Rosas-Murrieta Nora, Herrera-Camacho Irma, Vallejo-Ruiz Verónica, Millán-Pérez-Peña Lourdes, Cruz Carlos, Tapia-Ramírez José, Santos-López Gerardo, Reyes-Leyva Julio
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.
Microbes Infect. 2007 Jun;9(7):864-72. doi: 10.1016/j.micinf.2007.03.005. Epub 2007 Mar 15.
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.
尿崩症 AM9 腮腺炎病毒疫苗可导致接种后脑膜炎。尿崩症 AM9 病毒的两个变体在人类神经细胞中的复制效率不同，HN - A(1081)变体比 HN - G(1081)更具嗜神经性。分析了干扰素（IFN）对病毒复制和转录的影响。用 IFN 预处理神经细胞，与 HN - A(1081)变体（从 10(2.5)降至 10(1.3) TCID(50)）相比，HN - G(1081)变体（从 10(3.5)降至 10(2.6) TCID(50)）的复制减少更为显著。IFN 预处理还降低了 HN - G(1081)基因的转录，但未降低 HN - A(1081)基因的转录。分析了病毒感染对细胞 IFN 反应性基因转录的影响。HN - A(1081)病毒在未预处理和 IFN 预处理的细胞中均降低了 STAT1、STAT2、p48 和 MxA 的转录；而 HN - G(1081)病毒仅降低了 MxA 的转录。由于腮腺炎病毒 V 蛋白抑制 IFN 信号传导，对 V mRNA 进行了克隆和测序，发现 HN - G(1081)而非 HN - A(1081)在 P/V 编辑位点有三个额外的 G，导致 V 蛋白中插入了 Gly156。我们的结果表明，尿崩症 AM9 腮腺炎病毒变体的复制效率受其对干扰素的敏感性及其降低抗病毒反应能力的影响。
