Improved prediction of HIV-1 coreceptor usage with sequence information from the second hypervariable loop of gp120.

摘要

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) uses the CD4 receptor and a coreceptor to gain cell entry. Coreceptor usage is mainly determined by the V3 loop of gp120. Therefore, coreceptor usage is currently inferred from the genotype on the basis of V3 alone. However, several mutations outside V3 have been repeatedly reported to influence coreceptor usage. In this study, the impact of the V2 loop on coreceptor usage prediction was analyzed. METHODS: Sequences were analyzed for differences at specific positions and position-independent features with the Fisher exact and Student t tests. Prediction models were trained with support vector machines and evaluated in cross-validation on clonal data. Models trained on the clonal data set were validated on 2 clinical data sets. RESULTS: Several mutations and position-independent features within V2 were statistically significantly different between R5 and X4 viruses. Cross-validation on the clonal data set revealed a statistically significantly higher area under the receiver operating characteristic curve if features of both loops were used, compared with those using only V2 or V3 alone. Similar results were found with clinically derived data sets. CONCLUSIONS: The ability of the V2 loop to improve coreceptor usage prediction has been shown in a large data set. Utilization of this information can lead to considerable improvements in the prediction of coreceptor use both on clonal data sets and on clinically derived data sets.