Nuclear Envelope Protein SUN2 Promotes Cyclophilin-A-Dependent Steps of HIV Replication
Xavier Lahaye,
Takeshi Satoh,
Matteo Gentili,
Silvia Cerboni,
Aymeric Silvin,
Cécile Conrad,
Abdelhakim Ahmed-Belkacem,
Elisa C. Rodriguez,
Jean-François Guichou,
Nathalie Bosquet,
Matthieu Piel,
Roger Le Grand,
Megan C. King,
Jean-Michel Pawlotsky,
Nicolas Manel
Affiliations
Xavier Lahaye
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France
Takeshi Satoh
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France
Matteo Gentili
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France
Silvia Cerboni
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France
Aymeric Silvin
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France
Cécile Conrad
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France
Abdelhakim Ahmed-Belkacem
INSERM U955, 94010 Créteil, France
Elisa C. Rodriguez
Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520-8002, USA
Jean-François Guichou
CNRS UMR5048, INSERM U1054 – Université de Montpellier, Centre de Biochimie Structurale, 34090 Montpellier, France
Nathalie Bosquet
Université Paris Sud, INSERM, CEA, DRF-Immunology of Viral Infections and Autoimmune Diseases department (IMVA), UMR1184, IDMIT Infrastructure, iMETI, 92260 Fontenay-aux-Roses, France
Matthieu Piel
Subcellular Structure and Cellular Dynamics Department, Institut Curie, PSL Research University, CNRS UMR144, 75005 Paris, France
Roger Le Grand
Université Paris Sud, INSERM, CEA, DRF-Immunology of Viral Infections and Autoimmune Diseases department (IMVA), UMR1184, IDMIT Infrastructure, iMETI, 92260 Fontenay-aux-Roses, France
Megan C. King
Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520-8002, USA
Jean-Michel Pawlotsky
INSERM U955, 94010 Créteil, France
Nicolas Manel
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France
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.
