Localization of neurovirulence determinant for rats on the S1 subunit of murine coronavirus JHMV.
A cloned virus of murine coronavirus JHMV, cl-2, was shown to be highly neurovirulent for rats in comparison with other JHMV variants. We have isolated cl-2-derived variant viruses resistant to neutralization by monoclonal antibodies (MAbs) specific for the spike (S) protein of cl-2. The variants MM6 and MM13, selected by the MAbs specific for the JHMV S protein, were revealed to have a point mutation located within the N-terminal 100 amino acids (aa) of the S1 protein. The variants MM56, MM85, and MM78, selected by MAbs specific for the larger S protein of JHMV, were shown to have a deletion composed of about 150 aa located in the middle of the S1 subunit (MM56 and MM85) or one amino acid deletion, aspartic acid at number 543 from the N-terminus of the S1 (MM78). These five MAb-resistant variants were not different from cl-2 in growth pattern on cultured DBT cells. MM6 and MM13 were shown to be highly neurovirulent for 4-week-old Lewis rats, growing to high titers in the brain and causing as high an incidence of neurological disease and death as the parental cl-2. In contrast, MM56 and MM85 were nonneurovirulent for rats. They did not cause any central nervous system disorders nor did they multiply in the rat brains. MM78 showed intermediate neurovirulence as well as intermediate growth potential in the rat brain. However, there was no apparent difference in neurovirulence between the parental and the MAb-resistant variants for mice; all of these viruses showed high neurovirulence for mice. These results suggest that the domain composed of about 150 aa in the middle of the S1 is critical for high neurovirulence of JHMV for rats. Furthermore, it is suggested that the neurovirulence of cl-2 for mice is controlled by a different viral factor.
Taguchi
F
F
National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan. taguchi@NCNPJA.ncnp.go.jp
Kubo
H
H
Takahashi
H
H
Suzuki
H
H
D000818:Animals; D001921:Brain / Q000821:virology; D002874:Chromosome Mapping; D018352:Coronavirus Infections / Q000235:genetics / Q000821:virology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D006517:Murine hepatitis virus / Q000235:genetics* / Q000472:pathogenicity*; D051381:Rats; D011917:Rats, Inbred Lew; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000235:genetics*; D014774:Virulence / Q000235:genetics*
D014759:Viral Envelope Proteins