GI-16 lineage (624/I or Q1), there and back again: The history of one of the major threats for poultry farming of our era

The genetic variability of Infectious bronchitis virus (IBV) is one of the main challenges for its control, hindering not only the development of effective vaccination strategies but also its classification and, consequently, epidemiology understanding. The 624/I and Q1 genotypes, now recognized to be part of the GI-16 lineage, represent an excellent example of the practical consequences of IBV molecular epidemiology limited knowledge. In fact, being their common origin unrecognized for a long time, independent epidemiological pictures were drawn for the two genotypes. To fix this misinterpretation, the present study reconstructs the history, population dynamics and spreading patterns of GI-16 lineage as a whole using a phylodynamic approach. A collection of worldwide available hypervariable region 1 and 2 (HVR12) and 3 (HVR3) sequences of the S1 protein was analysed together with 258 HVR3 sequences obtained from samples collected in Italy (the country where this genotype was initially identified) since 1963. The results demonstrate that after its emergence at the beginning of the XX century, GI-16 was able to persist until present days in Italy. Approximately in the late 1980s, it migrated to Asia, which became the main nucleus for further spreading to Middle East, Europe and especially South America, likely through multiple introduction events. A remarkable among-country diffusion was also demonstrated in Asia and South America. Interestingly, although most of the recent Italian GI-16 strains originated from ancestral viruses detected in the same country, a couple were closely related to Chinese ones, supporting a backward viral flow from China to Italy. Besides to the specific case-study results, this work highlights the misconceptions that originate from the lack of a unified nomenclature and poor molecular epidemiology data generation and sharing. This shortcoming appears particularly relevant since the described scenario could likely be shared by many other IBV genotypes and pathogens in general.

传染性支气管炎病毒（Infectious bronchitis virus, IBV）的遗传变异性是其防控的核心挑战之一，不仅阻碍了有效疫苗接种策略的研发，更干扰了该病毒的分类工作，进而制约了流行病学认知的深化。目前被划归为GI-16谱系的624/I与Q1基因型，正是IBV分子流行病学认知不足所引发实际后果的典型例证。由于长期未能识别二者的共同起源，学界曾为这两种基因型构建了相互独立的流行病学图景。为纠正这一认知偏差，本研究采用系统发育动力学（phylodynamic）方法，对GI-16谱系的演化历史、种群动态及传播模式进行了全面重构。研究整合了全球范围内公开的S1蛋白高变区1、2（HVR12）与高变区3（HVR3）序列数据集，并结合1963年以来在意大利（该基因型最初被发现的国家）采集的258条HVR3序列开展分析。结果显示，GI-16谱系于20世纪初出现后，便在意大利持续存续至今。约在20世纪80年代末，该谱系迁移至亚洲，并以此作为主要扩散枢纽，通过多次跨区域引入事件，进一步传播至中东、欧洲，尤其是南美洲。研究还证实，亚洲与南美洲内部同样存在显著的跨国传播现象。值得注意的是，尽管近期多数意大利GI-16毒株均起源于该国本土的祖先病毒，但有两株与中国毒株亲缘关系密切，这为病毒从中国反向流入意大利的假说提供了支持。除本案例的具体研究结果外，本研究还揭示了因统一命名体系缺失、分子流行病学数据生成与共享不足所导致的认知误区。这类缺陷尤为值得关注，因为上述传播模式很可能也广泛存在于其他多种IBV基因型乃至各类病原微生物中。