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-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.
Rosas-Murrieta
Nora
N
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.
Herrera-Camacho
Irma
I
Vallejo-Ruiz
Verónica
V
Millán-Pérez-Peña
Lourdes
L
Cruz
Carlos
C
Tapia-Ramírez
José
J
Santos-López
Gerardo
G
Reyes-Leyva
Julio
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000276:immunology / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009107:Mumps / Q000821:virology; D009109:Mumps virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D064547:Myxovirus Resistance Proteins; D009447:Neuroblastoma; D009474:Neurons / Q000276:immunology / Q000821:virology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D016207:Cytokines; C579071:MX1 protein, human; D008565:Membrane Proteins; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; C097656:polypeptide 48; D007372:Interferons; D019204:GTP-Binding Proteins