Coalescent estimates of HIV-1 generation time in vivo

被引:85
作者
Rodrigo, AG [1 ]
Shpaer, EG
Delwart, EL
Iversen, AKN
Gallo, MV
Brojatsch, J
Hirsch, MS
Walker, BD
Mullins, JI
机构
[1] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA
[2] Appl Biosyst Inc, Perkin Elmer, Foster City, CA 94404 USA
[3] Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
[4] Natl Univ Hosp, Dept Infect Dis, Copenhagen, Denmark
[5] Ontogeny Inc, Cambridge, MA 02138 USA
[6] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA
[7] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02129 USA
[8] Univ Washington, Dept Med, Seattle, WA 98195 USA
关键词
D O I
10.1073/pnas.96.5.2187
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The generation time of HIV Type 1 (HIV-1) in vivo has previously been estimated using a mathematical model of viral dynamics and was found to be on the order of one to two days per generation. Here, we describe a new method based on coalescence theory that allows the estimate of generation times to be derived by using nucleotide sequence data and a reconstructed genealogy of sequences obtained over time. The method is applied to sequences obtained from a long-term nonprogressing individual at five sampling occasions. The estimate of viral generation time using the coalescent method is 1.2 days per generation and is close to that obtained by mathematical modeling (1.8 days per generation), thus strengthening confidence in estimates of a short viral generation time. Apart from the estimation of relevant parameters relating to viral dynamics, coalescent modeling also allows us to simulate the evolutionary behavior of samples of sequences obtained over time.
引用
收藏
页码:2187 / 2191
页数:5
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