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单一 PA 突变作为高产禽流感疫苗的决定因素。

Single PA mutation as a high yield determinant of avian influenza vaccines.

机构信息

Department of Microbiology, the Institute for Viral Diseases, College of Medicine, Korea University, Seoul 02841, Republic of Korea.

Division of Influenza Virus, Center for Infectious Diseases, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong 28159, Republic of Korea.

出版信息

Sci Rep. 2017 Jan 13;7:40675. doi: 10.1038/srep40675.

DOI:10.1038/srep40675
PMID:28084423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5233958/
Abstract

Human infection with an avian influenza virus persists. To prepare for a potential outbreak of avian influenza, we constructed a candidate vaccine virus (CVV) containing hemagglutinin (HA) and neuraminidase (NA) genes of a H5N1 virus and evaluated its antigenic stability after serial passaging in embryonated chicken eggs. The passaged CVV harbored the four amino acid mutations (R136K in PB2; E31K in PA; A172T in HA; and R80Q in M2) without changing its antigenicity, compared with the parental CVV. Notably, the passaged CVV exhibited much greater replication property both in eggs and in Madin-Darby canine kidney and Vero cells. Of the four mutations, the PA E31K showed the greatest effect on the replication property of reverse genetically-rescued viruses. In a further luciferase reporter, mini-replicon assay, the PA mutation appeared to affect the replication property by increasing viral polymerase activity. When applied to different avian influenza CVVs (H7N9 and H9N2 subtypes), the PA E31K mutation resulted in the increases of viral replication in the Vero cell again. Taken all together, our results suggest the PA E31K mutation as a single, substantial growth determinant of avian influenza CVVs and for the establishment of a high-yield avian influenza vaccine backbone.

摘要

人感染禽流感病毒持续存在。为应对禽流感的潜在爆发，我们构建了一种含有 H5N1 病毒血凝素（HA）和神经氨酸酶（NA）基因的候选疫苗病毒（CVV），并评估了其在鸡胚中连续传代后的抗原稳定性。与亲本 CVV 相比，传代的 CVV 携带 4 个氨基酸突变（PB2 中的 R136K；PA 中的 E31K；HA 中的 A172T；和 M2 中的 R80Q），但其抗原性没有改变。值得注意的是，与亲本 CVV 相比，传代的 CVV 在鸡蛋和 Madin-Darby 犬肾和 Vero 细胞中的复制特性都大大增强。在这 4 个突变中，PA E31K 对反向遗传拯救病毒的复制特性影响最大。在进一步的荧光素酶报告基因、迷你复制子测定中，PA 突变似乎通过增加病毒聚合酶活性来影响复制特性。当应用于不同的禽流感 CVV（H7N9 和 H9N2 亚型）时，PA E31K 突变再次导致 Vero 细胞中病毒复制的增加。总的来说，我们的研究结果表明，PA E31K 突变是禽流感 CVV 的单一、重要的生长决定因素，也是建立高产量禽流感疫苗骨架的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/001f518e2e31/srep40675-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/35044f73fc92/srep40675-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/23b35f398c8d/srep40675-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/b375ab4a8164/srep40675-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/263f58e2c941/srep40675-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/dd8bc1ace38e/srep40675-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/001f518e2e31/srep40675-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/35044f73fc92/srep40675-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/23b35f398c8d/srep40675-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/b375ab4a8164/srep40675-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/263f58e2c941/srep40675-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/dd8bc1ace38e/srep40675-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c4f/5233958/001f518e2e31/srep40675-f6.jpg

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