ArticleJournal of virology2009
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.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- Neruodevelopmental Outcomes in Preschool Children Living With HIV-1 Subtypes A and D in Uganda.The Pediatric infectious disease journal · 2018Trial
- CSF inflammatory markers and neurocognitive function after addition of maraviroc to monotherapy darunavir/ritonavir in stable HIV patients: the CINAMMON study.Journal of neurovirology · 2018Trial
- A Canadian Survey of Research on HIV-1 Latency-Where Are We Now and Where Are We Heading?Viruses · 2024Review
- Resistance to Human Immunodeficiency Virus 1 Infection Conferred by a Compound CCR5Δ32 and CCR5 C20S Heterozygote.The Journal of infectious diseases · 2023Article
- Cell-to-Cell Transmission of HIV-1 and HIV-2 from Infected Macrophages and Dendritic Cells to CD4+ T Lymphocytes.Viruses · 2023Article
- Uptake of Biotinylated Spermine in Astrocytes: Effect of Cx43 siRNA, HIV-Tat Protein and Polyamine Transport Inhibitor on Polyamine Uptake.Biomolecules · 2021Article
- Longitudinal analysis of subtype C envelope tropism for memory CD4Retrovirology · 2020Article
- CXCR4-Using HIV Strains Predominate in Naive and Central Memory CD4Journal of virology · 2020Article
- Molecular Signatures of HIV-1 Envelope Associated with HIV-Associated Neurocognitive Disorders.Current HIV/AIDS reports · 2018Review
- HIV-associated synaptic degeneration.Molecular brain · 2017Review
- 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
- Frequency and Env determinants of HIV-1 subtype C strains from antiretroviral therapy-naive subjects that display incomplete inhibition by maraviroc.Retrovirology · 2016Article
- A HIV-Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice.Scientific reports · 2016Article
- CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies.Molecular psychiatry · 2016Article
- HIV-1 gp120Bal down-Regulates Phosphorylated NMDA Receptor Subunit 1 in Cortical Neurons via Activation of Glutamate and Chemokine Receptors.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2016Article
- Differences in coreceptor specificity contribute to alternative tropism of HIV-1 subtype C for CD4(+) T-cell subsets, including stem cell memory T-cells.Retrovirology · 2014Article
- Activation of TRPML1 clears intraneuronal Aβ in preclinical models of HIV infection.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Single genome analysis reveals genetic characteristics of Neuroadaptation across HIV-1 envelope.Retrovirology · 2014Article
- Genetic signatures of HIV-1 envelope-mediated bystander apoptosis.The Journal of biological chemistry · 2014Article
- Bioinformatic analysis of HIV-1 entry and pathogenesis.Current HIV research · 2014Review
Corrections and comments
- Erratum issuedSheffief, Shameem [corrected to Sherieff, Shameem]
Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Most human immunodeficiency virus type 1 (HIV-1) strains isolated from the brain use CCR5 for entry into macrophages and microglia. Strains that use both CCR5 and CXCR4 for entry (R5X4 strains) have been identified in the brains of some individuals, but mechanisms underlying the persistence of R5X4 viruses compartmentalized between the brain and other tissue reservoirs are unknown. Here, we characterized changes in the HIV-1 envelope (Env) that enhance the tropism of R5X4 variants for brain or lymphoid tissue. R5X4 Envs derived from the brains of two individuals had enhanced CCR5 usage in fusion assays compared to R5X4 Envs derived from matched spleen or blood, which was associated with reduced dependence on specific residues in the CCR5 N terminus and extracellular loop 1 (ECL1) and ECL3 regions. In contrast, spleen/blood-derived Envs had enhanced CXCR4 usage compared to brain-derived Envs, which was associated with reduced dependence on residues in the CXCR4 N terminus and ECL2 region. Consequently, brain-derived Envs had preferential CCR5 usage for HIV-1 entry into the JC53 cell line, could use either CCR5 or CXCR4 for entry into monocyte-derived macrophages (MDM), and could use CCR5 (albeit inefficiently) for entry into peripheral blood mononuclear cells (PBMC), whereas the entry of spleen-derived Envs was CXCR4 dependent in all three cell types. Mutagenesis studies of Env amino acid variants influencing coreceptor usage showed that S306 in the gp120 V3 region of brain-derived Envs reduces dependence on the CCR5 N terminus and enhances CCR5 usage for HIV-1 entry into PBMC and MDM, whereas R306 in spleen-derived Envs reduces dependence on the CXCR4 N terminus and confers the CXCR4 restricted phenotype. These results identify mechanisms underlying R5X4 HIV-1 persistence in different tissue reservoirs. Tissue-specific changes in the gp120 V3 region that increase the efficiency of CCR5 or CXCR4 usage, and thereby influence coreceptor preference, may enhance the tropism of R5X4 strains for CCR5-expressing macrophage lineage cells in the brain and CXCR4-expressing T cells in lymphoid tissues, respectively.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.