We read with interest the recent letter by Cai and colleagues who commented on recent cross-species activity of H5N1 Influenza virus and urged continuing surveillance of avian influenza. In March, the Texas Animal Health Commission announced the first cases of Highly Pathogenic Avian Influenza(HPAI) A(H5N1) in dairy cattle in the Texas. Subsequently, on April 1st, the CDC of United States confirmed the first case of human infection with HPAI H5N1 virus linked to an exposure to cattle in Texas. This epidemic had aroused widespread concern in the world and the outbreak-related emerging 2.3.4.4b H5N1 virus continues to spread in the United States. As of September 2024, more than 190 dairy herds and 14 individuals have been infected with the panzootic H5N1 viruses in 14 states of the United States.
Since the first case of human infection in Hong Kong in 1997, H5N1 avian influenza virus had attracted much attention as a highly pathogenic strain, posing a huge threat to the poultry industry and public health. From 2003 to 2005, H5N1 viruses had been widely spread to non-human mammal species, such as captive tigers, captive leopards, pigs, domestic cat and dogs. However, the H5N1 viruses were mainly confined to some countries in Southeast Asia, such as Vietnam Thailand, and Indonesia. Since 2006, with the migration of migratory birds, the H5N1 virus has continued to evolve into different branches and began to spread to Europe, India, Africa and eventually emerged and became prevalent in North and South America. Until 2022, the 2.3.4.4b H5N1 viruses were widely transmitted globally through wild birds, affecting many wild bird species, causing outbreaks in poultry and spilling unprecedentedly to a wide range of land and marine mammals, resulting in 2024 in transmission among dairy cattle with associated human cases.
In fact, ruminants were not previously considered to be the host species of influenza A virus (IAV). For many years, there has been only some serological evidence of sporadic IAV infection in cattle, and almost no IAV has been isolated. However, similar to the H7N9 avian influenza virus that has emerged in China, this novel reassortant HPAI H5N1 virus clade 2.3.4.4b genotype B3.13 has many new features due to the recombination and point mutations on key gene fragments such as HA and PB2. The new virus can effectively proliferate in the respiratory tract of calves and the mammary gland of dairy cows, causing obvious mastitis in dairy cows, resulting in a rapid and serious decline in milk production, and there are a large number of infectious viruses in milk. Meanwhile, bovine-origin H5N1 virus has sustained mammalian transmission and could be detected in other species, including domestic cats, wild birds,alpacas,goat and even spillover into humans. Although only a small number of sporadic human infections have been identified, the ongoing genetic reassortment, evolution, and spread of the new H5N1 virus in wild birds, along with transmission among some mammals, have raised concerns about the emergence of viruses with greater infection and transmission potential.As for what factors drive the sudden mammalian adaptive evolution of viruses in recent years, whether this factor will lead to similar changes in other subtypes such as H3 and H7 avian influenza viruses, and whether this change can spread to other regions of the world are worthy of our vigilance and exploration.
The farms that first reported and confirmed the HPAI H5N1 virus infection in cattle are all on the Central North American migratory bird flyway. China ´s dairy farms are mainly distributed in the northeast, northwest and north China. The northwest region, especially Xinjiang, Inner Mongolia are also important pastoral areas in China. A large number of cattle, sheep, horses and camels are distributed in the two places, and a variety of wild animals are bred here(Fig. 1A). More importantly, migratory birds travel through these two areas, and open-air farming(Fig. 1B) or grazing(Fig. 1C)create a large number of opportunities for these animals to contact with migratory birds directly or indirectly. In recent years, we had isolated a variety of subtypes of avian influenza viruses from the feces of migratory birds in Xinjiang, such as H1N2, H3N8, H4N6，H9N2 avian influenza virus etc(data not shown). In 2020, the death of swan infected with HPAI H5N6 virus clade 2.3.4.4h occurred in many areas of Xinjiang. Similar to the H5N6 avian influenza virus isolated in 2020, our results show that some wild bird-origin strains such as H1N2, H4N6 and H3N8 viruses could efficiently infect mice without prior adaptation, although they do not cause death and obvious symptoms in mice.15The ongoing incident of cows infected with wild bird-origin H5N1 virus in the United States has forced us to consider whether cows, sheep, horses or camels in the northwest region of china can be infected or have been infected with these wild bird sources AIV or AIV that are circulating in Chinese poultry. Subsquently, we will continue to carry out serological and etiological surveillance of influenza viruses in these open-air farmed or grazing animals.