Abstract

The goals of this project are to determine the frequency and mechanisms of HIV recombination, to characterize potential recombination between divergent lentiviruses, and to examine the properties of recombinant viruses. We have measured HIV-1 recombination rates at several distances and demonstrated that recombination is a very powerful tool for reassorting the HIV-1 genome. We are currently examining whether other lentiviruses can also recombines at high frequencies. We have identified a major restriction to intersubtype HIV-1 recombination, and are currently studying other restrictions to HIV recombination and replication. We have extended these studies to examine whether distinct lentiviruses can recombine with one another. In addition to studying the frequency and limitation of recombination, it is also important to understand the consequences of recombination. To address this aspect of recombination, we are currently examining the properties of recombinant viruses, and whether certain recombinants have a selective advantage in a given environment. Because it is thought that zoonotic events generated both HIV-1 and HIV-2, we have also constructed hybrid viruses to study whether recombination can facilitate the adaptation to new hosts.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010504-03
Application #
7291847
Study Section
(RML)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2005
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Moore, Michael D; Chin, Mario P S; Hu, Wei-Shau (2009) HIV-1 recombination: an experimental assay and a phylogenetic approach. Methods Mol Biol 485:87-105
Nikolaitchik, Olga A; Gorelick, Robert J; Leavitt, Maria G et al. (2008) Functional complementation of nucleocapsid and late domain PTAP mutants of human immunodeficiency virus type 1 during replication. Virology 375:539-49
Chin, Mario P S; Chen, Jianbo; Nikolaitchik, Olga A et al. (2007) Molecular determinants of HIV-1 intersubtype recombination potential. Virology 363:437-46
Fu, William; Prasad, V V S P; Chen, Jianbo et al. (2007) Molecular mechanisms of simian immunodeficiency virus SIV(agm) RNA encapsidation. Virology 363:210-9
Nikolaitchik, Olga; Rhodes, Terence D; Ott, David et al. (2006) Effects of mutations in the human immunodeficiency virus type 1 Gag gene on RNA packaging and recombination. J Virol 80:4691-7
Chen, Jianbo; Powell, Douglas; Hu, Wei-Shau (2006) High frequency of genetic recombination is a common feature of primate lentivirus replication. J Virol 80:9651-8
Chen, Jianbo; Rhodes, Terence D; Hu, Wei-Shau (2005) Comparison of the genetic recombination rates of human immunodeficiency virus type 1 in macrophages and T cells. J Virol 79:9337-40
Rhodes, Terence D; Nikolaitchik, Olga; Chen, Jianbo et al. (2005) Genetic recombination of human immunodeficiency virus type 1 in one round of viral replication: effects of genetic distance, target cells, accessory genes, and lack of high negative interference in crossover events. J Virol 79:1666-77
Chin, Mario P S; Rhodes, Terence D; Chen, Jianbo et al. (2005) Identification of a major restriction in HIV-1 intersubtype recombination. Proc Natl Acad Sci U S A 102:9002-7
Svarovskaia, Evguenia S; Cheslock, Sara R; Zhang, Wen-Hui et al. (2003) Retroviral mutation rates and reverse transcriptase fidelity. Front Biosci 8:d117-34

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