. 2019 Jun 28;11(7):590. doi: 10.3390/v11070590

Table 1.

CCHFV animal models.

Animal Model	Virus Strain(s)	Virus Dose	Route(s) of Infection	% lethality	Time to Death [days]	Salient Features	REF
Neonatal mice	IbAr 10200	100 Lethal-dose units	IP	100	3 d	Do not predict immunotherapeutic protection behavior in adult rodents, Ribavirin protects against lethality	[85]
STAT-1^−/− mice	IbAr 10200, Turkey-2004	10-1000 PFU	SC, IP	20–100	3–6 d	hepatic injury, subunit vaccines may not protect well in this model. 10 PFUtick dose is only 20% lethal, higher doses uniformly lethal	[78,86]
IFNAR^−/− mice	IbAr 10200, Afg09-2990, Hoti	10-10,000 TCID₅₀ or PFU	SC, IP, IN, IM	>90	4–8 d	Prototypical rodent model for CCHFV, C57BL/6 or 129 background develop severe disease. Strain Hoti has a reduced MTD	[76,77,82,87]
IFNAR^−/−, IFNAGR^−/− mice	Ank-2	100 TCID50	IP	100	4–6 d	Used to evaluate N subunit vaccines	[79]
C57BL/6, BALB/c, B6:129	IbAr 10200, Afg09-2990, Hoti	100 PFU	SC, IP	>90 (IFN-I blockade)	5 d	No disease ensues unless IFN-I signaling is blocked by antibody (MAR1-5A3)	[48,83]
Rag2^−/− mice	Afg09-2990, Hoti	100 PFU	IP	100	4–5 d after disruption of IFN-I signaling	Hepatitis in mice with active IFN-I signaling, disruption of IFN-I signaling results in 100% lethality similar to normal mice	[83]
SGM3 Humanized mice	Turkey-2004, Oman-199809166	1 × 10⁴ TCID₅₀	IP	0 or 100	15–23 d	Neurological disease ensues absent of systemic (visceral) disease. Only strain Turkey produced severe disease and lethality. Oman is not lethal	[84]
Cynomolgus Macaques	Hoti, Afg09-2990	5log₁₀ TCID₅₀ and 1 × 10⁶ PFU	IV, SC and IV/SC combo	0–60	6–7 d	Disease model with fever, increased liver enzymes, thrombocytopenia, leukocytopenia. In some studies animals meet euthanasia criteria	[88,89]