Classical Swine Fever Virus Structural Glycoprotein E2 Interacts with Host Protein ACADM during the Virus Infectious Cycle

Vuono, Elizabeth; Ramirez-Medina, Elizabeth; Silva, Ediane; Berggren, Keith; Rai, Ayushi; Espinoza, Nallely; Gladue, Douglas P.; Borca, Manuel V.

doi:10.3390/v15051036

Classical Swine Fever Virus Structural Glycoprotein E2 Interacts with Host Protein ACADM during the Virus Infectious Cycle

Journal Article · Sun Apr 23 00:00:00 EDT 2023 · Viruses

DOI:https://doi.org/10.3390/v15051036· OSTI ID:2471341

Vuono, Elizabeth ^[1]; Ramirez-Medina, Elizabeth ^[2]; ^[2]; Berggren, Keith ^[3]; Rai, Ayushi ^[3]; Espinoza, Nallely ^[2]; ^[2]; Borca, Manuel V. ^[2]

United States Department of Agriculture, Greenport, NY (United States); Mississippi State University, Starkville, MS (United States)
United States Department of Agriculture, Greenport, NY (United States)
United States Department of Agriculture, Greenport, NY (United States); Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

The E2 glycoprotein is one of the four structural proteins of the classical swine fever virus (CSFV) particle. E2 has been shown to be involved in many virus functions, including adsorption to host cells, virus virulence and interaction with several host proteins. Using a yeast two-hybrid screen, we have previously shown that the CSFV E2 specifically interacts with swine host protein medium-chain-specific acyl-Coenzyme A dehydrogenase (ACADM), an enzyme that catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Here, we show that interaction between ACADM and E2 also happens in swine cells infected with CSFV using two different procedures: coimmunoprecipitation and a proximity ligation assay (PLA). In addition, the amino acid residues in E2 critically mediating the interaction with ACADM, M49 and P130 were identified via a reverse yeast two-hybrid screen using an expression library composed of randomly mutated versions of E2. A recombinant CSFV, E2ΔACADMv, harboring substitutions at residues M49I and P130Q in E2, was developed via reverse genomics from the highly virulent Brescia isolate. E2ΔACADMv was shown to have the same kinetics growth in swine primary macrophages and SK6 cell cultures as the parental Brescia strain. Similarly, E2ΔACADMv demonstrated a similar level of virulence when inoculated to domestic pigs as the parental Brescia. Animals intranasally inoculated with 10⁵ TCID₅₀ developed a lethal form of clinical disease with virological and hematological kinetics changes undistinguishable from those produced by the parental strain. Therefore, interaction between CSFV E2 and host ACADM is not critically involved in the processes of virus replication and disease production.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC); USDA

Grant/Contract Number:: SC0014664

OSTI ID:: 2471341

Journal Information:: Viruses, Journal Name: Viruses Journal Issue: 5 Vol. 15; ISSN 1999-4915

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
CSFV
E2 glycoprotein
classical swine fever (CSF)
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virus virulence

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