Interaction of the Amino-Terminal Domain of the ISAV Fusion Protein with a Cognate Cell Receptor

Nicolás Ojeda,Sergio Marshall,Constanza Cárdenas

doi:10.3390/pathogens9060416

Nicolás Ojeda, Sergio Marshall + Show 1 more

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https://doi.org/10.3390/pathogens9060416

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Abstract

The infectious salmon anemia virus (ISAV), etiological agent of the disease by the same name, causes major losses to the salmon industry. Classified as a member of the Orthomyxoviridae family, ISAV is characterized by the presence of two surface glycoproteins termed hemagglutinin esterase (HE) and fusion protein (F), both of them directly involved in the initial interaction of the virus with the target cell. HE mediates receptor binding and destruction, while F promotes the fusion process of the viral and cell membranes. The carboxy-terminal end of F (F2) possesses canonical structural characteristics of a type I fusion protein, while no functional properties have been proposed for the amino-terminal (F1) region. In this report, based on in silico modeling, we propose a tertiary structure for the F1 region, which resembles a sialic acid binding domain. Furthermore, using recombinant forms of both HE and F proteins and an in vitro model system, we demonstrate the interaction of F with a cell receptor, the hydrolysis of this receptor by the HE esterase, and a crucial role for F1 in the fusion mechanism. Our interpretation is that binding of F to its cell receptor is fundamental for membrane fusion and that the esterase in HE modulates this interaction.

Highlights

Infectious salmon anemia (ISA) is an aggressive disease that primarily affects Atlantic salmon (Salmo salar), one of the most commercially relevant farmed fish
One of them is a hemagglutinin esterase (HE) which interacts with sialic acids on the susceptible cell surface via the hemagglutinin domain, promoting viral attachment; on the other hand, the esterase acts as a receptor-destroying enzyme (RDE), allowing the release of new viral particles in the context of a productive infection [10,11]
We propose a model where the stalk length in HE modulates the activity of the viral esterase over the putative F receptor and over the fusion process. These results demonstrate the important role of viral surface proteins in the regulation of infectivity; in particular, they may further define the influence of highly polymorphic region (HPR) on the fusion activity in infectious salmon anemia virus (ISAV), suggesting a novel role for F

Summary

Introduction

Infectious salmon anemia (ISA) is an aggressive disease that primarily affects Atlantic salmon (Salmo salar), one of the most commercially relevant farmed fish. ISA has affected all major salmon-producing countries, including Canada, Norway, Scotland, the Faroe Islands, and Chile [2,3,4,5,6]. The etiological agent of ISA is a relatively new virus within the Orthomyxoviridae family and is the only member of the novel Isavirus genus [7]. The infectious salmon anemia virus (ISAV) shares similarities with other members of the family, including a segmented single-stranded negative-sense. The ISAV envelope contains two major glycoproteins that mediate binding, membrane fusion, and receptor destruction.

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