Nuclear restriction of HIV-1 infection by SUN1.
Capsid
/ metabolism
Cell Nucleus
/ metabolism
Gene Knockout Techniques
HEK293 Cells
HIV Infections
/ pathology
HIV-1
/ metabolism
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Membrane Proteins
/ genetics
Microtubule-Associated Proteins
/ genetics
Nuclear Proteins
/ genetics
Virus Internalization
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 09 2021
27 09 2021
Historique:
received:
02
04
2021
accepted:
02
09
2021
entrez:
28
9
2021
pubmed:
29
9
2021
medline:
29
12
2021
Statut:
epublish
Résumé
Overexpression of the human Sad-1-Unc-84 homology protein 2 (SUN2) blocks HIV-1 infection in a capsid-dependent manner. In agreement, we showed that overexpression of SUN1 (Sad1 and UNC-84a) also blocks HIV-1 infection in a capsid-dependent manner. SUN2 and the related protein SUN1 are transmembrane proteins located in the inner membrane of the nuclear envelope. The N-terminal domains of SUN1/2 localizes to the nucleoplasm while the C-terminal domains are localized in the nuclear lamina. Because the N-terminal domains of SUN1/2 are located in the nucleoplasm, we hypothesized that SUN1/2 might be interacting with the HIV-1 replication complex in the nucleus leading to HIV-1 inhibition. Our results demonstrated that SUN1/2 interacts with the HIV-1 capsid, and in agreement with our hypothesis, the use of N-terminal deletion mutants showed that SUN1/2 proteins bind to the viral capsid by using its N-terminal domain. SUN1/2 deletion mutants correlated restriction of HIV-1 with capsid binding. Interestingly, the ability of SUN1/2 to restrict HIV-1 also correlated with perinuclear localization of these proteins. In agreement with the notion that SUN proteins interact with the HIV-1 capsid in the nucleus, we found that restriction of HIV-1 by overexpression of SUN proteins do not block the entry of the HIV-1 core into the nucleus. Our results showed that HIV-1 restriction is mediated by the interaction of SUN1/2N-terminal domains with the HIV-1 core in the nuclear compartment.
Identifiants
pubmed: 34580332
doi: 10.1038/s41598-021-98541-4
pii: 10.1038/s41598-021-98541-4
pmc: PMC8476499
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
Membrane Proteins
0
Microtubule-Associated Proteins
0
Nuclear Proteins
0
SUN1 protein, human
0
SUN2 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
19128Subventions
Organisme : NIAID NIH HHS
ID : R01 AI087390
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM086262
Pays : United States
Informations de copyright
© 2021. The Author(s).
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