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Research Project: Intervention Strategies to Support the Global Control and Eradication of Foot-and-Mouth Disease Virus (FMDV)

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Title: Swine host protein coiled-coil domain containing 115 (CCDC115) interacts with classical swine fever virus structural glycoprotein E2 during virus

item VUONNO, ELIZABETH - University Of Mississippi
item RAMIREZ-MEDIA, ELIZABETH - University Of Connecticut
item BERGGREN, KEITH - Princeton University
item RAI, AYUSHI - Oak Ridge Institute For Science And Education (ORISE)
item PRUITT, SARAH - Oak Ridge Institute For Science And Education (ORISE)
item SILVA, EDIANE - University Of Kansas
item VELAZQUEZ-SALINAS, LAURO - University Of Kansas
item Gladue, Douglas
item Borca, Manuel

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/31/2020
Publication Date: 4/12/2020
Citation: Vuonno, E., Ramirez-Media, E., Berggren, K., Rai, A., Pruitt, S., Silva, E., Velazquez-Salinas, L., Gladue, D.P., Borca, M.V. 2020. Swine host protein coiled-coil domain containing 115 (CCDC115) interacts with classical swine fever virus structural glycoprotein E2 during virus. Viruses.

Interpretive Summary: Classical swine fever virus (CSFV) causes a devastating disease in swine, one protein of this virus called E2 is probably the most important component of virus due to its involvement in many virus activities, particularly interacting with the hosts i.e. pig cells. Here we identified a protein in pig cells that interact with E2, this protein is called CCDC115. The E2 amino acid residues mediating the interaction with CCDC115 were also identified. A genetically modified CSFV was created harboring mutations disrupting E2- CCDC115. interaction. Disrupting the E2- CCDC115. interaction resulted in no significant phenotype of the virus when tested in pig.

Technical Abstract: Interactions between the major structural glycoprotein E2 of classical swine fever virus (CSFV) with host proteins have been identified as important factors affecting virus replication and virulence. Previously, using the yeast two-hybrid system, we identified swine host proteins specifically interacting with CSFV E2. In this report, we use a proximity ligation assay to demonstrate that swine host protein CCDC115 interacts with E2 in CSFV-infected swine cells. Using a randomly mutated E2 library in the context of a yeast two-hybrid methodology, specific amino acid mutations in the CSFV E2 protein responsible for disrupting the interaction with CCDC115 were identified. A recombinant CSFV mutant (E2'CCDC115v) harboring amino acid changes disrupting the E2 protein interaction with CCDC115 was produced and used as a tool to assess the role of the E2-CCDC115 interaction in viral replication and virulence in swine. CSFV E2'CCDC115v showed a slightly decreased ability to replicate in the SK6 swine cell line and a greater replication defect in primary swine macrophage cultures. Importantly, animals intranasally infected with E2'CCDC115v experienced a significantly longer survival period when compared with those infected with parental Brescia strain. This result would indicate that the ability of CSFV E2 to bind host CCDC115 protein during infection plays an important role in virus replication in swine macrophages and in virus virulence during