The E2 protein of classical swine fever virus (CSFV) is an envelope glycoprotein that is involved in virus attachment and entry. To date, the E2-interacting cellular proteins and their involvement in viral replication have been poorly documented. In this study, thioredoxin 2 (Trx2) was identified to be a novel E2-interacting partner using yeast two-hybrid screening from a porcine macrophage cDNA library. Trx2 is a mitochondrion-associated protein that participates in diverse cellular events. The Trx2-E2 interaction was further confirmed by glutathione S-transferase (GST) pulldown, in situ proximity ligation, and laser confocal assays. The thioredoxin domain of Trx2 and the asparagine at position 37 (N37) in the E2 protein were shown to be critical for the interaction. C lassical swine fever (CSF), caused by classical swine fever virus (CSFV), is a highly contagious, often fatal porcine disease with significant economic losses. CSFV belongs to the Pestivirus genus within the Flaviviridae family (1). It is an enveloped virus with a single-stranded, positive-sense RNA genome of approximately 12.3 kb in length. The RNA genome contains a single large open reading frame (ORF). This ORF is translated into a polyprotein, which is further processed into 12 mature proteins (N pro -C-E rns -E1-E2-p7-NS2-3-NS4A-NS4B-NS5A-NS5B) by viral and cellular proteases (2). The C, E rns , E1, and E2 proteins represent the structural components of the virion. The E1 and E2 glycoproteins are anchored to the envelope by their carboxyl termini, while E rns is loosely associated with the envelope. E rns presents as homodimers linked by disulfide bridges in virus-infected cells and in virions (3, 4). The C terminus of E2 functions as a membrane-spanning domain anchoring the E2-E1 or E2-E2 dimer to the viral envelope (5). E2 is also involved in virus attachment to and entry into the target cell (6). Furthermore, as a virulence determinant in pigs (7), the E2 protein can efficiently induce protective immune responses (8-13). Additionally, we recently showed that host -actin interacts with E2 and modulates the early life cycle of CSFV (14).Thioredoxins (Trxs) are a class of ubiquitously expressed redox proteins that contain a conserved consensus amino acid sequence (Cys-Gly-Pro-Cys) in the catalytic center. There are two distinct forms of Trxs (Trx1 and Trx2), which act as antioxidants facilitating the reduction of other proteins by cysteine thiol-disulfide exchange. Trx2 consists of 157 amino acid (aa) residues, and its thioredoxin domain is located in the C terminus of the protein.Trxs are involved in diverse biological processes, such as cell growth, proliferation, apoptosis, and gene regulation (15-18). Additionally, they interact with several transcription factors and
Classical swine fever (CSF) is an economically important infectious disease of pigs caused by classical swine fever virus (CSFV). Pseudorabies (PR), which is caused by pseudorabies virus (PRV), is another important infectious disease of pigs and other animals. Coinfections of pigs with PRV and CSFV occur occasionally in the field. The modified live vaccine Bartha-K61 strain has played an important role in the control of PR in many countries, including China. Since late 2011, however, increasing PR outbreaks caused by an emerging PRV variant have been reported in Bartha-K61-vaccinated swine populations on many farms in China. Previously, we generated a gE/gI-deleted PRV (rPRVTJ-delgE) based on this PRV variant, which was shown to be safe and can provide rapid and complete protection against lethal challenge with the PRV variant in pigs. Here, we generated a new recombinant PRV variant expressing the E2 gene of CSFV (rPRVTJ-delgE/gI-E2) and evaluated its immunogenicity and efficacy in pigs. The results showed that rPRVTJ-delgE/gI-E2 was safe for pigs, induced detectable anti-PRV and anti-CSFV neutralizing antibodies, and provided complete protection against the lethal challenge with either the PRV TJ strain or the CSFV Shimen strain. The data indicate that rPRVTJ-delgE/gI-E2 is a promising candidate bivalent vaccine against PRV and CSFV coinfections.
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