Estimating Costs and Benefits of CTL Escape Mutations in SIV/HIV Infection.
Estimating Costs and Benefits of CTL Escape Mutations in SIV/HIV Infection.
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DOI：
10.1371/journal.pcbi.0020024
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发表时间：
2006-03
影响因子：
4.3
通讯作者：
De Boer RJ
中科院分区：
文献类型：
--
作者：
Ganusov VV;De Boer RJ
Mutations that allow SIV/HIV to avoid the cytotoxic T lymphocyte (CTL) response are well documented. Recently, there have been a few attempts at estimating the costs of CTL escape mutations in terms of the reduction in viral fitness and the killing rate at which the CTL response specific to one viral epitope clears virus-infected cells. Using a mathematical model we show that estimation of both parameters depends critically on the underlying changes in the replication rate of the virus and the changes in the killing rate over time (which in previous studies were assumed to be constant). We provide a theoretical basis for estimation of these parameters using in vivo data. In particular, we show that 1) by assuming unlimited virus growth one can obtain a minimal estimate of the fitness cost of the escape mutation, and 2) by assuming no virus growth during the escape, one can obtain a minimal estimate of the average killing rate. We also discuss the conditions under which better estimates of the average killing rate can be obtained. Due to their high mutation rate, RNA viruses—like SIV and HIV—can avoid recognition by the host immune response by evolving new variants (i.e., immune escape mutants). Avoiding the cytotoxic T lymphocyte (CTL) immune responses is one of the major obstacles for the development of vaccines to HIV, and this avoidance seems a major mechanism of HIV disease progression to AIDS. Using a relatively general mathematical model, Ganusov and De Boer suggest a simple technique by which two main parameters determining the likelihood of viral escape can be estimated. First is the “cost” of the escape mutation, which is the relative fitness reduction in the virus replication rate. Second is the rate at which the CTL response specific for one epitope “clears” virus-infected cells. Application of their technique to data on virus escape helps to quantify the costs and benefits of CTL escape mutations in SIV/HIV infection.
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DOI：
10.1084/jem.190.6.841
发表时间：
1999-09-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Little SJ;McLean AR;Spina CA;Richman DD;Havlir DV
通讯作者：
Havlir DV
HIV-1 GAG中的簇突变是逃避HLA-B27限制的细胞毒性T淋巴细胞反应所必需的。
影响因子：
15.3
作者：
Kelleher, A D;Long, C;Holmes, E C;Allen, R L;Wilson, J;Conlon, C;Workman, C;Shaunak, S;Olson, K;Goulder, P;Brander, C;Ogg, G;Sullivan, J S;Dyer, W;Jones, I;McMichael, A J;Rowland-Jones, S;Phillips, R E
通讯作者：
Phillips, R E
影响因子：
5.4
作者：
Davenport, MP;Ribeiro, RM;Perelson, AS
通讯作者：
Perelson, AS
影响因子：
56.9
作者：
Carrington, M;Nelson, GW;O'Brien, SJ
通讯作者：
O'Brien, SJ
影响因子：
5.4
作者：
Allen, TM;Altfeld, M;Walker, BD
通讯作者：
Walker, BD