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Title: Structure of the infectious salmon anemia virus receptor complex illustrates a unique binding strategy for attachment

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America

Orthomyxoviruses are an important family of RNA viruses, which include the various influenza viruses. Despite global efforts to eradicate orthomyxoviral pathogens, these infections remain pervasive. One such orthomyxovirus, infectious salmon anemia virus (ISAV), spreads easily throughout farmed and wild salmonids, constituting a significant economic burden. ISAV entry requires the interplay of the virion-attached hemagglutinin-esterase and fusion glycoproteins. Preventing infections will rely on improved understanding of ISAV entry. Here, we present the crystal structures of ISAV hemagglutinin-esterase unbound and complexed with receptor. Several distinctive features observed in ISAV HE are not seen in any other viral glycoprotein. The structures reveal a unique mode of receptor binding that is dependent on the oligomeric assembly of hemagglutinin-esterase. Importantly, ISAV hemagglutinin-esterase receptor engagement does not initiate conformational rearrangements, suggesting a distinct viral entry mechanism. This work improves our understanding of ISAV pathogenesis and expands our knowledge on the overall diversity of viral glycoprotein-mediated entry mechanisms. Lastly, it provides an atomic-resolution model of the primary neutralizing antigen critical for vaccine development.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Scientific User Facilities Division; Natural Sciences and Engineering Research Council of Canada (NSERC); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); NIH; National Inst. of General Medical Sciences
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1349936
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 14 Vol. 114; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Human coronaviruses OC43 and HKU1 bind to 9- O -acetylated sialic acids via a conserved receptor-binding site in spike protein domain A journal January 2019
Infectious salmon anaemia virus—molecular biology and pathogenesis of the infection journal January 2020
Tilapia Lake Virus Does Not Hemagglutinate Avian and Piscine Erythrocytes and NH4Cl Does Not Inhibit Viral Replication In Vitro journal December 2019