Capsid-CPSF6 Interaction Licenses Nuclear HIV-1 Trafficking to Sites of Viral DNA Integration

Cell Host & Microbe
Vasudevan AchuthanAlan N Engelman

Abstract

HIV-1 integration into the host genome favors actively transcribed genes. Prior work indicated that the nuclear periphery provides the architectural basis for integration site selection, with viral capsid-binding host cofactor CPSF6 and viral integrase-binding cofactor LEDGF/p75 contributing to selection of individual sites. Here, by investigating the early phase of infection, we determine that HIV-1 traffics throughout the nucleus for integration. CPSF6-capsid interactions allow the virus to bypass peripheral heterochromatin and penetrate the nuclear structure for integration. Loss of interaction with CPSF6 dramatically alters virus localization toward the nuclear periphery and integration into transcriptionally repressed lamina-associated heterochromatin, while loss of LEDGF/p75 does not significantly affect intranuclear HIV-1 localization. Thus, CPSF6 serves as a master regulator of HIV-1 intranuclear localization by trafficking viral preintegration complexes away from heterochromatin at the periphery toward gene-dense chromosomal regions within the nuclear interior.

Citations

Mar 6, 2019·ELife·Lorena Zuliani-Alvarez, Greg J Towers
Jun 30, 2019·Genome Research·Kurt PattersonSuzanne B Sandmeyer
Aug 23, 2018·Multiple Sclerosis : Clinical and Laboratory Research·Lavanya Vijayasingham, Shanthi Viswanathan
Jan 17, 2020·Journal of Virology·Irena Zurnic BönischZeger Debyser
Apr 14, 2020·PLoS Pathogens·Molly OhainleMichael Emerman
Mar 11, 2020·The Journal of Biological Chemistry·Evan ChaudhuriChandravanu Dash
Apr 4, 2019·Retrovirology·Gerlinde VansantZeger Debyser
Nov 2, 2019·Diseases·Carole McArthurKamal Singh
May 21, 2020·Science China. Life Sciences·Xia LiXian-En Zhang
Aug 30, 2020·Viruses·Alex B Kleinpeter, Eric O Freed
Mar 13, 2020·Proceedings of the National Academy of Sciences of the United States of America·Shinichi MachidaMonsef Benkirane
Jul 1, 2020·Nucleic Acids Research·Gerlinde VansantZeger Debyser
Jan 16, 2020·Viruses·Gerlinde VansantZeger Debyser
Aug 31, 2019·The Journal of Biological Chemistry·Alan N Engelman
Feb 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Ryan C BurdickVinay K Pathak
Apr 23, 2020·Viruses·Sanjeev Kumar V VernekarZhengqiang Wang
Dec 4, 2020·The EMBO Journal·Elena RensenFrancesca Di Nunzio
Dec 19, 2020·Nucleic Acids Research·Gregory J Bedwell, Alan N Engelman
Jan 23, 2021·Viruses·Alan N Engelman
Feb 10, 2021·Viruses·Morganne Wilbourne, Peijun Zhang
Feb 14, 2021·Viruses·Viviana Scoca, Francesca Di Nunzio
Oct 17, 2020·Science·Stephanie M BesterMamuka Kvaratskhelia
Mar 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Chenglei LiVinay K Pathak
Apr 20, 2021·Frontiers in Microbiology·Julie JanssensZeger Debyser
Apr 20, 2021·Frontiers in Microbiology·Elenia ToccafondiMatteo Negroni

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