Next, the model was applied to predict the phenotype in an independent data set that included V3 sequence, co-receptor usage, and tropism determinations from studies in our laboratory of 24 viral isolates [14; unpublished data] (Table 2). The V3 charge ranged from +2 to +7, whereas actual phenotypes were 1 M-R5, or 2 either D-R5X4 or D-X4. The T-X4 phenotype was not detected among the primary isolates. The model predicted the correct phenotype for 22 of 24 isolates. Only two viruses, 1483-2 and 1907-2 (predicted 1.5, actual 1), were misclassified by the model. Both viruses displayed a rare combination of the M-R5 phenotype with a V3 net charge of +5. Overall, the model to predict phenotype was accurate for over 91% of viruses evaluated.
The predictive value of the model could by enhanced by variables such as the usage of co-receptors other than R5 and X4 or additional genetic determinants within or outside of V3. Nevertheless, the model as currently constituted, is accurate and easily applied to viruses with known V3 genotypes.
The authors would like to thank Jonathon L. Arnold, Brant R. Burkhardt, Paul P. Poole, and Gregory S. Taylor for helpful discussions and for their invaluable assistance in generating the data included in this study.
Daniel R. Briggsa
Daniel L. Tuttleb
John W. Sleasmanab
Maureen M. Goodenowab
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