1 infection.

Abstract:: BACKGROUND: CD8+ T cells play an important role in control of viral replication during acute and early human immunodeficiency virus type 1 (HIV-1) infection, contributing to containment of the acute viral burst and establishment of the prognostically-important persisting viral load. Understanding mechanisms that impair CD8+ T cell-mediated control of HIV replication in primary infection is thus of importance. This study addressed the relative extent to which HIV-specific T cell responses are impacted by viral mutational escape versus reduction in response avidity during the first year of infection. RESULTS: 18 patients presenting with symptomatic primary HIV-1 infection, most of whom subsequently established moderate-high persisting viral loads, were studied. HIV-specific T cell responses were mapped in each individual and responses to a subset of optimally-defined CD8+ T cell epitopes were followed from acute infection onwards to determine whether they were escaped or declined in avidity over time. During the first year of infection, sequence variation occurred in/around 26/33 epitopes studied (79%). In 82% of cases of intra-epitopic sequence variation, the mutation was confirmed to confer escape, although T cell responses were subsequently expanded to variant sequences in some cases. In contrast, < 10% of responses to index sequence epitopes declined in functional avidity over the same time-frame, and a similar proportion of responses actually exhibited an increase in functional avidity during this period. CONCLUSIONS: Escape appears to constitute a much more important means of viral evasion of CD8+ T cell responses in acute and early HIV infection than decline in functional avidity of epitope-specific T cells. These findings support the design of vaccines to elicit T cell responses that are difficult for the virus to escape.

Publication status:: Published

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APA Style

Turnbull, E., Baalwa, J., Conrod, K., Wang, S., Wei, X., Wong, M., Turner, J., Pellegrino, P., Williams, I., Shaw, G., & Borrow, P. (2011). Escape is a more common mechanism than avidity reduction for evasion of CD8+ T cell responses in primary human immunodeficiency virus type 1 infection. Retrovirology, 8(1), 41.

MLA Style

Turnbull, E, et al. “Escape Is a More Common Mechanism than Avidity Reduction for Evasion of CD8+ T Cell Responses in Primary Human Immunodeficiency Virus Type 1 Infection.” Retrovirology, vol. 8, no. 1, 2011, p. 41.

Chicago Style

Turnbull, E, J Baalwa, K Conrod, et al. 2011. “Escape Is a More Common Mechanism than Avidity Reduction for Evasion of CD8+ T Cell Responses in Primary Human Immunodeficiency Virus Type 1 Infection.” Retrovirology 8 (1): 41.
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