Bovine viral diarrhea virus (BVDV), a positive-strand RNA virus of the genus Pestivirus in the Flaviviridae family, is the causative agent of viral diarrheal disease in bovine. BVDV has been used as a surrogate model for the hepatitis C virus (HCV) to evaluate the efficacy of antiviral drugs. The plant flavonol quercetin causes multiple health-promoting effects in humans and animals. It can be made into a variety of additives, and it exerts a variety of immunomodulatory effects with the potential to be used as an antiviral agent. However, quercetin’s antiviral effect and mechanism of action on BVDV are still unclear. Therefore, this study was designed to evaluate quercetin’s effect on BVDV virus replication in vitro and in vivo and elucidate its mechanism of action. A CCK-8 kit was used to analyze the toxicity of the quercetin to the MDBK cells. Western blot, qRT-PCR, TCID₅₀, and histological analysis were used to determine the mechanism of quercetin’s anti-BVDV activity. An oxidative stress kit was used to evaluate the effects of quercetin on ROS, antioxidant enzymes, and MDA indexes. The effect of quercetin on IL-2 and IFN-γ in the serum of mice was determined by using an ELISA kit. The results showed that quercetin inhibits Hsp70, blocks BVDV infection in the early stage of virus infection and inhibits BVDV replication by inhibiting oxidative stress or ERK phosphorylation. In addition, quercetin alleviated the decrease in IFN-γ and IL-2 in the serum of BVDV-infected mice. Quercetin ameliorated BVDV-induced histopathological changes. In summary, this study demonstrated for the first time the role of Hsp70 in BVDV infection and the potential application of quercetin in treating BVDV infection.

Natural products have emerged as “rising stars” for treating viral diseases and useful chemical scaffolds for developing effective therapeutic agents. The nonstructural protein NS5B (RNA-dependent RNA polymerase) of NADL strain BVDV was used as the action target based on a molecular docking technique to screen herbal monomers for anti-BVDV viral activity. The in vivo and in vitro anti-BVDV virus activity studies screened the Chinese herbal monomers with significant anti-BVDV virus effects, and their antiviral mechanisms were initially explored. The molecular docking screening showed that daidzein, curcumin, artemisinine, and apigenin could interact with BVDV-NADL-NS5B with the best binding energy fraction. In vitro and in vivo tests demonstrated that none of the four herbal monomers significantly affected MDBK cell activity. Daidzein and apigenin affected BVDV virus replication mainly in the attachment and internalization phases, artemisinine mainly in the replication phase, and curcumin was active in the attachment, internalization, replication, and release phases. In vivo tests demonstrated that daidzein was the most effective in preventing and protecting BALB/C mice from BVDV infection, and artemisinine was the most effective in treating BVDV infection. This study lays the foundation for developing targeted Chinese pharmaceutical formulations against the BVDV virus.

Bovine viral diarrhea virus (BVDV), a positive-strand RNA virus of the genus Pestivirus in the Flaviviridae family, is the causative agent of bovine viral diarrhea–mucosal disease (BVD-MD). BVDV’s unique virion structure, genome, and replication mechanism in the Flaviviridae family render it a useful alternative model for evaluating the effectiveness of antiviral drugs used against the hepatitis C virus (HCV). As one of the most abundant and typical heat shock proteins, HSP70 plays an important role in viral infection caused by the family Flaviviridae and is considered a logical target of viral regulation in the context of immune escape. However, the mechanism of HSP70 in BVDV infection and the latest insights have not been reported in sufficient detail. In this review, we focus on the role and mechanisms of HSP70 in BVDV-infected animals/cells to further explore the possibility of targeting this protein for antiviral therapy during viral infection.

Introduction: Escherichia coli infection causes severe diarrhea, decreases growth performance, and increases mortality of poultry, which imposes a significant economic burden on the poultry industry and severely limits its growth.Methods: Here, to investigate the effects of Lactobacillus on the intestinal health, immune response, and growth performance of E. coli-infected goslings, we established a geese model infected with an Stx2f gene-carrying E. coli strain and analyzed the probiotic characteristics of three Lactobacillus isolates obtained from the cecum of healthy geese. In an in vivo study, Zi geese were administered daily gavage of L. johnsonii MC006, L. salivarius MC013, or L. fermentum MC018 (10⁹ CFU/mL) from 1 d of age for 21 d, followed by treatment with E. coli XH197291 gavage (10⁹ CFU/mL) on day 8.Results: The results showed that E. coli XH197291-infected geese exhibited depression, intestinal damage, reduced average daily gain, increased feed conversion ratio, and 100% diarrhea incidence within 48 h post-infection. Remarkably, among the three Lactobacillus isolates, L. fermentum MC018 showed the potential to function as a probiotic because of its ability to resist acid and bile degradation, antibacterial effect, and adhesion property. Notably, oral supplementation containing L. fermentum MC018 alleviated diarrhea and intestinal histological lesions, reduced E. coli counts in both ileum and rectum, increased the population of lactic acid bacteria, and improved the growth performance of E. coli-infected geese. Geese treated with L. fermentum MC018 gavage had higher serum diamine oxidase (p < 0.01) and IgM (p < 0.05) levels than those in the model group. L. fermentum MC018 reduced the levels of IL-1β, IL-6, and TNF-α in intestinal tissues following E. coli infection. Compared to L. salivarius MC013, L. fermentum MC018 increased the levels of ZO-1 in the duodenum and Claudin-1 in the ileum.Discussion: These findings suggest that L. fermentum MC018 is a promising probiotic strain for use as a potential alternative to antibiotics for controlling avian colibacillosis.