TY  - JOUR
A1  - Spannaus, Ralf
A1  - Hartl, Maximilian J.
A1  - Wöhrl, Birgitta M.
A1  - Rethwilm, Axel
A1  - Bodem, Jochen
T1  - The prototype foamy virus protease is active independently of the integrase domain
N2  - Background: 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. Results: 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. Conclusion: 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.
KW  - Medizin
KW  - Foamy virus
KW  - Regulation of protease activity
KW  - PARM
KW  - Integrase
KW  - GagPol fusion protein
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75370
ER  - 
TY  - JOUR
A1  - Hartl, Maximilian J.
A1  - Bodem, Jochen
A1  - Jochheim, Fabian
A1  - Rethwilm, Axel
A1  - Rösch, Paul
A1  - Wöhrl, Birgitta M.
T1  - Regulation of foamy virus protease activity by viral RNA
JF  - Retrovirology
N2  - No abstract available.
KW  - Virologie
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142248
VL  - 8
IS  - Suppl. 1
ER  - 
TY  - JOUR
A1  - Bodem, Jochen
A1  - Schrom, Eva-Maria
A1  - Moschall, Rebecca
A1  - Hartl, Maximilian J.
A1  - Weitner, Helena
A1  - Fecher, David
A1  - Langemeier, Jörg
A1  - Wöhrl, Brigitta M.
T1  - U1snRNP-mediated suppression of polyadenylation in conjunction with the RNA structure controls poly (A) site selection in foamy viruses
JF  - Retrovirology
N2  - Background

During reverse transcription, retroviruses duplicate the long terminal repeats (LTRs). These identical LTRs carry both promoter regions and functional polyadenylation sites. To express full-length transcripts, retroviruses have to suppress polyadenylation in the 5′LTR and activate polyadenylation in the 3′LTR. Foamy viruses have a unique LTR structure with respect to the location of the major splice donor (MSD), which is located upstream of the polyadenylation signal.

Results

Here, we describe the mechanisms of foamy viruses regulating polyadenylation. We show that binding of the U1 small nuclear ribonucleoprotein (U1snRNP) to the MSD suppresses polyadenylation at the 5′LTR. In contrast, polyadenylation at the 3′LTR is achieved by adoption of a different RNA structure at the MSD region, which blocks U1snRNP binding and furthers RNA cleavage and subsequent polyadenylation.

Conclusion

Recently, it was shown that U1snRNP is able to suppress the usage of intronic cryptic polyadenylation sites in the cellular genome. Foamy viruses take advantage of this surveillance mechanism to suppress premature polyadenylation at the 5’end of their RNA. At the 3’end, Foamy viruses use a secondary structure to presumably block access of U1snRNP and thereby activate polyadenylation at the end of the genome. Our data reveal a contribution of U1snRNP to cellular polyadenylation site selection and to the regulation of gene expression.
KW  - Polyadenylation
KW  - foamy virus
KW  - RNA structure
KW  - Major splice donor
KW  - Polyadenylierung
KW  - RNS
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96085
UR  - http://www.retrovirology.com/content/10/1/55
ER  -