Development of a transgenic mouse model susceptible to human coronavirus 229E

Abstract

Human coronavirus (HCoV) 229E is a group 1 coronavirus and is specific to humans. So far, no animal model is available to study the pathogenesis of infection by HCoV-229E. We show here that the expression of aminopeptidase N (APN, also termed CD13), the receptor for HCoV-229E, is required but not sufficient to confer susceptibility in vivo. HCoV-229E infection was facilitated by crossing APN transgenic mice into signal transducers and activators of transcription (Stat) 1 null mice and by adaptation of HCoV-229E to grow in primary APN transgenic, Stat1 null fibroblasts. Double transgenic mice allow the study of human coronavirus group 1 infections in an animal model, in particular, viral tropism, replication, recombination, and spread in an immunocompromised situation. Furthermore, these mice provide an important tool for the evaluation of biosafety and efficacy of coronavirus-based vectors.

Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis

“…Since they eventually become macrophages as they invade tissues, this activation suggests that HCoV-229E-infected monocytes would serve to facilitate their passage toward other tissues including the CNS, especially in immune-compromised individuals, as this was observed for murine cytomegalovirus (MCMV) (Reuter et al, 2004). The fact that HCoV-229E could only infect partially immune-compromised transgenic mice (Lassnig et al, 2005) suggests that, being an opportunistic pathogen, HCoV-229E could take advantage of an immune-suppressed environment and disseminate to the CNS within susceptible individuals. The establishment of a persistent infection in a human leukocytic cell line is also consistent with the possibility that monocytes/macrophages serve as a reservoir and vector for this neuroinvasive HCoV (Arbour et al, 2000).…”

Development of transgenic mouse model expressing porcine aminopeptidase N and its susceptibility to porcine epidemic diarrhea virus

“…Reynaud et al, 2014). In the field of coronavirus research, studies of severe acute respiratory syndrome coronavirus (SARS-CoV) and human coronavirus 229E (hCoV-229E) have been conducted with transgenic mouse models (Lassnig et al, 2005;Tseng et al, 2007). The host range of the porcine coronaviruses is strongly limited to pigs, so pigs are the only animals available in which to study viral pathogenesis.…”

Production of Transgenic Nonhuman Primates

“…Transgenic animal modeling of human diseases has led to biomedical breakthroughs that have significant impact on the diagnoses, treatments, and interventions in human diseases (Chan, 2004;Chan et al, 2001;Yang and Chan, 2011;Yang et al, 2008;Brosh et al, 2000;Cayzac et al, 2011;Hitz et al, 2009;Lassnig et al, 2005;Ramaswamy et al, 2009;Shavlakadze et al, 2005;Tsunematsu et al, 2011). Since the development of the first transgenic rodents in the early 1980s, thousands of transgenic rodents that captured conditions of human diseases have been developed.…”