Functional role of Alix in HIV-1 replication Export

@article{citeulike:5274241, abstract = {Retroviral Gag proteins encode small peptide motifs known as late domains that promote the release of virions from infected cells by interacting directly with host cell factors. Three types of retroviral late domains, with core sequences P(T/S)AP, YPX n L, and PPPY, have been identified. HIV-1 encodes a primary P(T/S)AP-type late domain and an apparently secondary late domain sequence of the YPX n L type. The P(T/S)AP and YPX n L motifs interact with the endosomal sorting factors Tsg101 and Alix, respectively. Although biochemical and structural studies support a direct binding between HIV-1 p6 and Alix, the physiological role of Alix in HIV-1 biology remains undefined. To elucidate the function of the p6–Alix interaction in HIV-1 replication, we introduced a series of mutations in the p6 Alix binding site and evaluated the effects on virus particle production and virus replication in a range of cell types, including physiologically relevant primary T cells and macrophages. We also examined the effects of the Alix binding site mutations on virion morphogenesis and single-cycle virus infectivity. We determined that the p6–Alix interaction plays an important role in HIV-1 replication and observed a particularly severe impact of Alix binding site mutations when they were combined with mutational inactivation of the Tsg101 binding site.}, author = {Fujii, Ken and Munshi, Utpal M. and Ablan, Sherimay D. and Demirov, Dimiter G. and Soheilian, Ferri and Nagashima, Kunio and Stephen, Andrew G. and Fisher, Robert J. and Freed, Eric O.}, citeulike-article-id = {5274241}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.virol.2009.06.016}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0042682209003638}, day = {01}, doi = {10.1016/j.virol.2009.06.016}, issn = {00426822}, journal = {Virology}, keywords = {assembly, hiv, replication}, month = {September}, number = {2}, pages = {284--292}, posted-at = {2009-08-19 13:47:10}, priority = {2}, title = {Functional role of Alix in HIV-1 replication}, url = {http://dx.doi.org/10.1016/j.virol.2009.06.016}, volume = {391}, year = {2009} }

TY - JOUR ID - citeulike:5274241 L3 - citeulike-article-id:5274241 N2 - Retroviral Gag proteins encode small peptide motifs known as late domains that promote the release of virions from infected cells by interacting directly with host cell factors. Three types of retroviral late domains, with core sequences P(T/S)AP, YPX n L, and PPPY, have been identified. HIV-1 encodes a primary P(T/S)AP-type late domain and an apparently secondary late domain sequence of the YPX n L type. The P(T/S)AP and YPX n L motifs interact with the endosomal sorting factors Tsg101 and Alix, respectively. Although biochemical and structural studies support a direct binding between HIV-1 p6 and Alix, the physiological role of Alix in HIV-1 biology remains undefined. To elucidate the function of the p6–Alix interaction in HIV-1 replication, we introduced a series of mutations in the p6 Alix binding site and evaluated the effects on virus particle production and virus replication in a range of cell types, including physiologically relevant primary T cells and macrophages. We also examined the effects of the Alix binding site mutations on virion morphogenesis and single-cycle virus infectivity. We determined that the p6–Alix interaction plays an important role in HIV-1 replication and observed a particularly severe impact of Alix binding site mutations when they were combined with mutational inactivation of the Tsg101 binding site. IS - 2 JF - Virology SN - 00426822 EP - 292 TI - Functional role of Alix in HIV-1 replication VL - 391 SP - 284 KW - assembly KW - hiv KW - replication AU - Fujii, Ken AU - Munshi, Utpal AU - Ablan, Sherimay AU - Demirov, Dimiter AU - Soheilian, Ferri AU - Nagashima, Kunio AU - Stephen, Andrew AU - Fisher, Robert AU - Freed, Eric PY - 2009/09/01/ UR - http://dx.doi.org/10.1016/j.virol.2009.06.016 ER -