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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2007-7-12
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pubmed:abstractText |
Human cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) inhibit replication of Vif-deficient human immunodeficiency virus type 1 (HIV-1). HIV-1 Vif overcomes these host restriction factors by binding to them and inducing their proteasomal degradation. The Vif-A3G and Vif-A3F interactions are attractive targets for antiviral drug development because inhibiting the interactions could allow the host defense mechanism to control HIV-1 replication. It was recently reported that the Vif amino acids D(14)RMR(17) are important for functional interaction and degradation of the previously identified Vif-resistant mutant of A3G (D128K-A3G). However, the Vif determinants important for functional interaction with A3G and A3F have not been fully characterized. To identify these determinants, we performed an extensive mutational analysis of HIV-1 Vif. Our analysis revealed two distinct Vif determinants, amino acids Y(40)RHHY(44) and D(14)RMR(17), which are essential for binding to A3G and A3F, respectively. Interestingly, mutation of the A3G-binding region increased Vif's ability to suppress A3F. Vif binding to D128K-A3G was also dependent on the Y(40)RHHY(44) region but not the D(14)RMR(17) region. Consistent with previous observations, subsequent neutralization of the D128K-A3G antiviral activity required substitution of Vif determinant D(14)RMR(17) with SEMQ, similar to the SERQ amino acids in simian immunodeficiency virus SIV(AGM) Vif, which is capable of neutralizing D128K-A3G. These studies are the first to clearly identify two distinct regions of Vif that are critical for independent interactions with A3G and A3F. Pharmacological interference with the Vif-A3G or Vif-A3F interactions could result in potent inhibition of HIV-1 replication by the APOBEC3 proteins.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17522216-10022537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17522216-10074113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17522216-10359577,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17522216-2441266,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17522216-9846577
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/APOBEC3F protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/APOBEC3G protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Alanine,
http://linkedlifedata.com/resource/pubmed/chemical/Cytidine Deaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Cytosine Deaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, vif,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleoside Deaminases,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/vif Gene Products, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-538X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8201-10
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17522216-Alanine,
pubmed-meshheading:17522216-Cell Line,
pubmed-meshheading:17522216-Cytidine Deaminase,
pubmed-meshheading:17522216-Cytosine Deaminase,
pubmed-meshheading:17522216-DNA Mutational Analysis,
pubmed-meshheading:17522216-Gene Products, vif,
pubmed-meshheading:17522216-HIV-1,
pubmed-meshheading:17522216-Humans,
pubmed-meshheading:17522216-Mutagenesis,
pubmed-meshheading:17522216-Nucleoside Deaminases,
pubmed-meshheading:17522216-Protein Binding,
pubmed-meshheading:17522216-Repressor Proteins,
pubmed-meshheading:17522216-vif Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2007
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pubmed:articleTitle |
Identification of two distinct human immunodeficiency virus type 1 Vif determinants critical for interactions with human APOBEC3G and APOBEC3F.
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pubmed:affiliation |
HIV Drug Resistance Program, National Cancer Institute-Frederick, P.O. Box B, Bldg. 535, Rm. 334, Frederick, MD 21702-1201, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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