Elucidating the Mechanisms of Reverse Transcription and Recombination

Hu, Wei-Shau

Abstract

Frequent recombination contributes significantly to the diversity of the HIV-1 population. We have studied multiple aspects of HIV-1 recombination. We have studied the recombination potential of subtype A HIV-1 using strains that are circulating in Russia, and we found that recombination occurs frequently and can easily assort mutation to generate variants resistant to multiple antivirals. We have also studied how host restriction factors APOBEC3G and APOBEC3F affect viral replication, and whether hypermutations induced by these restriction factors play a role in viral evolution. Additionally, we have assisted in the construction of replication-dependent vectors that can be used to monitor cell-to-cell infection. 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, renamed the HIV Dynamics and Replication Program in 2015]

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Cancer Institute (NCI)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIABC010504-13
• Application #: 9153588
• Support Year: 13
• Fiscal Year: 2015

Institution

• Name: Basic Sciences

Publications

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

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

Nikolaitchik, Olga; Keele, Brandon; Gorelick, Robert et al. (2015) High recombination potential of subtype A HIV-1. Virology 484:334-40

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