Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1

Nature
David M SayahJeremy Luban

Abstract

In Old World primates, TRIM5-alpha confers a potent block to human immunodeficiency virus type 1 (HIV-1) infection that acts after virus entry into cells. Cyclophilin A (CypA) binding to viral capsid protects HIV-1 from a similar activity in human cells. Among New World primates, only owl monkeys exhibit post-entry restriction of HIV-1 (ref. 1). Paradoxically, the barrier to HIV-1 in owl monkey cells is released by capsid mutants or drugs that disrupt capsid interaction with CypA. Here we show that knockdown of owl monkey CypA by RNA interference (RNAi) correlates with suppression of anti-HIV-1 activity. However, reintroduction of CypA protein to RNAi-treated cells did not restore antiviral activity. A search for additional RNAi targets unearthed TRIMCyp, an RNAi-responsive messenger RNA encoding a TRIM5-CypA fusion protein. TRIMCyp accounts for post-entry restriction of HIV-1 in owl monkeys and blocks HIV-1 infection when transferred to otherwise infectable human or rat cells. It seems that TRIMCyp arose after the divergence of New and Old World primates when a LINE-1 retrotransposon catalysed the insertion of a CypA complementary DNA into the TRIM5 locus. This is the first vertebrate example of a chimaeric gene generated by t...Continue Reading

References

Feb 9, 1978·Nature·W Gilbert
Nov 24, 1994·Nature·E K FrankeJ Luban
Nov 24, 1994·Nature·M ThaliH G Göttlinger
Mar 5, 1999·Science·J V MoranH H Kazazian
Nov 13, 1999·Journal of Virology·W HofmannJ Sodroski
Mar 31, 2000·Nature Genetics·C EsnaultT Heidmann
Feb 7, 2001·Molecular and Cellular Biology·W WeiJ V Moran
May 2, 2001·The EMBO Journal·A ReymondA Ballabio
Mar 9, 2002·Journal of Molecular Biology·Astrid M Roy-EngelMark A Batzer
Mar 23, 2002·Science·Thijn R BrummelkampReuven Agami
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
May 20, 2003·Nature Biotechnology·Aimee L JacksonPeter S Linsley
May 23, 2003·Human Molecular Genetics·Yosuke Ejima, Lichun Yang
Aug 5, 2003·Nature Medicine·Greg J TowersPaul D Bieniasz
Aug 5, 2003·Nature Genetics·Marie DewannieuxThierry Heidmann
Mar 16, 2004·Science·Haig H Kazazian
Jun 1, 1950·Proceedings of the National Academy of Sciences of the United States of America·B McCLINTOCK

❮ Previous
Next ❯

Citations

Sep 23, 2009·Apoptosis : an International Journal on Programmed Cell Death·Manoj Kumar Tripathy, Debashis Mitra
Mar 9, 2006·Current HIV/AIDS Reports·Omar Perez, Thomas J Hope
Dec 24, 2011·Current HIV/AIDS Reports·Zana Lukic, Edward M Campbell
Aug 20, 2010·Immunologic Research·Marisa S Briones, Samson A Chow
Jan 12, 2011·Biochemistry·Andrew M L Lever, Kuan-Teh Jeang
Apr 23, 2011·Nature·Thomas PertelJeremy Luban
Sep 21, 2013·Nature·Caroline GoujonMichael H Malim
Feb 22, 2012·Nature Immunology·Nan Yan, Zhijian J Chen
Oct 22, 2004·Nature Immunology·Paul D Bieniasz
Nov 26, 2008·Nature Reviews. Genetics·Henrik KaessmannManyuan Long
Sep 19, 2009·Nature Reviews. Genetics·Richard Cordaux, Mark A Batzer
Aug 21, 2013·Nature Reviews. Genetics·Sidi ChenManyuan Long
Sep 15, 2012·Nature Reviews. Immunology·Nisha K Duggal, Michael Emerman
Sep 22, 2005·Nature Reviews. Microbiology·Sébastien NisoleAli Saïb
Sep 22, 2009·Nature Structural & Molecular Biology·Amanda J PriceLeo C James
Mar 13, 2012·Nature Structural & Molecular Biology·Matthew E C CainesLeo C James
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 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Greg BrennanShiu-Lok Hu
Feb 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jonathan P Stoye, Melvyn W Yap
Mar 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Theodora HatziioannouPaul D Bieniasz
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
Aug 31, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yiping ZhuGuangxia Gao
Jan 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ray Malfavon-BorjaHarmit Singh Malik
Nov 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jeremy Luban
Dec 21, 2010·The Journal of Biological Chemistry·Pierre V MaillardDidier Trono
Dec 6, 2006·The Journal of Experimental Medicine·Marjorie PionVincent Piguet
Jul 29, 2009·The Journal of Experimental Medicine·Silvia Bolland, Adolfo Garcia-Sastre
Jan 21, 2011·AIDS Research and Human Retroviruses·Jaya Sastri, Edward M Campbell
Aug 19, 2011·AIDS Research and Human Retroviruses·Abdul A Waheed, Eric O Freed
Jun 19, 2007·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·N SongD Durand
Oct 13, 2005·Human Gene Therapy·Greg J Towers
Aug 22, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Stuart Neil, Paul Bieniasz
Mar 18, 2009·Molecular Biology and Evolution·Kenji K Kojima, Norihiro Okada
Aug 14, 2013·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Alex A ComptonMichael Emerman
Aug 14, 2013·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Gkikas MagiorkinisAris Katzourakis
May 4, 2012·Cold Spring Harbor Perspectives in Medicine·Michael H Malim, Paul D Bieniasz
Jul 24, 2010·Genome Research·Henrik Kaessmann

❮ 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.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Sébastien NisoleMelvyn W Yap
Proceedings of the National Academy of Sciences of the United States of America
Zuzana KeckesovaGreg J Towers
Proceedings of the National Academy of Sciences of the United States of America
Melvyn W YapJonathan P Stoye
Proceedings of the National Academy of Sciences of the United States of America
Matthew StremlauJoseph G Sodroski
© 2022 Meta ULC. All rights reserved