Abstract
Old World monkey TRIM5α targets incoming human immunodeficiency virus type 1 (HIV-1) viral capsid, whereas the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC)3 family hypermutate/degrade viral sequences. Here, we show the potentials of simian TRIM5α and APOBEC3G as therapeutic sequences for AIDS gene therapy. Both rhesus and African green monkey (agm) TRIM5α efficiently restrict HIV-1 vectors with divergent Gag from different HIV-1 subtypes. Human T cells genetically engineered to express agm-TRIM5α block or delay HIV-1 replication. Although agm-APOBEC3G expression alone only transiently suppresses HIV-1 replication, co-expression of agm-APOBEC3G and agm-TRIM5α successfully block the virus replication for more than 5 weeks.
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Acknowledgements
We thank Dr Greg J Towers, University College London for reagents and helpful discussion. The following reagents were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: 174xCEM from Dr Peter Cresswell, GHOST(3)R3/X4/R5 from Dr Vineet N KewalRamani and Dr Dan R Littman, p89.6 from Dr Ronald G Collman, pNL4-3 from Dr Malcolm Martin and pc-AGM-APOBEC3G-HA from Dr Nathaniel Landau. This work was supported by the Mayo Foundation (to YI).
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Sakuma, R., Noser, J., Ohmine, S. et al. Inhibition of HIV-1 replication by simian restriction factors, TRIM5α and APOBEC3G. Gene Ther 14, 185–189 (2007). https://doi.org/10.1038/sj.gt.3302852
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DOI: https://doi.org/10.1038/sj.gt.3302852
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