Pathogenicity of Bovine H5N1 Influenza Virus in Human, Dairy Cow, and Big Feline Animal

Highly pathogenic avian influenza virus (HPAI/H5N1) has caused widespread infections in dairy cattle and poultry in the United States. Sporadic cases of human HPAI/H5N1 infections have also been confirmed. To prevent human HPAI/H5N1 infections and establish treatments for infected individuals, researchers at medical institutions in the United States are analyzing the biological characteristics of HPAI/H5N1 strains confirmed in the country from March to October 2024. In particular, health care staff at such institutions are investigating human infection with the HPAI/H5N1 virus. Confirmed cases mainly involved adults who have come into contact with infected animals. HPAI/H5N1 infection causes mild illness, such as conjunctivitis, and is short-lived. Most infected patients improve or are cured with early antiviral treatment. However, on January 7, 2025, the Louisiana State Health Department reported the death of a person believed to have been infected with HPAI/H5N1 through contact with captive or wild birds. Although cases of HPAI/H5N1 infection with unknown routes of transmission have been reported, reports on cases of person-to-person HPAI/H5N1 transmission are limited. Therefore, our research team compared the infectivity of the HPAI/H5N1 virus to humans and dairy cows through the molecular pathological analysis of mammary gland tissues obtained from humans and dairy cows. The results revealed that more receptors for HPAI/H5N1 viruses were expressed in dairy cow than human tissues. Furthermore, in silico analysis revealed that the HPAI/H5N1 virus obtained from infected dairy cows can infect humans. In other words, the backbone molecule of the HPAI/H5N1 virus may mutate within the infected host, resulting in infectivity to humans. Furthermore, molecular pathological analysis of respiratory tissue obtained from lions revealed the expression of both human (α2.6SA) and avian (α2.3SA) influenza virus receptors in lion respiratory tissue, as well as the expression of angiotensin converting enzyme 2, a receptor for severe acute respiratory syndrome coronavirus 2. Therefore, One Health guidelines should be emphasized to prevent HPAIV/H5N1 infection from becoming a pandemic. In this manuscript, we express our assessments of current information on prevention of the spread of HPAI/H5N1 infection, including the status of vaccine development against the HPAI/H5N1 virus.