Influenza virus neuraminidase contributes to the dextran sulfate-dependent suppressive replication of some influenza A virus strains.
Influenza virus neuraminidase contributes to the dextran sulfate-dependent suppressive replication of some influenza A virus strains.
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DOI：
10.1016/j.antiviral.2012.09.012
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发表时间：
2012-12
影响因子：
7.6
通讯作者：
H. Yamada;E. Moriishi;Ahmad M. Haredy;N. Takenaka;Y. Mori;K. Yamanishi;S. Okamoto
中科院分区：
文献类型：
--
作者：
H. Yamada;E. Moriishi;Ahmad M. Haredy;N. Takenaka;Y. Mori;K. Yamanishi;S. Okamoto
葡聚糖硫酸盐(DS)是一种带负电荷的硫酸盐多糖，它能抑制甲型流感病毒株的复制，这种抑制作用与抑制血凝素(HA)依赖的融合活性有关。然而，目前尚不清楚DS是否抑制了所有或仅部分甲型流感病毒株的复制，或者HA是否是复制抑制的唯一靶点。在目前的研究中，我们发现DS抑制了部分但不是所有甲型流感病毒株的复制。DS敏感菌株的抑制作用呈剂量依赖关系，并可被带正电荷的二乙氨基乙基葡聚糖(DD)中和。DS的抑制作用不仅表现在病毒感染的初期，包括病毒的附着和进入，还表现在病毒的晚期，包括病毒的组装和从感染细胞中释放。电子显微镜显示DS诱导病毒在细胞表面聚集。病毒复制后期被抑制的菌株的神经氨酸酶(NA)活性也受到DS的抑制，这种抑制作用也被带正电荷的DD所中和。此外，我们发现，用病毒复制未被抑制的毒株的NA基因替换病毒复制在后期被DS抑制的毒株的NA基因，消除了DS依赖的抑制。这些结果表明，流感病毒NA参与了病毒从感染细胞中释放DS的晚期，其抑制作用可能与DS负电荷对NA活性的抑制有关。
Dextran sulfate (DS), a negatively charged, sulfated polysaccharide, suppresses the replication of an influenza A virus strain, and this suppression is associated with inhibition of the hemagglutinin (HA)-dependent fusion activity. However, it remains unknown whether the replication of all or just some influenza A virus strains is suppressed by DS, or whether HA is the only target for the replication suppression. In the present study, we found that DS inhibited the replication of some, but not all influenza A virus strains. The suppression in the DS-sensitive strains was dose-dependent and neutralized by diethylaminoethyl-dextran (DD), which has a positive charge. The suppression by DS was observed not only at the initial stage of viral infection, which includes viral attachment and entry, but also at the late stage, which includes virus assembly and release from infected cells. Electron microscopy revealed that the DS induced viral aggregation at the cell surface. The neuraminidase (NA) activity of the strains whose viral replication was inhibited at the late stage was also more suppressed by DS than that of the strains whose replication was not inhibited, and this inhibition of NA activity was also neutralized by adding positively charged DD. Furthermore, we found that replacing the NA gene of a strain in which viral replication was inhibited by DS at the late stage with the NA gene from a strain in which viral replication was not inhibited, eliminated the DS-dependent suppression. These results suggest that the influenza virus NA contributes to the DS-suppressible virus release from infected cells at the late stage, and the suppression may involve the inhibition of NA activity by DS’s negative charge.