The reason the H5N1 avian influenza virus, prevalent in North America, is highly contagious and deadly has been identified. A domestic research team discovered two critical mutations that increase the pathogenicity of the H5N1 strain prevalent in North America.

The research team led by Choi Young-gi, head of the Korea Virus Research Institute at the Institute for Basic Science (IBS), confirmed that the high pathogenicity of the H5N1 strain prevalent in North America is due to two mutations, 'PB2478I' and 'NP450N'. The research findings were published on the 27th in the international journal 'Science Advances'.

H5N1 was originally known to infect only birds, but it was confirmed to be a zoonotic disease capable of infecting humans when a human fatality occurred due to avian influenza in Hong Kong in 1997.

In March of last year, there was a case where a human was infected through cattle infected with H5N1. This was the first instance of human infection through mammals other than poultry, indicating that H5N1 continues to evolve. The World Health Organization (WHO) has warned that if H5N1 evolves to the point of human-to-human transmission, it could become a more dangerous infectious disease than Severe Acute Respiratory Syndrome (SARS).

Among the H5N1 strains, the 'GA/W22-145E/22' prevalent in North America is particularly contagious. The case where a human tested positive after contact with cattle was also due to GA/W22-145E/22.

The research team compared the highly pathogenic GA/W22-145E/22 with the relatively less lethal Eurasian strain 'KR/W811/21'. Animal experiments were conducted by injecting H5N1 into ferrets.

The results showed that the Eurasian strain exhibited symptoms limited to the respiratory system, whereas the North American strain resulted in a severe outcome with a 100% fatality rate. The research team used 'single-cell RNA sequencing analysis technology' to analyze the cause. It was confirmed that the North American strain invades immune cells such as T cells and B cells in ferrets, spreading throughout the body and invading the nervous system. The North American strain uses immune cells as carriers to spread systemically.

It was also revealed through reverse genetics technology that the two mutations, PB2478I and NP450N, are decisive factors for the strong pathogenicity. Reverse genetics technology involves modifying specific genes to determine their function. The research team used this technology to replace PB2478I and NP450N in the North American strain with amino acids from the Eurasian strain. As a result, the North American strain did not cause systemic infection and remained limited to respiratory infection. This confirmed that the two mutations, PB2478I and NP450N, are decisive factors in increasing the pathogenicity of the North American strain.

Additional tests by the research team confirmed that H5N1 with these two mutations also proliferates through strong replication capabilities in human peripheral blood mononuclear cells and bovine-derived mammary organoids (organ-like structures). The ability to proliferate in human peripheral blood mononuclear cells indicates that H5N1 can expand its host range, and proliferation in the mammary gland suggests the possibility of vertical transmission of the pathogen from mother to child.

The research team stated, "This is the first proof that the H5N1 strain prevalent in North America spreads throughout the body and invades the nervous system," adding, "Urgent surveillance and intervention are required to prevent H5N1 from becoming a pandemic threat due to zoonotic infection."

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