Department of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.
Present address: Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
J Gen Virol. 2023 Aug;104(8). doi: 10.1099/jgv.0.001881.
Influenza A viruses of the H2N2 subtype sparked a pandemic in 1957 and circulated in humans until 1968. Because A/H2N2 viruses still circulate in wild birds worldwide and human population immunity is low, the transmissibility of six avian A/H2N2 viruses was investigated in the ferret model. None of the avian A/H2N2 viruses was transmitted between ferrets, suggesting that their pandemic risk may be low. The transmissibility, receptor binding preference and haemagglutinin (HA) stability of human A/H2N2 viruses were also investigated. Human A/H2N2 viruses from 1957 and 1958 bound to human-type α2,6-linked sialic acid receptors, but the 1958 virus had a more stable HA, indicating adaptation to replication and spread in the new host. This increased stability was caused by a previously unknown stability substitution G205S in the 1958 H2N2 HA, which became fixed in A/H2N2 viruses after 1958. Although individual substitutions were identified that affected the HA receptor binding and stability properties, they were not found to have a substantial effect on transmissibility of A/H2N2 viruses via the air in the ferret model. Our data demonstrate that A/H2N2 viruses continued to adapt during the first year of pandemic circulation in humans, similar to what was previously shown for the A/H1N1pdm09 virus.
H2N2 亚型的甲型流感病毒于 1957 年引发大流行，并在人类中传播，直到 1968 年。由于 A/H2N2 病毒仍在全球野生鸟类中传播，且人类群体的免疫力较低，因此在雪貂模型中研究了六种禽源 A/H2N2 病毒的传播能力。没有一种禽源 A/H2N2 病毒在雪貂之间传播，这表明它们引发大流行的风险可能较低。还研究了人源 A/H2N2 病毒的传播能力、受体结合偏好和血凝素（HA）稳定性。1957 年和 1958 年的人源 A/H2N2 病毒与人类型α2,6 连接的唾液酸受体结合，但 1958 年的病毒具有更稳定的 HA，表明其适应了在新宿主中复制和传播。这种稳定性增加是由于 1958 年 H2N2 HA 中一个先前未知的稳定性取代 G205S 引起的，该取代在 1958 年后成为 A/H2N2 病毒中的固定取代。尽管鉴定出了影响 HA 受体结合和稳定性特性的个别取代，但它们并未对 A/H2N2 病毒通过雪貂模型空气传播的能力产生实质性影响。我们的数据表明，A/H2N2 病毒在人类大流行传播的第一年继续适应，这与之前对 A/H1N1pdm09 病毒的研究结果相似。
