General observations
Like NiV, HeV is primarily vasotropic and/or neurotropic and induces syncytia in vascular epithelial tissues. Interstitial pneumonia and encephalitis frequently result (Daniels et al. 2001, Hooper et al. 2001). HeV infections in cats, horses, and guinea pigs produce virus in the urine and kidney but generally not in nasal, oral, rectal, or conjunctival swabs, suggesting limited transmission through urine or the placenta (Williamson et al. 2001).
Bats
There is no gross pathology or attributable illness among bats naturally or experimentally infected with HeV, which suggests bats have long served as hosts (Field et al. 2001). Some transmission studies of P. poliocephalus have shown subclinical vascular lesions in a few blood vessels similar to those found in guinea pigs (Hooper et al. 2001).
In September 1996, HeV was isolated from the uterine fluids of an injured P. poliocephalus near Brisbane that had miscarried twin fetuses, from which virus was also isolated (Halpin et al. 1996). HeV has also been obtained from the lung of a female P. alecto near Brisbane (Halpin et al. 2000). In experimental infections, Williamson et al. (1999) isolated HeV from the blood, spleen, kidney, heart, and fetus of a pregnant Pteropus. In one experiment, six of eight male P. poliocephalus inoculated with HeV developed detectable levels of HeV antibody by ELISA, and two developed microscopic vascular lesions. Those bats developing lesions circulated the highest titers; subcutaneous inoculations yielded higher titers than oronasal inoculations (Williamson et al. 1998). In another experiment, four pregnant P. poliocephalus were inoculated subcutaneously with 50,000 TCID50 and killed on days 14 and 21. All four seroconverted but none developed clinical signs; vascular lesions were predominant in the spleen and similar to those in non-pregnant bats. Placental vessels immunostained but did not develop lesions. Virus was isolated 10 days PI but not at 21 days, suggesting brief viremia. Virus was not isolated from the mouth, nose, rectum, or urine. No abnormalities were detected in the fetuses, which were seronegative and whose tissues did not immunostain, though virus was isolated in one fetus (Williamson et al. 1999).
Horses
HeV replicates in the respiratory vascular endothelia, causing cellular destruction (Hyatt et al. 2001). The most frequent gross lesions are dilated pulmonary lymphatics, severe pulmonary edema and congestion; less frequent effects are edema of the mesentary, increased pleural and pericardial fluids, and congested lymph nodes (Hooper et al. 2001). In natural infections, airways were often filled with a stable, blood-tinged foam. In laboratory infections, this foam was not observed, though there was advanced dilation of the ventral lymphatics (Murray et al. 1995). Two horses were inoculated intravenously and intranasally via aerosol using spleen and lung homogenates from two infected Brisbane horses. The recipients were asymptomatic for six and ten days, developed disease for two days, and were euthanized on days eight and ten, respectively. Murray et al. (1995) note that higher titers correlated with a faster course of infection. Only one of eight experimentally infected horses that developed clinical disease recovered (Westbury 2000). Oral infection has been experimentally demonstrated (Williamson et al. 1998).
HeV has been isolated from horses’ kidneys, urine, blood, lungs, spleen, lymph nodes, liver, and minor oral cavities, including throat (see Daniels et al. 2001 for references). Virus has not been found in the rectum or feces (Williamson et al. 1998).
Guinea pigs
Experimentally infected guinea pigs showed generalized vascular disease but no pulmonary edema. Williamson et al. (2001) found syncytia in the transitional epithelium of the bladder and isolated virus from urine but not nasal, oral, or rectal swabs. Only subcutaneous inoculations produced meningitis. Virus has been isolated in guinea pig urine, blood, CNS, lungs, spleen, kidneys, and the fetus, uterus, and placenta of pregnant females (Williamson et al. 1999, 2001). Viral titers in uterus were similar to or exceed titers from other tissues, and the placentas of some guinea pigs developed severe histological lesions (Williamson et al. 1999). Of 18 inoculated pregnant guinea pigs, HeV was isolated in 11, and 10 of the 11 guinea pigs yielded virus from the uterus and placenta, and four from fetal tissue. In addition, one of the guinea pigs aborted (Williamson et al. 1999). Viral titers in tissues of pregnant guinea pigs tended to be higher than those of non-pregnant guinea pigs in other experiments inoculated with the same dose and stock of inoculum (Williamson et al. 1999).
Cats
HeV has been isolated from the kidneys, blood, CNS (including meninges), spleen, lymph nodes, trachea, liver, rectum, and urine of experimentally infected animals (Daniels et al. 2001). Pathology is similar to that of horses, with most vascular disease affecting the lungs, though encephalitis has not been observed (Hooper et al. 2001, Westbury et al. 1996). Cats infected subcutaneously with 50,000 TCID50 became sick 6-7 days after inoculation and died one day later (Westbury et al. 1995); 4-8 days is the incubation period for most experimental infections (Westbury et al. 1996). Cats can also be infected intranasally and orally and through contact with infected cats (Westbury et al. 1996). The disease progresses rapidly, typically leading to death within a day of the onset of symptoms.
Humans
Vic Rail’s autopsy revealed lesions of congestion in his lungs, hemorrhage, and edema associated with histological chronic alveolitis with syncytia. The stablehand developed flu-like respiratory signs and recovered. The veterinarian’s husband’s autopsy showed leptomeningitis with lymphocytes and plasma cells and foci of necrosis in various parts of the brain parenchyma (Hooper et al. 2001). Virus was isolated in Rail’s kidneys, which had a 1:64 antibody titer (Murray et al. 1995). The veterinarian’s husband, who suffered relapsing meningoencephalitis, had a lower initial titer.
Other animals
Mice, rats, rabbits, chickens, and dogs showed no remarkable gross or histological lesions 21 days after subcutaneous inoculation with TCID50. Mice and chickens lacked specific neutralizing or fluorescing antibodies, and virus could not be isolated from any of the animals (Westbury et al. 1995).
Author: S. Cobey.