Viral infection converts the normal constitution of a cell to optimise viral entry, replication, and virion production. These conversions contain alterations or disruptions of the tight and adherens junctions between cells as part of their pathogenesis, and reorganise cellular microfilaments that initiate, sustain and spread the viral infections and so on. Using porcine epidemic diarrhoea virus (PEDV), transmissible gastroenteritis virus (TGEV) and a model of normal intestinal epithelial cells (IPEC-J2), we researched the interaction between tight and adherens junctions and microfilaments of IPEC-J2 cells with these viruses. In our work, the results showed that IPEC-J2 cells were susceptible to TGEV and PEDV infection. And TGEV could impair the barrier integrity of IPEC-J2 cells at early stages of infection through down-regulating some proteins of tight and adherens junctions, while PEDV cloud cause a slight of damage in the integrity of epithelial barrier. In addition, they also could affect the microfilaments remodelling of IPEC-J2 cells, and the drug-interfered microfilaments could inhibit viral replication and release. Furthermore, PEDV+TGEV co-infection was more aggravating to damage of tight junctions and remodelling of microfilaments than their single infection. Finally, the PEDV and TGEV infection affected the MAPK pathway, and inhibition of MAPK pathway regulated the changes of tight junctions and microfilaments of cells. These studies provide a new insight from the perspective of the epithelial barrier and microfilaments into the pathogenesis of PEDV and TGEV.
To develop a safe, effective, and convenient vaccine for the prevention of highly pathogenic avian influenza (HPAI), we have successfully constructed two recombinant lactobacillus strains (LA4356-pH and DLD17-pH) that express the foreign HPAI virus protein hemagglutinin 1 (HA 1 ). The mucosal and systemic immune responses triggered by these two recombinant lactobacilli following oral administration to BALB/c mice were evaluated. The results showed that both LA4356-pH and DLD17-pH could significantly increase the specific anti-HA 1 IgA antibody level in the mucosa and the anti-HA 1 IgG level in serum, as well as stimulating the splenic lymphocyte proliferative reaction through increased expression of interleukin-4 (IL-4). Compared with LA4356-pH, DLD17-pH was more effective at inducing systemic and mucosal immune responses, with higher anti-HA 1 -specific IgA and IgG levels. Therefore, DLD17-pH could be a promising oral vaccine candidate against HPAI. Highly pathogenic avian influenza (HPAI) virus (H5N1) is a threat to the world's poultry industry. As a zoonotic agent, this virus also has the potential to cause a human pandemic (29). Current vaccination (by intramuscular immunization) against HPAI has succeeded in reducing morbidity and mortality in poultry. However, the intense stress caused by injection could hamper the animal's growth (34). Thus, many investigators are pursuing more convenient and economical avenues for construction of new vaccine candidates, such as recombinant subunit vaccines using baculovirus (28), plasmid DNA (3), or replication-incompetent adenovirus (rAd) (26, 27) vectors. The H5N1 strain can infect animals through their respiratory and intestinal tracts (10). Because there are many mucosa-associated lymphoid tissues underneath the epithelia of the respiratory and intestinal tracts, protective HPAI virus antigens may induce an effective mucosal immune response to prevent the invasion of HPAI virus if they can be transported easily to these tissues. Thus, developing mucosal vaccine candidates based on these considerations is a feasible strategy.Mucosal vaccines, which are administered mainly orally or intranasally, cause less stress in the animal and have been the subject of growing interest due to the advantages that they offer over conventional parenteral vaccines. The biggest advantage is the stimulation of mucosal immune responses (15,24). Lactobacillus is a genus of Gram-positive facultative anaerobic or microaerophilic rod-shaped bacteria. These beneficial bacteria normally live in the digestive, urinary, and genital systems without causing disease. Their abilities to transit through the stomach intact and to associate closely with the intestinal epithelium, combined with their immunomodulatory properties, have made Lactobacillus spp. attractive candidates as live vehicles for the delivery of immunogens to the intestinal mucosa (6, 12). It was recently shown that specific Lactobacillus species can induce inflammatory responses against infection, increase IgA production, activate mo...
LL36EH triggered the anti-HA(1)-specific humoral and cellular immune responses and protective immunity. Therefore, oral immunization with LL36EH could be a valuable strategy against highly pathogenic avian influenza for humans and animals.
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