Host genetic diversity contributes to disease outcome in Crimean-Congo hemorrhagic fever virus infection DOI Creative Commons
Deepashri Rao,

Matthew Lewis,

Kimberly Meade‐White

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 17, 2024

Abstract The Crimean-Congo hemorrhagic fever virus (CCHFV) causes (CCHF), a widely distributed disease with significant morbidity and mortality. has high genetic diversity correlated geographic distribution, but limited temporal evolution within regions. Despite this, cases of CCHF region present as spectrum from often unrecognized asymptomatic infections to severe, fatal viral fever, suggesting host factors may play role in outcome. We investigated the effect on outcome CCHFV infection genetically diverse Collaborative Cross mouse model. Infected mice recapitulated full recognized humans similar human disease, replication, tissue pathology inflammatory responses were associated severity. Our study demonstrates that genetics contribute establishes resource model understand how contributes

Language: Английский

Mapping of susceptibility loci for Ebola virus pathogenesis in mice DOI Creative Commons

Alexandra Schäfer,

Andrea Marzi,

Wakako Furuyama

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(5), P. 114127 - 114127

Published: April 21, 2024

Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays critical role, yet the identity of host susceptibility loci mammals remains unknown. Using reference populations, we generate an F2 mapping cohort to identify that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible severe liver pathology consistent with EVD-like and transcriptional signatures associated inflammatory metabolic processes. A significant quantitative trait locus (QTL) for RNA load blood is identified chromosome (chr)8, clinical mortality QTL mapped chr7, which includes Trim5 locus. knockout mice, validate as one potential driver failure after infection. The identification provides insight into molecular mechanisms regulating EVD progression severity, potentially informing therapeutics vaccination strategies.

Language: Английский

Citations

6
Animal models of Long Covid: A hit-and-run disease DOI Open Access
Alexandra Schaefer, Sarah R. Leist, John M. Powers

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(773)

Published: Nov. 13, 2024

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) pandemic has caused more than 7 million deaths globally. Despite the presence of infection- and vaccine-induced immunity, SARS-CoV-2 infections remain a major global health concern because emergence variants that can cause disease 2019 (COVID-19) or enhance Long Covid phenotypes. About 5 to 10% SARS-CoV-2-infected individuals develop Covid, which, similar COVID 19, often affects lung. However, also affect other peripheral organs, especially brain. causal relationships between phenotypes, long-term symptoms, involvement multiple organ systems elusive, animal model mimicking both post-acute phases are imperative. Here, we review current state models, including possible future applications.

Language: Английский

Citations

5
Host genetic diversity contributes to disease outcome in Crimean-Congo hemorrhagic fever virus infection DOI Creative Commons
Deepashri Rao,

Matthew Lewis,

Kimberly Meade-White

et al.

npj Viruses, Journal Year: 2025, Volume and Issue: 3(1)

Published: Feb. 27, 2025

Abstract The Crimean-Congo hemorrhagic fever virus (CCHFV) causes (CCHF), a widely distributed disease with significant morbidity and mortality. has high genetic diversity correlated geographic distribution but limited temporal evolution within regions. Despite this, cases of CCHF region present as spectrum from often unrecognized asymptomatic infections to severe, fatal viral fever, suggesting host factors may play role in outcome. We investigated the effect on outcome CCHFV infection genetically diverse Collaborative cross (CC)-mouse model. Infected mice recapitulated full recognized humans, similar human disease, replication, tissue pathology, inflammatory responses were associated severity. Our study demonstrates that genetics contribute establishes CC mouse resource model understand how contributes

Language: Английский

Citations

0
Sarbecovirus disease susceptibility is conserved across viral and host models DOI Creative Commons
Sarah R. Leist,

Alexandra Schäfer,

Ellen L Risemberg

et al.

Virus Research, Journal Year: 2024, Volume and Issue: 346, P. 199399 - 199399

Published: June 14, 2024

Coronaviruses have caused three severe epidemics since the start of 21

Language: Английский

Citations

1
Host genetic diversity contributes to disease outcome in Crimean-Congo hemorrhagic fever virus infection DOI Creative Commons
Deepashri Rao,

Matthew Lewis,

Kimberly Meade‐White

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 17, 2024

Abstract The Crimean-Congo hemorrhagic fever virus (CCHFV) causes (CCHF), a widely distributed disease with significant morbidity and mortality. has high genetic diversity correlated geographic distribution, but limited temporal evolution within regions. Despite this, cases of CCHF region present as spectrum from often unrecognized asymptomatic infections to severe, fatal viral fever, suggesting host factors may play role in outcome. We investigated the effect on outcome CCHFV infection genetically diverse Collaborative Cross mouse model. Infected mice recapitulated full recognized humans similar human disease, replication, tissue pathology inflammatory responses were associated severity. Our study demonstrates that genetics contribute establishes resource model understand how contributes

Language: Английский

Citations

0