Bioinformatic Prediction Programs Underestimate the Frequency of CXCR4 Usage by R5X4 HIV Type 1 in Brain and Other Tissues
- 1 September 2008
- journal article
- research article
- Published by Mary Ann Liebert Inc in AIDS Research and Human Retroviruses
- Vol. 24 (9), 1215-1220
- https://doi.org/10.1089/aid.2008.0009
Abstract
Human immunodeficiency virus (HIV-1) variants in brain primarily use CCR5 for entry into macrophages and microglia, but dual-tropic (R5X4) HIV-1 has been detected in brain and cerebral spinal fluid (CSF) of some patients with HIV-associated dementia (HAD). Here, we sequenced the gp120 coding region of nine full-length dual-tropic (R5X4) env genes cloned directly from autopsy brain and spleen tissue from an AIDS patient with severe HAD. We then compiled a dataset of 30 unique clade B R5X4 Env V3 sequences from this subject and 16 additional patients (n = 4 brain and 26 lymphoid/blood) and used it to compare the ability of six bioinformatic algorithms to correctly predict CXCR4 usage in R5X4 Envs. Only one program (SVMgeno2pheno) correctly predicted the ability of R5X4 Envs in this dataset to use CXCR4 with 90% accuracy (n = 27/30 predicted to use CXCR4). The PSSMSINSI, Random Forest, and SVMgenomiac programs and the commonly used charge rule correctly predicted CXCR4 usage with >50% accuracy (22/30, 16/30, 19/30, and 25/30, respectively), while the PSSMX4R5 matrix and “11/25” rule correctly predicted CXCR4 usage in geno2pheno is the most accurate predictor of CXCR4 usage by R5X4 HIV-1.This publication has 28 references indexed in Scilit:
- Changes in the V3 region of gp120 contribute to unusually broad coreceptor usage of an HIV-1 isolate from a CCR5 Δ32 heterozygoteVirology, 2007
- Structural Basis for Coreceptor Selectivity by The HIV Type 1 V3 LoopAIDS Research and Human Retroviruses, 2007
- Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusionVirology, 2006
- Genetic and Functional Analysis of R5X4 Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Derived from Two Individuals Homozygous for the CCR5Δ32 AlleleJournal of Virology, 2006
- Env gp120 Sequence Analysis of HIV Type 1 Strains from Diverse Areas of the Brain Shows Preponderance of CCR5 UsageAIDS Research and Human Retroviruses, 2006
- Human Immunodeficiency Virus Type 1 Variants Isolated from Single Plasma Samples Display a Wide Spectrum of Neutralization SensitivityJournal of Virology, 2005
- 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
- Variability in the Human Immunodeficiency Virus Type 1 gp120 Env Protein Linked to Phenotype-Associated Changes in the V3 LoopJournal of Virology, 2002
- Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic resultsAIDS, 1999