Identification of residues within the L2 region of rhesus TRIM5α that are required for retroviral restriction and cytoplasmic body localization

Jaya Sastri, Christopher O'Connor, Cindy M. Danielson, Michael McRaven, Patricio Perez, Felipe Diaz-Griffero, Edward M. Campbell

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The intracellular restriction factor TRIM5α, inhibits infection by numerous retroviruses in a species-specific manner. The best characterized example of this restriction is the TRIM5α protein from rhesus macaques (rhTRIM5α), which potently inhibits HIV-1 infection. TRIM5α 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 TRIM5α, which is required for cytoplasmic body localization. Deletion of this region in the context of full-length rhTRIM5α 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 TRIM5α localization to cytoplasmic bodies play a requisite role in retroviral restriction.

Original languageEnglish (US)
Pages (from-to)259-266
Number of pages8
JournalVirology
Volume405
Issue number1
DOIs
StatePublished - Sep 2010

Fingerprint

Retroviridae Infections
Macaca mulatta
Mutagenesis
Alanine
HIV Infections
HIV-1
Proteins
Amino Acids
B30.2-SPRY Domain

Keywords

  • HIV-1
  • Multimerization
  • Restriction factor
  • TRIM
  • TRIM5α

ASJC Scopus subject areas

  • Virology

Cite this

Identification of residues within the L2 region of rhesus TRIM5α that are required for retroviral restriction and cytoplasmic body localization. / Sastri, Jaya; O'Connor, Christopher; Danielson, Cindy M.; McRaven, Michael; Perez, Patricio; Diaz-Griffero, Felipe; Campbell, Edward M.

In: Virology, Vol. 405, No. 1, 09.2010, p. 259-266.

Research output: Contribution to journalArticle

Sastri, Jaya ; O'Connor, Christopher ; Danielson, Cindy M. ; McRaven, Michael ; Perez, Patricio ; Diaz-Griffero, Felipe ; Campbell, Edward M. / Identification of residues within the L2 region of rhesus TRIM5α that are required for retroviral restriction and cytoplasmic body localization. In: Virology. 2010 ; Vol. 405, No. 1. pp. 259-266.
@article{ad7b07cba6954a98b012c3901193baba,
title = "Identification of residues within the L2 region of rhesus TRIM5α that are required for retroviral restriction and cytoplasmic body localization",
abstract = "The intracellular restriction factor TRIM5α, inhibits infection by numerous retroviruses in a species-specific manner. The best characterized example of this restriction is the TRIM5α protein from rhesus macaques (rhTRIM5α), which potently inhibits HIV-1 infection. TRIM5α 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 TRIM5α, which is required for cytoplasmic body localization. Deletion of this region in the context of full-length rhTRIM5α 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 TRIM5α localization to cytoplasmic bodies play a requisite role in retroviral restriction.",
keywords = "HIV-1, Multimerization, Restriction factor, TRIM, TRIM5α",
author = "Jaya Sastri and Christopher O'Connor and Danielson, {Cindy M.} and Michael McRaven and Patricio Perez and Felipe Diaz-Griffero and Campbell, {Edward M.}",
year = "2010",
month = "9",
doi = "10.1016/j.virol.2010.06.015",
language = "English (US)",
volume = "405",
pages = "259--266",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Identification of residues within the L2 region of rhesus TRIM5α that are required for retroviral restriction and cytoplasmic body localization

AU - Sastri, Jaya

AU - O'Connor, Christopher

AU - Danielson, Cindy M.

AU - McRaven, Michael

AU - Perez, Patricio

AU - Diaz-Griffero, Felipe

AU - Campbell, Edward M.

PY - 2010/9

Y1 - 2010/9

N2 - The intracellular restriction factor TRIM5α, inhibits infection by numerous retroviruses in a species-specific manner. The best characterized example of this restriction is the TRIM5α protein from rhesus macaques (rhTRIM5α), which potently inhibits HIV-1 infection. TRIM5α 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 TRIM5α, which is required for cytoplasmic body localization. Deletion of this region in the context of full-length rhTRIM5α 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 TRIM5α localization to cytoplasmic bodies play a requisite role in retroviral restriction.

AB - The intracellular restriction factor TRIM5α, inhibits infection by numerous retroviruses in a species-specific manner. The best characterized example of this restriction is the TRIM5α protein from rhesus macaques (rhTRIM5α), which potently inhibits HIV-1 infection. TRIM5α 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 TRIM5α, which is required for cytoplasmic body localization. Deletion of this region in the context of full-length rhTRIM5α 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 TRIM5α localization to cytoplasmic bodies play a requisite role in retroviral restriction.

KW - HIV-1

KW - Multimerization

KW - Restriction factor

KW - TRIM

KW - TRIM5α

UR - http://www.scopus.com/inward/record.url?scp=77955512200&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955512200&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2010.06.015

DO - 10.1016/j.virol.2010.06.015

M3 - Article

VL - 405

SP - 259

EP - 266

JO - Virology

JF - Virology

SN - 0042-6822

IS - 1

ER -