Cellular interactions of virion infectivity factor (Vif) as potential therapeutic targets: APOBEC3G and more?
Vif is an HIV accessory protein whose primary function is to negate the action of APOBEC3G, a naturally occurring cellular inhibitor of HIV replication. Vif acts by binding to APOBEC3G, inducing its protein degradation within infected cells and reducing its levels in progeny virions. Interventions that interfere with the Vif-APOBEC3G interaction, raise intracellular or virion associated levels of APOBEC3G, or reduce intracellular levels of Vif, all could hold promise as potential therapeutic approaches aimed at enhancing the cells innate antiviral activity. Levels of APOBEC3G might be increased or Vif levels decreased, by strategies targeting protein synthesis, protein degradation or cellular localisation and function, and properties of APOBEC3G and Vif relevant to these strategies are discussed. Recent data have suggested that Vif may have other mechanisms of action apart from the above activities against APOBEC3G, including effects against other anti-viral mechanisms independent of APOBEC3G cytidine deaminase activity. In addition to interaction with APOBEC3G, Vif may have other accessory functions, which are discussed in relation to potential therapies that may affect multiple stages of the HIV life cycle. Future development of strategies that combine enhancement of APBOEC3G functional with inhibition of multiple Vif functions may become useful tools for HIV therapy.
Carr
J M
JM
Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Adelaide, South Australia, 5000. jill.carr@imvs.sa.gov.au
Davis
A J
AJ
Feng
F
F
Burrell
C J
CJ
Li
P
P
D000071480:APOBEC-3G Deaminase; D000123:Acetyltransferases / Q000502:physiology; D019380:Anti-HIV Agents / Q000494:pharmacology*; D003564:Cytidine Deaminase; D024882:Drug Resistance, Viral; D016346:Gene Products, vif / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D009700:Nucleoside Deaminases / Q000502:physiology*; D010641:Phenotype; D011485:Protein Binding; D051572:Proto-Oncogene Proteins c-hck / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases; D019065:Virus Assembly; D014779:Virus Replication; D000099228:Diamine N-Acetyltransferase
D000071480:APOBEC-3G Deaminase; D000123:Acetyltransferases; D019380:Anti-HIV Agents; D003564:Cytidine Deaminase; D016346:Gene Products, vif; D016333:HIV Protease; D047908:Intracellular Signaling Peptides and Proteins; D009700:Nucleoside Deaminases; D051572:Proto-Oncogene Proteins c-hck; D012097:Repressor Proteins; D044767:Ubiquitin-Protein Ligases; D000099228:Diamine N-Acetyltransferase; C458527:RNF216 protein, human; C496631:HCK protein, human; C464924:APOBEC3G protein, human