title: Nuclear Envelope Protein SUN2 Promotes Cyclophilin-A-Dependent Steps of HIV Replication.
abstract: During the early phase of replication, HIV reverse transcribes its RNA and crosses the nuclear envelope while escaping host antiviral defenses. The host factor Cyclophilin A (CypA) is essential for these steps and binds the HIV capsid; however, the mechanism underlying this effect remains elusive. Here, we identify related capsid mutants in HIV-1, HIV-2, and SIVmac that are restricted by CypA. This antiviral restriction of mutated viruses is conserved across species and prevents nuclear import of the viral cDNA. Importantly, the inner nuclear envelope protein SUN2 is required for the antiviral activity of CypA. We show that wild-type HIV exploits SUN2 in primary CD4+T cells as an essential host factor that is required for the positive effects of CypA on reverse transcription and infection. Altogether, these results establish essential CypA-dependent functions of SUN2 in HIV infection at the nuclear envelope.
authors.affiliation: Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Lahaye
authors.affiliation: Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.
authors.forename: Matteo
authors.initials: M
authors.lastname: Gentili
authors.affiliation: Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cerboni
authors.affiliation: Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Silvin
authors.affiliation: Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Conrad
authors.affiliation: INSERM U955, 94010 Créteil, France.
authors.forename: Abdelhakim
authors.initials: A
authors.lastname: Ahmed-Belkacem
authors.affiliation: Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520-8002, USA.
authors.forename: Elisa C
authors.initials: EC
authors.lastname: Rodriguez
authors.affiliation: CNRS UMR5048, INSERM U1054 - Université de Montpellier, Centre de Biochimie Structurale, 34090 Montpellier, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Guichou
authors.affiliation: Université Paris Sud, INSERM, CEA, DRF-Immunology of Viral Infections and Autoimmune Diseases department (IMVA), UMR1184, IDMIT Infrastructure, iMETI, 92260 Fontenay-aux-Roses, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bosquet
authors.affiliation: Subcellular Structure and Cellular Dynamics Department, Institut Curie, PSL Research University, CNRS UMR144, 75005 Paris, France; Institut Pierre-Gilles de Gennes, PSL Research University, 75005 Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Piel
authors.affiliation: Université Paris Sud, INSERM, CEA, DRF-Immunology of Viral Infections and Autoimmune Diseases department (IMVA), UMR1184, IDMIT Infrastructure, iMETI, 92260 Fontenay-aux-Roses, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.affiliation: Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520-8002, USA.
authors.forename: Megan C
authors.initials: MC
authors.lastname: King
authors.affiliation: INSERM U955, 94010 Créteil, France; Department of Virology, National Reference Center for Viral Hepatitis B, C and D, Hôpital Henri Mondor, Université Paris-Est, 94010 Créteil, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.affiliation: Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. Electronic address: nicolas.manel@curie.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Manel