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.
Goonetilleke, Nilu, et al. "The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection." Journal of Experimental Medicine, vol. 206, no. 6, Jun. 2009. https://doi.org/10.1084/jem.20090365
Goonetilleke, Nilu, Liu, Michael K. P., Salazar-Gonzalez, Jesus F., Ferrari, Guido, Giorgi, Elena, Ganusov, Vitaly V., Keele, Brandon F., Learn, Gerald H., Turnbull, Emma L., Salazar, Maria G., Weinhold, Kent J., Moore, Stephen, Letvin, Norman, Haynes, Barton F., Cohen, Myron S., Hraber, Peter, Bhattacharya, Tanmoy, Borrow, Persephone, ... McMichael, Andrew J. (2009). The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. Journal of Experimental Medicine, 206(6). https://doi.org/10.1084/jem.20090365
Goonetilleke, Nilu, Liu, Michael K. P., Salazar-Gonzalez, Jesus F., et al., "The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection," Journal of Experimental Medicine 206, no. 6 (2009), https://doi.org/10.1084/jem.20090365
@article{osti_1625194,
author = {Goonetilleke, Nilu and Liu, Michael K. P. and Salazar-Gonzalez, Jesus F. and Ferrari, Guido and Giorgi, Elena and Ganusov, Vitaly V. and Keele, Brandon F. and Learn, Gerald H. and Turnbull, Emma L. and Salazar, Maria G. and others},
title = {The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection},
annote = {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.},
doi = {10.1084/jem.20090365},
url = {https://www.osti.gov/biblio/1625194},
journal = {Journal of Experimental Medicine},
issn = {ISSN 0022-1007},
number = {6},
volume = {206},
place = {United States},
publisher = {Rockefeller University Press},
year = {2009},
month = {06}}
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
Bill and Melinda Gates Foundation; Center for HIV/AIDS Vaccine Immunology; Jenner Fellowship; National Institute for Health; USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1625194
Journal Information:
Journal of Experimental Medicine, Journal Name: Journal of Experimental Medicine Journal Issue: 6 Vol. 206; ISSN 0022-1007