Department of Viroscience, Erasmus Medical Centre, Rotterdam 3015 CE, The Netherlands.
Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
Proc Natl Acad Sci U S A. 2022 Oct 18;119(42):e2211616119. doi: 10.1073/pnas.2211616119. Epub 2022 Oct 10.
Influenza B virus primarily infects humans, causing seasonal epidemics globally. Two antigenic variants-Victoria-like and Yamagata-like-were detected in the 1980s, of which the molecular basis of emergence is still incompletely understood. Here, the antigenic properties of a unique collection of historical virus isolates, sampled from 1962 to 2000 and passaged exclusively in mammalian cells to preserve antigenic properties, were determined with the hemagglutination inhibition assay and an antigenic map was built to quantify and visualize the divergence of the lineages. The antigenic map revealed only three distinct antigenic clusters-Early, Victoria, and Yamagata-with relatively little antigenic diversity in each cluster until 2000. Viruses with Victoria-like antigenic properties emerged around 1972 and diversified subsequently into two genetic lineages. Viruses with Yamagata-like antigenic properties evolved from one lineage and became clearly antigenically distinct from the Victoria-like viruses around 1988. Recombinant mutant viruses were tested to show that insertions and deletions (indels), as observed frequently in influenza B virus hemagglutinin, had little effect on antigenic properties. In contrast, amino-acid substitutions at positions 148, 149, 150, and 203, adjacent to the hemagglutinin receptor binding site, determined the main antigenic differences between the Early, Victoria-like, and Yamagata-like viruses. Surprisingly, substitutions at two of the four positions reverted in recent viruses of the Victoria lineage, resulting in antigenic properties similar to viruses circulating ∼50 y earlier. These data shed light on the antigenic diversification of influenza viruses and suggest there may be limits to the antigenic evolution of influenza B virus.
乙型流感病毒主要感染人类，在全球范围内引起季节性流行。在 20 世纪 80 年代检测到两种抗原变体——维多利亚样和山形样，但其出现的分子基础仍不完全清楚。在这里，通过血凝抑制试验确定了从 1962 年到 2000 年采集的独特历史病毒分离物的抗原特性，并构建了抗原图谱，以量化和可视化谱系的分化。抗原图谱仅显示了三个不同的抗原簇——早期、维多利亚和山形，每个簇的抗原多样性相对较小，直到 2000 年。具有维多利亚样抗原特性的病毒大约在 1972 年出现，并随后分化为两个遗传谱系。具有山形样抗原特性的病毒从一个谱系进化而来，大约在 1988 年左右与维多利亚样病毒明显不同。测试重组突变病毒表明，在乙型流感病毒血凝素中经常观察到的插入和缺失（indels）对抗原特性几乎没有影响。相比之下，位于血凝素受体结合位点附近的位置 148、149、150 和 203 的氨基酸取代决定了早期、维多利亚样和山形样病毒之间的主要抗原差异。令人惊讶的是，维多利亚谱系最近的病毒中，四个位置中的两个位置的取代发生了逆转，导致抗原特性与大约 50 年前流行的病毒相似。这些数据揭示了流感病毒的抗原多样化，并表明乙型流感病毒的抗原进化可能存在限制。
