Zinc-finger CCHC-type containing protein 8 promotes RNA virus replication by suppressing the type-I interferon responses.

Host cells have evolved an intricate regulatory network to fine tune the type-I interferon responses. However, the full picture of this regulatory network remains to be depicted. In this study, we found that knock out of zinc-finger CCHC-type containing protein 8 (ZCCHC8) impairs the replication of influenza A virus (IAV), Sendai virus (Sev), Japanese encephalitis virus (JEV), and vesicular stomatitis virus (VSV). Further investigation unveiled that ZCCHC8 suppresses the type-I interferon responses by targeting the interferon regulatory factor 3 (IRF3) signaling pathway. Mechanistically, ZCCHC8 associates with phosphorylated IRF3 and disrupts the interaction of IRF3 with the co-activator CREB-binding protein (CBP). Additionally, the direct binding of ZCCHC8 with the IFN-stimulated response element (ISRE) impairs the ISRE-binding of IRF3. Our study contributes to the comprehensive understanding for the negative regulatory network of the type-I interferon responses and provides valuable insights for the control of multiple viruses from a host-centric perspective.IMPORTANCEThe innate immune responses serve as the initial line of defense against invading pathogens and harmful substances. Negative regulation of the innate immune responses plays an essential role in avoiding auto-immune diseases and over-activated immune responses. Hence, the comprehensive understanding of the negative regulation network for innate immune responses could provide novel therapeutic insights for the control of viral infections and immune dysfunction. In this study, we report that ZCCHC8 negatively regulates the type-I interferon responses. We illustrate that ZCCHC8 impedes the IRF3-CBP association by interacting with phosphorylated IRF3 and competes with IRF3 for binding to ISRE. Our study demonstrates the role of ZCCHC8 in the replication of multiple RNA viruses and contributes to a deeper understanding of the negative regulation system for the type-I interferon responses.

Inhibition of RAN attenuates influenza a virus replication and nucleoprotein nuclear export.

Nuclear export of the viral ribonucleoprotein (vRNP) is a critical step in the influenza A virus (IAV) life cycle and may be an effective target for the development of anti-IAV drugs. The host factor ras-related nuclear protein (RAN) is known to participate in the life cycle of several viruses, but its role in influenza virus replication remains unknown. In the present study, we aimed to determine the function of RAN in influenza virus replication using different cell lines and subtype strains. We found that RAN is essential for the nuclear export of vRNP, as it enhances the binding affinity of XPO1 toward the viral nuclear export protein NS2. Depletion of RAN constrained the vRNP complex in the nucleus and attenuated the replication of various subtypes of influenza virus. Using in silico compound screening, we identified that bepotastine could dissociate the RAN-XPO1-vRNP trimeric complex and exhibit potent antiviral activity against influenza virus both in vitro and in vivo. This study demonstrates the important role of RAN in IAV replication and suggests its potential use as an antiviral target.

The recombinant vaccine of Lactobacillus plantarum elicits immune protection against H1N1 and H9N2 influenza virus infection.

Influenza A virus (IAV) causes annual epidemics and occasional pandemics, resulting in significant economic losses and numerous fatalities. Current vaccines, typically administered through injection, provide limited protection due to the frequent antigenic shift and drift of IAV strains. Therefore, the development of alternative broad-spectrum vaccine strategies is imperative. Lactic acid bacteria (LAB) represent promising candidates for vaccine engineering due to their low cost, high safety profile, and suitability for oral administration. In this study, we identified a strain of Lactobacillus plantarum (Lp) that is resistant to acid and bile salts and capable of colonizing the intestines of mice. Subsequently, we employed the RecE/T gene editing system to integrate headless hemagglutinins (mini-HA) into the genome of Lp, generating Lp-mini-HA-SP. Remarkably, immunization with Lp-mini-HA-SP elicited serum IgG antibody responses and conferred immune protection against H9N2 and H1N1 influenza virus challenges. Collectively, our findings offer a novel approach for the development of orally administered IAV vaccines and hold significant potential for future drug development endeavors.

How public environmental appeals affect the collaborative governance in pollution and carbon reduction: Evidence from spatial effects across Chinese cities.

