2026-06-14T03:44:38Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Ministerio de Ciencia e Innovación (España)
funder
Instituto de Salud Carlos III
funder
Comunidad de Madrid (España)
funder
Deutsche Forschungsgemeinschaft (Alemania)
2021-04-23T09:22:22Z
2021-04-23T09:22:22Z
2015
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
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.
eng
A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities.
journal article
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URL
https://repisalud.isciii.es/bitstreams/c59e2724-c818-4090-866b-064e1c61f117/download
File
MD5
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application/pdf
AConservedGPGMotif_2015.pdf
URL
https://repisalud.isciii.es/bitstreams/d0e4fa83-f2c7-4a5b-a736-577be1f3ba2d/download
File
MD5
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text/plain
AConservedGPGMotif_2015.pdf.txt