N-terminally truncated C protein, CNDelta25, of human parainfluenza virus type 3 is a potent inhibitor of viral replication.
N-terminally truncated C protein, CNDelta25, of human parainfluenza virus type 3 is a potent inhibitor of viral replication.
复制标题
3 型人副流感病毒 N 末端截短的 C 蛋白 CNDelta25 是病毒复制的有效抑制剂。
DOI：
10.1016/j.virol.2009.08.026
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Banerjee,AmiyaK
中科院分区：
文献类型：
--
作者：
Mao,Hongxia;Chattopadhyay,Santanu;Banerjee,AmiyaK
人副流感病毒3型（HPIV 3）的C蛋白是一种多功能辅助蛋白，可抑制病毒转录和干扰素（IFN）信号传导。在本研究中，我们发现从C蛋白（CNΔ25或CNΔ50）去除N-末端25或50个氨基酸残基完全消除了HPIV 3微型基因组系统中的病毒RNA合成。进一步的N-末端或C-末端缺失削弱了CNΔ25和CNΔ50的抑制能力。随后的诱变分析表明，N-末端带电荷的氨基酸残基（K3、K6、K12、E16和R24）导致CNΔ25比C蛋白引起更高的抑制。与病毒RNA合成抑制一致，HPIV 3的生长在表达CNΔ25的HeLa衍生细胞系中显著降低5个对数。有趣的是，另一种重要的呼吸道病原体呼吸道合胞病毒（RSV）的复制在CNΔ25的存在下也受到强烈抑制。这些发现提供了使用CNΔ25作为抗病毒剂对抗由HPIV 3和RSV引起的临床上重要的呼吸道疾病的有希望的潜力。
The C protein of human parainfluenza virus type 3 (HPIV3) is a multifunctional accessory protein that inhibits viral transcription and interferon (IFN) signaling. In the present study, we found that removal of N-terminal 25 or 50 amino acid residues from the C protein (CNΔ25 or CNΔ50) totally abolished viral RNA synthesis in the HPIV3 minigenome system. Further N-terminal or C-terminal deletion impaired the inhibitory ability of CNΔ25 and CNΔ50. Subsequent mutagenesis analysis suggested that the N-terminal-charged amino acid residues (K3, K6, K12, E16, and R24) contribute to the higher inhibition caused by CNΔ25 than the C protein. Consistent with viral RNA synthesis inhibition, the growth of HPIV3 was significantly decreased by 5 logs in HeLa-derived cell line expressing CNΔ25. Interestingly, replication of respiratory syncytial virus (RSV), another important respiratory tract pathogen, was also strongly inhibited in the presence of CNΔ25. These findings provide a promising potential to use CNΔ25 as an antiviral agent against the clinically important respiratory tract diseases caused by HPIV3 and RSV.