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Abstract Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ’s role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ’s effectiveness.

ABSTRACT Corynebacterium pseudotuberculosis (C. p), a facultative intracellular bacterium, is an important zoonotic pathogen that causes abscesses and pyogenic granulomas. The relationship between gut microbiota and host health or diseases has received increasing attention. However, the role of gut microbiota in the process of C. p infection is still unclear. In this study, we established a C. p infection model in C57BL/6 mice and examined the impact of preemptive oral administration Lactobacillus acidophilus (L. acidophilus) on infection. Our findings revealed that C. p infection led to pronounced pathological alterations in the liver and kidneys, characterized by abscess formation, intense inflammatory responses, and bacterial overload. Remarkably, these deleterious effects were greatly relieved by oral administration of L. acidophilus before infection with C. p. Additionally, we further found that during C. p infection, peritoneal macrophages (PMs) of mice orally administered with L. acidophilus accumulated more rapidly at sites of infection. Furthermore, our results showed that PMs from mice with oral L. acidophilus administration showed a stronger C. p clearance effect, and this was mediated by high expression of LC3-II protein. Meanwhile, oral administration of L. acidophilus protected the gut microbiota disorder in C57BL/6 mice caused by C. p infection. In summary, our study demonstrates that oral administration of L. acidophilus confers effective protection against C. p infection in C57BL/6 mice by modulating macrophage autophagy, thereby augmenting bacterial clearance and preserving gut microbiota and function stability. These findings position L. acidophilus as a viable probiotic candidate for the clinical prevention of C. p infection.IMPORTANCECorynebacterium pseudotuberculosis (C. p) is known to induce a range of chronic diseases in both animals and humans. Currently, clinical treatment for C. p infection mainly relies on antibiotic therapy or surgical intervention. However, excessive use of antibiotics may increase the risk of drug-resistant strains, and the effectiveness of treatment remains unsatisfactory. Furthermore, surgical procedures do not completely eradicate pathogens and can easily cause environmental pollution. Probiotic interventions are receiving increasing attention for improving the body’s immune system and maintaining health. In this study, we established a C. p infection model in C57BL/6 mice to explore the impact of Lactobacillus acidophilus during C. p infection. Our results showed that L. acidophilus effectively protected against C. p infection by regulating the autophagy of macrophages and maintaining intestinal microbiota homeostasis. This study may provide a new strategy for the prevention of C. p infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the major threats to swine industry, resulting in huge economic losses worldwide. Currently, PRRSV has diversified into multiple lineages with characteristics of extensive recombination in China. In this research, three virus strains were isolated and four virus whole genome sequences were generated and analyzed from clinical samples collected in Gansu province of China in 2023. The four virus strains were designated GSTS4-2023, GSLX2-2023, GSFEI2-2023 and GSBY4-2023. Phylogenetic analysis based on ORF5 sequences showed that GSTS4-2023, GSLX2-2023, GSFEI2-2023 and GSBY4-2023 shared 91.7, 91.2, 93.2 and 92.9% homology with NADC30 strain respectively, and belonged to lineage 1 of PRRSV-2. In addition, one amino acid deletion was observed at position 33 in ORF5 of GSTS4-2023, GSLX2-2023 and GSFEI2-2023. Moreover, amino acid alignment of the four strains showed a typical discontinuous 131-amino acid (aa) deletion in NSP2 for NADC30-like virus strains. Recombination analysis revealed that all four strains originated from NADC30 (lineage 1), with their minor parents coming from JXA1-like strains (lineage 8), VR-2332-like strains (lineage5) and QYYZ-like strains (lineage3). Finally, the three isolated virus strains, GSTS4-2023, GSLX2-2023 and GSFEI2-2023 showed relatively low levels of replication in cell culture. Our findings provide important implications for the field epidemiology of PRRSV.

Summary: Long interspersed element 1 (LINE-1) is the only currently known active autonomous transposon in humans, and its retrotransposition may cause deleterious effects on the structure and function of host cell genomes and result in sporadic genetic diseases. Host cells therefore developed defense strategies to restrict LINE-1 mobilization. In this study, we demonstrated that IFN-inducible Schlafen5 (SLFN5) inhibits LINE-1 retrotransposition. Mechanistic studies revealed that SLFN5 interrupts LINE-1 ribonucleoprotein particle (RNP) formation, thus diminishing nuclear entry of the LINE-1 RNA template and subsequent LINE-1 cDNA production. The ability of SLFN5 to bind to LINE-1 RNA and the involvement of the helicase domain of SLFN5 in its inhibitory activity suggest a mechanism that SLFN5 binds to LINE-1 RNA followed by dissociation of ORF1p through its helicase activity, resulting in impaired RNP formation. These data highlight a new mechanism of host cells to restrict LINE-1 mobilization.

