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

• HIV capsid mutants reveal that Cyclophilin A can restrict viral nuclear import
• Nuclear envelope protein SUN2 is implicated in the restriction of HIV mutants
• SUN2 is essential for wild-type HIV infection in CD4+ T cells and dendritic cells
• In CD4+ T cells, the activities of CypA on HIV-1 infection require SUN2

SummaryDuring 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.

Graphical AbstractFigure optionsDownload as PowerPoint slide