title: Genotypic prediction of HIV-1 subtype D tropism.
abstract: BACKGROUND
  HIV-1 subtype D infections have been associated with rapid disease progression and phenotypic assays have shown that CXCR4-using viruses are very prevalent. Recent studies indicate that the genotypic algorithms used routinely to assess HIV-1 tropism may lack accuracy for non-B subtypes. Little is known about the genotypic determinants of HIV-1 subtype D tropism.
  
  
  RESULTS
  We determined the HIV-1 coreceptor usage for 32 patients infected with subtype D by both a recombinant virus phenotypic entry assay and V3-loop sequencing to determine the correlation between them. The sensitivity of the Geno2pheno10 genotypic algorithm was 75% and that of the combined 11/25 and net charge rule was 100% for predicting subtype D CXCR4 usage, but their specificities were poor (54% and 68%). We have identified subtype D determinants in the V3 region associated with CXCR4 use and built a new simple genotypic rule for optimizing the genotypic prediction of HIV-1 subtype D tropism. We validated this algorithm using an independent GenBank data set of 67 subtype D V3 sequences of viruses of known phenotype. The subtype D genotypic algorithm was 68% sensitive and 95% specific for predicting X4 viruses in this data set, approaching the performance of genotypic prediction of HIV-1 subtype B tropism.
  
  
  CONCLUSIONS
  The genotypic determinants of HIV-1 subtype D coreceptor usage are slightly different from those for subtype B viruses. Genotypic predictions based on a subtype D-specific algorithm appear to be preferable for characterizing coreceptor usage in epidemiological and pathophysiological studies.
authors.affiliation: INSERM, U1043, Toulouse, F-31300 France. raymond.s@chu-toulouse.fr
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Raymond
authors.forename: Pierre
authors.initials: P
authors.lastname: Delobel
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Michelle
authors.initials: M
authors.lastname: Cazabat
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Encinas
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruel
authors.forename: Karine
authors.initials: K
authors.lastname: Sandres-Sauné
authors.forename: Bruno
authors.initials: B
authors.lastname: Marchou
authors.forename: Patrice
authors.initials: P
authors.lastname: Massip
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
mesh_terms: D000595:Amino Acid Sequence; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D056189:Viral Tropism
chemical_list: C527276:CXCR4 protein, human; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D011991:Receptors, Virus