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SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends

Awatef Allouch 1, 2, 3 Cristina Di Primio 4 Audrey Paoletti 1, 2, 3 Gabrielle Lê-Bury 5 Frédéric Subra 6 Valentina Quercioli 4 Roberta Nardacci 7 Annie David 8 Héla Saidi 9 Anna Cereseto 10 David M. Ojcius 11, 12 Guillaume Montagnac 13 Florence Niedergang 5 Gianfranco Pancino 8 Asier Sáez-Cirión 8 Mauro Piacentini 14, 15 Marie-Lise Gougeon 9 Guido Kroemer 16, 17, 18, 19, 20 Jean-Luc Perfettini 2, 1, 3, 11, * 
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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Submitted on : Thursday, June 18, 2020 - 11:43:39 AM
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Awatef Allouch, Cristina Di Primio, Audrey Paoletti, Gabrielle Lê-Bury, Frédéric Subra, et al.. SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends. Cell Death and Differentiation, 2020, Online ahead of print, pp.18 - 22. ⟨10.1038/s41418-020-0573-5⟩. ⟨pasteur-02868173⟩



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