Cornu Tatjana I, Feldmann Heinz, de la Torre Juan Carlos
Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Virol. 2004 Mar;78(6):2979-83. doi: 10.1128/jvi.78.6.2979-2983.2004.
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 LCMV 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.
沙粒病毒包括拉沙热病毒（LFV）和南美出血热病毒。这些病毒可导致严重的人类疾病，并且作为生物恐怖主义制剂构成威胁。沙粒病毒是包膜病毒，具有双节段负链RNA基因组，其蛋白质组能力仅限于四种多肽：核蛋白（NP）；表面糖蛋白（GP），经蛋白水解加工成GP1和GP2；聚合酶（L）；以及一种小的（11 kDa）环状结构域蛋白（Z）。我们的研究人员先前已表明，Z对由原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合成具有强烈的抑制活性。在本报告中，我们表明用表达Z的复制缺陷型重组腺病毒（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，由LCMV或LFV GP介导的病毒细胞进入不受影响，但病毒转录和复制均受到强烈且特异性的抑制，这导致感染性病毒的产生显著减少。这些发现为开发对抗包括LFV在内的高致病性人类沙粒病毒的抗病毒策略开辟了新途径。
