ArticleProceedings of the National Academy of Sciences of the United States of America2021
HIV envelope tail truncation confers resistance to SERINC5 restriction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. 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, 25 citations in OpenAlex.
- Human Coronavirus 229E Uses ORF4/4a to Antagonize the Host Restriction Factor SERINC5.MedComm · 2026Article
- A tissue-intrinsic mechanism sensitizes HIV-1 particles for TLR-triggered innate immune responses.Nature communications · 2026Article
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- HIV-2 glycoproteins upregulate microRNAs 25 and 93 to counter the MARCH1 antiviral effect in macrophages.Journal of virology · 2025Article
- Characterization of full-length and cytoplasmic tail-truncated envelope glycoproteins incorporated into human immunodeficiency virus (HIV-1) virions and virus-like particles.Journal of virology · 2025Article
- Article
- HIV-2 evades restriction by ZAP through adaptations in the U3 LTR region despite increased CpG levels.Nucleic acids research · 2025Article
- Antiviral factors and their counteraction by HIV-1: many uncovered and more to be discovered.Journal of molecular cell biology · 2024Review
- Disruption of Transmembrane Phosphatidylserine Asymmetry by HIV-1 Incorporated SERINC5 Is Not Responsible for Virus Restriction.Biomolecules · 2024Article
- Beyond Impairment of Virion Infectivity: New Activities of the Anti-HIV Host Cell Factor SERINC5.Viruses · 2024Review
- Role of Viral Envelope Proteins in Determining Susceptibility of Viruses to IFITM Proteins.Viruses · 2024Review
- SERINC5 counters retroviruses and non-retroviruses.Frontiers in cellular and infection microbiology · 2024Review
- Article
- Host cell restriction factors of equine infectious anemia virus.Virologica Sinica · 2023Review
- HIV-1 restriction by SERINC5.Medical microbiology and immunology · 2023Review
- Article
- SERINC5: One antiviral factor to bind them all.PLoS pathogens · 2023Article
- Restriction of Influenza A Virus by SERINC5.mBio · 2022Article
- A Conserved Tryptophan in the Envelope Cytoplasmic Tail Regulates HIV-1 Assembly and Spread.Viruses · 2022Article
- The Emerging Role of the Serine Incorporator Protein Family in Regulating Viral Infection.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
SERINC5 is a potent lentiviral restriction factor that gets incorporated into nascent virions and inhibits viral fusion and infectivity. The envelope glycoprotein (Env) is a key determinant for SERINC restriction, but many aspects of this relationship remain incompletely understood, and the mechanism of SERINC5 restriction remains unresolved. Here, we have used mutants of HIV-1 and HIV-2 to show that truncation of the Env cytoplasmic tail (ΔCT) confers complete resistance of both viruses to SERINC5 and SERINC3 restriction. Critically, fusion of HIV-1 ΔCT virus was not inhibited by SERINC5 incorporation into virions, providing a mechanism to explain how EnvCT truncation allows escape from restriction. Neutralization and inhibitor assays showed ΔCT viruses have an altered Env conformation and fusion kinetics, suggesting that EnvCT truncation dysregulates the processivity of entry, in turn allowing Env to escape targeting by SERINC5. Furthermore, HIV-1 and HIV-2 ΔCT viruses were also resistant to IFITMs, another entry-targeting family of restriction factors. Notably, while the EnvCT is essential for Env incorporation into HIV-1 virions and spreading infection in T cells, HIV-2 does not require the EnvCT. Here, we reveal a mechanism by which human lentiviruses can evade two potent Env-targeting restriction factors but show key differences in the capacity of HIV-1 and HIV-2 to exploit this. Taken together, this study provides insights into the interplay between HIV and entry-targeting restriction factors, revealing viral plasticity toward mechanisms of escape and a key role for the long lentiviral EnvCT in regulating these processes.
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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.