Syntaxin-6 restricts SARS-CoV-2 infection by facilitating virus trafficking to autophagosomes DOI Creative Commons
Hao Sun, Qi Yang, Yecheng Zhang

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

ABSTRACT Despite the diminishing global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus continues to circulate and undergo mutations, posing ongoing challenges for public health. A comprehensive understanding entry mechanisms is crucial managing new epidemic strains. However, cellular processes post-endocytosis remain largely unexplored. This study employs proximity labeling examine proteins near ACE2 post-viral infection identified syntaxin-6 (STX6) as a factor that inhibits SARS-CoV-2 by impeding endocytic release virus. enhances early endosome recruitment STX6. STX6 appears hinder maturation viral particles-laden endosomes into late endosomes, from which could escape. Instead, it promotes trafficking toward autophagy-lysosomal degradation pathway. exhibits broad-spectrum effect against various variants several other viruses enter via endocytosis. We report first time function restrictive in infection. IMPORTANCE Virus step life cycle, exploitation endo-lysosome pathway has been well documented. Meanwhile, intrinsic defense present within cells interferes with entry. host restriction facilitating Notably, antiviral activity diverse employing endocytosis

Язык: Английский

PLSCR1 suppresses SARS-CoV-2 infection by downregulating cell surface ACE2 DOI Creative Commons

Ruiyi Ma,

Xinyi Zhang, Ruonan Li

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

ABSTRACT Type I interferons exert their antiviral effects against SARS-CoV-2 by inducing the expression of interferon-stimulated genes (ISGs), including but not limited to LY6E, CH25H, IFITM2/3, and IFIH1. However, effect underlying mechanisms action most ISGs in infection are yet fully understood. By screening 109 ISG-knockout cell lines, we identify that phospholipid scramblase 1 (PLSCR1), an interferon-inducible protein, acts as a crucial restriction factor infection. Cells lacking PLSCR1 highly susceptible Conversely, overexpression inhibits Depletion enhances cellular entry both pseudotyped authentic SARS-CoV-2. Mechanistically, specifically downregulating plasma membrane ACE2, virus’s receptor, without affecting overall levels ACE2 within cell. As such, unraveled previously unappreciated which exerts its restrictive on These data provide new insights into interplay between host innate immunity shed light novel therapeutics. IMPORTANCE Phospholipid (PLSCR1) has been identified critical In this study, demonstrated inhibited primary receptor for viral entry. Our findings elucidate host-pathogen interaction only deepens our understanding immune response offers potential strategies therapeutic interventions COVID-19.

Язык: Английский

Процитировано

1
Alternative Splicing as a Modulator of the Interferon-Gamma Pathway DOI Open Access
Parul Suri,

Ariana Badalov,

Matteo Ruggiu

и другие.

Cancers, Год журнала: 2025, Номер 17(4), С. 594 - 594

Опубликована: Фев. 10, 2025

Interferon-gamma (IFN-γ) is a critical cytokine that plays pivotal role in immune system regulation. It key mediator of both cellular defense mechanisms and antitumor immunity. As the sole member type II interferon family, IFN-γ modulates responses by activating macrophages, enhancing natural killer cell function, regulating gene expression across multiple processes. Alternative splicing post-transcriptional regulatory mechanism generates mature messenger RNAs from single gene, dramatically increasing proteome diversity without need proportional genome expansion. This process occurs 90–95% human genes, with alternative events allowing for production diverse protein isoforms can have distinct—or even opposing—functional properties. crucial cancer immunology, potentially generating tumor neoepitopes modulating responses. However, how affects IFN-γ’s activity still poorly understood. review explores regulates function upstream regulators downstream effectors IFN-γ, revealing complex response modulation. Key transcription factors signaling molecules pathway are alternatively spliced, alter signaling, to environmental cues. Specific splice variants enhance or inhibit IFN-γ-mediated responses, influencing immunotherapy, autoimmune conditions, infectious disease outcomes. The emerging understanding these offers promising therapeutic strategies manipulating through targeted molecular interventions.

Язык: Английский

Процитировано

0
CRISPR-Cas: a game-changer in vaccine development and the fight against viral infections DOI
Fayu Yang,

Saba R. Aliyari,

Zixiang Zhu

и другие.

