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Displaying record number 1527
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- Therapy provided during acute infection resulted in a narrower CTL response, stronger T help response, and a less diverse viral population than was seen in individuals treated during chronic infection.
- The breadth and specificity of the response was determined using ELISPOT by studying 19 individuals with pre-seroconversion therapy (Group 1), 11 individuals with primary infection but post-seroconversion therapy (Group 2), and 10 individuals who responded to HAART given during chronic infection (Group 3), using 259 overlapping peptides spanning p17, p24, RT, gp41, gp120 and Nef.
- Previously described and newly defined optimal epitopes were tested for CTL response.
- Number of HLA-A3+ individuals that had a CTL response to this epitope broken down by group: 3/7 group 1, 1/4 group 2, and 1/2 group 3.
References
Altfeld2001b
M. Altfeld, E. S. Rosenberg, R. Shankarappa, J. S. Mukherjee, F. M. Hecht, R. L. Eldridge, M. M. Addo, S. H. Poon, M. N. Phillips, G. K. Robbins, P. E. Sax, S. Boswell, J. O. Kahn, C. Brander, P. J. Goulder, J. A. Levy, J. I. Mullins, and B. D. Walker. Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J. Exp. Med., 193(2):169-80, 15 Jan 2001. URL: http://www.jem.org/cgi/content/full/193/2/169. PubMed ID: 11148221.
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Displaying record number 54680
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- In order to reconcile apparent conflicts between a CTL-protective role as suggested by HLA-1 alleles associated with different rates of progression to AIDS, and a CTL non-protective role as suggested by the fact that virus clearance following ART is not impaired in advanced AIDS, a model is made that quantifies the efficiency of HIV-1-specific CTLs in vivo. As a surrogate for the actual rate of CTL-killing of infected cells, the model rests on calculating virus escape rate for an epitope and subtracting its reversion rate upon transmission to a non-restricting HLA bearing host. It is shown that CTLs recognizing a single epitope kill only 2% of productively infected CD4+ cells. The rate of CTL lysis was found to be significantly faster during primary infection than in chronic infection. However, the authors suggest that small differences in CTL lysis rate can translate into large differences in terms of absolute numbers of infected cells killed, which are likely to be clinically relevant.
- The best estimates of escape rate for this epitope, QVPLRRMTYK, were found to be 0.022 and 0.003/day (upper bound on rate of escape = 0.05 and 0.011), with SEs of 0.013 and 0.003 respectively, in 2 subjects.
- In the first subject, a number of mutations arose in Nef 73-82; all but one of these (V74A) elicited a very weak ELISpot response compared to the wild type. In the second subject, large epitope deletions and a V74I substitution in the recognized epitope were selected for.
References
Asquith2006
Becca Asquith, Charles T. T. Edwards, Marc Lipsitch, and Angela R. McLean. Inefficient Cytotoxic T Lymphocyte-Mediated Killing of HIV-1-Infected Cells In Vivo. PLoS Biol., 4(4):e90, Apr 2006. PubMed ID: 16515366.
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