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oai:docta.ucm.es:20.500.14352/979152025-02-14T19:20:18Zcom_20.500.14352_14col_20.500.14352_15

A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities Martínez-Bonet, Marta Palladino, Claudia Briz, Veronica Rudolph, Jochen M. Fackler, Oliver T. Relloso, Miguel Muñoz-Fernández, María Ángeles Madrid González, Ricardo Yuntao Wu 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. 2024-02-01T16:57:19Z 2024-02-01T16:57:19Z 2015 journal article Martínez-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.0145239 1932-6203 10.1371/journal.pone.0145239 https://hdl.handle.net/20.500.14352/97915 https://doi.org/10.1371/journal.pone.0145239 eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International Public Library of Science