Inhibition of HIV-1 replication by simian restriction factors, TRIM5|[alpha]| and APOBEC3G

doi:doi:10.1038/sj.gt.3302852

Gene Therapy (2007) 14, 185–189. doi:10.1038/sj.gt.3302852; published online 31 August 2006

Inhibition of HIV-1 replication by simian restriction factors, TRIM5 and APOBEC3G

R Sakuma¹, J A Noser¹, S Ohmine¹ and Y Ikeda¹

¹Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN, USA

Correspondence: Dr Y Ikeda, Molecular Medicine Program, Mayo Clinic College of Medicine, Guggenheim 18-11c, 200 First Street SW, Rochester, MN 55905, USA. E-mail: ikeda.yasuhiro@mayo.edu

Received 30 May 2005; Revised 20 July 2006; Accepted 20 July 2006; Published online 31 August 2006.

Top

Abstract

Old World monkey TRIM5 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 TRIM5 and APOBEC3G as therapeutic sequences for AIDS gene therapy. Both rhesus and African green monkey (agm) TRIM5 efficiently restrict HIV-1 vectors with divergent Gag from different HIV-1 subtypes. Human T cells genetically engineered to express agm-TRIM5 block or delay HIV-1 replication. Although agm-APOBEC3G expression alone only transiently suppresses HIV-1 replication, co-expression of agm-APOBEC3G and agm-TRIM5 successfully block the virus replication for more than 5 weeks.