PMID- 16842218
OWN - NLM
STAT- MEDLINE
DCOM- 20060829
LR  - 20190911
IS  - 1389-4501 (Print)
IS  - 1389-4501 (Linking)
VI  - 7
IP  - 7
DP  - 2006 Jul
TI  - Reversal of HIV drug resistance and novel strategies to curb HIV infection: the 
      viral infectivity factor Vif as a target and tool of therapy.
PG  - 881-5
AB  - Due to the high genetic variability of human immunodeficiency virus (HIV), 
      treatment of AIDS (acquired immunodeficiency syndrome) patients with inhibitors 
      of reverse trancriptase (RT) and drugs blocking the viral protease regularly 
      results in the accumulation of drug resistant HIV variants and treatment failure. 
      The sensitivity of clinically derived resistant HIV-1 strains to nucleotide RT 
      inhibitors could be restored, however, in several laboratories by pharmacological 
      depletion of the appropriate endogenous deoxynucleotide triphosphate (dNTP), and 
      such a manipulation (induction of dCTP pool imbalance during reverse 
      transcription in the presence of a non-nucleoside RT inhibitor) altered the 
      mutation spectrum of the HIV-1 genome, resulting in a lower level of HIV 
      resistance to certain drugs. The cytoplasmic single-stranded DNA cytidine 
      deaminases APOBEC3G and APOBEC3F block HIV replication by introducing premature 
      stop codons into the viral genome. We suggest that the resulting crippled, 
      defective HIV (dHIV) variants could interfere with replication of "wild type" 
      viruses and curbe disese progression in long term non-progressor individuals. 
      Vif, an accessory protein encoded by HIV, counteracts APOBEC3G/F action. We 
      speculate that small molecule inhibitors of Vif could permit lethal or sublethal 
      mutagenesis of HIV genomes. We suggest that an artificial dHIV construct carrying 
      a mutated vif gene (coding for a Vif protein unable to block APOBEC3G/F) could 
      have a therapeutic effect as well in HIV infected individuals and AIDS patients.
FAU - Mezei, M
AU  - Mezei M
AD  - Microbiological Research Group, National Center for Epidemiology, H-1529 
      Budapest, Piheno u. 1, Hungary.
FAU - Minarovits, J
AU  - Minarovits J
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Targets
JT  - Current drug targets
JID - 100960531
RN  - 0 (AIDS Vaccines)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Gene Products, vif)
RN  - 0 (vif Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - AIDS Vaccines/administration & dosage/therapeutic use
MH  - Anti-HIV Agents/pharmacology/therapeutic use
MH  - Drug Resistance, Multiple, Viral/*drug effects/genetics
MH  - Gene Products, vif/*antagonists & inhibitors/genetics/metabolism
MH  - Genetic Therapy/methods
MH  - HIV/drug effects/genetics/immunology
MH  - HIV Infections/genetics/immunology/*therapy
MH  - Humans
MH  - Immunotherapy, Active/methods
MH  - vif Gene Products, Human Immunodeficiency Virus
RF  - 50
EDAT- 2006/07/18 09:00
MHDA- 2006/08/30 09:00
CRDT- 2006/07/18 09:00
PHST- 2006/07/18 09:00 [pubmed]
PHST- 2006/08/30 09:00 [medline]
PHST- 2006/07/18 09:00 [entrez]
AID - 10.2174/138945006777709610 [doi]
PST - ppublish
SO  - Curr Drug Targets. 2006 Jul;7(7):881-5. doi: 10.2174/138945006777709610.