Table 1 Animal models investigated for SFTSV.

Mouse

BALB/C

Newborns

HYSV

3*10⁷ copies IP, IC

L

100% mortality by IC, 35–50% mortality by IP

Time to death varies by route and dose.

¹¹⁸

C57BL/6

Newborns

HYSV

3*10⁷ copies IP, IC

L

100% mortality by IC, 35–50% mortality by IP

Time to death varies by route and inoculum.

¹¹⁸

CD-1

Newborns

YL-1

10³ FFU IC

L

100% mortality after multiple passages in newborn CD-1.

¹¹⁹

Kunming

Newborns

HYSV

3*10⁷ copies IP, IC

L

100% mortality by IC, 40% mortality by IP Necrotic neurons observed when infected IC. Liver damage observed with high viral titers detected in the liver by RT-PCR.

Time to death varies by route and dose.

¹¹⁸

IFNAR−/− 129/Sv

Adult

YL-1

10⁶ PFU

L

Virus detected in blood, brain, heart, kidney, liver, lung, and spleen. Antigen detected in brain, heart, intestine, lymph nodes, liver, kidney, and spleen. Time to death 2–3 days.

¹¹⁹

IFNAR−/− C57BL/6

Adult

SD45

10⁵ TCID₅₀

L

Necrotizing lymphadenitis in spleen and lymph nodes. Activated macrophages and virus in multiple tissues (spleen, liver, bone marrow). Time to death 5–7 days.

⁷⁷

BALB/C

Adult

HYSV, HB29

10⁵ TCID₅₀ 5*10⁷ IP, IC

NL

Not reported.

^110,112

C57BL/6

Adult

HB29

HYSV

SD4

10⁵ TCID₅₀ IP

5*10⁷ IP, IC

NL

Observed increased megakaryocytes in spleen and bone marrow. Necrosis in the liver. Elevated AST, ALT, and BUN. Reduced WBC. RNA detected in spleen, kidney, and liver.

Pre-treatment with Mitomycin C (an immunosuppressant) induces severe/lethal disease within 9–10 days.

^77,110,112

CD-1

Adult

YL-1

10⁵ FFU IP

NL

Not reported.

¹¹¹

Kunming

Adult

HYSV

5*10⁷ copies IP, IC

NL

Not reported.

¹¹⁰

129S1/SvlmJ

Adult

SD4

10⁵ TCID₅₀ ID, IP, IM, SC

NL

Not reported.

⁷⁷

A/J

Adult

SD4

10⁵ TCID₅₀ ID, IP, IM, SC

NL

Not reported.

⁷⁷

BXD34/TyJ

Adult

SD4

10⁵ TCID₅₀ ID, IP, IM, SC

NL

Not reported.

⁷⁷

BXD68/RwwJ

Adult

SD4

10⁵ TCID₅₀ ID, IP, IM, SC

NL

Not reported.

⁷⁷

CAST/EiJ

Adult

SD4

10⁵ TCID₅₀ ID, IP, IM, SC

NL

Not reported.

⁷⁷

DBA/1J

Adult

SD4

10⁵ TCID₅₀ ID, IP, IM, SC

NL

Not reported.

⁷⁷

DBA/2J

Adult

SD4

10⁵ TCID₅₀ ID, IP, IM, SC

NL

Not reported.

⁷⁷

FVB/NJ

Adult

SD4

10⁵ TCID₅₀ ID, IP, IM, SC

NL

Not reported.

⁷⁷

NZBWF1/J

Adult

SD4

10⁵ TCID₅₀ ID, IP, IM, SC

NL

Not reported.

⁷⁷

SLJ/J

Adult

SD4

10⁵ TCID₅₀ ID, IP, IM, SC

NL

Not reported.

⁷⁷

STAT1−/− C57BL/6

6–8 week

YG-1

10 FFU ID

NL

Slight weight loss with recovery. Significant platelet loss without complete recovery by 7 dpi.

¹¹³

STAT2−/− C57BL/6

6–8 week

YG-1

10 FFU ID

L

100% lethal by 8 dpi. Significant weight loss as well as platelet loss. Detectable virus in the brain, lungs, liver, spleen, kidney and intestines at 5 dpi.

¹¹³

BALB/c

Aged (≥20 months)

CB1/2014

10^6.6 TCID₅₀ IM

NL

Mild weight loss.

¹¹⁵

C3H

Aged (≥20 months)

CB1/2014

10^6.6 TCID₅₀ IM

NL

Mild weight loss.

¹¹⁵

C57BL/6

Aged (≥20 months)

CB1/2014

10^6.6 TCID₅₀ IM

NL

Mild weight loss.

¹¹⁵

FVB

Aged (≥20 months)

CB1/2014

10^6.6 TCID₅₀ IM

NL

Mild weight loss.

¹¹⁵

Hamster

Syrian Golden Hamster

Newborns

HYSV

5*10⁷ copies IP, IC

L

NR

¹¹⁰

Syrian Golden Hamster STAT2 KO

Adult

HB29

1 PFU SC

L

Heterozygous STAT2 mice are resistant to SFTSV infection. Viral RNA detected in serum, liver, spleen, kidney, heart, lung, brain, and intestines. Low levels of platelets observed on day 3. Immature neutrophils elevated between days 2 and 3. Moribund animals had elevated ALP, AST, ALT, GGT, and TBIL. Lesions observed in spleen and liver. Favipiravir provided complete protection against infection.

⁹⁰

Syrian Golden Hamster

Adult

HB29

HYSV

YL-1

10⁵ TCID₅₀ IP

5*10⁷ IP, IC

10 PFU SC

10⁵ FFU IP

NL

NR

^{90,110,111,112}

Rat

Wistar

Newborn

HYSV

5*10⁷ copies IP, IC

L

100% mortality by IC, 40% mortality by IP.

¹¹⁰

Wistar

Adult

HYSV

1.25*10⁸ copies

NL

NR

¹¹⁰

Ferret

Young

≤20–24 Months

10^7.6 TCID₅₀

NL

Increase in body temperature at 2 dpi and a return to normal by 12dpi. Slight body weight decrease. Slight thrombocytopenia and leukopenia beginning at 2dpi. Elevated AST and ALT between 2dpi and 8 dpi. Detectable virus in the spleen, liver, kidneys, lungs, and serum with clearance by 8 dpi.

¹¹⁵

Old

≤48–50 Months

10^7.6 TCID₅₀

L

Increase in body temperature at 2 dpi with death occurring by 6dpi. Significant body weight decrease. Severe thrombocytopenia and leukopenia beginning at 2 dpi. Highly elevated AST and ALT by 2 dpi. Detectable virus in the spleen, liver, kidneys, lungs, brain, spinal cord, intestines, and serum.

¹¹⁵

Non-human primates

Rhesus macaque

4–5 years

HB29

10⁷ TCID₅₀

NL

Moderate fever of 4–5 days. Peak viremia of 10⁵ copies/mL. 0.5-fold decrease of WBC. 0.5-fold decrease of platelet count. 0.7-fold decrease of RBC. Elevated ALT, AST, LDH, creatinine, IFN-y, TNF-a, eotaxin, MIP-1B, IL-10, IP-10, IL-5, GM-CSF, and IL-9. Viral RNA detected in spleen, lymph nodes, kidneys, liver (only 1 animal), and intestines. Mild lesions detected in liver and kidneys.

¹⁰⁴

Cynomolgus macaque

Not Reported

SD4

10⁶ TCID₅₀

NL

Slight drop in platelets in ¼ of animals.

⁷⁷