Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18 pharmacologically active components including melittin (MLT), phospholipase A (PLA), and apamin etc. BV is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. Nevertheless, antiviral properties of BV have not well investigated. Hence, we identified the potential antiviral properties of BV and its component against a broad panel of viruses. Co-incubation of non-cytotoxic amounts of BV and MLT, the main component of BV, significantly inhibited the replication of enveloped viruses such as Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes Simplex Virus (HSV). Additionally, BV and MLT also inhibited the replication of non-enveloped viruses such as Enterovirus-71 (EV-71) and Coxsackie Virus (H3). Such antiviral properties were mainly explained by virucidal mechanism. Moreover, MLT protected mice which were challenged with lethal doses of pathogenic influenza A H1N1 viruses. Therefore, these results provides the evidence that BV and MLT could be a potential source as a promising antiviral agent, especially to develop as a broad spectrum antiviral agent.

Antimicrobial resistance (AMR) has become an emerging health issue globally, posing a threat to zoonotic pathogens and foodborne diseases. In Bangladesh, the poultry sector supplies the majority of the demand for animal-source protein. The irrational and excessive use of antimicrobials (AMU) has been observed in the poultry sector. The development of AMR is associated with many factors, including the knowledge and attitudes of poultry farmers. Therefore, AMR reduction requires intervention from all the stockholders, including the farmers who are considered as end users of antimicrobials. This current research conducted a cross-sectional study to assess the knowledge, attitudes, and practices (KAP) of poultry farmers on AMU and AMR in Bangladesh. We determined the KAP of poultry farmers (broiler and layer farmers) of some selected districts of the country using a tested and paper-based questionnaire. The results demonstrated that most of the respondents have insufficient KAP regarding AMU and AMR. The respondents used a variety of antimicrobials primarily in the treatment of various diseases in poultry. One-third of the farmers did not seek antimicrobials from registered vets. Instead, they depended on others or themselves. The factor score analysis further revealed that the farmers’ demographic and socioeconomic variables were significant factors influencing the KAP. An adjusted logistic regression analysis showed that older farmers with 9–12 years of farming experience and graduate-level education, engaging in medium-sized layer farming, were more likely to have correct KAP on AMU and AMR. Further, farmers from the Cox’s Bazar region showed correct knowledge, whereas farmers of the Chattogram region showed a correct attitude towards AMU and AMR. A Spearman’s rank-order correlation revealed a positive association between knowledge–attitudes and knowledge–practices. The findings of the current investigation provide baseline evidence about the KAP of poultry farmers from low-income resources and offer insights into designing interventions and policies for the use of AMU and AMR in Bangladesh.

Tryptophanyl-tRNA synthetase (WRS) is one of the aminoacyl-tRNA synthetases (ARSs) that possesses noncanonical functions. Full-length WRS is released during bacterial infection and primes the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex to elicit innate immune responses. However, the role of WRS in viral infection remains unknown. Here, we show that full-length WRS is secreted by immune cells in the early phase of viral infection and functions as an antiviral cytokine. Treatment of cells with recombinant WRS protein promotes the production of inflammatory cytokines and type I interferons (IFNs) and curtails virus replication in THP-1 and Raw264.7 cells but not in TLR4−/− or MD2−/− bone marrow-derived macrophages (BMDMs). Intravenous and intranasal administration of recombinant WRS protein induces an innate immune response and blocks viral replication in vivo. These findings suggest that secreted full-length WRS has a noncanonical role in inducing innate immune responses to viral infection as well as to bacterial infection. IMPORTANCE ARSs are essential enzymes in translation that link specific amino acids to their cognate tRNAs. In higher eukaryotes, some ARSs possess additional, noncanonical functions in the regulation of cell metabolism. Here, we report a novel noncanonical function of WRS in antiviral defense. WRS is rapidly secreted in response to viral infection and primes the innate immune response by inducing the secretion of proinflammatory cytokines and type I IFNs, resulting in the inhibition of virus replication both in vitro and in vivo. Thus, we consider WRS to be a member of the antiviral innate immune response. The results of this study enhance our understanding of host defense systems and provide additional information on the noncanonical functions of ARSs.

