TY - JOUR
T1 - Reciprocal cross-packaging of primate lentiviral (HIV-1 and SIV) RNAs by heterologous non-lentiviral MPMV proteins
AU - Al Shamsi, Iman Rashed
AU - Al Dhaheri, Noura Salem
AU - Phillip, Pretty Susan
AU - Mustafa, Farah
AU - Rizvi, Tahir A.
N1 - Funding Information:
This work was supported in part by grants from Terry Fox Funds for Cancer Research (2001/03) and Medical Research Grants from Sheikh Hamdan Award for Medical Sciences ( MRG-26/2001–2002 and MRG-8/2003–2004 ). We express our thanks to Dr. Didier Trono (Ecole Polytechnique Fédérale de Lausanne, Switzerland) for providing CMVΔR8.2 and MD.G. and Dr. Vicente Planelles (University of Utah) for providing SIV pack.
PY - 2011/1
Y1 - 2011/1
N2 - Retroviral RNA packaging signal (ψ) allows the preferential packaging of genomic RNA into virus particles through its interaction with the nucleocapsid protein. The specificity of this interaction came into question when it was shown that primate retroviruses, such as HIV-1, could cross-package RNA from its simian cousin, SIV, and vice versa and that feline retrovirus, FIV could cross-package RNA from a distantly related primate retrovirus, MPMV. To study the generality of this phenomenon further, we determined whether there is a greater packaging restriction between the lentiviral class of retroviruses (HIV-1 and SIV) and a non-lentivirus, MPMV. Our results revealed that primate lentiviral RNAs can be cross-packaged by primate non-lentiviral particles reciprocally, but the cross-packaged RNAs could not be propagated by the heterologous particles. Packaging of RNA in the context of both retroviral vectors as well as non-retroviral RNA containing SIV, HIV, and MPMV packaging determinants by each others proteins further confirmed the specificity of cross-packaging conferred by the packaging sequences. These results reveal the promiscuous nature of retroviral packaging determinants and raise caution against their wide spread presence on retroviral vectors to be used for human gene therapy.
AB - Retroviral RNA packaging signal (ψ) allows the preferential packaging of genomic RNA into virus particles through its interaction with the nucleocapsid protein. The specificity of this interaction came into question when it was shown that primate retroviruses, such as HIV-1, could cross-package RNA from its simian cousin, SIV, and vice versa and that feline retrovirus, FIV could cross-package RNA from a distantly related primate retrovirus, MPMV. To study the generality of this phenomenon further, we determined whether there is a greater packaging restriction between the lentiviral class of retroviruses (HIV-1 and SIV) and a non-lentivirus, MPMV. Our results revealed that primate lentiviral RNAs can be cross-packaged by primate non-lentiviral particles reciprocally, but the cross-packaged RNAs could not be propagated by the heterologous particles. Packaging of RNA in the context of both retroviral vectors as well as non-retroviral RNA containing SIV, HIV, and MPMV packaging determinants by each others proteins further confirmed the specificity of cross-packaging conferred by the packaging sequences. These results reveal the promiscuous nature of retroviral packaging determinants and raise caution against their wide spread presence on retroviral vectors to be used for human gene therapy.
KW - Gene therapy
KW - Human immunodeficiency virus (HIV-1)
KW - Mason-Pfizer monkey virus (MPMV)
KW - RNA cross-packaging
KW - Retroviral vectors
KW - Simian immunodeficiency virus (SIV)
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U2 - 10.1016/j.virusres.2010.09.018
DO - 10.1016/j.virusres.2010.09.018
M3 - Article
C2 - 20875467
AN - SCOPUS:78650548523
SN - 0168-1702
VL - 155
SP - 352
EP - 357
JO - Virus Research
JF - Virus Research
IS - 1
ER -