Surface-Displayed Porcine IFN-λ3 in Lactobacillus plantarum Inhibits Porcine Enteric Coronavirus Infection of Porcine Intestinal Epithelial Cells

Abstract

Interferon (IFN)-λ plays an essential role in mucosal cells which exhibit strong antiviral activity.Lactobacillus plantarum (L. plantarum) has substantial application potential in the food and medical industries because of its probiotic properties. Alphacoronaviruses, especially porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), cause high morbidity and mortality in piglets resulting in economic loss. Co-infection by these two viruses is becoming increasingly frequent. Therefore, it is particularly important to develop a new drug to prevent diarrhea infected with mixed viruses in piglets. In this study, we first constructed an anchored expression vector with CWA (C-terminal cell wall anchor) on L. plantarum. Second, we constructed two recombinant L. plantarum strains that anchored IFN-λ3 via pgsA (N-terminal transmembrane anchor) and CWA. Third, we demonstrated that both recombinant strains possess strong antiviral effects against coronavirus infection in the intestinal porcine epithelial cell line J2 (IPEC-J2). However, recombinant L. plantarum with the CWA anchor exhibited a more powerful antiviral effect than recombinant L. plantarum with pgsA. Consistent with this finding, Lb.plantarum-pSIP-409-IFN-λ3-CWA enhanced the expression levels of IFN-stimulated genes (ISGs) (ISG15, OASL, and Mx1) in IPEC-J2 cells more than did recombinant Lb.plantarum-pSIP-409-pgsA'-IFN-λ3. Our study verifies that recombinant L. plantarum inhibits PEDV and TGEV infection in IPEC-J2 cells, which may offer great potential for use as a novel oral antiviral agent in therapeutic applications for combating porcine epidemic diarrhea and transmissible gastroenteritis. This study is the first to show that recombinant L. plantarum suppresses PEDV and TGEV infection of IPEC-J2 cells.

The emerging role of probiotics as a mitigation strategy against coronavirus disease 2019 (COVID-19)

“…Lactobacillus casei oral vaccine could induce the production of IgG (systemic) and SIgA antibody (mucosal) in a murine model [196]. Several other studies have employed various probiotics to present PEDV genes or antigens of interest [111,114,196,197]. Liu et al [111] showed that an altered Lactobacillus plantarum strain had antiviral activity against coronavirus infections in a porcine intestinal epithelial cell line.…”

Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic

“…Evidence for antiviral activity of probiotic strains against common respiratory viruses, including influenza, rhinovirus, and respiratory syncytial virus comes from clinical and experimental studies (17)(18)(19)41). While none of these effects or mechanisms have been tested on the new SARS-CoV-2 virus, this should not negate considering this approach, especially when effects of probiotics against other coronavirus strains have been reported (42)(43)(44)(45). Furthermore, patients are dying from secondary bacterial infections.…”

Modulatory Effects of Probiotics During Pathogenic Infections With Emphasis on Immune Regulation

“…Probiotics and recombinant probiotics with antiviral effects are effectively used to combat and minimize the detrimental effects of other coronaviruses, such as alphacoronavirusesparticularly transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV)-which cause substantial economic losses in the pork meat industry. Recombinant L. plantarum inhibits TGEV and PEDV infections in the IPEC-J2 cell line by enhancing ISGs (OASL, ISG15, and Mx1) which have strong antiviral effects (199). Recombinant L. plantarum (containing the surface S antigen of TGEV) elicits an immune response characterized by higher numbers of activated DC cells, B + IgA + cells, secretory IgA (sIgA), serum IgG, IFN-γ, and IL4 which help the host to combat TGEV (200).…”