Proteasome inhibitors uncouple rhesus TRIM5alpha restriction of HIV-1 reverse transcription and infection.

Proceedings of the National Academy of Sciences of the United States of America
Xiaolu WuThomas J Hope

Abstract

The primate TRIM5alpha proteins have recently been defined as cellular restriction factors, preventing primate infection by retroviruses from different species. For instance, rhesus TRIM5alpha (rhTRIM5alpha) restricts infection by HIV-1. Virtually all TRIM5alpha proteins block the early replication of retroviruses by preventing the accumulation of reverse transcription products, but the underlying mechanism remains unclear. In this article, we find that disrupting proteasome function alters rhTRIM5alpha localization and allows the normal generation of HIV-1 late reverse transcription products, even though HIV-1 infection and the generation of nuclear 1-LTR and 2-LTR viral cDNA forms remain impaired. This finding suggests rhTRIM5alpha restricts HIV infection in two distinct phases: (i) altering the normal passage of the reverse-transcribing viral genome to the nucleus and (ii) targeting the reverse transcription complex to be disrupted by the proteasome. Because proteasome inhibitor blocks the second phase, accumulation of a nonfunctional viral DNA genome can be readily observed. Defining each phase may reveal HIV-1 targets for future antiviral therapy in which dual blockade may be equally as effective as naturally occurring rhT...Continue Reading

References

Nov 1, 1995·The Journal of General Virology·R ShibataA Adachi
Oct 28, 1998·Trends in Cell Biology·D H Lee, A L Goldberg
Nov 13, 1999·Journal of Virology·W HofmannJ Sodroski
Oct 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·G TowersO Danos
Nov 23, 2000·Proceedings of the National Academy of Sciences of the United States of America·A PatnaikJ W Wills
May 1, 2001·Nature Medicine·S L ButlerF D Bushman
May 2, 2001·The EMBO Journal·A ReymondA Ballabio
Feb 12, 2002·Journal of Virology·Greg TowersYasuhiro Takeuchi
Mar 22, 2002·Journal of Virology·Scott L ButlerFrederic D Bushman
Aug 3, 2002·Proceedings of the National Academy of Sciences of the United States of America·Simone CowanPaul D Bieniasz
Aug 3, 2002·Proceedings of the National Academy of Sciences of the United States of America·Caroline BesnierGreg Towers
Oct 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Carsten MünkNathaniel R Landau
Jan 30, 2003·The EMBO Journal·Theodora HatziioannouGreg J Towers
Dec 3, 2003·Journal of Virology·Caroline BesnierGreg J Towers
Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Theodora HatziioannouPaul D Bieniasz
Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Zuzana KeckesovaGreg J Towers
Oct 22, 2004·Nature Immunology·Paul D Bieniasz
Jan 15, 2005·Current Biology : CB·Melvyn W YapJonathan P Stoye
Feb 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Sara L SawyerHarmit S Malik
May 18, 2005·The Journal of Biological Chemistry·Hassan JavanbakhtJoseph Sodroski
Jul 5, 2005·Journal of Virology·David Perez-CaballeroPaul D Bieniasz
Sep 22, 2005·Nature Reviews. Microbiology·Sébastien NisoleAli Saïb

❮ Previous
Next ❯

Citations

Dec 24, 2011·Current HIV/AIDS Reports·Zana Lukic, Edward M Campbell
Aug 20, 2010·Immunologic Research·Marisa S Briones, Samson A Chow
Mar 19, 2013·Veterinary Immunology and Immunopathology·Ryota KobaHiroshi Sentsui
Jan 12, 2011·Biochemistry·Andrew M L Lever, Kuan-Teh Jeang
Oct 7, 2008·Nature Reviews. Immunology·Keiko OzatoHerbert C Morse
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sam J WilsonGreg J Towers
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cesar A VirgenTheodora Hatziioannou
Feb 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jonathan P Stoye, Melvyn W Yap
Dec 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Barbie K Ganser-PornillosMark Yeager
Jun 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Amy E HulmeThomas J Hope
Jan 21, 2011·AIDS Research and Human Retroviruses·Jaya Sastri, Edward M Campbell
Jun 27, 2013·AIDS Research and Human Retroviruses·Cindy M Danielson, Thomas J Hope
Aug 22, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Stuart Neil, Paul Bieniasz
May 4, 2012·Cold Spring Harbor Perspectives in Medicine·Michael H Malim, Paul D Bieniasz
Jun 26, 2007·Science·Shari M KaiserMichael Emerman
Apr 23, 2010·Journal of Virology·Lesa R Black, Christopher Aiken
Jun 15, 2012·Journal of Virology·P JáureguiR Reina
Jun 18, 2010·Journal of Virology·Isabelle DietrichBrian J Willett
Dec 14, 2007·Journal of Virology·Jenny L AndersonThomas J Hope
Aug 19, 2007·Journal of Virology·Frederick ArnaudMassimo Palmarini
Jan 18, 2008·Journal of Virology·Melanie GallaChristopher Baum
Mar 12, 2010·Journal of Virology·Marisa S BrionesSamson A Chow
Mar 12, 2010·Journal of Virology·Pierre V MaillardDidier Trono
Mar 28, 2008·Journal of Virology·Melvyn W YapJonathan P Stoye
Mar 29, 2013·Journal of Virology·Sadayuki Ohkura, Jonathan P Stoye

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.