# Host genetic diversity contributes to disease outcome in Crimean-Congo hemorrhagic fever virus infection

## TL;DR

This study shows that host genetic diversity influences the severity of Crimean-Congo hemorrhagic fever in a mouse model, mirroring human disease outcomes.

## Contribution

The study introduces the Collaborative Cross mouse model to investigate how host genetics affect CCHFV disease outcomes.

## Key findings

- Infected mice showed a disease spectrum similar to humans, from asymptomatic to severe.
- Virus replication and inflammation levels correlated with disease severity in mice.
- Host genetics were shown to significantly contribute to CCHFV infection outcomes.

## Abstract

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