Prediction of HIV type 1 subtype C tropism by genotypic algorithms built from subtype B viruses.
BACKGROUND
Genotypic predictions of HIV-1 tropism could simplify CCR5 antagonist usage. However, the genotypic algorithms built from subtype B viruses could be inadequate for non-B subtypes. We therefore performed paired genotypic and phenotypic determination of subtype C tropism.


METHODS
We studied 52 patients recruited in Malawi and 21 patients recruited in France. We directly sequenced the V3 env region and performed a recombinant virus phenotypic entry assay in parallel.


RESULTS
The Malawi patients had 29% of CXCR4-using subtype C viruses compared with only 5% in the patients from France. For detecting CXCR4-using subtype C viruses, the genotypic rule combining the amino acids at positions 11/25 and the net charge of V3 was 93.3% sensitive and 96.4% specific. The Geno2pheno tool was 86.7% sensitive and 89.1% specific. The WebPSSM tool with the SI/NSI matrix was 80% sensitive and 98.2% specific in its subtype B version and 93.3% sensitive and 81.8% specific in its subtype C version.


CONCLUSIONS
The genotypic determinants of coreceptor usage for HIV-1 subtype C were mainly in V3 and were globally similar to those previously reported for subtype B viruses. The main genotypic algorithms built from subtype B viruses perform well when applied to subtype C viruses.
Raymond
Stéphanie
S
INSERM, U563, Toulouse, F-31300 France.
Delobel
Pierre
P
Mavigner
Maud
M
Ferradini
Laurent
L
Cazabat
Michelle
M
Souyris
Corinne
C
Sandres-Sauné
Karine
K
Pasquier
Christophe
C
Marchou
Bruno
B
Massip
Patrice
P
Izopet
Jacques
J
D000465:Algorithms; D000595:Amino Acid Sequence; D005602:France / Q000453:epidemiology; D015967:Gene Expression Regulation, Viral; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics*; D006801:Humans; D008295:Malawi / Q000453:epidemiology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5; D012680:Sensitivity and Specificity; D056189:Viral Tropism / Q000235:genetics*; D053586:Virus Internalization
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5