ArticleAIDS research and human retroviruses2008
Bioinformatic prediction programs underestimate the frequency of CXCR4 usage by R5X4 HIV type 1 in brain and other tissues.
Article in AIDS research and human retroviruses, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Recent Advances in the Molecular and Cellular Mechanisms of gp120-Mediated Neurotoxicity.Cells · 2022Review
- Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.Journal of neurovirology · 2018Article
- Delineating CD4 dependency of HIV-1: Adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality.PLoS pathogens · 2017Article
- Astrocytes as an HIV Reservoir: Mechanism of HIV Infection.Current HIV research · 2016Review
- Article
- HIV-1 target cells in the CNS.Journal of neurovirology · 2015Review
- Effect of lysine to arginine mutagenesis in the V3 loop of HIV-1 gp120 on viral entry efficiency and neutralization.PloS one · 2015Article
- Defining differential genetic signatures in CXCR4- and the CCR5-utilizing HIV-1 co-linear sequences.PloS one · 2014Article
- Dual-mixed HIV-1 coreceptor tropism and HIV-associated neurocognitive deficits.Journal of neurovirology · 2013Article
- Hybrid approach for predicting coreceptor used by HIV-1 from its V3 loop amino acid sequence.PloS one · 2013Article
- Appraising the performance of genotyping tools in the prediction of coreceptor tropism in HIV-1 subtype C viruses.BMC infectious diseases · 2012Article
- Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue.Retrovirology · 2012Article
- R5X4 HIV-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies.Journal of translational medicine · 2011Review
- Editorial neuroAIDS review.AIDS (London, England) · 2011Review
- HIVBrainSeqDB: a database of annotated HIV envelope sequences from brain and other anatomical sites.AIDS research and therapy · 2010Article
- Low frequency of CXCR4-using viruses in patients at the time of primary non-subtype-B HIV-1 infection.Journal of clinical microbiology · 2010Article
- Distinct molecular pathways to X4 tropism for a V3-truncated human immunodeficiency virus type 1 lead to differential coreceptor interactions and sensitivity to a CXCR4 antagonist.Journal of virology · 2010Article
- Comparative analysis of cell culture and prediction algorithms for phenotyping of genetically diverse HIV-1 strains from Cameroon.AIDS research and therapy · 2009Article
- Tissue-specific sequence alterations in the human immunodeficiency virus type 1 envelope favoring CCR5 usage contribute to persistence of dual-tropic virus in the brain.Journal of virology · 2009Article
- Should antiretroviral therapy for HIV infection be tailored for intracerebral penetration?The Netherlands journal of medicine · 2009Review
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
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 (SVM(geno2pheno)) correctly predicted the ability of R5X4 Envs in this dataset to use CXCR4 with 90% accuracy (n = 27/30 predicted to use CXCR4). The PSSM(SINSI), Random Forest, and SVM(genomiac) 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 PSSM(X4R5) matrix and "11/25" rule correctly predicted CXCR4 usage in <50% of the R5X4 Envs (10/30 and 13/30, respectively). Two positions in the V3 loop (19 and 32) influenced coreceptor usage predictions of nine R5X4 Envs from patient MACS1 and a total of 12 Envs from the dataset (40% of unique V3 sequences). These results demonstrate that most predictive algorithms underestimate the frequency of R5X4 HIV-1 in brain and other tissues. SVM(geno2pheno) is the most accurate predictor of CXCR4 usage by R5X4 HIV-1.
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