Serological assays with modern influenza A/H3N2 viruses have become problematic due to the progressive reduction in the ability of viruses of this subtype to bind and agglutinate red blood cells (RBCs). This is due to reduced ability of the viral haemagglutinin (HA) glycoprotein to bind to the sialic acid-containing receptors presented by these cells. Additionally, as a result of reduced HA-mediated binding in cell culture, modern A/H3N2 viruses often acquire compensatory mutations during propagation that enable binding of cellular receptors through their neuraminidase (NA) surface protein. Viruses that have acquired this NA-mediated binding agglutinate RBCs through their NA, confusing the results of serological assays designed to assess HA antigenicity. Here we confirm with a large dataset that the acquisition of mutations that confer NA binding of RBCs is a culture artefact, and demonstrate that modern A/H3N2 isolates with acquired NA-binding mutations revert to a clinical-like NA sequence after a single passage in human airway epithelial (HAE) cells.

中文翻译：

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甲型/ H3N2流感病毒在人气道细胞中的传播去除了与神经氨酸酶介导的结合相关的人工变种。

由于这种亚型病毒结合和凝集红细胞（RBC）的能力逐渐降低，因此现代A / H3N2流感病毒的血清学检测已成为问题。这是由于病毒血凝素（HA）糖蛋白与这些细胞呈递的含唾液酸受体结合的能力降低。此外，由于细胞培养物中HA介导的结合减少，现代A / H3N2病毒通常在繁殖过程中获得代偿性突变，使细胞受体能够通过其神经氨酸酶（NA）表面蛋白结合。通过其NA获得这种NA介导的结合凝集性RBC的病毒，混淆了旨在评估HA抗原性的血清学检测结果。