Rao Deepashri, Lewis Matthew, Meade-White Kimberly, Shaia Carl, Okumura Atsushi, Ferris Martin T, Schäfer Alexandra, Baric Ralph, Feldmann Heinz, Hawman David W
Laboratory of Virology, Rocky Mountain Laboratories, NIAID/NIH, Hamilton, MT, USA.
Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, NIAID/NIH, Hamilton, MT, USA.
Npj Viruses. 2025 Feb 27;3(1):16. doi: 10.1038/s44298-025-00100-5.
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.
克里米亚-刚果出血热病毒（CCHFV）可引发克里米亚-刚果出血热（CCHF），这是一种广泛传播且具有显著发病率和死亡率的疾病。该病毒具有高度的遗传多样性，与地理分布相关，但在各区域内的时间演变有限。尽管如此，一个区域内的CCHF病例呈现出一系列疾病表现，从常常未被识别的无症状感染到严重的、致命的病毒性出血热，这表明宿主因素可能在疾病转归中发挥作用。我们在具有遗传多样性的协作杂交（CC）小鼠模型中研究了宿主遗传多样性对CCHFV感染结果的影响。受感染的小鼠重现了人类所认识的完整疾病谱，并且与人类疾病相似，病毒复制、组织病理学和炎症反应都与疾病严重程度相关。我们的研究表明，宿主基因在CCHF感染的疾病转归中起作用，并将CC小鼠资源确立为一种模型，以了解宿主遗传多样性如何影响CCHF的结果。
