Grant: Operating Grant - PA: Regional Partnership Program : Manitoba

The human immunodeficiency virus type 1 (HIV-1) pandemic is a major health problem worldwide. During virus infection, the HIV-1 virus must convert its own RNA into double stranded DNA (a process called reverse transcription) before HIV-1 can replicate in the cell. The HIV-1 has its own protein, called reverse transciptase, for the DNA synthesis, but it also has to use the cell's machinery for effective reverse transcription to occur. However, the cell's proteins that are used by HIV-1 to help the virus perform reverse transcription are not known. Recently, we identified a cellular protein, Dynein light chain-1 (DYNLL1), which works together with another viral protein, integrase, to allow efficient reverse transcription. We also found that an HIV-1 envelope protein (gp120) stimulated the reverse transcriptase process. We think that gp120 acts through a signaling pathway that includes Pak1, which regulates the DYNLL1 protein. In this proposal, we will continue to study how HIV-1 uses cell proteins to help with its own replication. We also want to study how gp120 stimulates HIV-1 reverse transcription. The results of this study will help us to discover the new mechanism/s underlying HIV-1 reverse transcription and may provide information to develop novel strategies to control HIV-1 infection through blocking reverse transcription. This study is relevant to the CIHR HIV/AIDS Research Initiative research priority area: HIV Pathogenesis, and Prevention, Technologies and Interventions. Finding new interactions between HIV-1 and host signaling pathways that favor HIV-1 reverse transcription will help us to better understand how HIV works. Also, results of this project may reveal new ways to control HIV infection.