China has always adhered to the strategy of sustainable development. It is prevalent the public want a good living environment, which requires local governments and businesses to enhance their environmental governance capabilities. Using the panel data from Chinese cities from 2012 to 2019 and econometrics models, we examine the impact mechanisms of public environmental appeals (PEA) on efficiency of collaborative governance in pollution reduction and carbon mitigation (GPC). Results indicate that there is a positive spatial clustering of GPC across cities, with high-high clustering is notably concentrated in the southern regions of China and low-low clustering is prevalent in the northern regions. Spatial econometrics model results reveal that the stronger PEA, the higher GPC. The result of mechanism analysis shows the mediation of environmentally friendly technological innovation is crucial. Subsequent inquiry uncovers that the digital economy positively moderates the impact of PEA on GPC. The Belt and Road policy region exhibits heightened sensitivity to PEA, thereby enhancing the positive impact of PEA on GPC.

Seroprevalence of the novel swine acute diarrhea syndrome coronavirus in China assessed by enzyme-linked immunosorbent assay.

The endemic outbreak of SADS-CoV has resulted in economic losses and potentially threatened the safety of China's pig industry. The molecular epidemiology of SADS-CoV in pig herds has been investigated in many provinces in China. However, there are no data over a long-time span, and there is a lack of extensive serological surveys to assess the prevalence of SADS-CoV in Chinese swine herds since the discovery of SADS-CoV. In this study, an indirect anti-SADS-CoV IgG enzyme-linked immunosorbent assay (ELISA) based on the SADS-CoV S1 protein was established to investigate the seroprevalence of SADS-CoV in Chinese swine herds. Cross-reactivity assays, indirect immunofluorescence, and western blotting assays showed that the developed ELISA had excellent SADS-CoV specificity. In total, 12,978 pig serum samples from 29 provinces/municipalities/autonomous regions in China were tested from 2022 to 2023. The results showed that the general seroprevalence of SADS-CoV in China was 59.97%, with seroprevalence ranging from 16.7% to 77.12% in different provinces and from 42.61% to 68.45% in different months. SADS-CoV is widely prevalent in China, and its seroprevalence was higher in Northeast China, North China, and Central China than in other regions. Among the four seasons, the prevalence of SADS-CoV was the highest in spring and the lowest in autumn. The results of this study provide the general seroprevalence profile of SADS-CoV in China, facilitating the understanding of the prevalence of SADS-CoV in pigs. More importantly, this study is beneficial in formulating preventive and control measures for SADS-CoV and may provide directions for vaccine development.

Saccharomyces cerevisiae oral immunization in mice using multi-antigen of the African swine fever virus elicits a robust immune response.

African swine fever virus (ASFV) is one of the most complex viruses. ASFV is a serious threat to the global swine industry because no commercial vaccines against this virus are currently available except in Vietnam. Moreover, ASFV is highly stable in the environment and can survive in water, feed, and aerosols for a long time. ASFV is transmitted through the digestive and respiratory tract. Mucosal immunity is the first line of defense against ASFV. Saccharomyces cerevisiae (SC), which has been certified by the U.S. Food and Drug Administration and has a generally recognized as safe status in the food industry, was used for oral immunization in this study. ASFV antigens were effectively expressed in recombinant SC strains with high DNA copy numbers and stable growth though surface display technology and chromosome engineering (δ-integration). The recombinant SC strains containing eight ASFV antigens-KP177R, E183L, E199L, CP204L, E248R, EP402R, B602L, and B646L- induced strong humoral and mucosal immune responses in mice. There was no antigenic competition, and these antigens induced Th1 and Th2 cellular immune responses. Therefore, the oral immunization strategy using recombinant SC strains containing multiple ASFV antigens demonstrate potential for future testing in swine, including challenge studies to evaluate its efficacy as a vaccine against ASFV.

Whole-genome resequencing of Chinese indigenous sheep provides insight into the genetic basis underlying climate adaptation.

