V3 net charge: additional tool in HIV-1 tropism prediction

Area of Science:

• Virology
• Molecular Biology
• Computational Biology

Background:

• Genotype-based algorithms are crucial for selecting patients for CCR5 inhibitor therapy.
• geno2pheno[coreceptor] (G2P) is a widely used online tool for predicting HIV tropism.
• Accurate tropism prediction is essential for effective treatment strategies.

Purpose of the Study:

• To evaluate if combining G2P predictions with V3 peptide net charge (NC) improves tropism prediction accuracy.
• To investigate the correlation between NC values and HIV tropism.
• To assess the utility of this combined approach for identifying dual/mixed-tropic variants.

Main Methods:

• Analysis of 172 V3 bulk sequences from 143 patients using G2P and NC values.
• Phenotypic tropism assays performed by cloning the complete env gene.
• Stratification of sequences based on agreement between NC values and G2P predictions.

Main Results:

• 61% of G2P-predicted X4 sequences had NC > 5; 76% of G2P-predicted R5 sequences had NC < 4.
• NC values between 4 and 5 were associated with mixed G2P predictions (65% R5, 35% X4).
• Phenotypic assays confirmed that NC values between 4 and 5 correlate with dual/mixed tropism.

Conclusions:

• The combination of G2P and NC values enhances the accuracy of HIV tropism prediction.
• NC values between 4 and 5 are indicative of dual/mixed tropism.
• Improved tropism prediction aids in selecting patients for Maraviroc and understanding coreceptor switching.