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Cell Rep. 2016 Apr 26;15(4):879-892. doi: 10.1016/j.celrep.2016.03.074. Epub 2016 Apr 14.

Nuclear Envelope Protein SUN2 Promotes Cyclophilin-A-Dependent Steps of HIV Replication.

Author information

1
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.
2
INSERM U955, 94010 Créteil, France.
3
Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520-8002, USA.
4
CNRS UMR5048, INSERM U1054 - Université de Montpellier, Centre de Biochimie Structurale, 34090 Montpellier, France.
5
Université Paris Sud, INSERM, CEA, DRF-Immunology of Viral Infections and Autoimmune Diseases department (IMVA), UMR1184, IDMIT Infrastructure, iMETI, 92260 Fontenay-aux-Roses, France.
6
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.
7
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.
8
Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. Electronic address: nicolas.manel@curie.fr.

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.

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