The contribution of RING and B-box 2 domains to retroviral restriction mediated by monkey TRIM5α

Hassan Javanbakht, Felipe Diaz-Griffero, Matthew Stremlau, Zhihai Si, Joseph Sodroski

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

TRIM5α is a cytoplasmic protein that mediates a post-entry block to infection by some retroviruses. TRIM5α contains a tripartite motif (TRIM), which includes RING, B-box 2, and coiled-coil domains, and a C-terminal B30.2 (SPRY) domain. We investigated the contribution of the RING and B-box 2 domains to the antiretroviral activity of rhesus monkey TRIM5α (TRIM5αrh), which potently restricts infection by human immunodeficiency virus, type 1 (HIV-1) and simian immunodeficiency virus of African green monkeys (SIVagm). Disruption of the RING domain caused mislocalization of TRIM5αrh so that the cytoplasmic level of the protein was decreased compared with that of the wild-type protein. Nonetheless, partial ability to restrict HIV-1 and SIVagm was retained by the RING domain mutants. By contrast, although TRIM5α rh mutants with disrupted B-box 2 domains were efficiently expressed and correctly localized to the cytoplasm, antiretroviral activity was absent. The B-box 2 mutants colocalized and associated with wild-type TRIM5αrh and exerted dominant-negative effects on the antiretroviral activity of the wild-type protein. Taken together with other data, these results indicate that functionally defective TRIM5α rh molecules that retain a coiled coil can act as dominant-negative inhibitors of wild-type TRIM5αrh function. The RING domain of TRIM5αrh is not absolutely required for retrovirus restriction but can influence cytoplasmic levels of the protein and thus indirectly alter function. The B-box 2 domain, by contrast, appears to be essential for efficient retrovirus restriction.

Original languageEnglish (US)
Pages (from-to)26933-26940
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number29
DOIs
StatePublished - Jul 22 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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