Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor

Matthew Stremlau, Michel Perron, Mark Lee, Yuan Li, Byeongwoon Song, Hassan Javanbakht, Felipe Diaz-Griffero, Donovan J. Anderson, Wesley I. Sundquist, Joseph Sodroski

Research output: Contribution to journalArticle

511 Citations (Scopus)

Abstract

The host restriction factor TRIM5α mediates species-specific, early blocks to retrovirus infection; susceptibility to these blocks is determined by viral capsid sequences. Here we demonstrate that TRIM5α variants from Old World monkeys specifically associate with the HIV type 1 (HIV-1) capsid and that this interaction depends on the TRIM5α B30.2 domain. Human and New World monkey TRIM5α proteins associated less efficiently with the HIV-1 capsid, accounting for the lack of restriction in cells of these species. After infection, the expression of a restricting TRIM5α in the target cells correlated with a decrease in the amount of particulate capsid in the cytosol. In some cases, this loss of particulate capsid was accompanied by a detectable increase in soluble capsid protein. Inhibiting the proteasome did not abrogate restriction. Thus, TRIM5α restricts retroviral infection by specifically recognizing the capsid and promoting its rapid, premature disassembly.

Original languageEnglish (US)
Pages (from-to)5514-5519
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number14
DOIs
StatePublished - Apr 4 2006
Externally publishedYes

Fingerprint

Capsid
HIV-1
Retroviridae Infections
Platyrrhini
Cercopithecidae
Capsid Proteins
Proteasome Endopeptidase Complex
Infection
Cytosol
Proteins

Keywords

  • B30.2(SPRY) domain
  • HIV-1
  • Innate immunity
  • RING, B-box, and coiled-coil protein
  • Tripartite motif

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor. / Stremlau, Matthew; Perron, Michel; Lee, Mark; Li, Yuan; Song, Byeongwoon; Javanbakht, Hassan; Diaz-Griffero, Felipe; Anderson, Donovan J.; Sundquist, Wesley I.; Sodroski, Joseph.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 14, 04.04.2006, p. 5514-5519.

Research output: Contribution to journalArticle

Stremlau, Matthew ; Perron, Michel ; Lee, Mark ; Li, Yuan ; Song, Byeongwoon ; Javanbakht, Hassan ; Diaz-Griffero, Felipe ; Anderson, Donovan J. ; Sundquist, Wesley I. ; Sodroski, Joseph. / Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 14. pp. 5514-5519.
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