Inhibition of HIV infection by structural proteins of the inner nuclear membrane is associated with reduced chromatin dynamics

• DOI: 10.1016/j.celrep.2021.109763
• Publication Date: 2021-09-30T01:18:00Z
• Authors: Anvita Bhargava; Alice Williart; Mathieu Maurin; Patricia M. Davidson; Mabel Jouve; Matthieu Piel; Xavier Lahaye; Nicolas Manel
• Keywords: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology; Cell Nucleus; 0301 basic medicine; Lamin A/C; QH301-705.5; Nuclear Envelope; [SDV]Life Sciences [q-bio]; Intracellular Signaling Peptides and Proteins; HIV; Membrane Proteins; Nuclear Proteins; HIV Infections; nuclear envelope; LINC; Chromatin; 3. Good health; 03 medical and health sciences; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; SUN2; SUN1; Humans; Biology (General); Microtubule-Associated Proteins

The human immunodeficiency virus (HIV) enters the nucleus to establish infection, but the role of nuclear envelope proteins in this process is incompletely understood. Inner nuclear transmembrane proteins SUN1 and SUN2 connect nuclear lamins to the cytoskeleton and participate in the DNA damage response (DDR). Increased levels of SUN1 or SUN2 potently restrict HIV infection through an unresolved mechanism. Here, we find that the antiviral activities of SUN1 and SUN2 are distinct. HIV-1 and HIV-2 are preferentially inhibited by SUN1 and SUN2, respectively. We identify DNA damage inducers that stimulate HIV-1 infection and show that SUN1, but not SUN2, neutralizes this effect. Finally, we show that chromatin movements and nuclear rotations are associated with the effects of SUN proteins and Lamin A/C on infection. These results reveal an emerging role of chromatin dynamics and the DDR in the control of HIV infection by structural components of the nuclear envelope.