Phospholipid Scramblase 1 (PLSCR1) Regulates Interferon-Lambda Receptor 1 (IFN-lambdaR1) and IFN-lambda Signaling in Influenza A Virus (IAV) Infection DOI Creative Commons
Alina X. Yang,

Lisa Ramos-Rodriguez,

Parand Sorkhdini

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Phospholipid scramblase 1 (PLSCR1) is an antiviral interferon-stimulated gene (ISG) that has several known anti-influenza functions such as interfering with viral nuclear import, regulating toll-like receptor (TLR) 9 and potentiating the expression of other ISGs. However, exact mechanisms anti-flu activity PLSCR1 in relation to its compartment enzymatic activity, molecular cellular involved have not been completely explored. Moreover, only limited animal models studied delineate role at tissue level influenza infections. We hypothesize protects hosts against IAV infection by type 3 interferon (IFN-λ) signaling pathways. Our results showed Plscr1 was highly induced

Language: Английский

Interferon- γ and infectious diseases: Lessons and prospects DOI
Jean‐Laurent Casanova, John D. MacMicking, Carl Nathan

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6693)

Published: April 18, 2024

Infectious diseases continue to claim many lives. Prevention of morbidity and mortality from these would benefit not just new medicines vaccines but also a better understanding what constitutes protective immunity. Among the major immune signals that mobilize host defense against infection is interferon-γ (IFN-γ), protein secreted by lymphocytes. Forty years ago, IFN-γ was identified as macrophage-activating factor, and, in recent years, there has been resurgent interest biology its role human defense. Here we assess current IFN-γ, revisit designation an "interferon," weigh prospects therapeutic globally pervasive microbial pathogens.

Language: Английский

Citations

44
Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection DOI
Shiwei Zhu, Clinton J. Bradfield, Agnieszka Mamińska

et al.

Science, Journal Year: 2024, Volume and Issue: 383(6686)

Published: Feb. 29, 2024

All living organisms deploy cell-autonomous defenses to combat infection. In plants and animals, large supramolecular complexes often activate immune proteins for protection. this work, we resolved the native structure of a massive host-defense complex that polymerizes 30,000 guanylate-binding (GBPs) over surface gram-negative bacteria inside human cells. Construction giant nanomachine took several minutes remained stable hours, required guanosine triphosphate hydrolysis, recruited four GBPs plus caspase-4 Gasdermin D as cytokine cell death signaling platform. Cryo-electron tomography suggests GBP1 can adopt an extended conformation bacterial membrane insertion establish platform, triggering lipopolysaccharide release activated coassembled caspase-4. Our "open conformer" model provides dynamic view into how defense mobilizes innate immunity

Language: Английский

Citations

17
Bacterial-induced or passively administered interferon gamma conditions the lung for early control of SARS-CoV-2 DOI Creative Commons
Kerry L. Hilligan, Sivaranjani Namasivayam, Chad S. Clancy

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 12, 2023

Type-1 and type-3 interferons (IFNs) are important for control of viral replication; however, less is known about the role Type-2 IFN (IFNγ) in anti-viral immunity. We previously observed that lung infection with Mycobacterium bovis BCG achieved though intravenous (iv) administration provides strong protection against SARS-CoV-2 mice yet drives low levels type-1 IFNs but robust IFNγ. Here we examine ongoing IFNγ responses to pre-established bacterial on disease outcomes two murine models. report required iv induced reduction pulmonary loads, an outcome dependent receptor expression by non-hematopoietic cells. Importantly, show prompts epithelial cells upregulate IFN-stimulated genes reported activity IFNγ-dependent manner, suggesting a possible mechanism protection. Finally, confirm properties demonstrating recombinant cytokine itself challenge when administered intranasally. Together, our data response within protective infection, concurrent or recent infections drive may limit pathogenesis supporting prophylactic uses COVID-19 management.

Language: Английский

Citations

26
TiO2-based photocatalysts for emerging gaseous pollutants removal: From photocatalysts to reactors design DOI

Chinnadurai Ayappan,

Ruimin Xing, Xintong Zhang

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 515, P. 215960 - 215960

Published: May 23, 2024

Language: Английский

Citations

13
PLSCR1 suppresses SARS-CoV-2 infection by downregulating cell surface ACE2 DOI Creative Commons

Ruiyi Ma,

Xinyi Zhang, Ruonan Li

et al.

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

Citations

1
Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination DOI
Lizhen Wu, Anurupa Devi Yadavalli,

Filip Šenigl

et al.

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
The antiviral state of the cell: lessons from SARS-CoV-2 DOI
Jérémie Le Pen, Charles M. Rice

Current Opinion in Immunology, Journal Year: 2024, Volume and Issue: 87, P. 102426 - 102426

Published: April 1, 2024

Language: Английский

Citations

7
TMEFF1 is a neuron-specific restriction factor for herpes simplex virus DOI

Yao Dai,

Manja Idorn, Manutea Serrero

et al.

Nature, Journal Year: 2024, Volume and Issue: 632(8024), P. 383 - 389

Published: July 24, 2024

Language: Английский

Citations

7
A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist DOI Creative Commons
Jérémie Le Pen,

Gabrielle Paniccia,

Volker Kinast

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(9), P. e3002767 - e3002767

Published: Sept. 24, 2024

Interferons (IFNs) play a crucial role in the regulation and evolution of host–virus interactions. Here, we conducted genome-wide arrayed CRISPR knockout screen presence absence IFN to identify human genes that influence Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. We then performed an integrated analysis interacting with SARS-CoV-2, drawing from selection 67 large-scale studies, including our own. identified 28 high relevance both genetic studies Disease 2019 (COVID-19) patients functional screens cell culture, many related pathway. Among these was IFN-stimulated gene PLSCR1 . did not require induction restrict SARS-CoV-2 contribute signaling. Instead, specifically restricted spike-mediated entry. The PLSCR1-mediated restriction alleviated by TMPRSS2 overexpression, suggesting primarily restricts endocytic entry route. In addition, recent variants have adapted circumvent barrier via currently undetermined mechanisms. Finally, investigate effects present humans discuss association between severe COVID-19 reported recently.

Language: Английский

Citations

6
DAZAP2 functions as a pan-coronavirus restriction factor by inhibiting viral entry and genomic replication DOI Creative Commons

Fei Feng,

Jiannan Chen, Rong Li

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

ABSTRACT The SARS-CoV-2 pandemic and the emergence of novel variants underscore need to understand host-virus interactions identify host factors that restrict viral infection. Here, we perform a genome-wide CRISPR knockout screen restriction for SARS-CoV-2, revealing DAZAP2 as potent antiviral gene. DAZAP2, previously implicated in restriction, is found inhibit entry by blocking virion fusion with both endolysosomal plasma membranes. Additionally, suppresses genomic RNA replication without affecting primary translation replicases. We demonstrate functions pan-coronavirus factor across four genera coronaviruses. Importantly, enhances infection mouse models human airway epithelial cells, confirming its physiological relevance. Mechanistically, activity appears be indirect, potentially through regulation gene expression, it primarily localizes nucleus. Our findings provide new insights into defense system against coronaviruses highlight potential target host-directed therapies. IMPORTANCE During infection, response mediated variety distinct mechanisms have yet fully elucidated. Although was action vivo relevance remain unclear. In this study, inhibits dual mechanisms: membranes, suppressing replication. confirm using cell cultures. This study advances our understanding host-pathogen interactions. Targeting or regulatory pathways could approach enhance current future coronavirus threats.

Language: Английский

Citations

0