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Mutations in Retroviral Genes Associated with Drug Resistance

 

Jennifer Hammond,1 Charles Calef,2 Brendan Larder,3 Raymond Schinazi,4 and John W. Mellors1

 

1 University of Pittsburgh, 603 Parran Hall, Pittsburgh, PA 15261.

2 T10, MS K710, Los Alamos National Laboratory, Los Alamos, NM 87545.

3 Virco, U.K., 162A Cambridge Science Park, Milton Road, Cambridge CB4 4GH, U.K.

4 Emory University/VAMC, 1670 Clairmont Rd., Decatur, GA 30033.

 

Introduction

Drug resistance is the inevitable consequence of incomplete suppression of HIV replication. The rapid replication rate of HIV and its inherent genetic variation have led to the identification of many HIV variants that exhibit altered drug susceptibility. The growing number of drug resistance mutations listed in this revised compilation stands as a testimony to the genetic flexibility of HIV. This updated database lists 148 mutations, of which 45 occur in protease, 70 in reverse transcriptase, and 33 in envelope. Although the tables are quite comprehensive, the reader should be reminded that the mutations described are predominantly found in clade B virus and not in other HIV genotypes. The revised database also includes drug resistance mutations that have been identified for SIV and FIV.

 

In the database the phrase "Enzyme resist." refers to inhibition assays done just with a mutated enzyme. Instead of introducing the mutations into a virus and testing the susceptibility of the mutant virus to a drug, researchers introduce the mutation(s) into the enzyme and determine their effect by running enzyme activity assays. This type of susceptibility testing does not take into account changes in other viral proteins (like gag) that would also help confer resistance, which is the reason for distinguishing enzyme resistance from whole virus resistance.

 

The original tables printed in the 1999 "HIV Molecular Immunology Database" are not reproduced here but their content is available in a searchable database located at our Web.

 

Acknowledgments

The authors would like to gratefully acknowledge their colleagues for assistance in assembling this table. This work was supported in part by the National Institutes of Health and the Department of Veterans Affairs.

last modified: Thu Dec 12 13:38 2013


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