Table 1.

Animal models of HeV and NiV infection.

Animals	Type of Infection	Onset of Illness (Days)	First Clinical Signs	Symptoms	Virus-Positive Tissues or Fluids	References
Bat (P. alecto, P. poliocephalus)	s.c.	N/A	vascular lesions	N/A	blood, kidney, urine, uterus	[67,68,149]
	s.c.	N/A	mild nephritis, focal vasculitis, cell infiltration in liver	N/A	kidney, urine, rectum	[42,159]
Cat	o.i., i.n., s.c.	5–7/9	inappetence, increased respiratory rate	severe respiratory disease, pneumonia, hemorrhagic lungs, vascular lesions, syncytial cells	arteries, veins, lung, spleen, kidney, brain, gastrointestinal tract, urine	[52,149,236,237]
	o.n.i., s.c.	4–10/12	fever, respiratory and neurological disease, depression, constipation,	ulcera, inflammation, meningitis, meningeal vasculitis	oropharynx, tonsil, trachea, lung, brain, kidney, liver, uterus	[17,238,239,240]
Dog	s.c. natural	N/A	no signs of ill health, although wincing several times	reddening and dark patchy discoloration in the lung and the tonsils, white streaks in kidney, spleen and liver inflammation, fibrinoid necrosis, vasculitis and inflammatory infiltrates in kidney, brain, LN, spleen, liver, intestine, lung, expanded meninges	kidney, brain, lymph nodes, spleen, and liver Equivocal NAb	[52,241,242]
	natural	N/A	fever, respiratory distress, conjunctivitis, nasal discharge	severe pulmonary edema, atrophy, vascular degeneration, syncytia, necrosis, glomerulonephritis, meningitis	N/A	[46,240,243,244]
Ferret	o.n.i., i.n.	6–9	fever, depression, serous nasal discharge, dyspnea, hind limb paresis and generalized tremors	cutaneous petechiation, s.c. edema in head and neck, pulmonary petechiation, hemorrhagic lymph nodes, systemic vasculitis, necrosis, splenitis, bronchoalveolitis, endothelial and epithelial syncytial cells	kidney, heart, bladder, LN, lung, spleen, brain, nose, endothelial cells, neurons, bronchoalveolar epithelium, urine	[190,245,246,247]
	o.n.i., i.n.	5–9	pyrexia, depression, cough, dyspnea, hind limb paresis, generalized tremors	multisystemic inflammatory lesions in respiratory tract, spleen, kidneys and liver, neurologic disease, meningitis, encephalitis, hemorrhaging, necrosis, syncytia, bronchoalveolitis, tonsillitis, nasopharyngitis, thrombocytopenia, multisystemic vasculitis	nasal turbinates, pharynx, retropharyngeal lymph nodes, spleen, lung, liver, kidney, LN, uterus, ovaries, heart, brain, bladder, mouth, rectum, vascular endothelium, feces, neurons, glial cells, urine	[246,247,248,249,250,251,252,253]
Horse	s.c., i.n., o.n.i., i.v.	5–16	fever, high cardiac rates, depression, dyspnea, recumbency, loss of appetite, neurological signs	lung edema, thrombosis, hemorrhage, tissue necrosis, syncytia, vascular damage	kidney, lung, mouth, nasal cavities, urine	[48,49,89,149,254,255,256]
	natural	N/A	neurological signs	vascular damage, meningitis (only brain and spinal cord were analyzed)	brain, spinal cord seroconversion	[240,257]
Monkey (African green monkey, AGM)	i.n., i.t.	7	piloerection, respiratory distress, nasal discharge, depression, seizures, muscle fasciculations	severe systemic vasculitis, necrosis, hemorrhage and edema in most organs, splenomegaly, hemorrhaging, syncytial cells, meningitis	tonsils, trachea, lungs, heart, liver, spleen, kidney, pancreas, intestine, LN, brain, testes/ovaries, bone marrow, urine	[115,258,259]
	i.n., i.t., o.i.	7–12	fever, loss of appetite, respiratory disease, lethargy, rash, depression, behavioral changes	severe systemic vasculitis, hemorrhage and edema in most organs, thrombocytopenia, meningitis	blood, trachea, lungs, heart, liver, spleen, kidney, pancreas, intestine, LN, brain, testes/ovaries, bone marrow, rectum, urine	[24,59,259,260,261,262,263,264,265,266,267,268]
Monkey (Squirrel Monkey)	N/A	N/A	N/A	N/A	N/A	N/A
	i.v., i.n.	7–19	respiratory disease, loss of appetite, depression, uncoordinated motor movements	inflammation of lung parenchyma, mild vasculitis	spleen, liver, lung, heart, bladder, kidney, LN, spinal cord, brain	[269]
