TY  - JOUR
A1  - Jacobs, Graeme
A1  - Bock, Stefanie
A1  - Schuch, Anita
A1  - Moschall, Rebecca
A1  - Schrom, Eva-Maria
A1  - Zahn, Juliane
A1  - Reuter, Christian
A1  - Preiser, Wolfgang
A1  - Rethwilm, Axel
A1  - Engelbrecht, Susan
A1  - Krekau, Thomas
A1  - Bodem, Jochen
T1  - Construction of a high titer Infectious HIV-1 subtype C proviral clone from South Africa
N2  - The Human Immunodeficiency Virus type 1 (HIV-1) subtype C is currently the predominant subtype worldwide. Cell culture studies of Sub-Saharan African subtype C proviral plasmids are hampered by the low replication capacity of the resulting viruses, although viral loads in subtype C infected patients are as high as those from patients with subtype B. Here, we describe the sequencing and construction of a new HIV-1 subtype C proviral clone (pZAC), replicating more than one order of magnitude better than the previous subtype C plasmids. We identify the env-region for being the determinant for the higher viral titers and the pZAC Env to be M-tropic. This higher replication capacity does not lead to a higher cytotoxicity compared to previously described subtype C viruses. In addition, the pZAC Vpu is also shown to be able to down-regulate CD4, but fails to fully counteract CD317.
KW  - HIV
KW  - HIV-1; subtype C; proviral plasmid; viral replication; resistance assays; Vpu; CD317; CD4
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76340
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  -