IntroductionRabies is a worldwide epidemic that poses a serious threat to global public health. At present, rabies in domestic dogs, cats, and some pets can be effectively prevented and controlled by intramuscular injection of rabies vaccine. But for some inaccessible animals, especially stray dogs, and wild animals, it is difficult to prevent with intramuscular injection. Therefore, it is necessary to develop a safe and effective oral rabies vaccine.MethodsWe constructed recombinant Bacillus subtilis (B. subtilis) expressing two different strains of rabies virus G protein, named CotG-E-G and CotG-C-G, immunogenicity was studied in mice.ResultsThe results showed that CotG-E-G and CotG-C-G could significantly increase the specific SIgA titers in feces, serum IgG titers, and neutralizing antibodies. ELISpot experiments showed that CotG-E-G and CotG-C-G could also induce Th1 and Th2 to mediate the secretion of immune-related IFN-γ and IL-4. Collectively, our results suggested that recombinant B. subtilis CotG-E-G and CotG-C-G have excellent immunogenicity and are expected to be novel oral vaccine candidates for the prevention and control of wild animal rabies.

Abstract Background Feline calicivirus (FCV) is a common and highly prevalent pathogen causing upper respiratory diseases in kittens and felines in recent years. Due to the substantial genetic variability of the viral genes, existing vaccines cannot provide complete protection. Therefore, research on FCV antiviral drugs has received much attention. Results In this study, we found that copper chloride had dose-dependent antiviral effects on FCV in F81 cells. We also found that the combination of copper chloride and ribavirin had a synergistic protective effect against FCV in F81 cells. In contrast, the combination of copper chloride and horse anti-FCV immunoglobulin F (ab’)2 showed an antagonistic effect, likely because copper chloride has an effect on F (ab’)2 immunoglobulin; however, further research is needed to clarify this supposition. Conclusions In summary, we found that copper chloride had low cytotoxicity and significant antiviral effects on FCV in F81 cells, providing a new drug candidate for the prevention and treatment of FCV infection.

West Nile virus disease (WND) is an arthropod-borne zoonosis responsible for nonspecific fever or severe encephalitis. The pathogen is West Nile virus belonging to the genus Flavivirus, family Flaviviridae. Every year, thousands of cases were reported, which poses significant public health risk. Here, we constructed a West Nile virus chimera, ChiVax-WN01, by replacing the prMΔE gene of JEV SA14-14-2 with that of the West Nile virus NY99. The ChiVax-WN01 chimera showed clear, different characters compared with that of JEV SA14-14-2 and WNV NY99 strain. An animal study indicated that the ChiVax-WN01 chimera presented moderate safety and immunogenicity for 4-week female BALB/c mice.

Feline calicivirus (FCV), a highly contagious virus, is one of the major causes of upper respiratory infections in domestic cat populations and wild felines. It is a ubiquitous issue around the world, which constantly demands veterinary attention. Vaccination for FCV has generally been proposed as a cure for its infections. However, the high antigenic variability of this virus hinders the development of efficacious FCV vaccines. In this study, the experimental inactivated vaccine was developed with strain FCV CH-JL2 at 108.00 TCID50/mL, 1% binary ethylenimine (BEI) was utilized for inactivation at 37°C for 48 h, then was mixed with aluminum hydroxide which was used as an adjuvant. Through regular observation and monitoring, it was confirmed that the kittens in each group had a good mental state and appetite after the vaccination, and their body temperature was normal. Compared with the control group, the antibody levels increased, and no adverse reactions were seen. Its effects were evaluated using the previously constructed animal infection model to measure clinical symptoms after vaccination and FCV challenging. All kittens were challenged with FCV CH-JL2 at 42 days of post vaccination (dpv). The clinical signs of body weight, body temperature, viral shedding, survival rates were monitored daily during 14 days of post challenge (dpc). It has been shown that serum IgG levels and neutralization titer were significantly higher than the commercial inactivated vaccine, and kittens manifested normal clinical signs, good mental status and appetite after vaccination and subsequent viral challenging, the protection rate is 100% (5/5). Collectively, these preliminary data indicate that inactivated vaccine can provide complete protection against infection caused by the challenge FCV CH-JL2 for kittens, and FCV CHJL2 strain is a promising candidate for developing a safe and effective FCV vaccine in the future. [ABSTRACT FROM AUTHOR]