Differential sensitivity to interferon influences the replication and transcription of Urabe AM9 mumps virus variants in nerve cells

Urabe AM9 mumps virus vaccine causes post-vaccination meningitis. Two variants of Urabe AM9 virus differ in their replication efficiency in human nerve cells, HN-A1081 variant being more neurotropic than HN-G1081. The effect of interferon (IFN) on viral replication and transcription was analyzed. Priming of nerve cells with IFN reduced more significantly the replication of HN-G1081 variant (from 102.5 to 101.3 TCID50) than that of HN-A1081 (from 103.5 to 102.6 TCID50). IFN-priming also reduced the transcription of HN-G1081 genes, but not of HN-A1081. The effect of viral infection on the transcription of cellular IFN responsive genes was analyzed. HN-A1081 virus reduced the transcription of STAT1, STAT2, p48 and MxA in both unprimed and IFN-primed cells; whereas HN-G1081 virus just reduced MxA transcription. Since rubulavirus V protein inhibits IFN signaling, the V mRNA was cloned and sequenced, finding that HN-G1081 but not HN-A1081 presented three extra G in the P/V edition site, producing the insertion of Gly156 in the V protein. Our results suggest that the replication efficiency of Urabe AM9 mumps virus variants is influenced by their sensitivity to interferon and their capacity to reduce the antiviral response.