Neurovirulence for rats of the JHMV variants escaped from neutralization with the S1-specific monoclonal antibodies

Abstract

We have studied the neurovirulence for rats of the MAb-resistant variants isolated from a highly neurovirulent JHMV, c1-2. The variants, MM6 and MM13, with point mutation located within the N terminal 100 amino acids (aa) of the S1 protein showed no alteration in neurovirulence in comparison with c1-2, showing high neurovirulence. The variants, MM65 and MM85, with a deletion composed of about 150 aa located in the middle of the S1 subunit were revealed to be non-neurovirulent. A variant MM78 with one aa deletion, asparagic acid at number 543 from the N terminus of the S1, was shown to be low-virulence. The neurovirulence of these viruses paralleled with the viral growth potential in the rat brain. However, all of these variants as well as parental c1-2 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.