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oai:repisalud.isciii.es:20.500.12105/127492024-11-29T10:22:05Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16978

00925njm 22002777a 4500 dc Martínez-Bonet, Marta author Palladino, Claudia author Briz, Veronica author Rudolph, Jochen M author Fackler, Oliver T author Relloso, Miguel author Muñoz-Fernandez, Maria Angeles author Madrid, Ricardo author 2015 To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121-137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection. PLoS One. 2015 Dec 23;10(12):e0145239. 10.1371/journal.pone.0145239 1932-6203 PloS one 26700863 http://hdl.handle.net/20.500.12105/12749 A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities.