title: Cross-packaging of genetically distinct mouse and primate retroviral RNAs.
abstract: 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 (psi), 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 psi by the heterologous virus proteins.
  
  
  CONCLUSIONS
  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.
authors: Department of Microbiology & Immunology, Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University (UAEU), Al Ain, UAE. 200301922@uaeu.ac.ae
authors: Noura Salem
authors: NS
authors: Al Dhaheri
authors: Pretty Susan
authors: PS
authors: Phillip
authors: Akela
authors: A
authors: Ghazawi
authors: Jahabar
authors: J
authors: Ali
authors: Elizabeth
authors: E
authors: Beebi
authors: Soumeya Ali
authors: SA
authors: Jaballah
authors: Tahir A
authors: TA
authors: Rizvi
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000502:physiology*; D016093:Mason-Pfizer monkey virus / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D016415:Sequence Alignment; D019065:Virus Assembly
chemical_list: D012367:RNA, Viral; D016601:RNA-Binding Proteins