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)

1 IGR - Institut Gustave Roussy
2 RaMo-IT - Radiothérapie Moléculaire et Innovation Thérapeutique
3 Université Paris-Saclay
4 SNS - Scuola Normale Superiore di Pisa
5 IC UM3 (UMR 8104 / U1016) - Institut Cochin
6 LBPA - Laboratoire de biologie et pharmacologie appliquée
7 National Institute for Infectious Diseases "Lazzaro Spallanzani"
8 HIV, Inflammation et persistance - HIV, Inflammation and Persistence
9 Immunité Antivirale, Biothérapie et Vaccins
10 CIBIO - Centre for Integrative Biology (CIBIO), University of Trento
11 Arthur A. Dugoni School of Dentistry [San Francisco]
12 UPD7 - Université Paris Diderot - Paris 7
13 U1170 Inserm - Hématopoïèse normale et pathologique
14 INMI - Istituto Nazionale di Malattie Infettive "Lazzaro Spallanzani"
15 Università degli Studi di Roma Tor Vergata [Roma] = University of Rome Tor Vergata
16 UPD5 - Université Paris Descartes - Paris 5
17 Plateforme de métabolomique
18 Equipe labellisée Ligue contre le cancer - Métabolisme, cancer et immunité = Metabolism, Cancer & Immunity [CRC]
19 Pôle de biologie
20 Department of Women's and Children's Health

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.

Mots clés: Infectious diseases; Immunopathogenesis; HIV-1; microtubules; nuclear import; SUGT1

Domaines: Virologie

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⟩