Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated.
The human coronavirus HCoV-OC43 causes a significant fraction of upper respiratory tract infections. Most coronaviruses show a strong species specificity, although the SARS-Coronavirus crossed species from palm civet cats to infect humans. Similarly, HCoV-OC43, likely a member of the same coronavirus group as SARS-CoV, readily crossed the species barrier as evidenced by its rapid adaptation to the murine brain [McIntosh, K., Becker, W.B., Chanock, R.M., 1967. Growth in suckling-mouse brain of "IBV-like" viruses from patients with upper respiratory tract disease. Proc Natl Acad Sci U.S.A. 58, 2268-73]. Herein, we investigated two consequences of this plasticity in species tropism. First, we showed that HCoV-OC43 was able to infect cells from a large number of mammalian species. Second, we showed that virus that was passed exclusively in suckling mouse brains was highly virulent and caused a uniformly fatal encephalitis in adult mice. The surface glycoprotein is a major virulence factor in most coronavirus infections. We identified three changes in the HCoV-OC43 surface glycoprotein that correlated with enhanced neurovirulence in mice; these were located in the domain of the protein responsible for binding to host cells. These data suggest that some coronaviruses, including HCoV-OC43 and SARS-CoV, readily adapt to growth in cells from heterologous species. This adaptability has facilitated the isolation of HCoV-OC43 viral variants with markedly differing abilities to infect animals and tissue culture cells.
Butler
Noah
N
Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
Pewe
Lecia
L
Trandem
Kathryn
K
Perlman
Stanley
S
D000818:Animals; D002460:Cell Line; D018352:Coronavirus Infections / Q000503:physiopathology / Q000662:veterinary / Q000821:virology; D028962:Coronavirus OC43, Human / Q000472:pathogenicity*; D018792:Encephalitis, Viral / Q000401:mortality / Q000473:pathology / Q000662:veterinary* / Q000821:virology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013116:Spinal Cord / Q000473:pathology