Infections of rodents by murine coronaviruses can lead to
chronic diseases of the central nervous system. These
infections are interesting systems to study mechanisms which could be relevant for the pathogenesis of certain human diseases. One major factor influencing the outcome of
infection is related to the virus. To understand the virological basis for neurovirulence we compared JHM-virus isolates with different
biological properties. JHM-Wt causes only
acute disease, JHM-Ts43 a demyelinating
encephalomyelitis and a virus shedded from persistently infected cells (JHM-Pi) is not virulent at all. The spread of these viruses in glial cell cultures reflects their different neurovirulence for animals. The peplomer E2 of these viruses reveals structural and antigenic differences. We characterised the
epitopes of E2 with a panel of
monoclonal antibodies. Four
epitopes are associated with regions important for neutralisation, cell fusion and attachment. More than five
epitopes are not related to such functions.
Epitopes differ in their location and accessibility on the E2
protein subunits between JHM-Wt, JHM-Ts43 and JHM-Pi. To identify
epitopes in regions important for pathogenesis, we performed animal studies with variants selected by
monoclonal antibodies. Variants changed in a defined
epitope (E2-Ba) induce in Balb/c mice a
chronic disease. Variants changed in only one of the other three neutralisation
epitopes induce
acute disease. These results support and extend the observation that the peplomer
protein E2 is a major determinant for virulence and antigenic variability of coronaviruses 1,4,5,6,8,10,17,19,22,23. Increasing evidence had been obtained that certain structural features of this
protein are important for the cell tropism of the virus. Furthermore, this
protein influences strongly the type and specificity of immune responses against viral and host
antigens. The highly advanced knowledge on structure and replication of coronaviruses will be of great value to analyze further mechanisms leading to inflammatory
demyelinating diseases associated with a persistent
virus infection.