BACKGROUND: Chinese indigenous sheep are valuable resources with unique features and characteristics. They are distributed across regions with different climates in mainland China; however, few reports have analyzed the environmental adaptability of sheep based on their genome. We examined the variants and signatures of selection involved in adaptation to extreme humidity, altitude, and temperature conditions in 173 sheep genomes from 41 phenotypically and geographically representative Chinese indigenous sheep breeds to characterize the genetic basis underlying environmental adaptation in these populations. RESULTS: Based on the analysis of population structure, we inferred that Chinese indigenous sheep are divided into four groups: Kazakh (KAZ), Mongolian (MON), Tibetan (TIB), and Yunnan (YUN). We also detected a set of candidate genes that are relevant to adaptation to extreme environmental conditions, such as drought-prone regions (TBXT, TG, and HOXA1), high-altitude regions (DYSF, EPAS1, JAZF1, PDGFD, and NF1) and warm-temperature regions (TSHR, ABCD4, and TEX11). Among all these candidate genes, eight ABCD4, CNTN4, DOCK10, LOC105608545, LOC121816479, SEM3A, SVIL, and TSHR overlap between extreme environmental conditions. The TSHR gene shows a strong signature for positive selection in the warm-temperature group and harbors a single nucleotide polymorphism (SNP) missense mutation located between positions 90,600,001 and 90,650,001 on chromosome 7, which leads to a change in the protein structure of TSHR and influences its stability. CONCLUSIONS: Analysis of the signatures of selection uncovered genes that are likely related to environmental adaptation and a SNP missense mutation in the TSHR gene that affects the protein structure and stability. It also provides information on the evolution of the phylogeographic structure of Chinese indigenous sheep populations. These results provide important genetic resources for future breeding studies and new perspectives on how animals can adapt to climate change.

Whole-Genome Scanning for Selection Signatures Reveals Candidate Genes Associated with Growth and Tail Length in Sheep.

Compared to Chinese indigenous sheep, Western sheep have rapid growth rate, larger physique, and higher meat yield. These excellent Western sheep were introduced into China for crossbreeding to expedite the enhancement of production performance and mutton quality in local breeds. Here, we investigated population genetic structure and genome-wide selection signatures among the Chinese indigenous sheep and the introduced sheep based on whole-genome resequencing data. The PCA, N-J tree and ADMIXTURE results showed significant genetic difference between Chinese indigenous sheep and introduced sheep. The nucleotide diversity (π) and linkage disequilibrium (LD) decay results indicated that the genomic diversity of introduced breeds were lower. Then, Fst & π ratio, XP-EHH, and de-correlated composite of multiple signals (DCMS) methods were used to detect the selection signals. The results showed that we identified important candidate genes related to growth rate and body size in the introduced breeds. Selected genes with stronger selection signatures are associated with growth rate (CRADD), embryonic development (BVES, LIN28B, and WNT11), body size (HMGA2, MSRB3, and PTCH1), muscle development and fat metabolism (MSTN, PDE3A, LGALS12, GGPS1, and SAR1B), wool color (ASIP), and hair development (KRT71, KRT74, and IRF2BP2). Thus, these genes have the potential to serve as candidate genes for enhancing the growth traits of Chinese indigenous sheep. We also identified tail-length trait-related candidate genes (HOXB13, LIN28A, PAX3, and VEGFA) in Chinese long-tailed breeds. Among these genes, HOXB13 is the main candidate gene for sheep tail length phenotype. LIN28A, PAX3, and VEGFA are related to embryonic development and angiogenesis, so these genes may be candidate genes for sheep tail type traits. This study will serve as a foundation for further genetic improvement of Chinese indigenous sheep and as a reference for studies related to growth and development of sheep.

Application of Recombinant Lactic Acid Bacteria (LAB) Live Vector Oral Vaccine in the Prevention of F4+ Enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in piglets. The current primary approach for ETEC prevention and control relies on antibiotics, as few effective vaccines are available. Consequently, an urgent clinical demand exists for developing an effective vaccine to combat this disease. Here, we utilized food-grade Lactococcus lactis NZ3900 and expression plasmid pNZ8149 as live vectors, together with the secreted expression peptide Usp45 and the cell wall non-covalent linking motif LysM, to effectively present the mutant LTA subunit, the LTB subunit of heat-labile enterotoxin, and the FaeG of F4 pilus on the surface of recombinant lactic acid bacteria (LAB). Combining three recombinant LAB as a live vector oral vaccine, we assessed its efficacy in preventing F4+ ETEC infection. The results demonstrate that oral immunization conferred effective protection against F4+ ETEC infection in mice and piglets lacking maternal antibodies during weaning. Sow immunization during late pregnancy generated significantly elevated antibodies in colostrum, which protected piglets against F4+ ETEC infection during lactation. Moreover, booster immunization on piglets during lactation significantly enhanced their resistance to F4+ ETEC infection during the weaning stage. This study highlights the efficacy of an oral LAB vaccine in preventing F4+ ETEC infection in piglets by combining the sow immunization and booster immunization of piglets, providing a promising vaccination strategy for future prevention and control of ETEC-induced diarrhea in piglets.

