Animal Models for Crimean-Congo Hemorrhagic Fever Human Disease

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is an important tick-borne human pathogen endemic throughout Asia, Africa and Europe. CCHFV is also an emerging virus, with recent outbreaks in Western Europe. CCHFV can infect a large number of wild and domesticated mammalian species and some avian species, however the virus does not cause severe disease in these animals, but can produce viremia. In humans, CCHFV infection can lead to a severe, life-threating disease characterized by hemodynamic instability, hepatic injury and neurological disorders, with a worldwide lethality rate of ~20–30%. The pathogenic mechanisms of CCHF are poorly understood, largely due to the dearth of animal models. However, several important animal models have been recently described, including novel murine models and a non-human primate model. In this review, we examine the current knowledge of CCHF-mediated pathogenesis and describe how animal models are helping elucidate the molecular and cellular determinants of disease. This information should serve as a reference for those interested in CCHFV animal models and their utility for evaluation of medical countermeasures (MCMs) and in the study of pathogenesis.

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

“…However, in some individuals, the infection can cause the Crimean-Congo hemorrhagic fever, a severe disease characterized by fever, myalgia, hemorrhage, among other manifestations. Neurological complications can also occur, being the spectrum and intensity of the disease quite variable (Ergönül, 2006;Bente et al, 2013;Garrison et al, 2019).…”

“…Deregulation of several cytokines and chemokines is involved in the pathogenesis of Crimean-Congo hemorrhagic fever (Ergönül, 2006;Saksida et al, 2010;Bente et al, 2013;Garrison et al, 2019). In a study performed by Arasli et al (2015), expression of the CCR5 ligands CCL2, CCL3, and CCL4 was increased in CCHFV-infected adults compared to controls.…”

Towards a Sustainable One Health Approach to Crimean–Congo Hemorrhagic Fever Prevention: Focus Areas and Gaps in Knowledge

“…In animal models, vaccination has been shown to generate humoral immunity and can generate up to 100% protective efficacy depending on the platform and approach to vaccination. For the last decade, disease models of CCHFV have been limited to immunocompromised mouse strains [ 89 , 90 ]. The most effective antigen component(s) and correlates of protection for CCHFV vaccines are not yet clear.…”

“…The most effective antigen component(s) and correlates of protection for CCHFV vaccines are not yet clear. When used in experimental vaccines, the nucleoprotein generates a more T-cell based response, while other viral antigens, such as whole or portions of the glycoprotein precursor, can generate potent immunoglobulin responses [ 88 , 89 , 90 ]. Passive transfer of sera and T-cells generated to either the nucleoprotein or glycoprotein molecules also did not protect but delayed time to death [ 91 , 92 , 93 ].…”

Quantitative analysis of Anaplasma marginale acquisition and transmission by Dermacentor andersoni fed in vitro

“…Tick-borne diseases caused by bacteria, protozoa, and viruses are responsible for a significant burden in human beings and animals [1][2][3][4][5][6] . Recent reports indicate that ticks transmit the majority of emerging arthropod-borne pathogens [7][8][9][10] .…”