Neuraminidase hemadsorption activity, conserved in avian influenza A viruses, does not influence viral replication in ducks

Neuraminidase hemadsorption activity, conserved in avian influenza A viruses, does not influence viral replication in ducks
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DOI:
10.1128/jvi.71.9.6706-6713.1997
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发表时间:
1997-09-01
影响因子:
5.4
通讯作者:
Kawaoka, Y
Kawaoka, Y
中科院分区:
医学2区
文献类型:
--
作者:
Kobasa, D;Rodgers, ME;Kawaoka, Y

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甲型流感病毒的N1和N9神经氨酸酶(NA)亚型表现出显著的红细胞吸附活性,其定位于与酶活性位点不同的位点。为了确定不同NA之间红细胞吸附活性的保守性,我们检测了来自禽、猪、马和人病毒分离株的大多数NA亚型,所有亚型的禽病毒NA和一种马病毒N8 NA具有高水平的血吸附活性,猪病毒N1 NA仅表现出弱的血吸附活性,而人病毒N1和N2 NA,对鸡红细胞(RBC)具有血吸附活性的NA同样能够吸附人RBC,然而,血吸附阳性NA均不能结合马、猪或牛RBC,表明来自这些物种的RBC缺乏分子,A/duck/Hong Kong/7/75 N2 NA的推定血吸附位点的突变消除了野生型蛋白质所表现出的高水平血吸附活性,但也导致NA酶活性降低50%。A转染病毒,通过反向遗传学产生,含有这种突变NA的病毒在鸡胚成纤维细胞培养物中的复制效率比表达野生型NA的转染病毒低10倍,然而,两种病毒在北京鸭中复制得同样好。尽管禽病毒NA中NA血细胞吸附活性的保守性表明NA维持了所需的功能,活性的丧失并不排除病毒在禽类宿主中的复制。
The N1 and N9 neuraminidase (NA) subtypes of influenza A viruses exhibit significant hemadsorption activity that localizes to a site distinct from that of the enzymatic active site, To determine the conservation of hemadsorption activity among different NAs, we have examined most of the NA subtypes from avian, swine, equine, and human virus isolates, All subtypes of avian virus NAs examined and one equine virus N8 NA possessed high levels of hemadsorption activity, A swine virus N1 NA exhibited only weak hemadsorption activity, while in human virus N1 and N2 NAs, the activity was detected at a much lower level than in avian virus NAs, NAs which possessed hemadsorption activity for chicken erythrocytes (RBCs) were similarly able to adsorb human RBCs, However, none of the hemadsorption-positive NAs could bind equine, swine, or bovine RBCs, suggesting that RBCs from these species lack molecules, recognized by the NA hemadsorption site, present on human and chicken RBCs, Mutagenesis of the putative hemadsorption site of A/duck/Hong Kong/7/75 N2 NA abolished the high level of hemadsorption activity exhibited by the wild-type protein but also resulted in a 50% reduction of the NA enzymatic activity, A transfectant virus, generated by reverse genetics, containing this mutated NA replicated 10-fold less efficiently in chicken embryo fibroblast cultures than did a transfectant virus expressing the wild-type NA, However, both viruses replicated equally well in Peking ducks, Although conservation of NA hemadsorption activity among avian virus NAs suggests the maintenance of a required function of NA, loss of the activity does not preclude the replication of the virus in an avian host.