Neuropathogenesis of a mouse-adapted porcine epidemic diarrhea virus infection in suckling mice

Abstract

A mouse-adapted porcine epidemic diarrhea virus, MK-p10, showed higher neurovirulence in suckling mice than a non-adapted MK strain. There was no difference in virus growth, whereas clear differences between these two virus infections existed in the type of target cells infected, the spread of virus and the cytokine levels produced in the brain. In the early phase of infection, neurons, astrocytes and neural progenitor cells were infected by MK-p10, whereas neural progenitor cells were the only target cells infected by MK. On days 4-5 post-inoculation, MK-p10 antigens were distributed in a number of neurons in a wide area of the brain; however, antigens were restricted in MK infection. In moribund mice in both infection groups, viral antigens were found in a wide area of the brain. The wide spectrum of initial target cells following MK-p10 infection, as well as its faster spread in the brain, may be evidence of enhanced virulence in suckling mice.Porcine epidemic diarrhea virus (PEDV) is an enveloped alphacoronavirus with a single-stranded, positive-sense RNA genome of about 30 kb and is a causative agent for diarrhoea in pigs. It induces mild intestinal disease in adult pigs, whereas it causes lethal diarrhoea in piglets (Pensaert & de Bouck, 1978). However, the pathogenesis of diseases caused by PEDV is not well understood, since there are no animal models available for the study of infection.We have recently obtained a PEDV strain adapted to suckling mice (Shirato et al., 2010). Although the neurovirulence of PEDV has not been described thus far in pigs, we reported the establishment of a highly neurovirulent strain of PEDV via adaptation of a celladapted MK strain (Kusanagi et al., 1992) to the mouse brain (Shirato et al., 2010). MK showed weak neurovirulence when injected into a suckling mouse brain, whereas MK-p10 showed increased neurovirulence. When inoculated with MK-p10 via the oral route, mice showed slight weight loss with no other clinical symptoms, but no viral antigen or histological changes were observed in the intestine. In this study, we investigated the enhanced neuropathological features of the MK-p10 strain compared with those of the MK strain in suckling mice by histopathological and immunochemical analysis. Our study suggests that the alteration of the cell tropism in the suckling mouse brain, as well as the faster spread of the virus to a variety of cells, mainly neurons, leads to higher neurovirulence in the adapted MK-p10 strain.MK and MK-p10 were prepared as previously reported (Shirato et al., 2010). Pregnant BALB/c mice were obtained from Japan SLC and Sankyo Labo Service Corporation, and newborn mice were inoculated intracerebrally with 10 ml containing ca 10 4 p.f.u. virus solution. Those mice were clinically observed and their brains were histologically or immunohistochemically examined. Kaplan-Meier analysis was used for statistics, and P,0.05 was considered to be statistically significant. Animal experiments were approved by the Committees on Experimental Animals, National Inst...

Metagenomics screening of viruses in Arusha, north Tanzania: a one health perspective across wild rodents, domestic dogs and humans

“…These viruses traditionally cause diseases in pigs and cats, respectively [40][41]. While previous studies did not label them as zoonotic, an experimental study involving mice suggested the potential for the Porcine epidemic diarrhea virus to cause neuropathogenic effects [42]. This study thus introduces the notion that the Porcine epidemic diarrhea virus, along with the Feline infectious peritonitis virus, might possess the capability to infect a broader range of animals.…”

Development of a Model of Porcine Epidemic Diarrhea in Microminipigs

“…[3][4][5]11 The body weight (BW) of neonatal MMPigs is approximately 400 g, and thus the neonates can be housed in isolation cages designed for rats, 5 so the MMPig might be an effective small animal model for PED and may overcome the disadvantages of using mouse models of PED. 7 In this study, to develop a novel small animal model for PED, we infected a neonatal MMPig with PEDV and pathologically examined the infected pig.…”