Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021

Highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage (GsGd), which threaten the health of poultry, wildlife and humans, are spreading across Asia, Europe and Africa, but are currently absent from Oceania and the Americas. In December 2021, H5N1 HPAI viruses were detected in poultry and a free-living gull in St. John, Newfoundland and Labrador, Canada. Phylogenetic analysis showed that these viruses were most closely related to HPAI GsGd viruses circulating in northwestern Europe in spring 2021. Analysis of wild bird migration suggested that these viruses may have been carried across the Atlantic via Iceland, Greenland/Arctic or pelagic routes. The here documented incursion of HPAI GsGd viruses into North America raises concern for further virus spread across the Americas by wild bird migration.

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.

Bridging the Local Persistence and Long-Range Dispersal of Highly Pathogenic Avian Influenza Virus (HPAIv): A Case Study of HPAIv-Infected Sedentary and Migratory Wildfowls Inhabiting Infected Premises

The past two decades have seen the emergence of highly pathogenic avian influenza (HPAI) infections that are characterized as extremely contagious, with a high fatality rate in chickens, and humans; this has sparked considerable concerns for global health. Generally, the new variant of the HPAI virus crossed into various countries through wild bird migration, and persisted in the local environment through the interactions between wild and farmed birds. Nevertheless, no studies have found informative cases associated with connecting local persistence and long-range dispersal. During the 2016–2017 HPAI H5N6 epidemic in South Korea, we observed several waterfowls with avian influenza infection under telemetric monitoring. Based on the telemetry records and surveillance data, we conducted a case study to test hypotheses related to the transmission pathway between wild birds and poultry. One sedentary wildfowl naturally infected with HPAI H5N6, which overlapped with the home range of one migratory bird with H5-specific antibody-positive, showed itself to be phylogenetically close to the isolates from a chicken farm located within its habitat. Our study is the first observational study that provides scientific evidence supporting the hypothesis that the HPAI spillover into poultry farms is caused by local persistence in sedentary birds, in addition to its long-range dispersal by sympatric migratory birds.

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.

Analisis Bioinformatika dan Ekspresi Protein Rekombinan Hemagglutinin Domain Globular dari Virus H5N1 Indonesia pada Eschericia coli BL21 (DE3) sebagai Komponen Vaksin Subunit Influenza

Flu burung merupakan salah satu penyakit zoonosis yang patut diwaspadai di Indonesia, khususnya galur High Pathogenic Avian Influenza (HPAI) karena dapat mematikan jika menular kepada manusia. Penggunaan vaksin influenza pada unggas, merupakan langkah preventif terhadap evolusi virus yang berbahaya dan juga penyebarannya. Selama ini, Indonesia masih menggunakan seed vaksin impor yang berasal dari luar Indonesia. Namun, karena Indonesia merupakan negara yang berada di garis khatulistiwa, karakteristik virus bisa berbeda dengan virus dari nothern-hemispere maupun southern-hemispere. Mengingat hal tersebut, Indonesia harus mengembangkan vaksin influenza menggunakan galur virus lokal. Berbeda dengan vaksin whole virus, vaksin rekombinan memiliki keunggulan dari sisi kemurnian, kecepatan produksi, dan kesesuaian galur terhadap virus yang beredar saat diperlukan. Penelitian ini bertujuan untuk menganalisis sekuen hemagglutinin (HA) Indonesia dengan strain lainnya serta mengekspresikkan protein HA1 rekombinan pada Escherichia coli BL21 (DE3). Galur yang digunakan pada studi ini berasal dari virus H5N1 (A/Indonesia/05/05), khususnya bagian domain globular dari HA1. Sekuen HA1 bervariasi antara strain Indonesia dengan nothern-hemispere maupun southern-hemispere dan merupakan protein yang terpapar ke luar virus. Gen HA1 disisipkan pada vektor pET-28a, kemudian plasmid diisolasi menggunakan meoe manniatis, setelah itu diekspresikan dengan induksi 1 mM IPTG selama 4 jam. Protein HA1 telah berhasil diekspresikan secara intraseluler dan telah dikonfirmasi pada berat molekul 40 kDa menggunakan SDS-PAGE. Penelitian ini dapat digunakan untuk mengembangkan vaksin subunit yang lebih spesifik terhadap virus yang beredar di lapangan.