Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes
Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes
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DOI：
10.1016/j.antiviral.2006.10.004
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发表时间：
2007-03-01
影响因子：
7.6
通讯作者：
Barr, I. G.
中科院分区：
文献类型：
--
作者：
Hurt, A. C.;Selleck, P.;Barr, I. G.
自2003年以来，高致病性甲型（H5N）流感病毒已造成家禽大规模死亡，并随后造成140多人感染和死亡。研究人员测试了2004年至2006年间从东南亚不同地区分离出的55种甲型流感病毒对抗流感药物神经氨酸酶抑制剂和金刚烷类药物的敏感性。大多数菌株对神经氨酸酶抑制剂羧酸奥司他韦、扎那米韦和帕拉米韦完全敏感；但有两株菌株的IC50值升高。这些菌株的序列分析显示，NI神经氨酸酶通常高度保守的116和117残基发生了突变。M2基因序列分析显示，来自越南、马来西亚和柬埔寨的所有甲型h5n1病毒均含有与金刚烷类药物（金刚烷胺和金刚烷胺）耐药相关的突变（L261和S31N），而来自印度尼西亚的毒株是金刚烷类耐药病毒（S31N）和敏感病毒的混合物。来自缅甸的A（H5NI）病毒均未含有已知赋予金刚烷抗性的突变。这些结果支持使用神经氨酸酶抑制剂作为预防或治疗人类甲型（H5NI）病毒感染的最合适的抗病毒药物。(c) 2006 Elsevier B.V.版权所有
Since 2003, highly pathogenic A(H5N]) influenza viruses have been the cause of large-scale death in poultry and the subsequent infection and death of over 140 humans. A group of 55 influenza A(H5N]) viruses isolated from various regions of South East Asia between 2004 and 2006 were tested for their susceptibility to the anti-influenza drugs the neuraminidase inhibitors and adamantanes. The majority of strains were found to be fully sensitive to the neuraminidase inhibitors oseltamivir carboxylate, zanamivir and peramivir; however two strains demonstrated increased IC50 values. Sequence analysis of these strains revealed mutations in the normally highly conserved residues 116 and 117 of the NI neuraminidase. Sequence analysis of the M2 gene showed that all of the A(H5N 1) viruses from Vietnam, Malaysia and Cambodia contained mutations (L261 and S31N) associated with resistance to the adamantane drugs (rimantadine and amantadine), while strains from Indonesia were found to be a mix of both adamantane resistant (S31N) and sensitive viruses. None of the A(H5NI) viruses from Myanmar contained mutations known to confer adamantane resistance. These results support the use of neuraminidase inhibitors as the most appropriate class of antiviral drug to prevent or treat human A(H5NI) virus infections. (c) 2006 Elsevier B.V. All rights reserved.