Analysis of the efficacy of blunt separation combined with uncrosslinked sodium hyaluronate composite solution for the treatment of tear trough deformity in Asians.

BACKGROUND: Filling therapy is becoming increasingly popular for correcting tear trough deformities (TTD). However, its therapeutic effect and retention time are limited. AIMS: To improve the clinical efficacy and safety of TTD treatment in Asians, we used a blunt separation technique to break the adhesion site of periorbital subcutaneous tissue, and while repairing skin dermis after injury, it was combined with uncrosslinked hyaluronic acid compound solution to promote collagen regeneration and treat TTDs. PATIENTS/METHODS: Twenty-six Chinese patients (21 women and 5 men) with TTD, with a mean age of 34.54 ± 9.21 (range, 20-56) years, were enrolled. Symptom improvement, recurrence rates, treatment safety, and patient satisfaction were evaluated. RESULTS: All patients' tear trough rating scale (TTRS) scores decreased significantly immediately after treatment. The TTRS scores at 1, 3, and 6 months, and 1 year after treatment demonstrated significant differences from those before treatment (all p < 0.05). All patients' experienced mild pain, erythema, and swelling during the treatment. Three patients developed postinjection bruising after treatment, which lasted for 6-7 days and subsequently disappeared. No other adverse reactions were observed during the follow-up. There were no recurrent cases, and patient satisfaction was very high. CONCLUSIONS: Blunt separation combined with an uncrosslinked sodium hyaluronate composite solution is safe and effective for treating TTDs in Asians with few side effects and has good clinical application prospects.

Bacillus subtilis partially inhibits African swine fever virus infection in vivo and in vitro based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II.

IMPORTANCE: African swine fever virus (ASFV) is a highly fatal swine disease that severely affects the pig industry. Although ASFV has been prevalent for more than 100 years, effective vaccines or antiviral strategies are still lacking. In this study, we identified four Bacillus subtilis strains that inhibited ASFV proliferation in vitro. Pigs fed with liquid biologics or powders derived from four B. subtilis strains mixed with pellet feed showed reduced morbidity and mortality when challenged with ASFV. Further analysis showed that the antiviral activity of B. subtilis was based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II. Our findings offer a promising new strategy for the prevention and control of ASFV that may significantly alleviate the economic losses in the pig industry.

GlcNac produced by the gut microbiome enhances host influenza resistance by modulating NK cells.

Microbiota are known to modulate the host response to influenza infection, but the mechanisms remain largely unknown. Gut metabolites are the key mediators through which gut microbes play anti-influenza effect. Transferring fecal metabolites from mice with high influenza resistance into antibiotic-treated recipient mice conferred resistance to influenza infections. By comparing the metabolites of different individuals with high or low influenza resistance, we identified and validated N-acetyl-D-glucosamine (GlcNAc) and adenosine showed strong positive correlations with influenza resistance and exerted anti-influenza effects in vivo or in vitro, respectively. Especially, GlcNAc mediated the anti-influenza effect by increasing the proportion and activity of NK cells. Several gut microbes, including Clostridium sp., Phocaeicola sartorii, and Akkermansia muciniphila, were positively correlated with influenza resistance, and can upregulate the level of GlcNAc in the mouse gut by exogenous supplementation. Subsequent studies confirmed that administering a combination of the three bacteria to mice via gavage resulted in similar modulation of NK cell responses as observed with GlcNAc. This study demonstrates that gut microbe-produced GlcNAc protects the host against influenza by regulating NK cells, facilitating the elucidation of the action mechanism of gut microbes mediating host influenza resistance.

Whole Genome Resequencing Reveals Selection Signals Related to Wool Color in Sheep.

