Table 2.
Phenotypic and Genotypic Characterization of the Biological Viral Clones Obtained at Baseline and End of Maraviroc Treatment
| Genotypeb | |||||
|---|---|---|---|---|---|
| Biological viral clones | Phenotypea | geno2pheno | PSSM | FPR %c | Amino acid sequence of the env V3 loop |
| Baseline | CTRPNNNTRKSIHIGPGRAFYTTGEIIGDIRQAYCd | ||||
| CL_0.01 | R5X4 | R5 | R5 | 15.6 | .............L.L..RW.A.-N......K... |
| CL_0.02 | R5X4 | R5 | R5 | 15.6 | .............L.L..RW.A.-N......K... |
| CL_0.03e | R5X4 | R5 | R5 | 15.6 | .............L.L..RW.A.-N......K... |
| CL_0.04 | R5X4 | R5 | R5 | 15.6 | .............L.L..RW.A.-N......K... |
| T=16 months | |||||
| CL_16.01e | R5N | R5 | R5 | 9 | .I........G........W.A.-D......K... |
| CL_16.02 | R5N | R5 | R5 | 9 | .I........G........W.A.-D......K... |
| CL_16.03 | R5N | R5 | R5 | 9 | .I........G........W.A.-D......K... |
| CL_16.04 | R5B (FC2) | R5 | R5 | 9 | .I........G........W.A.-D......K... |
| CL_16.05 | R5B (FC2) | R5 | R5 | 9 | .I........G........W.A.-D......K... |
| CL_16.06 | R5B (FC4) | R5 | R5 | 9 | .I........G........W.A.-D......K... |
| CL_16.07 | R5X4 | X4 | X4 | 1.7 | .........RD..L.L..RW.A.-K.V....K... |
| CL_16.08e | R5X4 | X4 | X4 | 1.7 | .........RD..L.L..RW.A.-K.V....K... |
| CL_16.09 | X4 | X4 | X4 | 1.7 | .........RD..L.L..RW.A.-K.V....K... |
| CL_16.10e | X4 | X4 | X4 | 1.7 | .........RD..L.L..RW.A.-K......K... |
| CL_16.11 | X4 | X4 | X4 | 1.7 | .........RD..L.L..RW.A.-K.V....K... |
Phenotype of each biological viral clone was determined in the cell line U87.CD4 expressing the chemochine receptors CCR5 or CXCR4 or the chimeric receptors FC 2, 4b, 5, 6, and 7. R5N stays for narrow, which means that the viral clones were able to use only the wild-type CCR5 as coreceptor, whereas R5B stays for broad, which means that the virus was able to use at least one of the chimeric receptors in addition to CCR5. The use of the chimeric receptor is indicated in parentheses.
The predicted phenotype was obtained by the geno2pheno approach setting the FPR cut off at 2–5.75% and by position-specific scoring matrices (PSSM).
FPR means false positive rate and is expressed in %.
Amino acid sequences are aligned to the HIV-1 subtype B consensus sequence. (.) means identical amino acid, (-) lacking amino acid, or otherwise the alternative amino acid is indicated.
Sensitivity to RANTES and MVC of the indicated viral clones has been evaluated in a PBMC-based assay. Clone CL_16.01 is the only one sensitive to RANTES (ID50 7.8 ng/ml) and MVC (ID50 14 nM).