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

Rosas-Murrieta N, Herrera-Camacho I, Vallejo-Ruiz V, Millán-Pérez-Peña L, Cruz C, Tapia-Ramírez J, Santos-López G, Reyes-Leyva J

Lab. de Virología y Biología Molecular, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Hospital General de Zona No. 5, Km. 4.5 Carretera Atlixco-Metepec, 74360 Metepec, Pue., Mexico; Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Complejo de Ciencias, Ciudad Universitaria, 72570 Puebla, Pue., Mexico.

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-A(1081) variant being more neurotropic than HN-G(1081). 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-G(1081) variant (from 10(2.5) to 10(1.3) TCID(50)) than that of HN-A(1081) (from 10(3.5) to 10(2.6) TCID(50)). IFN-priming also reduced the transcription of HN-G(1081) genes, but not of HN-A(1081). The effect of viral infection on the transcription of cellular IFN responsive genes was analyzed. HN-A(1081) virus reduced the transcription of STAT1, STAT2, p48 and MxA in both unprimed and IFN-primed cells; whereas HN-G(1081) virus just reduced MxA transcription. Since rubulavirus V protein inhibits IFN signaling, the V mRNA was cloned and sequenced, finding that HN-G(1081) but not HN-A(1081) 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.

Published 18 June 2007 in Microbes Infect, 9(7): 864-872.
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