Norwegian Veterinary Institute, 1433 Ås, Norway.
Unit for Fish and Shellfish Diseases, National Institute of Aquatic Resources, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
Viruses. 2022 Feb 2;14(2):310. doi: 10.3390/v14020310.
Infectious salmon anaemia virus (ISAV) binds circulating Atlantic salmon erythrocytes, but the relevance of this interaction for the course of infection and development of disease remains unclear. We here characterise ISAV-erythrocyte interactions in experimentally infected Atlantic salmon and show that ISAV-binding to erythrocytes is common and precedes the development of disease. Viral RNA and infective particles were enriched in the cellular fraction of blood. While erythrocyte-associated ISAV remained infectious, erythrocytes dose-dependently limited the infection of cultured cells. Surprisingly, immunostaining of blood smears revealed expression of ISAV proteins in a small fraction of erythrocytes in one of the examined trials, confirming that ISAV can be internalised in this cell type and engage the cellular machinery in transcription and translation. However, viral protein expression in erythrocytes was rare and not required for development of disease and mortality. Furthermore, active transcription of ISAV mRNA was higher in tissues than in blood, supporting the assumption that ISAV replication predominantly takes place in endothelial cells. In conclusion, Atlantic salmon erythrocytes bind ISAV and sequester infective virus particles during infection, but do not appear to significantly contribute to ISAV replication. We discuss the implications of our findings for infection dynamics and pathogenesis of infectious salmon anaemia.
传染性鲑鱼贫血病毒（ISAV）可与循环中的大西洋鲑红细胞结合，但这种相互作用对感染过程和疾病发展的相关性尚不清楚。我们在此描述了实验感染大西洋鲑中的 ISAV-红细胞相互作用，并表明 ISAV 与红细胞的结合很常见，且先于疾病的发生。病毒 RNA 和感染性颗粒在血液的细胞部分得到了富集。虽然与红细胞结合的 ISAV 仍具有感染性，但红细胞会使培养细胞的感染呈剂量依赖性受限。令人惊讶的是，在其中一项试验的血涂片免疫染色中，发现了一小部分红细胞中表达 ISAV 蛋白，这证实了 ISAV 可以在这种细胞类型中被内化，并使细胞的转录和翻译机制参与其中。然而，红细胞中病毒蛋白的表达很少，且对疾病的发生和死亡率没有影响。此外，与血液相比，ISAV mRNA 的活跃转录在组织中更高，这支持了 ISAV 复制主要发生在内皮细胞中的假设。总之，大西洋鲑的红细胞可与 ISAV 结合，并在感染过程中隔离有感染性的病毒颗粒，但似乎对 ISAV 的复制没有显著贡献。我们讨论了这些发现对传染性鲑鱼贫血感染动力学和发病机制的影响。
