Review
Innate immune responses of salmonid fish to viral infections

https://doi.org/10.1016/j.dci.2013.08.017Get rights and content

Highlights

  • The type I Interferon is induced in salmonids following infection with all known types of viruses.

  • Dendritic cells and natural killer cell markers have been identified in salmonids and their involvement in viral infection confirmed.

  • Viruses have evolved immune evasion mechanisms.

Abstract

Viruses are the most serious pathogenic threat to the production of the main aquacultured salmonid species the rainbow trout Oncorhynchus mykiss and the Atlantic salmon Salmo salar. The viral diseases Infectious Pancreatic Necrosis (IPN), Pancreatic Disease (PD), Infectious Haemorrhagic Necrosis (IHN), Viral Haemorrhagic Septicaemia (VHS), and Infectious Salmon Anaemia (ISA) cause massive economic losses to the global salmonid aquaculture industry every year. To date, no solution exists to treat livestock affected by a viral disease and only a small number of efficient vaccines are available to prevent infection. As a consequence, understanding the host immune response against viruses in these fish species is critical to develop prophylactic and preventive control measures. The innate immune response represents an important part of the host defence mechanism preventing viral replication after infection. It is a fast acting response designed to inhibit virus propagation immediately within the host, allowing for the adaptive specific immunity to develop. It has cellular and humoral components which act in synergy. This review will cover inflammation responses, the cell types involved, apoptosis, antimicrobial peptides. Particular attention will be given to the type I interferon system as the major player in the innate antiviral defence mechanism of salmonids. Viral evasion strategies will also be discussed.

Introduction

The majority of serious diseases in fish farming, causing important economic losses worldwide, have a viral aetiology (OIE, 2012). In most cases, viral infection leads to significant livestock losses. Curative measures are very limited and there is a high risk from new emerging viral diseases (Rimstad, 2010). Traditionally, the research in salmonid immunology has focused mostly on the farmed species including Atlantic salmon Salmo salar, Pacific salmon including Chum salmon Oncorhynchus keta and Coho salmon Oncorhynchus kisutch, and the Rainbow trout Oncorhynchus mykiss. According to the FAO tonnage statistics for 2010 (FAO, 2010), salmon production is mainly located in Norway, Chile, UK and Canada, rainbow trout production predominantly occurs in Chile, Iran, Turkey, Norway, US, Denmark and France, and Pacific or Coho salmon production in Chile. Understanding which components of the immune system limit viral replication and are responsible for host recovery is critical in developing adequate prophylactic control strategies. The causative agents of the major salmonid viral diseases include double stranded RNA virus such as Infectious Pancreatic Necrosis Virus (IPNV, Birnaviridae), Piscine Reovirus (PRV) recently renamed as Atlantic Salmon ReoVirus (ASRV, Reoviridae), Piscine MyoCarditis Virus (PMCV, Totiviridae), negative single stranded RNA viruses such as Infectious Haemorrhagic Necrosis Virus (IHNV, Rhabdoviridae), Viral Haemorrhagic Septicaemia Virus (VHSV, Rhabdoviridae), positive single stranded RNA virus Salmonid Alphavirus (SAV, Alphaviridae), negative segmented single stranded RNA virus Infectious Salmon Anaemia Virus (ISAV, Orthomyxoviridae) and DNA virus Epizootic hematopoietic necrosis virus (EHNV, Iridoviridae) (Crane and Hyatt, 2011). Innate immunity is induced quickly after infection and is characterised by an absence of immunological memory, is not specific to the antigen and is modulated by molecules encoded by germ-line genes. A recent study based on paired clonal rainbow trout and fibroblastic cell lines suggest that innate immune factors contribute to a great part of the overall resistance to viral infection (Verrier et al., 2012). In vertebrates, the fast induction of innate defence mechanisms is critical to prevent viral replication before the later more specific adaptive response is established. However innate antiviral defence mechanisms have humoral and cellular components that can directly and, on their own, exclusively eradicate the virus in an infected animal (Takeuchi and Akira, 2009). This chapter will give an update on the current knowledge of the different components of the innate immune system acting against viruses in the main farmed salmonids species.

