Neurotropism of Swine Haemagglutinating Encephalomyelitis Virus (Coronavirus) in Mice Depending upon Host Age and Route of Infection

Abstract

Mice aged 1, 4 or 8 weeks were inoculated with haemagglutinating encephalomyelitis virus (HEV), strain 67N, by the intracerebral (i.c.), intranasal (i.n.), intraperitoneal (i.p.), subcutaneous (s.c.), intravenous (i.v.) or oral route, with different doses. In 1-week-old mice, mortality and mean time to death were mostly the same regardless of the inoculation route, except for the oral route, which appeared to be the least effective. The virus killed 4-week-old mice readily by all routes of inoculation except the oral, and 8-week-old mice by i.c., i.n. or s.c. inoculation. In descending order of efficacy, the routes of HEV infection were: i.c., i.n., s.c., i.p., i.v. and oral. To follow the spread of HEV from peripheral nerves to the central nervous system (CNS), the virus was inoculated subcutaneously into the right hind leg of 4-week-old mice. The virus was first detected in the spinal cord on day 2, and in the brain on day 3. The brain titres became higher than those of the spinal cord, reaching a maximum of 10(7)PFU/0.2 g when the animals were showing CNS signs. Viral antigen was first detected immunohistochemically in the lumbar spinal cord and the dorsal root ganglion ipsilateral to the inoculated leg; it was detected later in the pyramidal cells of the hippocampus and cerebral cortex, and in the Purkinje cells of the cerebellum but not in the ependymal cells, choroid plexus cells or other glial cells. The infected neurons showed no cytopathological changes.

Propagation of Swine Hemagglutinating Encephalomyelitis Virus and Pseudorabies Virus in Dorsal Root Ganglia Cells

“…In the present study, PRV infected nerve cells and nonneuronal cells, but HEV antigen was found only in nerve cells. These in vitro findings were consistent with previous in vivo studies in which PRV antigens were found in astrocytes and nerve cells [3,9], whereas HEV particles could be found in nerve cells but were not detected in glial cells and infiltrating cells [11,12,23]. Based on these in vivo and in vitro findings, infectivity of HEV may be more strictly restricted to nerve cells than PRV and rabies virus, for which non-neuronal cells may support viral entry and replication [19].…”

“…The virus was first isolated in Canada from the brains of suckling piglets [25], and causes encephalomyelitis or vomiting and wasting disease in suckling piglets [6,25]. In previous in vivo studies using piglets and mice, HEV has been suggested to invade the central nervous system via the peripheral nervous system (neural spread) [2,11,25,32,33]. However, the neural spread of HEV has not been demonstrated by in vitro studies.…”

Coronavirus infection of rat dorsal root ganglia: Ultrastructural characterization of viral replication, transfer, and the early response of satellite cells

“…), and productive infection of the contralateral primary motor cortex at day 4 p.i. (Hirano et al, 1993(Hirano et al, , 1998(Hirano et al, , 2004Bai et al, 2008).…”

Coronaviruses as Encephalitis - Inducing Infectious Agents

“…In that latter case, neuroinvasion depends on a number of variables such as the route of inoculation and the age of the mice (Yagami et al, 1986;Hirano et al, 1990;. As for the SARS-CoV in mice, HEV induced a poor inflammatory reaction in CNS (Hirano et al, 2004) and unlike HCoV-OC43-infected neurons (Jacomy & Talbot, 2003), HEV-infected cells showed no cytopathological changes.…”