ArticleProceedings of the National Academy of Sciences of the United States of America2019
TIM-mediated inhibition of HIV-1 release is antagonized by Nef but potentiated by SERINC proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- IFN-inducible human phospholipid scramblase 1 (PLSCR1) protein restricts HIV-1 infection by inhibiting membrane fusion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- IFN-inducible Human Phospholipid Scramblase 1 (PLSCR1) Protein Restricts HIV-1 Infection by Inhibiting Membrane Fusion.bioRxiv : the preprint server for biology · 2025Article
- SERINC4 is dispensable for male fertility and spermatogenesis in mice.American journal of translational research · 2025Article
- Chikungunya virus release is reduced by TIM-1 receptors through binding of envelope phosphatidylserine.Journal of virology · 2024Article
- Review
- 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
- HIV-1 release requires Nef-induced caspase activation.PloS one · 2023Article
- TMEM106A inhibits enveloped virus release from cell surface.iScience · 2022Article
- The Emerging Role of the Serine Incorporator Protein Family in Regulating Viral Infection.Frontiers in cell and developmental biology · 2022Review
- Japanese Encephalitis Virus NS2B-3 Protein Complex Promotes Cell Apoptosis and Viral Particle Release by Down-Regulating the Expression of AXL.Virologica Sinica · 2021Article
- SERINC proteins potentiate antiviral type I IFN production and proinflammatory signaling pathways.Science signaling · 2021Article
- Enveloped RNA virus utilization of phosphatidylserine receptors: Advantages of exploiting a conserved, widely available mechanism of entry.PLoS pathogens · 2021Review
- Development of a blocker of the universal phosphatidylserine- and phosphatidylethanolamine-dependent viral entry pathways.Virology · 2021Article
- CoelacanthJournal of virology · 2021Article
- SARS-CoV-2 Spreads through Cell-to-Cell Transmission.bioRxiv : the preprint server for biology · 2021Article
- Chikungunya and Zika Viruses: Co-Circulation and the Interplay between Viral Proteins and Host Factors.Pathogens (Basel, Switzerland) · 2021Review
- SERINC5 Inhibits HIV-1 Infectivity by Altering the Conformation of gp120 on HIV-1 Particles.Journal of virology · 2020Article
- Variation in HIV-1 Nef function within and among viral subtypes reveals genetically separable antagonism of SERINC3 and SERINC5.PLoS pathogens · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The T cell Ig and mucin domain (TIM) proteins inhibit release of HIV-1 and other enveloped viruses by interacting with cell- and virion-associated phosphatidylserine (PS). Here, we show that the Nef proteins of HIV-1 and other lentiviruses antagonize TIM-mediated restriction. TIM-1 more potently inhibits the release of Nef-deficient relative to Nef-expressing HIV-1, and ectopic expression of Nef relieves restriction. HIV-1 Nef does not down-regulate the overall level of TIM-1 expression, but promotes its internalization from the plasma membrane and sequesters its expression in intracellular compartments. Notably, Nef mutants defective in modulating membrane protein endocytic trafficking are incapable of antagonizing TIM-mediated inhibition of HIV-1 release. Intriguingly, depletion of SERINC3 or SERINC5 proteins in human peripheral blood mononuclear cells (PBMCs) attenuates TIM-1 restriction of HIV-1 release, in particular that of Nef-deficient viruses. In contrast, coexpression of SERINC3 or SERINC5 increases the expression of TIM-1 on the plasma membrane and potentiates TIM-mediated inhibition of HIV-1 production. Pulse-chase metabolic labeling reveals that the half-life of TIM-1 is extended by SERINC5 from <2 to ∼6 hours, suggesting that SERINC5 stabilizes the expression of TIM-1. Consistent with a role for SERINC protein in potentiating TIM-1 restriction, we find that MLV glycoGag and EIAV S2 proteins, which, like Nef, antagonize SERINC-mediated diminishment of HIV-1 infectivity, also effectively counteract TIM-mediated inhibition of HIV-1 release. Collectively, our work reveals a role of Nef in antagonizing TIM-1 and highlights the complex interplay between Nef and HIV-1 restriction by TIMs and SERINCs.
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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.