The disassembly of apoptotic cells into small membrane-bound vesicles termed apoptotic bodies (ApoBDs) is a hallmark of apoptosis; however, the functional significance of this process is not well defined. We recently discovered a new membrane protrusion (termed beaded apoptopodia) generated by apoptotic monocytes which fragments to release an abundance of ApoBDs. To investigate the function of apoptotic monocyte disassembly, we used influenza A virus (IAV) infection as a proof-of-concept model, as IAV commonly infects monocytes in physiological settings. We show that ApoBDs generated from IAV-infected monocytes contained IAV mRNA, protein and virions and consequently, could facilitate viral propagation in vitro and in vivo, and induce a robust antiviral immune response. We also identified an antipsychotic, Haloperidol, as an unexpected inhibitor of monocyte cell disassembly which could impair ApoBD-mediated viral propagation under in vitro conditions. Together, this study reveals a previously unrecognised function of apoptotic monocyte disassembly in the pathogenesis of IAV infections.
Existing mRNA COVID-19 vaccines have shown efficacy in reducing severe cases and fatalities. However, their effectiveness against infection caused by emerging SARS-CoV-2 variants has waned considerably, necessitating the development of variant vaccines. Ideally, next-generation vaccines will be capable of eliciting broader and more sustained immune responses to effectively counteract new variants. Additionally, in vitro assays that more closely represent virus neutralization in humans would greatly assist in the analysis of protective vaccine-induced antibody responses. Here, we present findings from a SARS-CoV-2 VLP vaccine encompassing three key structural proteins: Spike (S), Envelope (E), and Membrane (M). The VLP vaccine effectively produced neutralizing antibodies as determined by surrogate virus neutralization test, and induced virus-specific T-cell responses: predominantly CD4+, although CD8+ T cell responses were detected. T cell responses were more prominent with vaccine delivered with AddaVax compared to vaccine alone. The adjuvanted vaccine was completely protective against live virus challenge in mice. Furthermore, we utilized air–liquid-interface (ALI)-differentiated human nasal epithelium (HNE) as an in vitro system, which authentically models human SARS-CoV-2 infection and neutralization. We show that immune sera from VLP-vaccinated mice completely neutralized SARS-CoV-2 virus infection, demonstrating the potential of ALI-HNE to assess vaccine induced Nab.
Influenza A virus (IAV) is one of the major global public health concerns but the emerging resistance of IAV to currently available antivirals requires the need to identify potential alternatives. Polyphenol rich sugarcane extract (PRSE) is an extract prepared from the sugarcane plant Saccharum Officinarum. Herein we aimed to determine if PRSE had antiviral activity against IAV. We showed that treatment of IAV-infected cells with PRSE results in a dose-dependent inhibition of virus infection at concentrations that were non-cytotoxic. PRSE treatment limited the early stages of infection, reducing viral genome replication, mRNA transcription and viral protein expression. PRSE did not affect the ability of IAV to bind sialic acid or change the morphology of viral particles. Additionally, PRSE treatment attenuated the replication of multiple IAV strains of the H3N2 and H1N1 subtype. In conclusion, we show that PRSE displays antiviral activity against a broad range of IAV strains, in vitro.
The European Union (EU) regulations mandate 10% of all food packaging to be reusable by 2030. United States (U.S.) exporters of specialty crops face new challenges in ensuring microbiological food safety using reusable packaging. A novel antimicrobial formulation consisting of ammonium carboxylate salt of capric acid and L-arginine (GS-2) was recently developed as a spray coating chemical for food packaging materials. In this study, we evaluated the antimicrobial efficacy of GS-2 against microbial strains representing three foodborne bacterial pathogens (Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica), one fungal spoilage organism (Aspergillus niger), and one surrogate viral pathogen (murine norovirus) on three reusable plastic materials (acrylonitrile butadiene styrene, high-density polyethylene, and polypropylene) and one cardboard packaging material, respectively. Different chemical concentrations, exposure times, and storage conditions were individually evaluated for the relative antimicrobial efficacies of GS-2 against these microorganisms. Our results showed that GS-2 was highly effective for inactivating bacterial pathogens on both plastic and cardboard surfaces. For instance, 3% GS-2 achieved a >5 log CFU/in2 reduction in E. coli O157:H7, L. monocytogenes, and S. enterica on tested plastic surfaces at an exposure time of 60 min. However, its efficacy against A. niger and murine norovirus was less optimal, resulting in a ≤1 log CFU/in2 reduction on all tested surfaces. Based on our study, GS-2 demonstrated a strong potential as an antibacterial coating reagent for reusable food packaging materials to minimize pathogen contamination and ensure the safety of the specialty crops.