The ISAV has a genome composed of eight segments of (–)ssRNA, segment 6 codes for the hemagglutinin–esterase protein, and has the most variable region of the genome, the highly polymorphic region (HPR), which is unique among orthomyxoviruses. The HPR has been associated with virulence, infectivity and pathogenicity. The full length of the HPR is called HPR0 and the strain with this HPR is avirulent, in contrast to strains with deleted HPR that are virulent to varying degrees. The molecular mechanism that gives rise to the different HPRs remains unclear. Here, we studied in vitro the evolution of reassortant recombinant ISAV (rISAV) in Atlantic salmon head kidney (ASK) cells. To this end, we rescued and cultivated a set of rISAV with different segment 6‐HPR genotypes using a reverse genetics system and then sequencing HPR regions of the viruses. Our results show rapid multiple recombination events in ISAV, with sequence insertions and deletions in the HPR, indicating a dynamic process. Inserted sequences can be found in four segments of the ISAV genome (segments 1, 5, 6, and 8). The results suggest intra‐segmental heterologous recombination, probably by class I and class II template switching, similar to the proposed segment 5 recombination mechanism.

中文翻译：

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传染性鲑鱼贫血病毒（ISAV）的血凝素基因的高度多态性区域（HPR）中的快速序列修饰表明，节内模板转换重组。

ISAV的基因组由（-）ssRNA的8个片段组成，第6段编码血凝素-酯酶蛋白，具有基因组中变化最大的区域，即高正态性区域（HPR），在正粘病毒中是独特的。HPR与毒力，传染性和致病性有关。HPR的全长称为HPR0，具有该HPR的菌株是无毒的，与具有不同程度毒性的具有删除的HPR的菌株相反。引起不同HPR的分子机制仍不清楚。在这里，我们研究了大西洋鲑头肾（ASK）细胞中重配重组ISAV（rISAV）的进化。为此，我们使用反向遗传学系统拯救并培养了一组具有不同区段6-HPR基因型的rISAV，然后对该病毒的HPR区进行了测序。我们的结果显示了ISAV中快速的多重重组事件，以及HPR中的序列插入和缺失，表明该过程是动态的。可以在ISAV基因组的四个片段（片段1、5、6和8）中找到插入的序列。结果表明，可能通过I类和II类模板转换进行了片段内异源重组，类似于拟议的第5段重组机制。