A Multitrait Locus Regulates Sarbecovirus Pathogenesis

Schäfer, Alexandra; Leist, Sarah R.; Gralinski, Lisa E.; Martinez, David R.; Winkler, Emma S.; Okuda, Kenichi; Hawkins, Padraig; Gully, Kendra L.; Graham, Rachel L.; Scobey, D Trevor; Bell, Timothy A.; Hock, Pablo; Shaw, Ginger D.; Loome, Jennifer F.; Madden, Emily A.; Anderson, Elizabeth J.; Baxter, Victoria K.; Taft-Benz, Sharon; Zweigart, Mark R.; May, Samantha R.; Dong, Stephanie; Clark, Matthew; Miller, Darla R.; Lynch, Rachel; Heise, Mark T.; Tisch, Roland; Boucher, Richard C.; Villena, Fernando Pardo Manuel de; Montgomery, Stephanie A.; Diamond, Michael S.; Ferris, Martin T.; Baric, Ralph S.

doi:10.1128/mbio.01454-22

Cited by 17 publications

(19 citation statements)

References 60 publications

(93 reference statements)

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“…Schäfer showed that knocking out two of the six ortholog genes in this region, CCR9 and CXCR6 , prevented recovery from SARS‐CoV‐2 infection, increased inflammatory response and mortality, and was associated with prolonged lung dysfunction. This study validates the collaborative cross as a platform to identify and validate novel susceptibility genes that regulate emerging virus pathogenesis across species 86 …”

Section: Innate Immunity and Evasionsupporting

confidence: 64%

“…Schäfer used the genetically diverse collaborative cross mice to identify strains that demonstrate a range of phenotypes to SARS‐CoV infection in terms of weight loss, viral titers, and mortality. These phenotypes were associated with a quantitative trait locus that clustered in a region on chromosome 9 86 . Several of these genes display synteny with genes identified in a human GWAS study that correlate with COVID‐19 disease severity 87,88 .…”

Section: Innate Immunity and Evasionmentioning

confidence: 97%

“…These phenotypes were associated with a quantitative trait locus that clustered in a region on chromosome 9. 86 Several of these genes display synteny with genes identified in a human GWAS study that correlate with COVID-19 disease severity. 87,88 Schäfer showed that knocking out two of the six ortholog genes in this region, CCR9 and CXCR6, prevented recovery from SARS-CoV-2 infection, increased inflammatory response and mortality, and was associated with prolonged lung dysfunction.…”

Section: A Multitrait Locus Associated With Sarbecovirus Pathogenesismentioning

confidence: 99%

“…This study validates the collaborative cross as a platform to identify and validate novel susceptibility genes that regulate emerging virus pathogenesis across species. 86…”

Section: A Multitrait Locus Associated With Sarbecovirus Pathogenesismentioning

confidence: 99%

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Positive‐strand RNA viruses—a Keystone Symposia report

Cable¹,

Denison

Kielian

et al. 2023

Annals of the New York Academy of Sciences

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Positive-strand RNA viruses have been the cause of several recent outbreaks and epidemics, including the Zika virus epidemic in 2015, the SARS outbreak in 2003, and the ongoing SARS-CoV-2 pandemic. On June 18-22, 2022, researchers focusing on positive-strand RNA viruses met for the Keystone Symposium "Positive-Strand RNA Viruses" to share the latest research in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development. This report presents concise summaries of the scientific discussions at the symposium.

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Section: Innate Immunity and Evasionsupporting

confidence: 64%

Section: Innate Immunity and Evasionmentioning

confidence: 97%

Section: A Multitrait Locus Associated With Sarbecovirus Pathogenesismentioning

confidence: 99%

“…This study validates the collaborative cross as a platform to identify and validate novel susceptibility genes that regulate emerging virus pathogenesis across species. 86…”

Section: A Multitrait Locus Associated With Sarbecovirus Pathogenesismentioning

confidence: 99%

See 2 more Smart Citations

Positive‐strand RNA viruses—a Keystone Symposia report

Cable¹,

Denison

Kielian

et al. 2023

Annals of the New York Academy of Sciences

Self Cite

View full text Add to dashboard Cite

show abstract

“…; https://doi.org/10.1101/2023.03. 18.533278 doi: bioRxiv preprint CoV-2 19 , and influenza A virus 20 , and also to map the genetic determinants responsible for complex phenotypic traits 13 .…”

Section: Introductionmentioning

confidence: 99%

Host genetic variation guides hepacivirus clearance, chronicity, and liver fibrosis in mice

Brown

Won

Wolfisberg

et al. 2023

Preprint

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Background & Aims: Human genetic variation is thought to guide the outcome of hepatitis C virus (HCV) infection but model systems within which to dissect these host genetic mechanisms are limited. Norway rat hepacivirus (NrHV), closely related to HCV, causes chronic liver infection in rats but causes acute self-limiting hepatitis in typical strains of laboratory mice, which resolves in two weeks. The Collaborative Cross (CC) is a robust mouse genetics resource comprised of a panel of recombinant inbred strains, which model the complexity of the human genome and provide a system within which to understand diseases driven by complex allelic variation. Approach & Results: We infected a panel of CC strains with NrHV and identified several that failed to clear virus after 4 weeks. Strains displayed an array of virologic phenotypes ranging from delayed clearance (CC046) to chronicity (CC071, CC080) with viremia for at least 10 months. Body weight loss, hepatocyte infection frequency, viral evolution, T-cell recruitment to the liver, liver inflammation and the capacity to develop liver fibrosis varied among infected CC strains. Conclusions: These models recapitulate many aspects of HCV infection in humans and demonstrate that host genetic variation affects a multitude of virus and host phenotypes. These models can be used to better understand the molecular mechanisms that drive hepacivirus clearance and chronicity, the virus and host interactions that promote chronic disease manifestations like liver fibrosis, therapeutic and vaccine performance, and how these factors are affected by host genetic variation.

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Gut‐lung axis and asthma: A historical review on mechanism and future perspective

Song,

Liang,

Lin

et al. 2024

Clinical & Translational All

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BackgroundGut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut‐lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic.BodyThis review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut‐lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed.ConclusionThe gut‐lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.

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A Multitrait Locus Regulates Sarbecovirus Pathogenesis

Abstract: Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear.

Cited by 17 publications

References 60 publications

Positive‐strand RNA viruses—a Keystone Symposia report

Positive‐strand RNA viruses—a Keystone Symposia report

Host genetic variation guides hepacivirus clearance, chronicity, and liver fibrosis in mice

Gut‐lung axis and asthma: A historical review on mechanism and future perspective

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