Elsevier

Virus Research

Volume 155, Issue 1, January 2011, Pages 10-19
Virus Research

Review
Infectious salmon anemia virus—Genetics and pathogenesis

https://doi.org/10.1016/j.virusres.2010.10.021Get rights and content

Abstract

The infectious salmon anemia virus (ISAV) is the causative agent of the ISA syndrome that affects mainly Atlantic salmon (Salmo salar) and has caused high mortality epidemics in Norway, Scotland, Canada, the United States and Chile. It is classified as an Orthomyxoviridae, its genome is composed of 8 single-strand RNA segments with negative polarity that code for 11 polypeptides. Through functional studies of the coded proteins it has been established that RNA segments 5 and 6 code for a fusion protein and hemagglutinin, respectively, while two polypeptides coded by segments 7 and 8 inhibit interferon induction. The functions of the rest of the possible proteins coded by the viral genome have been assigned by comparison with the corresponding ones of the influenza virus genome. As to its pathogenicity, some growth parameters such as incubation period, resistance to chemical and physical factors, establishment of the infection in other marine species, and dissemination ability among the different organs have been evaluated in several salmonids. Genomic analysis has shown (i) the existence of a high polymorphism region (HPR) in segment 6, and (ii) sequence insertion in segment 5. More than 20 HPR variants have been determined, all originating from HPR0, which is associated with low pathogenicity, while 4 different sequence insertions in segment 5 have not been related with some characteristic of the virus infection. Much progress has been made in the characterization of the virus in 20 years of study, but more detailed knowledge of the specific function of the proteins coded by all the viral genes is still missing, including the pathogenicity mechanism at the molecular level.

Introduction

Infectious salmon anemia (ISA) is a high-mortality multisystemic syndrome described mainly in Atlantic salmon (Salmo salar), although it has also been observed in other salmonid species (Raynard et al., 2001). The pathology is characterized by the infected individuals showing macroscopic lesions such as gill paleness, liver congestion, spleen inflammation, intestinal congestion, and severe anemia (Falk et al., 1995, Jones et al., 1999, Simko et al., 2000, Speilberg et al., 1995). The disease has been described in aquacultures in Norway, Canada, the United States, Scotland, Faroe Islands and Chile (Bouchard et al., 2001, Kibenge et al., 2001a, Lovely et al., 1999, Rowley et al., 1999, Thorud and Djupvik, 1988).

The first reported outbreak occurred in Norway in 1984, affecting Atlantic salmon farms whose fish presented acute anemia together with the symptoms mentioned above (Thorud and Djupvik, 1988). The causal agent of the disease was seen for the first time by electron microscopy in samples of different tissues 10 years after the first infection, and was described as a 100-nm diameter enveloped virus-type particle, similar to a mixovirus (Dannevig et al., 1995, Hovland et al., 1994). Later, viral inocula obtained from kidney homogenates of infected fish were inoculated in the cell line derived from salmon head kidney (SHK-1), finding a cytopathic effect between 12 and 14 days post-infection, confirming the presence of the virus by electron microscopy (Dannevig et al., 1995). About 15 years after the first epidemic, the syndrome was again detected in other Atlantic salmon producing countries, and an etiologic agent was isolated that had characteristics similar to those described for the epidemics in Norway, affecting mostly the farms located on the east coast of Canada, in Scotland, the United States and Chile, with the virus appearing in that order. Characterization of the viral particles was made by infection and determination of the cytopathic effect in fish cell lines SHK-1, epithelioma papulosum cyprini (EPC) and chinook salmon embryo cells (CHSE-214), quantification of the viral load by quantitative reverse transcription PCR (qRT-PCR), and visualization of enveloped viral particles up to 100 nm in diameter by electron microscopy (Bouchard et al., 2001, Godoy et al., 2008, Lovely et al., 1999, Rowley et al., 1999).

Section snippets

Viral genome and protein pattern

The Orthomyxoviridae viral family is divided into five genera that are distinguished by their genetic characteristics and range of hosts (Palese and Shaw, 2007). The influenza virus genome, the family's type member, corresponds to a single-strand RNA, segmented and with negative polarity, the number of segments varying from 8 in influenza A and B, to 7 in influenza C, with sizes that vary between 2.2 and 1.0 kb, and they can code 12 polypeptides for influenza A and B, and 10 for influenza C (

Genetic variability of ISAV

Based on the variations that are found when comparing the genome of the ISAV isolates obtained in Europe and North America, especially using the sequences of segments 2, 6 and 8, it is possible to separate the viral isolates into two genotypes: genotype I corresponds to the European isolates, consisting of viruses obtained from Norway, Scotland and Chile, and genotype II to the North American viruses, consisting of isolates from Canada and the United States (Blake et al., 1999, Devold et al.,

Pathogenesis

In general, before causing the death of the salmon, infection by ISAV is related mainly to damage of the organs: the liver, kidneys, spleen and intestine, together with visible external features such as exophthalmus and abdominal petechiae, all the above associated with acute anemia during the course of the disease (Falk et al., 1995, Godoy et al., 2008, Jones et al., 1999, Moneke et al., 2005, Rimstad et al., 1999, Simko et al., 2000, Speilberg et al., 1995). Various studies on experimental

Conclusion

Although the general characteristics of the virus are already known, not much is known at the molecular level of the genome's structure and composition. To date it has only been associated with the role of hemagglutinin and fusion with two surface proteins of the virus (Aspehaug et al., 2005, Krossoy et al., 2001a), it is known that the nucleoprotein may have nuclear destination and does have the ability to bind RNA (Goic et al., 2008), and finally it has been associated with two proteins

Acknowledgements

This study was supported by Innova-CORFO grants: 09MCSS-6691, 09MCSS-6698 and 07CN13PBT-90 (Government of Chile). M.C. was supported by PBCT-CONICYT grant PDA-20 (Government of Chile). L.C. was supported by a fellowship from CONICYT (Government of Chile) and belongs to the Doctorate in Biotechnology Program, USACH. Samy Atala by help us with the translation and editing of the English text.

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