The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection
By N. Goonetilleke, Michael K P Liu, J. Salazar-Gonzalez, G. Ferrari, E. Giorgi, V. Ganusov, B. Keele, G. Learn, E. Turnbull, M. Salazar and 13 more. Journal of Experimental Medicine, 2009
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Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1–specific T cell response induced in three acutely infected patients. Cellular assays, together with new algorithms which identify sites of positive selection in the virus genome, showed that primary HIV-1–specific T cells rapidly select escape mutations concurrent with falling virus load in acute infection. Kinetic analysis and mathematical modeling of virus immune escape showed that the contribution of CD8 T cell–mediated killing of productively infected cells was earlier and much greater than previously recognized and that it contributed to the initial decline of plasma virus in acute infection. After virus escape, these first T cell responses often rapidly waned, leaving or being succeeded by T cell responses to epitopes which escaped more slowly or were invariant. These latter responses are likely to be important in maintaining the already established virus set point. In addition to mutations selected by T cells, there were other selected regions that accrued mutations more gradually but were not associated with a T cell response. These included clusters of mutations in envelope that were targeted by NAbs, a few isolated sites that reverted to the consensus sequence, and bystander mutations in linkage with T cell–driven escape.
Subfields: Immunology, Virology
View Paper: https://www.semanticscholar.org/paper/5d91e02c3da6dfd2407065575c5e165f66620ce8
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In Immunology
Citations in the corpus
- The immune response during acute HIV-1 infection: clues for vaccine development (2009, background): “NK cells do not contribute to the selection of virus escape mutants before peak viraemia, although it is possible, but not proved, that they account for some of the unexplained mutations that appear together with those that are selected by early T cell responses as viraemia decreases to reach the se”
- Global trends in molecular epidemiology of HIV-1 during 2000–2007 (2011, background): “HIV infection in humans induces humoral and cellular immune responses which control primary viraemia without completely eliminating infection due to the rapid selection of immune escape mutants [15,16].”