Molecular and Antigenic Characterization of Avian H9N2 Viruses in Southern China

The H9N2 low pathogenicity avian influenza (LPAI) virus has become endemic in poultry globally. In several Asian countries, vaccination against H9N2 avian influenza virus (AIV) was approved to reduce economic losses in the poultry industry.

Characterization of the in Vitro and in Vivo Efficacy of Baloxavir Marboxil against h5 Highly Pathogenic Avian Influenza Virus Infection

Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class of inhibitors for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but it has not yet been fully characterized. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants, was assessed in vitro. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested in comparison with seasonal and other zoonotic strains. Compared with oseltamivir phosphate (OSP), BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate, the A/Hong Kong/483/1997 strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, thereby preventing acute lung inflammation and reducing mortality. Furthermore, compared with BXM or OSP monotherapy, combination treatments with BXM and OSP using a 48-hour delayed treatment model showed a more potent effect on viral replication in the organs, accompanied by improved survival. In conclusion, BXM has a potent antiviral efficacy against H5 HPAIV infections.

Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against H5 Highly Pathogenic Avian Influenza Virus Infection

Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class of inhibitors for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but it has not yet been fully characterized. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants, was assessed in vitro. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested in comparison with seasonal and other zoonotic strains. Compared with oseltamivir phosphate (OSP), BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate, the A/Hong Kong/483/1997 strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, thereby preventing acute lung inflammation and reducing mortality. Furthermore, compared with BXM or OSP monotherapy, combination treatments with BXM and OSP using a 48-h delayed treatment model showed a more potent effect on viral replication in the organs, accompanied by improved survival. In conclusion, BXM has a potent antiviral efficacy against H5 HPAIV infections.

Characterization of the Role of Extracellular Vesicles Released from Chicken Tracheal Cells in the Antiviral Responses against Avian Influenza Virus

During viral respiratory infections, the innate antiviral response engages a complex network of cells and coordinates the secretion of key antiviral factors, such as cytokines, which requires high levels of regulation and communication. Extracellular vesicles (EVs) are particles released from cells that contain an array of biomolecules, including lipids, proteins, and RNAs. The contents of EVs can be influenced by viral infections and may play a role in the regulation of antiviral responses. We hypothesized that the contents of EVs released from chicken tracheal cells are influenced by viral infection and that these EVs regulate the function of other immune cells, such as macrophages. To this end, we characterized the protein profile of EVs during avian influenza virus (AIV) infection and evaluated the impact of EV stimulation on chicken macrophage functions. A total of 140 differentially expressed proteins were identified upon stimulation with various stimuli. These proteins were shown to be involved in immune responses and cell signaling pathways. In addition, we demonstrated that EVs can activate macrophages. These results suggest that EVs play a role in the induction and modulation of antiviral responses during viral respiratory infections in chickens.