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Mechanism of the H5N1 subtype influenza virus A/Guangxi/1/2005 resistance to antiviral drug
Author(s): 
Pages: 682-685
Year: Issue:  9
Journal: Chinese Journal of Preventive Veterinary Medicine

Keyword:  H5N1禽流感病毒抗药性金刚烷胺;
Abstract: 为研究H5N1亚型禽流感病毒(AIV)的抗药机制,本研究选取Clade2.3.4亚群中一株对金刚烷胺敏感的人源AIV A/Guangxi/1/2005(H5N1) (S-GX05),用抗流感病毒药物金刚烷胺对其进行定向诱导,筛选出一株抗药性病毒株,命名为R- A/Guangxi/1/2005 (R-GX05).通过全基因测序并与S-GX05全基因序列进行对比,结果显示S-GX05只在其M2蛋白中有一个氨基酸位点发生突变,即A30P;抗药性鉴定这两株病毒的半数药物抑制浓度(IC50)分别为0.9 μM和48.9 μM,表明R-GX05对金刚烷胺表现出一定程度的抗性.动物实验证实,这两株病毒对BALB/c小鼠的致病性基本一致,均表现出高致病性,其MLD50分别为4.7 log 10 EID50和5.0 log10 EID50,两株病毒在小鼠体内各组织脏器中的分布及增殖能力也基本相同.这些结果表明,S-GX05在药物压力下产生抗药性后,并未引起其它生物学特性的改变.A30P的发现为进一步从分子水平上研究H5N1亚型AIV的抗药机制及新型抗流感新药的研发奠定了基础.
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