ArticleProceedings of the National Academy of Sciences of the United States of America2014
TIM-family proteins inhibit HIV-1 release.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Multiple Inhibitory Factors Act in the Late Phase of HIV-1 Replication: a Systematic Review of the Literature.Microbiology and molecular biology reviews : MMBR · 2018Pooled it
- Plasma TIM-1 concentration: correlation with cytokines in pulmonary tuberculosis patients and development of a predictive model.BMC pulmonary medicine · 2026Article
- TAM receptor tyrosine kinases as potential mediators of the non-lytic spread of non-enveloped viruses.Biochemical Society transactions · 2026Review
- A novel plasma proteomic signature predicts long-term incident heart failure risk among persons living with HIV.medRxiv : the preprint server for health sciences · 2026Article
- Review
- The membrane-associated ubiquitin ligases MARCH2 and MARCH3 target TIM-1 to limit Zika virus infection.Cellular & molecular immunology · 2025Article
- Review
- Autophagy-mediated downregulation of AXL and TIM-1 promotes sustained Zika virus infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The ability of human TIM1 to bind phosphatidylethanolamine enhances viral uptake and efferocytosis compared to rhesus and mouse orthologs.Journal of virology · 2024Article
- Molecular Basis for the Differential Function of HAVCR1 Mucin Variants.Biomedicines · 2024Article
- Review
- Chikungunya virus release is reduced by TIM-1 receptors through binding of envelope phosphatidylserine.Journal of virology · 2024Article
- Review
- The ability of human TIM1 to bind phosphatidylethanolamine enhances viral uptake and efferocytosis compared to rhesus and mouse orthologs.bioRxiv : the preprint server for biology · 2024Article
- Chikungunya Virus Release is Reduced by TIM-1 Receptors Through Binding of Envelope Phosphatidylserine.bioRxiv : the preprint server for biology · 2024Article
- SERINC5 counters retroviruses and non-retroviruses.Frontiers in cellular and infection microbiology · 2024Review
- Regulation of phospholipid distribution in the lipid bilayer by flippases and scramblases.Nature reviews. Molecular cell biology · 2023Review
- Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells.Communications biology · 2023Article
- HIV-1 release requires Nef-induced caspase activation.PloS one · 2023Article
- Drugging the efferocytosis process: concepts and opportunities.Nature reviews. Drug discovery · 2022Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Accumulating evidence indicates that T-cell immunoglobulin (Ig) and mucin domain (TIM) proteins play critical roles in viral infections. Herein, we report that the TIM-family proteins strongly inhibit HIV-1 release, resulting in diminished viral production and replication. Expression of TIM-1 causes HIV-1 Gag and mature viral particles to accumulate on the plasma membrane. Mutation of the phosphatidylserine (PS) binding sites of TIM-1 abolishes its ability to block HIV-1 release. TIM-1, but to a much lesser extent PS-binding deficient mutants, induces PS flipping onto the cell surface; TIM-1 is also found to be incorporated into HIV-1 virions. Importantly, TIM-1 inhibits HIV-1 replication in CD4-positive Jurkat cells, despite its capability of up-regulating CD4 and promoting HIV-1 entry. In addition to TIM-1, TIM-3 and TIM-4 also block the release of HIV-1, as well as that of murine leukemia virus (MLV) and Ebola virus (EBOV); knockdown of TIM-3 in differentiated monocyte-derived macrophages (MDMs) enhances HIV-1 production. The inhibitory effects of TIM-family proteins on virus release are extended to other PS receptors, such as Axl and RAGE. Overall, our study uncovers a novel ability of TIM-family proteins to block the release of HIV-1 and other viruses by interaction with virion- and cell-associated PS. Our work provides new insights into a virus-cell interaction that is mediated by TIMs and PS receptors.
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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.