Abstract
Understanding the viral–host cell interface during HIV-1 infection is a prerequisite for the development of innovative antiviral therapies. Here we show that the suppressor of G2 allele of skp1 (SUGT1) is a permissive factor for human immunodeficiency virus (HIV)-1 infection. Expression of SUGT1 increases in infected cells on human brain sections and in permissive host cells. We found that SUGT1 determines the permissiveness to infection of lymphocytes and macrophages by modulating the nuclear import of the viral genome. More importantly, SUGT1 stabilizes the microtubule plus-ends (+MTs) of host cells (through the modulation of microtubule acetylation and the formation of end-binding protein 1 (EB1) comets). This effect on microtubules favors HIV-1 retrograde trafficking and replication. SUGT1 depletion impairs the replication of HIV-1 patient primary isolates and mutant virus that is resistant to raltegravir antiretroviral agent. Altogether our results identify SUGT1 as a cellular factor involved in the post-entry steps of HIV-1 infection that may be targeted for new therapeutic approaches.
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Acknowledgements
We acknowledge Dr Alessandro Donado, Yann Lecluse, Floriane Herit, and Pierre Bourdoncle (IMAG’IC facility of Institut Cochin) for their technical support, and Pr. Eric Solary for the pRLL-EF1-PGK-GFP lentiviral vector plasmid. This work was supported by funds from Agence Nationale de la Recherche (ANR-10-IBHU-0001, ANR-10-LABX33, and ANR-11-IDEX-003-01), Cancéropole Ile de France, Electricité de France, Fondation Gustave Roussy, Institut National du Cancer (INCA 9414), NATIXIS, SIDACTION, and the French National Agency for Research on AIDS and viral Hepatitis (ANRSH) (to J-LP and FN).
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Allouch, A., Di Primio, C., Paoletti, A. et al. SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends. Cell Death Differ 27, 3243–3257 (2020). https://doi.org/10.1038/s41418-020-0573-5
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DOI: https://doi.org/10.1038/s41418-020-0573-5
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