Wool color is controlled by a variety of genes. Although the gene regulation of some wool colors has been studied in relative depth, there may still be unknown genetic variants and control genes for some colors or different breeds of wool that need to be identified and recognized by whole genome resequencing. Therefore, we used whole genome resequencing data to compare and analyze sheep populations of different breeds by population differentiation index and nucleotide diversity ratios (Fst and θπ ratio) as well as extended haplotype purity between populations (XP-EHH) to reveal selection signals related to wool coloration in sheep. Screening in the non-white wool color group (G1 vs. G2) yielded 365 candidate genes, among which PDE4B, GMDS, GATA1, RCOR1, MAPK4, SLC36A1, and PPP3CA were associated with the formation of non-white wool; an enrichment analysis of the candidate genes yielded 21 significant GO terms and 49 significant KEGG pathways (p < 0.05), among which 17 GO terms and 21 KEGG pathways were associated with the formation of non-white wool. Screening in the white wool color group (G2 vs. G1) yielded 214 candidate genes, including ABCD4, VSX2, ITCH, NNT, POLA1, IGF1R, HOXA10, and DAO, which were associated with the formation of white wool; an enrichment analysis of the candidate genes revealed 9 significant GO-enriched pathways and 19 significant KEGG pathways (p < 0.05), including 5 GO terms and 12 KEGG pathways associated with the formation of white wool. In addition to furthering our understanding of wool color genetics, this research is important for breeding purposes.

Protein arginine methyltransferase 5 mediates arginine symmetric dimethylation of influenza A virus PB2 and supports viral replication.

Influenza A virus (IAV) relies on intricate and highly coordinated associations with host factors for efficient replication and transmission. Characterization of such factors holds great significance for development of anti-IAV drugs. Our study identified protein arginine methyltransferase 5 (PRMT5) as a novel host factor indispensable for IAV replication. Silencing PRMT5 resulted in drastic repression of IAV replication. Our findings revealed that PRMT5 interacts with each protein component of viral ribonucleoproteins (vRNPs) and promotes arginine symmetric dimethylation of polymerase basic 2 (PB2). Overexpression of PRMT5 enhanced viral polymerase activity in a dose-dependent manner, emphasizing its role in genome transcription and replication of IAV. Moreover, analysis of PB2 protein sequences across various subtypes of IAVs demonstrated the high conservation of potential RG motifs recognized by PRMT5. Overall, our study suggests that PRMT5 supports IAV replication by facilitating viral polymerase activity by interacting with PB2 and promoting its arginine symmetric dimethylation. This study deepens our understanding of how IAV manipulates host factors to facilitate its replication and highlights the great potential of PRMT5 to serve as an anti-IAV therapeutic target.

Whole-Genome Resequencing Reveals Selection Signal Related to Sheep Wool Fineness.

Wool fineness affects the quality of wool, and some studies have identified about forty candidate genes that affect sheep wool fineness, but these genes often reveal only a certain proportion of the variation in wool thickness. We further explore additional genes associated with the fineness of sheep wool. Whole-genome resequencing of eight sheep breeds was performed to reveal selection signals associated with wool fineness, including four coarse wool and four fine/semi-fine wool sheep breeds. Multiple methods to reveal selection signals (Fst and θπ Ratio and XP-EHH) were applied for sheep wool fineness traits. In total, 269 and 319 genes were annotated in the fine wool (F vs. C) group and the coarse wool (C vs. F) group, such as LGR4, PIK3CA, and SEMA3C and NFIB, OPHN1, and THADA. In F vs. C, 269 genes were enriched in 15 significant GO Terms (p < 0.05) and 38 significant KEGG Pathways (p < 0.05), such as protein localization to plasma membrane (GO: 0072659) and Inositol phosphate metabolism (oas 00562). In C vs. F, 319 genes were enriched in 21 GO Terms (p < 0.05) and 16 KEGG Pathways (p < 0.05), such as negative regulation of focal adhesion assembly (GO: 0051895) and Axon guidance (oas 04360). Our study has uncovered genomic information pertaining to significant traits in sheep and has identified valuable candidate genes. This will pave the way for subsequent investigations into related traits.

Prohibitin1 facilitates viral replication by impairing the RIG-I-like receptor signaling pathway.

IMPORTANCE: Type I interferon (IFN-I), produced by the innate immune system, plays an essential role in host antiviral responses. Proper regulation of IFN-I production is required for the host to balance immune responses and prevent superfluous inflammation. IFN regulatory factor 3 (IRF3) and subsequent sensors are activated by RNA virus infection to induce IFN-I production. Therefore, proper regulation of IRF3 serves as an important way to control innate immunity and viral replication. Here, we first identified Prohibitin1 (PHB1) as a negative regulator of host IFN-I innate immune responses. Mechanistically, PHB1 inhibited the nucleus import of IRF3 by impairing its binding with importin subunit alpha-1 and importin subunit alpha-5. Our study demonstrates the mechanism by which PHB1 facilitates the replication of multiple RNA viruses and provides insights into the negative regulation of host immune responses.

