The prototype foamy virus protease is active independently of the integrase domain
1 Institut für Virologie und Immunbiologie, Universität Würzburg, Versbacher Str. 7, Würzburg, 97078, Germany
2 Lehrstuhl für Struktur und Chemie der Biopolymere & Research Center for Biomacromolecules, Universität Bayreuth, Bayreuth, Germany
Retrovirology 2012, 9:41 doi:10.1186/1742-4690-9-41Published: 10 May 2012
Recently, contradictory results on foamy virus protease activity were published. While our own results indicated that protease activity is regulated by the viral RNA, others suggested that the integrase is involved in the regulation of the protease.
To solve this discrepancy we performed additional experiments showing that the protease-reverse transcriptase (PR-RT) exhibits protease activity in vitro and in vivo, which is independent of the integrase domain. In contrast, Pol incorporation, and therefore PR activity in the viral context, is dependent on the integrase domain. To further analyse the regulation of the protease, we incorporated Pol in viruses by expressing a GagPol fusion protein, which supported near wild-type like infectivity. A GagPR-RT fusion, lacking the integrase domain, also resulted in wild-type like Gag processing, indicating that the integrase is dispensable for viral Gag maturation. Furthermore, we demonstrate with a trans-complementation assays that the PR in the context of the PR-RT protein supports in trans both, viral maturation and infectivity.
We provide evidence that the FV integrase is required for Pol encapsidation and that the FV PR activity is integrase independent. We show that an active PR can be encapsidated in trans as a GagPR-RT fusion protein.