UNCOATING OF A RIMANTADINE-RESISTANT VARIANT OF INFLUENZA-VIRUS IN THE PRESENCE OF RIMANTADINE

UNCOATING OF A RIMANTADINE-RESISTANT VARIANT OF INFLUENZA-VIRUS IN THE PRESENCE OF RIMANTADINE
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DOI:
10.1099/0022-1317-60-1-61
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发表时间:
1982-01-01
影响因子:
3.8
通讯作者:
PUSHKARSKAYA, NL
PUSHKARSKAYA, NL
中科院分区:
医学3区
文献类型:
--
作者:
BUKRINSKAYA, AG;VORKUNOVA, NK;PUSHKARSKAYA, NL

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通过在鸡蛋和MDCK [Madin-Darby犬肾]细胞中连续传代,在药物存在的情况下获得了德克萨斯流感病毒株(Tr)的里曼他定耐药变异体,并将其在MDCK细胞中的脱壳与敏感变异体(Ts)进行了比较。第一步和第二步的脱壳,分别定义为亚病毒颗粒(SVP)的出现在核相关的细胞质(NAC)和核糖核蛋白(RNP)的核质。在Ts感染的细胞中,NAC中显示SVP和RNP,而金刚乙胺存在时,NAC和核质中均未发现RNP。在Tr感染的细胞中,NAC中观察到SVP而非RNP。在金刚乙胺处理的细胞中,核质中RNP的量几乎没有变化,表明金刚乙胺不干扰抗性变体的脱壳。金刚乙胺显然阻断了敏感流感病毒的第二步脱壳,显然,这一事件说明了药物预防流感病毒感染的原因。
A rimantadine-resistant variant of the Texas strain of influenza virus (Tr) was obtained by serial passages in eggs and in MDCK [Madin-Darby canine kidney] cells in the presence of the drug, and its uncoating in MDCK cells was compared to that of the sensitive variant (Ts). First and second steps of uncoating were defined, respectively, by the appearance of subviral particles (SVP) in nuclear-associated cytoplasm (NAC) and ribonucleoproteins (RNP) in nucleoplasm. In cells infected with Ts, SVP and RNP were revealed in NAC, while in the presence of rimantadine RNP were neither found in NAC nor in the nucleoplasm. In cells infected with Tr, SVP but not RNP were observed in NAC. The amount of RNP in the nucleoplasm was almost unchanged in rimantadine-treated cells, demonstrating that rimantadine did not interfere with uncoating of the resistant variant. Rimantadine apparently blocks the 2nd step of uncoating of sensitive influenza viruses, and evidently, this event accounts for the prevention of influenza virus infection by the drug.