Analysis of virus-receptor interaction and its application in veterinary science

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We have investigated the interaction of mouse hepatitis virus (MHV) and its receptor CEACAM1 (MHVR) by using soluble form of MHVR (soMHVR). soMHVR1 derived from MHV-susceptible BALB/c mouse showed high affinity and neutralizing activity to MHV, while soMHVR2 isolated from MHV-resistant SJL mouse was low in affinity and neutralization activity. We have isolated mutant virus resistant to neutralization (srr7) by soMHVR1 from MHV-JHMV. Srr7 infected as efficiently as wild type JHMV to cells expressing MHVR1, but did more than 2 logs less efficiently than wt virus to cells expressing MHVR2.This inefficient infection of srr7 was revealed to be due to its low fusogenicity, namely low capability to enter into these cells. These results suggested that the binding ofMHVR2 to wild type S protein triggered its conformational change, while it failed to do so for srr7 S proteins. We have also found that soMHVR1 activated or potentiated MHV infection to MHVR-deficient cells. This implied that binding of soMHVR converted fusion-negative S protein to fusion-positive phenotype. Using this system, we can further investigate in cell-free system the interaction of MHV and receptor as well as dynamics MHV particles following its interaction with receptor. Env protein ofmurine leukemia virus Fv-4r plays an important role for the resistance of mice to various leukemia viruses. We have conferred the resistance against leukemia virus to otherwise susceptible mice by expressing Env using retrovirus vectors. We have developed a highly pathogenic influenza A virus by passaging an avirulent virus through chickens. This conversion was accompanied with the mutations in HA protein, which resulted in enhanced cleavability of the protein. This suggested that HA cleavability influenced the pathogenicity of influenza virus.