FAS-associated factor-1 (FAF1) is a component of the death-inducing signaling complex involved in Fas-mediated apoptosis. It regulates NF-κB activity, ubiquitination, and proteasomal degradation. Here, we found that FAF1 positively regulates the type I interferon pathway. FAF1gt/gt mice, which deficient in FAF1, and FAF1 knockdown immune cells were highly susceptible to RNA virus infection and showed low levels of inflammatory cytokines and type I interferon (IFN) production. FAF1 was bound competitively to NLRX1 and positively regulated type I IFN signaling by interfering with the interaction between NLRX1 and MAVS, thereby freeing MAVS to bind RIG-I, which switched on the MAVS-RIG-I-mediated antiviral signaling cascade. These results highlight a critical role of FAF1 in antiviral responses against RNA virus infection.

Rubicon is part of a Beclin-1-Vps34-containing autophagy complex. Rubicon induces antimicrobial responses upon Toll-like receptor (TLR) stimulation and functions as a feedback inhibitor to prevent unbalanced proinflammatory responses depending on dectin-1 signaling. However, the role played by Rubicon during antiviral immune responses, particularly the type I interferon (IFN) responses, remains largely unknown. Here, we report that Rubicon acts as a negative regulator for virustriggered IFN signaling. Knockdown of Rubicon promoted type I interferon signaling and inhibited virus replication, while overexpression of Rubicon had the opposite effect. Rubicon specifically interacts with the interferon regulatory factor (IRF) association domain (IAD) of IRF3, and this interaction leads to inhibition of the dimerization of IRF3, which negatively regulates IFN-mediated antiviral response. Thus, our findings suggest the novel additional role of Rubicon as a negative regulator that inhibits the IFN signaling and cellular antiviral responses, providing a novel cellular mechanism of IRF3 inhibition. IMPORTANCEThe type I IFN system is a critical innate immune response that protects organisms against virus infection. However, type I IFN signaling must be tightly regulated to avoid excessive production of IFNs. Hence, negative regulatory mechanisms for type I IFN signaling are important, and to date, several related molecules have been identified. Here, we show that Rubicon is a major negative regulator of type I IFN signaling, and unlike previous reports of cellular molecules that inhibit IRF3 activation via proteasomal degradation or dephosphorylation of IRF3, we show that Rubicon interacts with IRF3 and that ultimately this interaction leads to inhibition of the dimerization of IRF3. Thus, we identified a novel negative regulator of type I IFN signaling pathways and a novel cellular mechanism of IRF3 inhibition. The results of this study will increase our understanding of the role of negative-feedback mechanisms that regulate type I IFN signaling and maintain immune homeostasis.

BackgroundCortex Phellodendri (C. Phellodendri), the dried trunk bark of Phellodendron amurense Ruprecht, has been known as a traditional herbal medicine, showing several bioactivities. However, antiviral activity of C. Phellodendri aqueous extract (CP) not reported in detail, particularly aiming the prophylactic effectiveness.MethodsIn vitro CP antiviral activity evaluated against Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Newcastle Disease Virus (NDV), Herpes Simplex Virus (HSV), Coxsackie Virus (H3-GFP) and Enterovirus-71 (EV-71) infection on immune (RAW264.7) and epithelial (HEK293T/HeLa) cells. Such antiviral effects were explained by the induction of antiviral state which was determined by phosphorylation of signal molecules, secretion of IFNs and cytokines, and cellular antiviral mRNA expression. Furthermore, Compounds present in the aqueous fractions confirmed by HPLC analysis and evaluated their anti-viral activities. Additionally, in vivo protective effect of CP against divergent influenza A subtypes was determined in a BALB/c mouse infection model.ResultsAn effective dose of CP significantly reduced the virus replication both in immune and epithelial cells. Mechanically, CP induced mRNA expression of anti-viral genes and cytokine secretion in both RAW264.7 and HEK293T cells. Furthermore, the main compound identified was berberine, and shows promising antiviral properties similar to CP. Finally, BALB/c mice treated with CP displayed higher protection levels against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2).ConclusionCP including berberine play an immunomodulatory role with broad spectrum antiviral activity, due to induction of antiviral state via type I IFN stimulation mechanism. Consequently, C. Phellodendri could be a potential source for promising natural antivirals or to design other antiviral agents for animal and humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1206-x) contains supplementary material, which is available to authorized users.

Results of the study may add value to bovine tuberculosis eradication campaigns to achieve the One Health initiative.

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