The RNA-Splicing Ligase RTCB Promotes Influenza A Virus Replication by Suppressing Innate Immunity via Interaction with RNA Helicase DDX1.

The RNA-splicing ligase RNA 2',3'-cyclic phosphate and 5'-OH ligase (RTCB) is a catalytic subunit of the tRNA-splicing ligase complex, which plays an essential role in catalyzing tRNA splicing and modulating the unfolded protein response. However, the function of RTCB in influenza A virus (IAV) replication has not yet been described. In this study, RTCB was revealed to be an IAV-suppressed host factor that was significantly downregulated during influenza virus infection in several transformed cell lines, as well as in primary human type II alveolar epithelial cells, and its knockout impaired the propagation of the IAV. Mechanistically, RTCB depletion led to a robust elevation in the levels of type I and type III IFNs and proinflammatory cytokines in response to IAV infection, which was confirmed by RTCB overexpression studies. Lastly, RTCB was found to compete with DDX21 for RNA helicase DDX1 binding, attenuating the DDX21-DDX1 association and thus suppressing the expression of IFN and downstream IFN-stimulated genes. Our study indicates that RTCB plays a critical role in facilitating IAV replication and reveals that the RTCB-DDX1 binding interaction is an important innate immunomodulator for the host to counteract viral infection.

Isolation and identification of Eurasian avian-like H1N1 swine influenza virus and evaluation of their pathogenicity and immune protective effects in pigs.

Swine influenza (SI) is a severe disease affecting pigs, with a huge economic impact on pig farmers. Currently, available SIV vaccines do not meet the requirements for Swine influenza prevention and control, indicating the need for vaccine development using predominant strains. Here, we isolated and identified the swine influenza virus in farms and slaughterhouses in nine provinces in China to determine the most prevalent strain. A total of 8383 samples were collected between 2013 and 2022, from which 87 swine influenza virus strains were isolated. Genome sequencing identified 62 strains of the H1N1 subtype, three strains of the H1N2 subtype, and 22 strains of the H3N2 subtype. The 521# strain virus possesses the viral ribonucleoprotein (vRNP) and matrix (M) genes from the pdm/09 lineage, the HA, NA from the original Eurasian avian-like (EA) H1N1 lineage, and the nonstructural (NS) gene from the triple-reassortant (TR) lineage. The 431# strain was also a TR, except its M-gene was derived from the original EA H1N1 lineage. The pathogenicity of two 431# strains and one typical 521# strain was evaluated in mice, and the 431# strain exhibited higher pathogenicity. Therefore, a new 521# strain was selected for vaccine production because it is the current circulating strain. The vaccine produced using the 521# strain and pre-evaluated adjuvants was effective against the homologous H05 strain, as evidenced by the normal body temperature of vaccinated pigs and low virus titer of nasal swabs. In contrast, infection with the H05 strain significantly increased the body temperature of unvaccinated pigs and increased the virus titer of nasal swabs. Notably, vaccination with the 521#-based vaccine conferred some level of protection against the heterologous B15 strain (H3N2 subtype), thus reducing the viral load in pigs.

Sodium taurocholate hydrate inhibits influenza virus replication and suppresses influenza a Virus-triggered inflammation in vitro and in vivo.

Influenza A virus is an important respiratory pathogen that poses serious threats to human health. Owing to the high mutation rate of viral genes, weaker cross-protection of vaccines, and rapid emergence of drug resistance, there is an urgent need to develop new antiviral drugs against influenza viruses. Taurocholic acid is a primary bile acid that promotes digestion, absorption, and excretion of dietary lipids. Here, we demonstrate that sodium taurocholate hydrate (STH) exhibits broad-spectrum antiviral activity against influenza strains H5N6, H1N1, H3N2, H5N1, and H9N2 in vitro. STH significantly inhibited the early stages of influenza A virus replication. The levels of influenza virus viral RNA (vRNA), complementary RNA (cRNA), and mRNA were specifically reduced in virus-infected cells following STH treatment. In vivo, STH treatment of infected mice alleviated clinical signs and reduced weight loss and mortality. STH also reduced TNF-α, IL-1ß, and IL-6 overexpression. STH significantly inhibited the upregulation of TLR4 and the NF-kB family member p65, both in vivo and in vitro. These results suggest that STH exerts a protective effect against influenza infection via suppression of the NF-kB pathway, highlighting the potential use of STH as a drug for treating influenza infection.