A Reliable Phenotype Predictor for Human Immunodeficiency Virus Type 1 Subtype C Based on Envelope V3 Sequences
- 15 May 2006
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 80 (10), 4698-704
- https://doi.org/10.1128/jvi.80.10.4698-4704.2006
Abstract
In human immunodeficiency virus type 1 (HIV-1) subtype B infections, the emergence of viruses able to use CXCR4 as a coreceptor is well documented and associated with accelerated CD4 decline and disease progression. However, in HIV-1 subtype C infections, responsible for more than 50% of global infections, CXCR4 usage is less common, even in individuals with advanced disease. A reliable phenotype prediction method based on genetic sequence analysis could provide a rapid and less expensive approach to identify possible CXCR4 variants and thus increase our understanding of subtype C coreceptor usage. For subtype B V3 loop sequences, genotypic predictors have been developed based on position-specific scoring matrices (PSSM). In this study, we apply this methodology to a training set of 279 subtype C sequences of known phenotypes (228 non-syncytium-inducing [NSI] CCR5 + and 51 SI CXCR4 + sequences) to derive a C-PSSM predictor. Specificity and sensitivity distributions were estimated by combining data set bootstrapping with leave-one-out cross-validation, with random sampling of single sequences from individuals on each bootstrap iteration. The C-PSSM had an estimated specificity of 94% (confidence interval [CI], 92% to 96%) and a sensitivity of 75% (CI, 68% to 82%), which is significantly more sensitive than predictions based on other methods, including a commonly used method based on the presence of positively charged residues (sensitivity, 47.8%). A specificity of 83% and a sensitivity of 83% were achieved with a validation set of 24 SI and 47 NSI unique subtype C sequences. The C-PSSM performs as well on subtype C V3 loops as existing subtype B-specific methods do on subtype B V3 loops. We present bioinformatic evidence that particular sites may influence coreceptor usage differently, depending on the subtype.Keywords
This publication has 25 references indexed in Scilit:
- Preferential Use of CXCR4 by R5X4 Human Immunodeficiency Virus Type 1 Isolates for Infection of Primary LymphocytesJournal of Virology, 2005
- Improved Coreceptor Usage Prediction and GenotypicMonitoring of R5-to-X4 Transition by Motif Analysis of HumanImmunodeficiency Virus Type 1 env V3 LoopSequencesJournal of Virology, 2003
- The CCR5 and CXCR4 Coreceptors Are Both Used by Human Immunodeficiency Virus Type 1 Primary Isolates from Subtype CJournal of Virology, 2003
- Genetic Characterization of Rebounding Human Immunodeficiency Virus Type 1 in Plasma during Multiple Interruptions of Highly Active Antiretroviral TherapyJournal of Virology, 2003
- A New Perspective on V3 Phenotype PredictionAIDS Research and Human Retroviruses, 2003
- Variability in the Human Immunodeficiency Virus Type 1 gp120 Env Protein Linked to Phenotype-Associated Changes in the V3 LoopJournal of Virology, 2002
- Phenotypic Characteristics of Human Immunodeficiency Virus Type 1 Subtype C Isolates of Ethiopian AIDS PatientsAIDS Research and Human Retroviruses, 1999
- The Impact of the Syncytium-Inducing Phenotype of Human Immunodeficiency Virus on Disease ProgressionThe Journal of Infectious Diseases, 1994
- Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp!20 geneNature, 1991
- Sequence logos: a new way to display consensus sequencesNucleic Acids Research, 1990