Cells expressing the RING finger Z protein are resistant to arenavirus infection
Cells expressing the RING finger Z protein are resistant to arenavirus infection
复制标题
DOI：
10.1128/jvi.78.6.2979-2983.2004
复制
发表时间：
2004-03-01
影响因子：
5.4
通讯作者：
de la Torre, JC
中科院分区：
文献类型：
--
作者：
Cornu, TI;Feldmann, H;de la Torre, JC
沙粒病毒包括拉沙热病毒（LFV）和南美出血热病毒。这些病毒引起严重的人类疾病，并作为生物恐怖主义的媒介构成威胁。沙粒病毒是一种包膜病毒，具有双片段负链RNA基因组，其蛋白质组学能力仅限于四种多肽：核蛋白（NP）；表面糖蛋白（GP），被蛋白水解成GP1和GP2；聚合酶(L);一个小的（11 kda）无名指蛋白(Z)。我们的研究人员先前已经证明，Z对典型沙粒病毒淋巴细胞性脉络丛脑膜炎病毒（LCMV）的聚合酶介导的RNA合成具有很强的抑制活性。在本报告中，我们证明了用表达Z的复制缺陷重组腺病毒（rAd-Z）转导的细胞对LCMV和LFV感染具有抗性。在rad - z转导的细胞中，LCMW或LFV GP介导的病毒进入细胞不受影响，但病毒的转录和复制都受到强烈和特异性的抑制，从而导致感染性病毒的产生急剧减少。这些发现为开发对抗高致病性人类沙粒病毒（包括LFV）的抗病毒策略开辟了新的途径。
Arenaviruses include Lassa fever virus (LFV) and the South American hemorrhagic fever viruses. These viruses cause severe human disease, and they pose a threat as agents of bioterrorism. Arenaviruses are enveloped viruses with a bisegmented negative-strand RNA genome whose proteomic capability is limited to four polypeptides: nucleoprotein (NP); surface glycoprotein (GP), which is proteolytically processed into GP1 and GP2; polymerase (L); and a small (11-kDa) RING finger protein (Z). Our investigators have previously shown that Z has a strong inhibitory activity on RNA synthesis mediated by the polymerase of the prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV). In this report we show that cells transduced with a replication-deficient recombinant adenovirus expressing Z (rAd-Z) are resistant to LCMV and LFV infection. Virus cell entry mediated by LCMW or LFV GP was not affected in rAd-Z-transduced cells, but both virus transcription and replication were strongly and specifically inhibited, which resulted in a dramatic reduction in production of infectious virus. These findings open new avenues for developing antiviral strategies to combat the highly pathogenic human arenaviruses, including LFV.