Martínez-Bonet, MartaPalladino, ClaudiaBriz, VeronicaRudolph, Jochen M.Fackler, Oliver T.Relloso, MiguelMuñoz-Fernández, María ÁngelesMadrid González, RicardoYuntao Wu2024-02-012024-02-012015Martínez-Bonet M, Palladino C, Briz V, Rudolph JM, Fackler OT, Relloso M, et al. (2015) A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities. PLoS ONE 10(12): e0145239. https://doi.org/10.1371/journal.pone.01452391932-620310.1371/journal.pone.0145239https://hdl.handle.net/20.500.14352/97915To 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.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://doi.org/10.1371/journal.pone.0145239open accessCiencias Biomédicas24 Ciencias de la Vida