Recently, an article in your journal reported the risks of the infections of humans and other mammals with H5 subtype highly pathogenic avian influenza viruses (AIVs) in 2020–2023.1 In April, the World Health Organization (WHO) reported a case of human infection with highly pathogenic H5N1 AIVs, the first case of human transmission of H5N1 AIVs from a mammal in the United States, and the second case of human H5N1 AIVs infection in the United States.2

The confirmed case is a farm worker at a Texas dairy farm who had a history of exposure to dairy cattle suspected of being infected with H5N1 AIVs. The infected person had no symptoms other than conjunctivitis and was advised to be isolated and receive antiviral drugs.2, 3 This is the first global case of highly pathogenic H5N1 AIVs infection in cattle and further infection of human. Furthermore, on May 22, the Centers for Disease Control and Prevention (CDC) of the United States announced a second case of human infection associated with the spread of H5N1 AIVs in dairy cattle. Human-to-human transmission of H5N1 AIVs has not been detected. By the end of April, several states in the United States reported H5N1 AIVs infections in dairy herds.2 This suggests that cattle-to-cattle transmission of H5N1 AIVs may have occurred. Additionally, fatal systemic influenza infections have been reported in domestic cats fed with milk from infected cows.4 This indicates that the virus can spread across species, posing a challenge to public health security in the United States.

The earliest known H5N1 AIVs infection in humans dates back to the outbreak of the highly virulent H5N1 avian influenza in a live poultry market in Hong Kong in 1997.5 This virus has spread globally since 2003. In recent years, highly pathogenic avian influenza caused by the H5N1, H5N2, H5N4, H5N5, and H5N6 subtypes of AIVs has become widespread in Europe, the Americas, Asia, and Africa, causing serious harm. Among them, H5N1 subtype AIVs are the most common, followed by the H5N8 subtype, and 2.3.4.4b is the dominant genotype of the circulating strain.6 Genetic analysis of the H5N1 patient confirmed that the infected virus belonged to the 2.3.4.4b branch.2 In recent years, most of the major circulating AIV strains in China have belonged to branch 2.3.4.4b.7 We downloaded and screened the HA sequences (206 in total) of H5 subtype AIVs strains isolated from China over the past 3 years (January 1, 21 to now) from the GISAID EpiFlu database. The H5 subtype influenza strain sequences isolated from American dairy cattle since January 24 (Idaho, New Mexico, Texas, South Dakota, Michigan, Ohio, and Kansas, a total of seven states, each of which involved randomly selecting five sequences as representatives) were collected for comparison and construction of a phylogenetic tree, with one of the sequences 2.3.4.4 h as the main root for tree plotting. The H5N1 AIV strains recently isolated from infected cattle in the United States (blue marks) and some H5N1 strains isolated from China in the last 3 years (green marks) are relatively close in genetic distance according to the phylogenetic tree (Fig. 1). This suggests that H5N1 AIVs circulating in the United States and China share a common origin, indicating that H5N1 AIVs in China are at risk of evolving into novel strains that infect mammals or even humans, potentially threatening public health security in China. Three strains of the H5 subtype AIVs isolated in China belong to the 2.3.4.4 h evolutionary branch. Although the genetic evolution is far from that of H5N1 AIVs strains in the United States, this threat remains a concern.