We are carrying out live-cell microscopy to examine the movement of HIV-1 complexes in infected cells, determine the kinetics of their association with the NE, and visualize their nuclear import. We will determine whether interactions between HIV-1 integrase and host proteins LEDGF and/or HRP-2 are critical for the tethering of HIV-1 PICs to the chromatin domains near the NE. We will develop methods to visualize integrated proviral DNAs and compare the distribution of PICs to proviral DNAs in infected cells. Wild-type HIV-1 can infect non-dividing cells, but some HIV-1 CA mutants and MLV can only infect dividing cells. We will analyze NE association and nuclear import of these HIV-1 mutants and MLV to determine the stage at which infection of non-dividing cells is blocked. HIV-1 viral cores are disassembled after infection in a poorly understood process known as uncoating. We will analyze the kinetics and nature of HIV-1 uncoating in infected cells by labeling viral complexes with A3F-YFP and other fluorescent markers. Host protein cyclophilin binds to HIV-1 CA in infected cells, but the functional consequences of this interaction on viral replication are not well understood. We are examining the impact of cyclophilin-binding CA mutants to NE association and nuclear import to elucidate this virus-host interaction. MX2 is a recently identified host restriction factor that inhibits HIV-1 replication by binding to viral cores. We are analyzing replication of A3F-YFP-labeled virions in MX2-expressing cells to determine the mechanism(s) by which MX2 inhibits HIV-1 replication. _____[Corresponds to Pathak Project 3 in the October 2011 site visit report of the HIV Drug Resistance Program]
| Liu, Yang; Nikolaitchik, Olga A; Rahman, Sheikh Abdul et al. (2017) HIV-1 Sequence Necessary and Sufficient to Package Non-viral RNAs into HIV-1 Particles. J Mol Biol 429:2542-2555 |
| Nikolaitchik, Olga; Keele, Brandon; Gorelick, Robert et al. (2015) High recombination potential of subtype A HIV-1. Virology 484:334-40 |
| Delviks-Frankenberry, Krista; Paprotka, Tobias; Cingöz, Oya et al. (2013) Generation of multiple replication-competent retroviruses through recombination between PreXMRV-1 and PreXMRV-2. J Virol 87:11525-37 |
| Delviks-Frankenberry, Krista A; Lengruber, Renan B; Santos, Andre F et al. (2013) Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance. Virology 435:433-41 |
| Hatch, Steven C; Sardo, Luca; Chen, Jianbo et al. (2013) Gag-dependent enrichment of HIV-1 RNA near the uropod membrane of polarized T cells. J Virol 87:11912-5 |
| Murgai, Meera; Thomas, James; Cherepanova, Olga et al. (2013) Xenotropic MLV envelope proteins induce tumor cells to secrete factors that promote the formation of immature blood vessels. Retrovirology 10:34 |
| Nikolaitchik, Olga A; Dilley, Kari A; Fu, William et al. (2013) Dimeric RNA recognition regulates HIV-1 genome packaging. PLoS Pathog 9:e1003249 |
| Del Prete, Gregory Q; Kearney, Mary F; Spindler, Jon et al. (2012) Restricted replication of xenotropic murine leukemia virus-related virus in pigtailed macaques. J Virol 86:3152-66 |
| Delviks-Frankenberry, Krista; Cingöz, Oya; Coffin, John M et al. (2012) Recombinant origin, contamination, and de-discovery of XMRV. Curr Opin Virol 2:499-507 |
| 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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