ArticleJournal of virology2002
Increased CCR5 affinity and reduced CCR5/CD4 dependence of a neurovirulent primary human immunodeficiency virus type 1 isolate.
Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed, 216 citations in OpenAlex.
- Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection.PLoS pathogens · 2015Trial
- Changes in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection.PLoS pathogens · 2024Article
- Molecular Role of HIV-1 Human Receptors (CCL5-CCR5 Axis) in neuroAIDS: A Systematic Review.Microorganisms · 2024Review
- Review
- Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology.The Journal of infectious diseases · 2023Article
- Evolution Driven By A Varying Host Environment Selects For Distinct HIV-1 Entry Phenotypes and Other Informative Variants.Frontiers in virology (Lausanne, Switzerland) · 2023Article
- Animal models for studies of HIV-1 brain reservoirs.Journal of leukocyte biology · 2022Review
- Shock and kill within the CNS: A promising HIV eradication approach?Journal of leukocyte biology · 2022Review
- HIV-1 cell-to-cell spread overcomes the virus entry block of non-macrophage-tropic strains in macrophages.PLoS pathogens · 2022Article
- Dopamine Levels Induced by Substance Abuse Alter Efficacy of Maraviroc and Expression of CCR5 Conformations on Myeloid Cells: Implications for NeuroHIV.Frontiers in immunology · 2021Article
- Review
- Nanoparticles presenting clusters of CD4 expose a universal vulnerability of HIV-1 by mimicking target cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- HIV-1 Central Nervous System Compartmentalization and Cytokine Interplay in Non-Subtype B HIV-1 Infections in Nigeria and Malawi.AIDS research and human retroviruses · 2020Article
- What can characterization of cerebrospinal fluid escape populations teach us about viral reservoirs in the central nervous system?AIDS (London, England) · 2019Review
- Cross-talk between microglia and neurons regulates HIV latency.PLoS pathogens · 2019Article
- Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- CROI 2019: neurologic complications of HIV disease.Topics in antiviral medicine · 2019Review
- No detection of CD4-independent human immunodeficiency virus 1 envelope glycoproteins in brain tissue of patients with or without neurological complications.Archives of virology · 2019Article
- CCR5 structural plasticity shapes HIV-1 phenotypic properties.PLoS pathogens · 2018Article
- Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Most human immunodeficiency virus type 1 (HIV-1) viruses in the brain use CCR5 as the principal coreceptor for entry into a cell. However, additional phenotypic characteristics are necessary for HIV-1 neurotropism. Furthermore, neurotropic strains are not necessarily neurovirulent. To better understand the determinants of HIV-1 neurovirulence, we isolated viruses from brain tissue samples from three AIDS patients with dementia and HIV-1 encephalitis and analyzed their ability to induce syncytia in monocyte-derived macrophages (MDM) and neuronal apoptosis in primary brain cultures. Two R5X4 viruses (MACS1-br and MACS1-spln) were highly fusogenic in MDM and induced neuronal apoptosis. The R5 viruses UK1-br and MACS2-br are both neurotropic. However, only UK1-br induced high levels of fusion in MDM and neuronal apoptosis. Full-length Env clones from UK1-br required lower CCR5 and CD4 levels than Env clones from MACS2-br to function efficiently in cell-to-cell fusion and single-round infection assays. UK1-br Envs also had a greater affinity for CCR5 than MACS2-br Envs in binding assays. Relatively high levels of UK1-br and MACS2-br Envs bound to CCR5 in the absence of soluble CD4. However, these Envs could not mediate CD4-independent infection, and MACS2-br Envs were unable to mediate fusion or infection in cells expressing low levels of CD4. The UK1-br virus was more resistant than MACS2-br to inhibition by the CCR5-targeted inhibitors TAK-779 and Sch-C. UK1-br was more sensitive than MACS2-br to neutralization by monoclonal antibodies (2F5 and immunoglobulin G1b12 [IgG1b12]) and CD4-IgG2. These results predict the presence of HIV-1 variants with increased CCR5 affinity and reduced dependence on CCR5 and CD4 in the brains of some AIDS patients with central nervous system disease and suggest that R5 variants with increased CCR5 affinity may represent a pathogenic viral phenotype contributing to the neurodegenerative manifestations of AIDS.
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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.