Section snippets

Physical barriers

The first line of defence against viruses occurs at the interface with the external environment on tissues such as skin, gut and the gill representing the main areas where infection can potentially originate. The exact natural port of viral entry is not known for all salmonid viruses but in the case of IHNV it has been suggested using a bioluminescent recombinant virus clone in rainbow trout that the base of the fins is the main entry site (Harmache et al., 2006). For other viruses that infect

Inflammation

An inflammatory reaction is critical to the efficiency of the innate and subsequent adaptive response to any type of infection including viral infections (Hussell and Goulding, 2010). It is characterised by the systemic release of specific cytokines such as IL1β, TNF-α and chemokines such as IL8 and by the chemotactic migration of leukocytes (neutrophils, macrophages) to the site of inflammation. Most of the proinflammatory cytokines have been isolated in salmonid fish and evidence of tissue

Complement system

Although traditionally described as an antibacterial defence mechanism, the complement system is also involved in immunity to viruses (Hirsch, 1982, Holland and Lambris, 2002). There is indirect evidence of involvement of complement in salmonid defences against viruses (Lorenzen et al., 1999, Yano, 1996). In higher vertebrates, the classical and mannan-binding lectin (MBL) complement activation pathways have been shown to contribute to the innate immunity to viruses where C1q and MBL directly

Macrophages

Macrophages are specialised immune cells that phagocytose and degrade pathogenic particles and produce cytokines or other soluble factors in order to stimulate the adaptive immune system (Gordon and Taylor, 2005, Gordon, 2007). Macrophages can be activated in four different pathways according to the type of pathogen they encounter (Forlenza et al., 2011, Liu and Yang, 2013). The classical (or M1) activation pathway (CAM, Classical Activated Macrophages) leads to a typical inflammatory phenotype

Pattern Recognition receptors (PRRs)

Recognition of viral pathogen patterns is often the first step in the detection of a danger signal and is an essential step in the bridge between innate and adaptive immunity (Koyama et al., 2008). The detailed mechanism of recognition is treated separately in this issue (TOLL-like receptors and their recognition of fish pathogens, Wiegertjes). Several receptors are dedicated to recognise patterns that are characteristic of viral pathogens such as ssRNA or dsRNA, intermediates of most viral

IFN genes

To date, three types of IFN have been described in vertebrates with type I and III signalling through distinct membrane-bound receptor complexes but utilising the same Jak/STAT pathway to induce a wide range of antiviral genes (Randall and Goodbourn, 2008, Robertsen, 2006, Robertsen, 2008). Some authors have suggested that zebrafish type I IFN is homologous to the mammalian type III IFN gene cluster (Levraud et al., 2007) but this hypothesis is still under discussion (Zou et al., 2007). More

Apoptosis

Apoptosis, or programmed cell-death is a defence mechanism against viruses functioning through the early destruction of infected cells thus limiting the propagation of the pathogen within the host (O’Brien, 1998, Roulston et al., 1999). In mammals, IFN has been described as an inducer of pro-apoptotic genes leading to the destruction of infected cells limiting propagation of the virus (Chawla-Sarkar et al., 2003). However, viruses often override this mechanism to their advantage, and depending

Innate immune evasion

In mammals some viruses can evade the immune response through targeting specific pathways such as IFN or apoptosis (O’Brien, 1998, Goodbourn et al., 2000), or general pathways such as protein translation (viral protein shut-down) (Xu et al., 2010). These evasion mechanisms occur at the same time as the host’s response to the viral infection. Therefore it is sometimes difficult to dissect out which mechanisms contribute the most to cellular takeover by the virus. Some mechanisms, such as host

Environmental parameters

Fish are subjected to variable environmental factors such as temperature, salinity, oxygen levels, or parameters related to water composition or quality. These indirectly affect the efficacy of the innate response to viruses often through interaction with stress responses (Robertsen, 2011). Temperature has been long known to be a modulator of the kinetics of the innate response in fish (Avtalion et al., 1973). The IFN response to viral mimick (poly I:C) was longer lasting at lower temperature

Antimicrobial peptides

In higher vertebrates antimicrobial peptides (AMPs) are involved primarily in anti-myco-bacterial immunity but also act in the defence against viruses (Gombart, 2009, Van Compernolle et al., 2005, Gordon et al., 2005, Smith and Fernandes, 2009). The same seems to be true for salmonid fish species (Smith et al., 2010) and antimicrobial peptides offer potential control chemotherapeutics (Falco et al., 2009, Rajanbabu and Chen, 2011). dsRNA synthetic viral mimic (poly I:C) induced the expression

General conclusion

The innate immune system in salmonids plays a significant role in antiviral protection. It is the first line of defence against viruses, rapid and, in many cases, it limits viral replication until an adaptive response can be mounted. It is particularly important in cold-blooded animals for which the kinetics of immune response is highly dependent on environmental parameters. Similar components and pathways of the innate immune system to those of higher vertebrates have been found in salmonids.

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