PATHOGENICITY OF NEUTRALIZATION ESCAPE MUTANTS OF MOUSE HEPATITIS-VIRUS - CORRELATION WITH T-CELL AND B-CELL DEPLETIONS

Viral pathogenicity is a result of an imbalance between viral replicat ion and the host's immune defences. When the virus is lymphotropic, un derstanding the pathogenic process of the viral disease becomes compli cated because virus/lymphocyte interactions can alter the cell's integ rity and subsequently induce immunodeficiency. The immune system plays an important role in the outcome of acute disease induced by the mous e hepatitis virus type 3 (MHV3). The use of attenuated escape mutants provides a tool to study the role of viral properties involved in its pathogenicity. We selected MHV3 mutants by virtue of their resistance to neutralization by monoclonal antibodies (mAb), in order to study th eir pathogenic properties. We reported that two MHV3 escape mutants we re attenuated in their pathogenic properties according to inoculation site and with regard to survival time and ability to deplete T- and B- cell subpopulations in the spleen, thymus and bone marrow of susceptib le Balb/c mice. The highly attenuated CL12 mutant could not induce dep letion in T or B cells following intraperitoneal (i.p.) or intranasal (i.n.) inoculations, at three days postinfection. The less attenuated 51.6 mutant, however, maintained the ability to deplete T and B cells following i.p. inoculation, as described with the pathogenic MHV3. In contrast, no depletion of T cells following i.n. inoculation was induc ed with this mutant, although B lineage cells decreased. The use of su ch mutants enabled us to examine the role of each compartment of the i mmune system, since the highly attenuated CL12 mutant induced no immun odeficiency, as defined by immune cell depletion, whereas the less att enuated 51.6 mutant maintained its ability to decrease only the B-cell compartment after i.n. inoculation. Results are discussed with regard to the virus/lymphocyte interactions during the pathogenic process.