Crimean–Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures

Abstract

Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral zoonosis with a case-fatality rate ranging from 9% to 50% in humans. Although a licensed vaccine to prevent infection by the CCHF virus (CCHFV) exists, its ability to induce neutralizing antibodies is limited and its efficacy against CCHFV remains undetermined. In addition, controlling CCHF infections by eradication of the tick reservoir has been ineffective, both economically and logistically, and the treatment options for CCHF remain limited. In this review, we first critically discuss the existing animal models to evaluate therapeutics for CCHF. We then review the therapeutic options for CCHF that have been investigated in human cases, followed by investigational drugs that have been evaluated in pre-clinical studies. We highlight the importance of understanding human prognostic factors in developing an animal model for CCHF that recapitulates hallmarks of human disease and its implication for selecting therapeutic candidates.

Differential Cell Line Susceptibility to Crimean-Congo Hemorrhagic Fever Virus

“…CCHFV may be asymptomatic in animals ( Spengler et al., 2016 ). To date, the disease development upon CCHFV infection has been demonstrated in only a subset of immunocompromised mice and a cynomolgus macaque model ( Haddock et al., 2018 ; Mendoza et al., 2018 ). The limits of appropriate animal models, as well as the requirement for high biosafety level containment may slow down the progress in developing CCHFV anti-viral drugs and vaccines.…”

Pathogen Dose in Animal Models of Hemorrhagic Fever Virus Infections and the Potential Impact on Studies of the Immune Response

“…Immunocompetent mice are not susceptible to infection as adults, so neonatal mice have been used as an infection model. However, this model does not recapitulate aspects of human disease and has practical limitations [ 107 , 108 ]. More recently, STAT-1 and IFNAR-/- mice have been used as a model of infection.…”

Innovative Technologies for Advancement of WHO Risk Group 4 Pathogens Research

“…Cell culture has been used as a simple tool to research specific aspects of viral infection, such as screening candidate therapeutics for antiviral activity [11][12][13][14][15][16][17][18][19][20][21] or quantifying host immune responses, such as virus-neutralizing antibody titers [22,23]. However, as current common cell culture methods cannot model the complexities of a body system, animal BSL-4 (ABSL-4) models, such as rodents or nonhuman primates, are generally used to model disease [24][25][26][27][28].…”