Foamy retrovirus integrase contains a Pol dimerization domain required for protease activation

J Virol. 2011 Feb;85(4):1655-61. doi: 10.1128/JVI.01873-09. Epub 2010 Dec 1.

Abstract

Unlike orthoretroviruses, foamy retroviruses (FV) synthesize Pol independently of Gag. The FV Pol precursor is cleaved only once between reverse transcriptase (RT) and integrase (IN) by the protease (PR), resulting in a PR-RT and an IN protein. Only the Pol precursor, not the cleaved subunits, is packaged into virions. Like orthoretroviral PRs, FV PR needs to dimerize to be active. Previously, we showed that a Pol mutant lacking IN has defects in PR activity and Pol packaging into virions. We now show that introduction of a leucine zipper (zip) dimerization motif in an IN truncation mutant can restore PR activity, leading to Pol processing in cells. However, these zip mutants neither cleave Gag nor incorporate Pol into virions. We propose that IN is required for Pol dimerization, which is necessary for the creation of a functional PR active site.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Catalytic Domain
  • Cell Line
  • Enzyme Activation
  • Gene Products, pol / chemistry
  • Gene Products, pol / genetics
  • Gene Products, pol / metabolism*
  • Genes, pol
  • Humans
  • Integrases / chemistry*
  • Integrases / genetics
  • Integrases / metabolism
  • Leucine Zippers
  • Mutation
  • Peptide Hydrolases / metabolism*
  • Protein Multimerization
  • Simian foamy virus / enzymology*
  • Simian foamy virus / genetics
  • Simian foamy virus / metabolism

Substances

  • Gene Products, pol
  • Integrases
  • Peptide Hydrolases