TY - JOUR
T1 - Cross-packaging of genetically distinct mouse and primate retroviral RNAs
AU - Al Dhaheri, Noura Salem
AU - Phillip, Pretty Susan
AU - Ghazawi, Akela
AU - Ali, Jahabar
AU - Beebi, Elizabeth
AU - Jaballah, Soumeya Ali
AU - Rizvi, Tahir A.
N1 - Funding Information:
This work was supported in part by grants from Terry Fox Foundation for Cancer Research (2001/03) and a medical research grant from Sheikh Ham-dan Award for Medical Sciences (MRG-8/2003-2004). We express our thanks to Dr. Didier Trono (Ecole Polytechnique Fédérale de Lausanne, Switzerland) for providing MD.G., Dr. Jaquelin Dudley (University of Texas at Austin, Austin, TX) for providing HYB MTV molecular clone and Mr. Allen Shahin (United Arab Emirates University, Al Ain, UAE) for helping in performing the FACS analysis. We would also like to thank Ms. Suraiya Jahan Aktar (United Arab Emirates University, Al Ain, UAE) for stimulating discussions and critical reading of the manuscript. The authors also wish to thank Ms. Noura Al Shamsi and Ms. Fatima Al Awadi for their assistance in cloning some of the vectors while volunteering in the laboratory.
PY - 2009/7/14
Y1 - 2009/7/14
N2 - Background: The mouse mammary tumor virus (MMTV) is unique from other retroviruses in having multiple viral promoters, which can be regulated by hormones in a tissue specific manner. This unique property has lead to increased interest in studying MMTV replication with the hope of developing MMTV based vectors for human gene therapy. However, it has recently been reported that related as well as unrelated retroviruses can cross-package each other's genome raising safety concerns towards the use of candidate retroviral vectors for human gene therapy. Therefore, using a trans complementation assay, we looked at the ability of MMTV RNA to be cross-packaged and propagated by an unrelated primate Mason-Pfizer monkey virus (MPMV) that has intracellular assembly process similar to that of MMTV. Results: Our results revealed that MMTV and MPMV RNAs could be cross-packaged by the heterologous virus particles reciprocally suggesting that pseudotyping between two genetically distinct retroviruses can take place at the RNA level. However, the cross-packaged RNAs could not be propagated further indicating a block at post-packaging events in the retroviral life cycle. To further confirm that the specificity of cross-packaging was conferred by the packaging sequences (ψ), we cloned the packaging sequences of these viruses on expression plasmids that generated non-viral RNAs. Test of these non-viral RNAs confirmed that the reciprocal cross-packaging was primarily due to the recognition of ψ by the heterologous virus proteins. Conclusion: The results presented in this study strongly argue that MPMV and MMTV are promiscuous in their ability to cross-package each other's genome suggesting potential RNA-protein interactions among divergent retroviral RNAs proposing that these interactions are more complicated than originally thought. Furthermore, these observations raise the possibility that MMTV and MPMV genomes could also co-package providing substrates for exchanging genetic information.
AB - Background: The mouse mammary tumor virus (MMTV) is unique from other retroviruses in having multiple viral promoters, which can be regulated by hormones in a tissue specific manner. This unique property has lead to increased interest in studying MMTV replication with the hope of developing MMTV based vectors for human gene therapy. However, it has recently been reported that related as well as unrelated retroviruses can cross-package each other's genome raising safety concerns towards the use of candidate retroviral vectors for human gene therapy. Therefore, using a trans complementation assay, we looked at the ability of MMTV RNA to be cross-packaged and propagated by an unrelated primate Mason-Pfizer monkey virus (MPMV) that has intracellular assembly process similar to that of MMTV. Results: Our results revealed that MMTV and MPMV RNAs could be cross-packaged by the heterologous virus particles reciprocally suggesting that pseudotyping between two genetically distinct retroviruses can take place at the RNA level. However, the cross-packaged RNAs could not be propagated further indicating a block at post-packaging events in the retroviral life cycle. To further confirm that the specificity of cross-packaging was conferred by the packaging sequences (ψ), we cloned the packaging sequences of these viruses on expression plasmids that generated non-viral RNAs. Test of these non-viral RNAs confirmed that the reciprocal cross-packaging was primarily due to the recognition of ψ by the heterologous virus proteins. Conclusion: The results presented in this study strongly argue that MPMV and MMTV are promiscuous in their ability to cross-package each other's genome suggesting potential RNA-protein interactions among divergent retroviral RNAs proposing that these interactions are more complicated than originally thought. Furthermore, these observations raise the possibility that MMTV and MPMV genomes could also co-package providing substrates for exchanging genetic information.
UR - http://www.scopus.com/inward/record.url?scp=68849092311&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68849092311&partnerID=8YFLogxK
U2 - 10.1186/1742-4690-6-66
DO - 10.1186/1742-4690-6-66
M3 - Article
C2 - 19602292
AN - SCOPUS:68849092311
SN - 1742-4690
VL - 6
JO - Retrovirology
JF - Retrovirology
M1 - 66
ER -