Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model.
Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model.
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DOI：
10.3390/v13050719
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发表时间：
2021-04-21
期刊：
影响因子：
--
通讯作者：
Lakdawala SS
中科院分区：
文献类型：
--
作者：
Le Sage V;Kormuth KA;Nturibi E;Lee JM;Frizzell SA;Myerburg MM;Bloom JD;Lakdawala SS
季节性和大流行性流感病毒的空气传播是它们在流行病学上取得成功和给人类造成公共卫生负担的原因。H1N1流感病毒的有效空气传播依赖于受体特异性和表面糖蛋白血凝素（HA）融合的pH值。在这项研究中，我们检测了融合的HA pH值对细胞培养适应的H3N2病毒传播性的作用。A/Perth/16/2009 (H3N2) HA头部78位和212位突变，在细胞培养适应后选择，使病毒的酸稳定性从pH 5.5 （WT）降低到pH 5.8（突变）。此外，突变H3N2病毒在细胞培养中复制到更高的滴度，但在雪貂模型中减少了空气传播。这些数据表明，与H1N1血凝素一样，H3N2血凝素的融合pH值是有效空气传播的决定因素。令人惊讶的是，NA片段的非编码区可以影响突变病毒融合的pH值。综上所述，我们的数据证实，HA酸稳定性是流行病学上成功的人流感病毒的一个重要特征，并受到HA/NA平衡的影响。
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.
影响因子：
7.8
作者：
Kawahara M;Wada T;Momose F;Nobusawa E;Morikawa Y
通讯作者：
Morikawa Y