ArticlePLoS pathogens2017
Delineating CD4 dependency of HIV-1: Adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality.
Article in PLoS pathogens, 2017. 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, 35 citations in OpenAlex.
- Natural variations at the E433 site in Env-gp120 β20-β21 cooperate with V2 and gp41 mutations to modulate HIV-1 infectivity.Frontiers in microbiology · 2026Article
- Rapamycin enhances CAR-T control of HIV replication and reservoir elimination in vivo.The Journal of clinical investigation · 2025Article
- In vivo evolution of env in SHIV-AD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Assessing bnAb potency in the context of HIV-1 envelope conformational plasticity.PLoS pathogens · 2025Article
- Role of Monocyte/Macrophages in the Pathogenesis of NeuroHIV.Results and problems in cell differentiation · 2024Review
- Protein overexpression can induce the elongation of cell membrane nanodomains.Biophysical journal · 2023Article
- 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
- Functional and Highly Cross-Linkable HIV-1 Envelope Glycoproteins Enriched in a Pretriggered Conformation.Journal of virology · 2022Article
- HIV-1 entry: Duels between Env and host antiviral transmembrane proteins on the surface of virus particles.Current opinion in virology · 2021Review
- A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruption.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Role of T Lymphocytes in HIV Neuropathogenesis.Current HIV/AIDS reports · 2019Review
- Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies.PLoS pathogens · 2019Article
- Concomitant Enhancement of HIV-1 Replication Potential and Neutralization-Resistance in Concert With Three Adaptive Mutations in Env V1/C2/C4 Domains.Frontiers in microbiology · 2019Article
- Manipulation of Mononuclear Phagocytes by HIV: Implications for Early Transmission Events.Frontiers in immunology · 2019Review
- CCR5 structural plasticity shapes HIV-1 phenotypic properties.PLoS pathogens · 2018Article
- 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
- Phenotypic deficits in the HIV-1 envelope are associated with the maturation of a V2-directed broadly neutralizing antibody lineage.PLoS pathogens · 2018Article
- Functional Stability of HIV-1 Envelope Trimer Affects Accessibility to Broadly Neutralizing Antibodies at Its Apex.Journal of virology · 2017Article
- More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins.Retrovirology · 2017Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A hallmark of HIV-1 infection is the continuously declining number of the virus' predominant target cells, activated CD4+ T cells. With diminishing CD4+ T cell levels, the capacity to utilize alternate cell types and receptors, including cells that express low CD4 receptor levels such as macrophages, thus becomes crucial. To explore evolutionary paths that allow HIV-1 to acquire a wider host cell range by infecting cells with lower CD4 levels, we dissected the evolution of the envelope-CD4 interaction under in vitro culture conditions that mimicked the decline of CD4high target cells, using a prototypic subtype B, R5-tropic strain. Adaptation to CD4low targets proved to severely alter envelope functions including trimer opening as indicated by a higher affinity to CD4 and loss in shielding against neutralizing antibodies. We observed a strikingly decreased infectivity on CD4high target cells, but sustained infectivity on CD4low targets, including macrophages. Intriguingly, the adaptation to CD4low targets altered the kinetic of the entry process, leading to rapid CD4 engagement and an extended transition time between CD4 and CCR5 binding during entry. This phenotype was also observed for certain central nervous system (CNS) derived macrophage-tropic viruses, highlighting that the functional perturbation we defined upon in vitro adaptation to CD4low targets occurs in vivo. Collectively, our findings suggest that CD4low adapted envelopes may exhibit severe deficiencies in entry fitness and shielding early in their evolution. Considering this, adaptation to CD4low targets may preferentially occur in a sheltered and immune-privileged environment such as the CNS to allow fitness restoring compensatory mutations to occur.
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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.