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

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.

Transcriptomic response to ISAV infection in the gills, head kidney and spleen of resistant and susceptible Atlantic salmon

“…Immunophilins such as FKBP5 have been previously reported to participate in viral replication during some infections such as HIV-1 [ 31 ]. Regarding serine protease 23, ISAV possesses a fusion glycoprotein (F) and an hemagglutinin esterase (HE), both necessary for viral attachment and internalization into salmon cells [ 32 , 33 ]. Influenza A has to be cleaved for the virus to enter the cell, and that is done by a serine protease secreted by the host cell [ 33 ].…”

Infectious Salmon Anemia Virus Infectivity Is Determined by Multiple Segments with an Important Contribution from Segment 5

“…In vitro studies have shown that co-expression of HE with deleted HPRs promotes the activity of the F protein, probably because full-length HPRs hide the cleavage site of the fusion protein, impeding its activation [ 18 ]. Additionally, a recent study described that the amino-termini of the fusion protein (F1) can interact with a cellular membrane receptor and modulates HE-mediated adsorption [ 19 ], suggesting that the HPR region is closely related to the activity of the F protein. However, the basis and implications of this interaction remain unknown.…”