Jacob S. Yount

NAT10 is critical to block RNA sensing-induced IFN-β transactivation in viral infection

Youngmin Park, Yan Liu, Jinshan He, Suha Eleya et autres

Cells detect invading viruses and produce type I interferons (IFNs) to stimulate an innate antiviral effector response. However, IFN levels must be fine-tuned to achieve antiviral efficacy while limiting hyperinflammatory and tissue-damaging effects. Here, we report that NAT10, a histone and cytidine …

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SARS-CoV-2 Delta variant re-emerges in US farmed mink and free-ranging white-tailed deer in 2022–2023

Alvin Crespo-Bellido, Madison C. Owsiany, Natalie N. Chillson, Devra D. Huey et autres

American mink (Neogale vison) are susceptible to SARS-CoV-2, but little is known about virus circulation in mink since 2021. Here, in the first active surveillance study of SARS-CoV-2 in apparently healthy farmed mink in the United States, we find a ~0.9% (760/85,656) …

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Gene duplication and retrotransposition diversify the antiviral repertoire of macaque IFITM proteins

Deepthi Kappala, Alexis Sauer, Emma Atwood, Yuexiu Zhang et autres

Interferon-induced transmembrane (IFITM) proteins are broad-spectrum antiviral restriction factors that inhibit viral entry of diverse enveloped viruses. Comparative genomic studies have revealed extensive lineage-specific diversification of IFITM genes, yet the functional consequences of this diversification remain poorly understood. We previously identified an …

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Influenza virus hitches a cellular ride to the heart

Jana M. Cable, Jacob S. Yount

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Gasdermin E is dispensable for H1N1 influenza virus pathogenesis in mice

Samuel Speaks, Jonathan L. Papa, Matthew I. McFadden, Jack E. Roettger et autres

ABSTRACT Targeting cell death pathways, including pyroptosis and necroptosis, has been shown to mitigate influenza virus infection severity. Here, we examined whether pyroptosis specifically driven by the pore-forming protein gasdermin E (GSDME) is involved in regulating influenza virus infection outcomes. We found …

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IFITM3 deficiency drives SARS-CoV-2 adaptation while preserving variant-specific traits

Parker J. Denz, Samuel Speaks, Matthew I. McFadden, Jana M. Cable et autres

SARS-CoV-2 can infect and adapt to multiple animal species, yet the host determinants that control interspecies viral adaptation remain poorly defined. Here we investigate whether interferon-induced transmembrane protein 3 (IFITM3), a key antiviral protein deficient in certain human populations, affects interspecies adaptation …

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Aiolos restricts the generation of antigen-inexperienced, virtual memory CD8+ T cells in mice

Srijana Pokhrel, Gayathri Dileepan, Melissa R. Leonard, Robert T. Warren et autres

CD8+ virtual memory T (TVM) cells rapidly respond to infection via antigen-independent bystander effector functions. While it is recognized that TVM cells arise independently of foreign antigen encounter, the mechanisms governing their development are not fully understood. Here, we identify the Ikaros …

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Caspase-11 Mediated Hyperinflammation Impairs CD8⁺ T Cell Immunity and Viral Clearance in Severe SARS-CoV-2 Infection

Mostafa M. Eltobgy, Mohamed Α. Shamseldin, Owen Whitham, Heba M. Amer et autres

Abstract Severe SARS-CoV-2 infection is characterized by lung hyperinflammation, impaired interferon responses, and defective T-cell activation, yet the molecular drivers of these immune dysregulations remain incompletely understood. Caspase-11 (CASP11), a key mediator of the non-canonical inflammasome, has been shown to mediate an …

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Caspase11 modulates the adaptive immune response in SARS-CoV-2 infection through innate immune regulation 4503

Mostafa M. Eltobgy, Benjamin Matthew Segal, Eugene M. Oltz, Jacob S. Yount et autres

Abstract Description Caspase 11 is a critical component of the noncanonical inflammasome with multifaceted roles in the innate immune response, contributing to host defense against pathogens. We demonstrated that Casp11 deletion improved disease outcomes in SARS-CoV-2 infection by modulating the innate inflammatory …

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SARS-CoV-2 innate immune recognition and implications for respiratory health

Vandana Anang, Pankaj Kumar, Jamaluddin Pracha, Richard Seonghun Nho et autres

The ongoing global health impact of SARS-CoV-2, particularly on lung and respiratory health, underscores the critical need to decipher the intricate interplay between the virus and the host innate immune system. This review provides an analysis of the key pattern recognition receptors …

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Cardioprotective effects of AMPK activation in H1N1 influenza virus infection

Steve Leumi, Matthew I. McFadden, Naresh Kumar, Jack E. Roettger et autres

Cardiac complications are among the most common and severe extrapulmonary manifestations of influenza virus infection, yet they are rarely recapitulated in mouse models without immunodeficiency. We found that influenza virus A/California/04/2009 (H1N1) carrying a mouse-adaptive amino acid substitution in the PB2 protein …

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O-GlcNAc transferase plays dual antiviral roles by integrating innate immunity and lipid metabolism

Hong Dong, Chenxi Liang, Junjie Zhang, Weidong Wu et autres

Viral infection induces robust reprogramming of metabolic pathways in host cells. However, whether host metabolic enzymes detect viral components remains unknown. Our group and others previously identified O-GlcNAc transferase (OGT), an important glucose metabolic enzyme, as a crucial mediator of the antiviral …

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