Inhibition of HIV-1 replication by simian restriction factors, TRIM5alpha and APOBEC3G.
Old World monkey TRIM5alpha 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 TRIM5alpha and APOBEC3G as therapeutic sequences for AIDS gene therapy. Both rhesus and African green monkey (agm) TRIM5alpha efficiently restrict HIV-1 vectors with divergent Gag from different HIV-1 subtypes. Human T cells genetically engineered to express agm-TRIM5alpha block or delay HIV-1 replication. Although agm-APOBEC3G expression alone only transiently suppresses HIV-1 replication, co-expression of agm-APOBEC3G and agm-TRIM5alpha successfully block the virus replication for more than 5 weeks.
Sakuma
R
R
Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Noser
J A
JA
Ohmine
S
S
Ikeda
Y
Y
D000818:Animals; D002460:Cell Line; D002520:Cercopithecidae; D004262:DNA Restriction Enzymes / Q000235:genetics*; D015870:Gene Expression; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins / Q000235:genetics; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009700:Nucleoside Deaminases / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology; D014161:Transduction, Genetic / Q000379:methods; D014779:Virus Replication
D012097:Repressor Proteins; D049452:Green Fluorescent Proteins; D004262:DNA Restriction Enzymes; D009700:Nucleoside Deaminases