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Multiple Roles of DDX17 in Human Immunodeficiency Virus Type 1 Replication

出版	McGill University Libraries, 2013
URL	http://books.google.com.hk/books?id=FBSQoAEACAAJ&hl=&source=gbs_api

註釋"Human immunodeficiency virus type 1 (HIV-1) is a small retrovirus that highly depends on the host cell machinery to replicate by completing its lifecycle and producing new infectious viral particles. The complexity of HIV-1 life cycle regulation only reflects the diversity of the virus-host interactions. Cellular helicases are enzymes involved in every step of nucleic acid metabolism, through rearranging ribonucleoprotein complexes. The understanding and the importance of helicases in HIV-1 replication started to emerge a decade ago. Since then, many studies reported the promoting or inhibiting effect of this protein family on HIV-1. My thesis project was to investigate the role of helicases in HIV-1 replication and comprises two parts. First, we performed a shRNA screen in SupT1 cells to knockdown 130 helicases and monitor their effect on the production of HIV-1 particles. This work allowed us to identify cellular pathways that are important for HIV-1 replication, as well as 35 potential helicases that dramatically affect virus production. Second, we chose to further investigate the role of DDX17 in HIV-1 replication. In addition to showing for the first time that a helicase is required for HIV-1 frameshift, we found that DDX17 promotes viral RNA packaging. Considering the role of DDX17 as a cofactor of the zinc antiviral protein (ZAP) in exosome-mediated HIV-1 mRNA degradation, this emphasizes the fact that helicases are multifunctional proteins. Finally, this work identifies helicases that potentially strongly modulate HIV-1 production. Individual investigation for each candidate will be needed to unravel the mechanisms underlying their effect on HIV-1 replication."--