Pig	i.n., o.n.i.	4/5	fever, loss of appetite, cough, respiratory distress, depression, uncoordinated movements	pulmonary edema, hemorrhages in lung, kidney and LN, syncytial cells, inflammation, vasculitis, necrosis	Tonsils, lung, nasal turbinates, LN, olfactory bulb, mouth, ocular secretions, rectum	[270,271,272,273]
	o.n.i., o.i., s.c., i.n., oc.i.	7–21	fever, nasal discharge, coughing, locomotor disturbances, agitation, muscle fasciculations, paresis, seizures	systemic vasculitis, vasculopathy, alveolitis, thrombosis, cell necrosis, pulmonary edema and inflammation, renal tubular degeneration, syncytia, meningitis,	tonsils, lung, LN, olfactory bulb, nose, oropharynx, spleen, endothelium, lymphatic vessels, kidneys, brain, blood, urine	[14,17,146,244,273,274,275,276,277,278]
ID mice (IFNAR-KO, NSG)	i.n., i.p.	3–21	agitation, lack of grooming, grimace, loss in body weight, lordosis, aggression, locomotor disability, head tilt, and paralysis	lung and brain congestion, hemorrhages, vasculitis, necrosis, meningitis, encephalitis	brain, lung, spleen, liver	[23]
	i.p., i.n., i.cer.	6–10	agitation, lack of grooming, grimace, loss in body weight, lordosis, aggression, locomotor disability, head tilt, and paralysis	inflammation, edema, focal necrosis in lung and vasculitis microscopic lesions in the brain, liver and kidney inflammation, syncytial cells, meningeal inflammation	brain, lung, spleen, liver	[23,121,279,280]
IC mice (C57BL/6, BALB/c, CB6F1/J)	i.n., s.c.	10–21	depression, ataxia, hypersensitivity, and tremors	necrosis, ulceration, encephalitis	respiratory tract, olfactory epithelium, brain	[52,281]
	i.n., i.p. i.cer.	4	N/A	subclinical, self-limiting respiratory infection	lung, spleen	[23,278,282,283,284,285,286,287]
Hamster	i.p.	3–25	breathing difficulties, paralysis, and trembling limbs	pulmonary edema, inflammation in lung and spleen, necrosis, syncytia cells, meningitis	lung, heart, liver, spleen, brain, serum, urine	[288,289,290,291]
	i.n., i.p., a.e., fom., d.c.	4–15	breathing difficulties, imbalance, limb paralysis, lethargy, muscle twitching	damage in lung, liver, kidney, heart, and brain, fibrinoid necrosis with surrounding inflammation in blood vessels, syncytial cells, necrosis, vasculitis, thrombosis, meningitis	lung, kidney, spleen, liver, heart, spinal cord, brain, urine	[22,93,111,124,147,288,289,292,293,294,295,296,297,298,299,300,301,302,303]
Guinea pig	s.c., i.n., i.d.	7–15 days	inappetence, increased respiratory rate, head tilt, ataxia, torticollis, depression	pneumonia, cyanose, oedema in gastrointestinal tract, systemic vascular disease in arteries, veins, lung, kidney, spleen, lymph nodes, syncytia in lungs	arteries, veins, lung, kidney, spleen, lymph nodes	[21,52,160,237]
	i.p., i.n.	7–9 days	ruffled hair, weight loss, abnormal behavior, ataxia	oedema, systemic vasculitis, endothelial syncytial cells, cell necrosis, lung hemorrhages	heart, spleen, kidney, lung, brain, LN, thymus, blood, ovaries, uterus	[22,159,304]
Rat	s.c.	N/A	no histological lesions	N/A	virus not observed Equivocal NAb	[52]
	N/A	N/A	N/A	N/A	N/A	N/A
Rabbit	s.c.	N/A	no histological lesions	N/A	virus not observed	[52]
	N/A	N/A	N/A	N/A	N/A	N/A
Chicken	s.c.	N/A	no histological lesions	N/A	virus not observed	[52]
	allantoic or yolk sac inoculation	5–7	only reported in embryos: 4–7	only reported in embryos: brain hemorrhage, congestion and hemorrhage in the skin of the toes and in the kidneys, syncytial cells, necrosis	only reported in embryos, lung, heart, liver, kidney, spleen, skin, CNS, blood vessels	[305]

s.i.: subcutaneous injection; i.cer.: intracerebral; i.d.: intradermal; o.c.i.: ocular infection; i.n.: intranasal; i.t.: intratracheal; o.i.: oral inoculation; o.n.i.: oronasal injection; i.p.: intra peritoneal; a.e.: aerosol exposure; fom.: fomites; d.c.: direct contact; Nab: neutralizing antibodies; LN: lymph nodes; CNS: central nervous system; N/A: not analyzed; IC: immunocompetent; ID: immunodeficient.