Results from the sequence alignment are consistent with the evolution process of the HE gene. The HE gene of coronavirus initially evolved from the HEF gene of influenza C virus. During this process, the HE was transformed from a trimer into a dimer but maintained its acetylcholine esterase domain. Based on the phylogenetic analysis of genes and antigens, bovine coronavirus (BCoV) from the group 2 coronaviruses, human coronavirus (HCoV-OC43) and porcine hemagglutinating encephalomyelitis virus (PHEV) are derived from a common ancestor . Their HE genes continue to evolve in the three different hosts.
PHEV independently evolved in North American and European regions. The viral strain found in the Siping area of Jilin Province in China is evolutionally closest to the HEV-67N stain (North American strain), indicating that this viral strain evolved from the PHEV from North America. In 1984, in a pig farm on the outskirts of Beijing, an HEV infection in the hybrid progenies of imported Landrace, Duroc, and Hampshire pigs was the first case reported in mainland China. In 1985, an HEV infection in the progenies of American Duroc and Hampshire lean pigs occurred at a pig farm in Jilin Province. The epidemiological and clinical characteristics reported in that case were very similar to the HEV cases reported in Canada and United States in the 1980 s . Therefore, we speculate that the viral strain isolated may be a mutated strain of HEV-67N, which was brought by the imported pigs and then spread and mutated in native pigs.
The replication of vomiting and wasting type encephalomyelitis virus initially occurs in nasal mucosa, tonsil, lung, and in some cases, in small intestine. From these invasive sites, the virus reaches the medulla oblongata through the peripheral nervous system, subsequently extends to the entire brain stem and finally reaches the cerebrum and cerebellum. Vomiting is caused by viral replication in the vagal sensory ganglia, whereas wasting occurs because of the vomiting and the delayed stomach emptying. The porcine vomiting and wasting type hemagglutinating encephalomyelitis damages the pig nervous system, as indicated by non-suppurative encephalitis and edema. The pathological changes appear as neuron degeneration, nuclear dissolution and perivascular edema; there are also some instances of satellitosis and neuronophagia.
The mice were inoculated through intracerebral injection using isolated virus, and all of the mice that were infected shared similar clinical signs observed from clinical cases. The major lesions of the infected mice were in the central nervous system; these lesions exhibited typical changes for non-suppurative encephalitis. The cortical neurons were swollen. Neurons were degenerated and necrotic, there was proliferation of glial cells, and typical neuronophagia could be seen.
This outbreak of porcine hemagglutinating encephalomyelitis in a pig farm follows a specific pattern, namely that the disease occurred in the early and middle birth period of first litter gilts; some piglets born during the middle and late birth period did not have the disease. Based on reports from other countries , these later piglets may be healthy because sows in the middle and late birth period have acquired an immune response due to earlier infection, and their piglets have obtained passive immunization and are protected through colostrum. Based on this theory, "sub-infection" may prevent the disease. In the "sub-infection" method, at least one month before giving birth, the sows have contact with diseased pigs or attenuated virus by spray or muscular injection to immunize the sows; then, the young piglets can be protected through the antibodies in the colostrum. During the birth period, once the piglets have the disease, they must be separated and treated, and the diseased must be treated.