{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Rohlfes N"],"funding":["NIAID NIH HHS"],"pubmed_abstract":["The early stages of HIV-1 infection include the trafficking of the viral core into the nucleus of infected cells. However, much remains to be understood about how HIV-1 accomplishes nuclear import and the consequences of the import pathways utilized on nuclear events. The host factor cleavage and polyadenylation specificity factor 6 (CPSF6) assists HIV-1 nuclear localization and post-entry integration targeting. Here, we used a CPSF6 truncation mutant lacking a functional nuclear localization signal (NLS), CPSF6-358, and appended heterologous NLSs to rescue nuclear localization. We show that some, but not all, NLSs drive CPSF6-358 into the nucleus. Interestingly, we found that some nuclear localized CPSF6-NLS chimeras supported inefficient HIV-1 infection. We found that HIV-1 still enters the nucleus in these cell lines but fails to traffic to speckle-associated domains (SPADs). Additionally, we show that HIV-1 fails to efficiently integrate in these cell lines. Collectively, our results demonstrate that the NLS of CPSF6 facilitates steps of HIV-1 infection subsequent to nuclear import and additionally identify the ability of canonical NLS sequences to influence cargo localization in the nucleus following nuclear import."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.06.20.599834"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11230232"],"repository":["biostudies-literature"],"pubmed_title":["The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection."],"pmcid":["PMC11230232"],"funding_grant_id":["U54 AI170791","R01 AI052014","R01 AI162694"],"pubmed_authors":["Dharan A","Campbell EM","Singh PK","Bedwell GJ","Engelman AN","Radhakrishnan R","Rohlfes N"],"additional_accession":[]},"is_claimable":false,"name":"The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.","description":"The early stages of HIV-1 infection include the trafficking of the viral core into the nucleus of infected cells. However, much remains to be understood about how HIV-1 accomplishes nuclear import and the consequences of the import pathways utilized on nuclear events. The host factor cleavage and polyadenylation specificity factor 6 (CPSF6) assists HIV-1 nuclear localization and post-entry integration targeting. Here, we used a CPSF6 truncation mutant lacking a functional nuclear localization signal (NLS), CPSF6-358, and appended heterologous NLSs to rescue nuclear localization. We show that some, but not all, NLSs drive CPSF6-358 into the nucleus. Interestingly, we found that some nuclear localized CPSF6-NLS chimeras supported inefficient HIV-1 infection. We found that HIV-1 still enters the nucleus in these cell lines but fails to traffic to speckle-associated domains (SPADs). Additionally, we show that HIV-1 fails to efficiently integrate in these cell lines. Collectively, our results demonstrate that the NLS of CPSF6 facilitates steps of HIV-1 infection subsequent to nuclear import and additionally identify the ability of canonical NLS sequences to influence cargo localization in the nucleus following nuclear import.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2025-08-31T03:20:11.453Z","creation":"2025-04-07T12:02:06.723Z"},"accession":"S-EPMC11230232","cross_references":{"pubmed":["38979149"],"doi":["10.1101/2024.06.20.599834"]}}