Christiansen Debes H, McBeath Alastair J A, Aamelfot Maria, Matejusova Iveta, Fourrier Mickael, White Patricia, Petersen Petra E, Falk Knut
Faroese Food and Veterinary Authority, National Reference Laboratory for Fish Diseases, Tórshavn, Faroe Islands.
Marine Scotland Science, Marine Laboratory, Aberdeen, Scotland.
J Gen Virol. 2017 Apr;98(4):595-606. doi: 10.1099/jgv.0.000741.
The putatively non-virulent subtype of infectious salmon anaemia virus (ISAV), ISAV-HPR0, is proposed to act as a progenitor and reservoir for all virulent ISAVs and thus represent a potential risk factor for the emergence of infectious salmon anaemia (ISA) disease. Here, we provide the first evidence of genetic and functional evolution from an ISAV-HPR0 variant (FO/07/12) to a low-virulent ISAV virus (FO/121/14) in a Faroese Atlantic salmon marine farm. The FO/121/14 virus infection was not associated with specific clinical signs of ISA and was confined to a single net-pen, while various ISAV-HPR0 subtypes were found circulating in most epidemiologically linked marine and freshwater farms. Sequence analysis of all eight segments revealed that the FO/121/14 virus was identical, apart from a substitution in the fusion (F) gene (Q266L) and a deletion in the haemagglutinin-esterase (HE) gene, to the FO/07/12 variant from a freshwater farm, which supplied smolts exclusively to the FO/121/14-positive net-pen. An immersion challenge with the FO/121/14 virus induced a systemic infection in Atlantic salmon associated with a low mortality and mild clinical signs confirming its low pathogenicity. Our results demonstrate that mutations in the F protein and deletions in the highly polymorphic region (HPR) of the HE protein represent a minimum requirement for ISAV to gain virulence and to switch cell tropism from a localized epithelial infection to a systemic endotheliotropic infection. This documents that ISAV-HPR0 represents a reservoir and risk factor for the emergence of ISA disease.
传染性鲑鱼贫血病毒（ISAV）的假定无毒力亚型ISAV-HPR0，被认为是所有有毒力ISAV的祖型和储存库，因此是传染性鲑鱼贫血（ISA）疾病出现的潜在风险因素。在此，我们提供了首个证据，证明在法罗群岛大西洋鲑鱼海洋养殖场中，一种ISAV-HPR0变体（FO/07/12）向低毒力ISAV病毒（FO/121/14）发生了基因和功能进化。FO/121/14病毒感染与ISA的特定临床症状无关，且局限于单个网箱，而在大多数有流行病学关联的海洋和淡水养殖场中发现了各种ISAV-HPR0亚型在传播。对所有八个片段的序列分析表明，除了融合（F）基因中的一个替换（Q266L）和血凝素酯酶（HE）基因中的一个缺失外，FO/121/14病毒与一个淡水养殖场的FO/07/12变体相同，该淡水养殖场仅向FO/121/14阳性网箱供应幼鲑。用FO/121/14病毒进行浸浴攻毒在大西洋鲑鱼中引发了全身性感染，伴有低死亡率和轻微临床症状，证实了其低致病性。我们的结果表明，F蛋白中的突变和HE蛋白高度多态性区域（HPR）中的缺失是ISAV获得毒力并将细胞嗜性从局部上皮感染转变为全身性内皮嗜性感染的最低要求。这证明ISAV-HPR0是ISA疾病出现的储存库和风险因素。
