Identification of residues within the L2 region of rhesus TRIM5alpha that are required for retroviral restriction and cytoplasmic body localization.

Virology
Jaya SastriEdward M Campbell

Abstract

The intracellular restriction factor TRIM5alpha, inhibits infection by numerous retroviruses in a species-specific manner. The best characterized example of this restriction is the TRIM5alpha protein from rhesus macaques (rhTRIM5alpha), which potently inhibits HIV-1 infection. TRIM5alpha localizes to cytoplasmic assemblies of protein referred to as cytoplasmic bodies, though the role that these bodies play in retroviral restriction is unclear. We employed a series of truncation mutants to identify a discrete region, located within the Linker2 region connecting the coiled-coil and B30.2/PRYSPRY domains of TRIM5alpha, which is required for cytoplasmic body localization. Deletion of this region in the context of full-length rhTRIM5alpha abrogates cytoplasmic body localization. Alanine mutagenesis of the residues in this region identifies two stretches of amino acids that are required for both cytoplasmic body localization and retroviral restriction. This work suggests that the determinants that mediate TRIM5alpha localization to cytoplasmic bodies play a requisite role in retroviral restriction.

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Citations

Jun 3, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Edward Campbell
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jacint G SanchezOwen Pornillos
Mar 26, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Max W RichardsonJames L Riley
Sep 3, 2010·The Journal of Biological Chemistry·Seiga OhmineYasuhiro Ikeda
Dec 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Barbie K Ganser-PornillosMark Yeager
Feb 2, 2013·Retrovirology·Zana LukicGloria Arriagada
Dec 13, 2012·Immunogenetics·Chang-Qing YuJian-Hua Zhou
Dec 24, 2011·Current HIV/AIDS Reports·Zana Lukic, Edward M Campbell
Apr 10, 2012·Current Opinion in Virology·Markus G Grütter, Jeremy Luban
Dec 10, 2013·The Journal of General Virology·Azah A TabahLouis M Mansky
Oct 16, 2016·Retrovirology·Ting YuanBinlian Sun
Oct 19, 2017·PLoS Pathogens·Marcin D RoganowiczOwen Pornillos
Jan 21, 2011·AIDS Research and Human Retroviruses·Jaya Sastri, Edward M Campbell
May 30, 2014·Journal of Virology·Jaya SastriEdward M Campbell
Jan 15, 2016·Journal of Virology·Sabrina ImamEdward M Campbell
Mar 29, 2013·Journal of Virology·Sadayuki Ohkura, Jonathan P Stoye
Jun 22, 2016·PLoS Pathogens·Adarsh DharanEdward M Campbell

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