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细胞培养适应的 H3N2 流感病毒影响其酸稳定性，并降低雪貂模型中的空气传播能力。

Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model.

机构信息

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburg, PA 15219, USA.

Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

出版信息

Viruses. 2021 Apr 21;13(5):719. doi: 10.3390/v13050719.

DOI:10.3390/v13050719
PMID:33919124
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8143181/
Abstract

Airborne transmission of seasonal and pandemic influenza viruses is the reason for their epidemiological success and public health burden in humans. Efficient airborne transmission of the H1N1 influenza virus relies on the receptor specificity and pH of fusion of the surface glycoprotein hemagglutinin (HA). In this study, we examined the role of HA pH of fusion on transmissibility of a cell-culture-adapted H3N2 virus. Mutations in the HA head at positions 78 and 212 of A/Perth/16/2009 (H3N2), which were selected after cell culture adaptation, decreased the acid stability of the virus from pH 5.5 (WT) to pH 5.8 (mutant). In addition, the mutant H3N2 virus replicated to higher titers in cell culture but had reduced airborne transmission in the ferret model. These data demonstrate that, like H1N1 HA, the pH of fusion for H3N2 HA is a determinant of efficient airborne transmission. Surprisingly, noncoding regions of the NA segment can impact the pH of fusion of mutant viruses. Taken together, our data confirm that HA acid stability is an important characteristic of epidemiologically successful human influenza viruses and is influenced by HA/NA balance.

摘要

空气传播是季节性流感病毒和大流行性流感病毒在人群中具有流行病学成功和公共卫生负担的原因。甲型 H1N1 流感病毒的有效空气传播依赖于表面糖蛋白血凝素（HA）的受体特异性和融合的 pH 值。在这项研究中，我们研究了 HA 融合的 pH 值对细胞培养适应的 H3N2 病毒传播能力的影响。在细胞培养适应后选择的 A/Perth/16/2009（H3N2）HA 头部位置 78 和 212 的突变降低了病毒的酸稳定性，从 pH5.5（野生型）降低到 pH5.8（突变体）。此外，突变的 H3N2 病毒在细胞培养中复制到更高的滴度，但在雪貂模型中的空气传播能力降低。这些数据表明，与 H1N1HA 一样，H3N2HA 的融合 pH 值是有效空气传播的决定因素。令人惊讶的是，NA 节段的非编码区可以影响突变病毒的融合 pH 值。总之，我们的数据证实了 HA 酸稳定性是具有流行病学成功的人类流感病毒的重要特征，并受 HA/NA 平衡的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/ee6dc502f060/viruses-13-00719-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/88cf08dddedb/viruses-13-00719-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/84b6a016df1f/viruses-13-00719-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/5e3df713b821/viruses-13-00719-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/7ca0755cf569/viruses-13-00719-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/ee6dc502f060/viruses-13-00719-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/88cf08dddedb/viruses-13-00719-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/84b6a016df1f/viruses-13-00719-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/5e3df713b821/viruses-13-00719-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/7ca0755cf569/viruses-13-00719-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1143/8143181/ee6dc502f060/viruses-13-00719-g005.jpg

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