TY - JOUR
T1 - SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends
AU - Allouch, Awatef
AU - Di Primio, Cristina
AU - Paoletti, Audrey
AU - Lê-Bury, Gabrielle
AU - Subra, Frédéric
AU - Quercioli, Valentina
AU - Nardacci, Roberta
AU - David, Annie
AU - Saïdi, Héla
AU - Cereseto, Anna
AU - Ojcius, David M.
AU - Montagnac, Guillaume
AU - Niedergang, Florence
AU - Pancino, Gianfranco
AU - Saez-Cirion, Asier
AU - Piacentini, Mauro
AU - Gougeon, Marie Lise
AU - Kroemer, Guido
AU - Perfettini, Jean Luc
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85086162626&partnerID=8YFLogxK
U2 - 10.1038/s41418-020-0573-5
DO - 10.1038/s41418-020-0573-5
M3 - 文章
C2 - 32514048
AN - SCOPUS:85086162626
SN - 1350-9047
VL - 27
SP - 3243
EP - 3257
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 12
ER -
