Recombination is a major mechanism to generate the genetic diversity of HIV-1. Recombination occurs during reverse transcription using information in the two RNAs to generate a hybrid DNA. Therefore, phenotypically distinct recombinants are generated from viruses containing two copies of different RNAs. Only cells that are doubly infected can generate virions containing two different RNAs. To better understand interactions within the HIV-1 population, we examined the dynamics of HIV-1 double infection. We have demonstrated that HIV-1 double infection occurs far more frequently than expected from random events, and preference in virus entry plays a key role in nonrandom double infection. We have measured HIV-1 recombination rates and have demonstrated that HIV-1 recombines at an exceedingly high rate, approximately 10-fold higher than that of murine leukemia virus (MLV) and spleen necrosis virus (SNV). We have demonstrated that recombination can occur between two viruses within the same HIV-1 subtypes, between viruses from different HIV-1 subtypes, and between distantly related viruses. We have determined factors that affect recombination and have shown that HIV-1 intersubtype recombinants undergo strong purifying selection. In this project, we hypothesize that reverse transcription is a well-choreographed event in the target cells;multiple viral and host factors can affect this process. We will explore the nucleic acid structure in the reverse transcription complex and the factors that affect the dynamics of reverse transcription and recombination. We will also continue to study recombination and viral fitness, including examining the cause of loss of fitness of the intersubtype recombinants and studying the viral population in the infected individuals. This work will further our understanding of the molecular basis for generating HIV genetic diversity and explore the possible emergence of novel human viruses via recombination. [Corresponds to Hu Project 1 in the April 2007 site visit report of the HIV Drug Resistance Program]

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National Cancer Institute (NCI)
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Desimmie, Belete A; Smith, Jessica L; Matsuo, Hiroshi et al. (2017) Identification of a tripartite interaction between the N-terminus of HIV-1 Vif and CBF? that is critical for Vif function. Retrovirology 14:19
Delviks-Frankenberry, Krista A; Nikolaitchik, Olga A; Burdick, Ryan C et al. (2016) Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation. PLoS Pathog 12:e1005646
Nikolaitchik, Olga; Keele, Brandon; Gorelick, Robert et al. (2015) High recombination potential of subtype A HIV-1. Virology 484:334-40
Shunaeva, Anastasia; Potashnikova, Daria; Pichugin, Alexey et al. (2015) Improvement of HIV-1 and Human T Cell Lymphotropic Virus Type 1 Replication-Dependent Vectors via Optimization of Reporter Gene Reconstitution and Modification with Intronic Short Hairpin RNA. J Virol 89:10591-601
Sato, Kei; Takeuchi, Junko S; Misawa, Naoko et al. (2014) APOBEC3D and APOBEC3F potently promote HIV-1 diversification and evolution in humanized mouse model. PLoS Pathog 10:e1004453
Burdick, Ryan C; Hu, Wei-Shau; Pathak, Vinay K (2013) Nuclear import of APOBEC3F-labeled HIV-1 preintegration complexes. Proc Natl Acad Sci U S A 110:E4780-9
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
Hu, Wei-Shau; Hughes, Stephen H (2012) HIV-1 reverse transcription. Cold Spring Harb Perspect Med 2:
Cingöz, Oya; Paprotka, Tobias; Delviks-Frankenberry, Krista A et al. (2012) Characterization, mapping, and distribution of the two XMRV parental proviruses. J Virol 86:328-38

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