Trends in Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Phospholipid scramblase 1: a frontline defense against viral infections DOI Creative Commons
Alina X. Yang, Carmelissa Norbrun, Parand Sorkhdini

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2025, Номер 15

Опубликована: Апрель 3, 2025

Phospholipid scramblase 1 (PLSCR1) is the most studied member of phospholipid protein family. Its main function to catalyze calcium (Ca 2+ )-dependent, ATP-independent, bidirectional and non-specific translocation phospholipids between inner outer leaflets plasma membrane. Additionally, PLSCR1 identified as an interferon-stimulated gene (ISG) with antiviral activities, its expression can be highly induced by all types interferons in various viral infections. Indeed, numerous studies have reported direct activities through interrupting replication processes a variety viruses, including entry severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), nuclear localization influenza A virus (IAV), transactivation human immunodeficiency (HIV), Epstein-Barr (EBV), T-cell leukemia type-1 (HTLV1), cytomegalovirus (HCMV) hepatitis B (HBV). In addition these also regulates endogenous immune components defend against viruses both nonimmune cells. Such include potentiation ISG transcription, activation JAK/STAT pathway, upregulation type 3 interferon receptor (IFN-λR1) recruitment Toll-like 9 (TLR9). This review aims summarize current understanding PLSCR1’s multiple roles frontline defense

Язык: Английский

Процитировано

0
RBM39 shapes innate immunity by controlling the expression of key factors of the interferon response DOI Creative Commons

Teng-Feng Li,

Paul Rothhaar,

Arthur Lang

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 22, 2025

Background and aims The contribution of innate immunity to clearance viral infections the liver, in particular sensing via Toll-like receptor 3 (TLR3), is incompletely understood. We aimed identify factors contributing TLR3 response hepatocytes CRISPR/Cas9 screening. Methods A genome-wide screen on pathway was performed two liver-derived cell lines, followed by siRNA knockdown validation. SiRNA indisulam treatment were used study role RNA-binding motif protein 39 (RBM39) upon poly(I:C) or cytokine infections. Transcriptome, proteome, alternative splicing studied RNA sequencing mass spectrometry depletion RBM39. Results Our identified RBM39, which highly expressed hepatocytes, as an important regulator pathway. Knockdown RBM39 with indisulam, aryl sulfonamide drug targeting for proteasomal degradation, strongly reduced induction interferon-stimulated genes (ISGs) double-stranded (dsRNA) (seq) that transcription and/or key components IRF3, RIG-I, MDA5 affected depletion, along multiple other cellular processes previously. further restrained type I III IFN pathways reducing expression individual subunits STAT1/2. function furthermore not restricted hepatocytes. Conclusion a regulatory factor intrinsic immune signaling. Depletion impaired TLR3, RIG-I/MDA5, responses affecting basal components.

Язык: Английский

Процитировано

0
Syntaxin-6 restricts SARS-CoV-2 infection by facilitating virus trafficking to autophagosomes DOI Creative Commons
Hao Sun, Qi Yang, Yecheng Zhang

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

ABSTRACT Despite the diminishing global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus continues to circulate and undergo mutations, posing ongoing challenges for public health. A comprehensive understanding entry mechanisms is crucial managing new epidemic strains. However, cellular processes post-endocytosis remain largely unexplored. This study employs proximity labeling examine proteins near ACE2 post-viral infection identified syntaxin-6 (STX6) as a factor that inhibits SARS-CoV-2 by impeding endocytic release virus. enhances early endosome recruitment STX6. STX6 appears hinder maturation viral particles-laden endosomes into late endosomes, from which could escape. Instead, it promotes trafficking toward autophagy-lysosomal degradation pathway. exhibits broad-spectrum effect against various variants several other viruses enter via endocytosis. We report first time function restrictive in infection. IMPORTANCE Virus step life cycle, exploitation endo-lysosome pathway has been well documented. Meanwhile, intrinsic defense present within cells interferes with entry. host restriction facilitating Notably, antiviral activity diverse employing endocytosis

Язык: Английский

Процитировано

0