Open AccessFoamy Retrovirus Integrase Contains a Pol Dimerization Domain Required for Protease Activation
Author(s) -
Eun Gyung Lee,
Jacqueline Roy,
Dana L. Jackson,
Pancreas Clark,
Paul L. Boyer,
Stephen H. Hughes,
Maxine L. Linial
Publication year - 2011
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01873-09
Subject(s) - integrase , processivity , biology , retrovirus , leucine zipper , mutant , reverse transcriptase , protease , microbiology and biotechnology , virology , rna directed dna polymerase , enzyme , polymerase , peptide sequence , biochemistry , virus , rna , gene , human immunodeficiency virus (hiv)
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.