Frequent recombination contributes significantly to the diversity of the HIV-1 population. We have studied multiple aspects of HIV-1 recombination, including the mechanisms that generate intersubtype recombinants, which are playing an increasingly important role in the current AIDS epidemic. By comparing intra- and intersubtype HIV-1 recombination, we have found that the sequence diversity between different HIV-1 subtypes decreases the crossover events and reduces the replication fitness of the recombinants, thereby causing the loss of newly generated chimeric viruses. Additionally, the dimerization initiation signal (DIS), a 6-nt palindromic sequence in the 5'untranslated region of the viral genome, affects the HIV-1 recombination frequency by two separate mechanisms: first, the identity of the DIS affects the generation of recombinants between genotypes with different DIS by dictating the frequency of viral RNA copackaging;second, discordant DIS sequences in the copackaged RNAs can further decrease crossovers at the 5'end of the viral genome and generate a recombination gradient. As HIV-1 is thought to be a recombinant generated from two distinct primate lentiviruses, we also studied recombination between different AIDS viruses. We demonstrated that recombination can occur between distantly related HIV-1 and HIV-2, as well as group O and group M HIV-1 variants, albeit at low rates. These studies revealed insights into the recombination mechanisms that generate diversity in the HIV-1 genome and potentially novel chimeric viruses. Our efforts in this project are focused on critical steps of reverse transcription including minus-strand DNA transfer and how host restriction factors can affect HIV replication. We are also studying recombination between subtype A viruses and mechanisms that cause a loss of replication fitness in newly generated recombinants. These studies will reveal insights into the replication mechanisms of HIV-1. [Corresponds to Hu Project 1 in the October 2011 site visit report of the HIV Drug Resistance Program]

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Chaipan, Chawaree; Smith, Jessica L; Hu, Wei-Shau et al. (2013) APOBEC3G restricts HIV-1 to a greater extent than APOBEC3F and APOBEC3DE in human primary CD4+ T cells and macrophages. J Virol 87:444-53
Izumi, Taisuke; Burdick, Ryan; Shigemi, Mayu et al. (2013) Mov10 and APOBEC3G localization to processing bodies is not required for virion incorporation and antiviral activity. J Virol 87:11047-62
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
Russell, Rebecca A; Moore, Michael D; Hu, Wei-Shau et al. (2009) APOBEC3G induces a hypermutation gradient: purifying selection at multiple steps during HIV-1 replication results in levels of G-to-A mutations that are high in DNA, intermediate in cellular viral RNA, and low in virion RNA. Retrovirology 6:16
Chen, Jianbo; Nikolaitchik, Olga; Singh, Jatinder et al. (2009) High efficiency of HIV-1 genomic RNA packaging and heterozygote formation revealed by single virion analysis. Proc Natl Acad Sci U S A 106:13535-40
Chin, Mario P S; Lee, Sook-Kyung; Chen, Jianbo et al. (2008) Long-range recombination gradient between HIV-1 subtypes B and C variants caused by sequence differences in the dimerization initiation signal region. J Mol Biol 377:1324-33
Motomura, Kazushi; Chen, Jianbo; Hu, Wei-Shau (2008) Genetic recombination between human immunodeficiency virus type 1 (HIV-1) and HIV-2, two distinct human lentiviruses. J Virol 82:1923-33