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

• Published in: Microbes and infection 2007-06, Vol.9 (7), p.864-872
• Main Authors: Rosas-Murrieta, Nora, Herrera-Camacho, Irma, Vallejo-Ruiz, Verónica, Millán-Pérez-Peña, Lourdes, Cruz, Carlos, Tapia-Ramírez, José, Santos-López, Gerardo, Reyes-Leyva, Julio
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Applied microbiology; Base Sequence; Biological and medical sciences; Cell Line, Tumor; Cytokines - genetics; Cytokines - immunology; Fundamental and applied biological sciences. Psychology; Genetic Variation - immunology; GTP-Binding Proteins - genetics; GTP-Binding Proteins - immunology; HeLa Cells; Humans; Interferon inhibition; Interferons - immunology; Interferons - pharmacology; Membrane Proteins - genetics; Membrane Proteins - immunology; Microbiology; Miscellaneous; Molecular Sequence Data; Mumps - virology; Mumps vaccine; Mumps virus; Mumps virus - drug effects; Mumps virus - genetics; Mumps virus - immunology; Myxovirus Resistance Proteins; Neuroblastoma; Neurons - immunology; Neurons - virology; Neurovirulence; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - chemistry; RNA, Messenger - genetics; Rubulavirus; Sequence Alignment; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - immunology; STAT2 Transcription Factor - genetics; STAT2 Transcription Factor - immunology; Transcription; Transcription, Genetic - immunology; Urabe AM9; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Virology; Virus Replication - immunology
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2007.03.005

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.