Cellular restriction of retrovirus particle-mediated mRNA transfer

Journal of Virology
Melanie GallaChristopher Baum

Abstract

Analyzing cellular restriction mechanisms provides insight into viral replication strategies, identifies targets for antiviral drug design, and is crucial for the development of novel tools for experimental or therapeutic delivery of genetic information. We have previously shown that retroviral vector mutants that are unable to initiate reverse transcription mediate a transient expression of any sequence which replaces the gag-pol transcription unit, a process we call retrovirus particle-mediated mRNA transfer (RMT). Here, we further examined the mechanism of RMT by testing its sensitivity to cellular restriction factors and short hairpin RNAs (shRNAs). We found that both human TRIM5alpha and, to a lesser extent, Fv1 effectively restrict RMT if the RNA is delivered by a restriction-sensitive capsid. While TRIM5alpha restriction of RMT led to reduced levels of retroviral mRNA in target cells, restriction by Fv1 did not. Treatment with the proteasome inhibitor MG132 partially relieved TRIM5alpha-mediated restriction of RMT. Finally, cells expressing shRNAs specifically targeting the retroviral mRNA inhibited RMT particles, but not reverse-transcribing particles. Retroviral mRNA may thus serve as a translation template if not used...Continue Reading

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Citations

Oct 21, 2011·Human Gene Therapy·Christine VoelkelChristopher Baum
May 26, 2011·Nucleic Acids Research·Melanie GallaChristopher Baum
May 24, 2008·PLoS Pathogens·Christopher James Rold, Christopher Aiken
Oct 14, 2011·Viruses·Tobias MaetzigAxel Schambach
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Feb 9, 2021·Molecular Therapy. Methods & Clinical Development·John R CounsellSimon N Waddington
Jul 3, 2021·Journal of Personalized Medicine·Julia DahlkeAxel Schambach

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