A new study reveals that the human immune protein MxA can block the replication of the H5N1 avian flu virus, but the virus is evolving and may soon be able to overcome this defense. This raises concerns about a potential new zoonotic threat.
A recent study published in the journal Emerging Infectious Diseases showed that the human immune factor, myxovirus resistance protein 1 (MxA), represses the replication of highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtype. HPAI H5N1 clade 2.3.4.4b viruses have increasingly caused mammalian outbreaks over the past few years.
In the United States (US), outbreaks have been detected in cows since Spring 2024, leading to viral transmission to farm workers, possibly via contact with contaminated milk or infected cows. This has sparked concerns that these viruses may adapt to humans. Intermediate hosts as incubators: Ongoing circulation of H5N1 in dairy cattle with active Mx1 proteins could drive the emergence of MxA-resistant variants, emphasizing the need for enhanced surveillance in these animal populations. Notably, some mammalian H5N1 clade 2.3.4.4b isolates already harbor mutations that enhance viral polymerase activity in mammalian cells, binding to mammalian receptors, or evasion from the BTN3A3 restriction factor. Specific mutations, such as PB2E627K and PB2M631L within the PB2 627 domain, are known to contribute to these adaptations. MxA is an innate immune protein that can repress the replication of zoonotic influenza A viruses (IAVs). Studies have reported that human-adapted IAVs, including the pandemic H1N1 virus A/Hamburg/4/2009 (pH1N1), escape MxA restriction through adaptive amino acids. However, avian IAVs, including the H5N1 clade 2.3.4.4b isolates and human HPAI H5N1 isolate A/Thailand/1(KAN-1)/2004, lack these MxA evasion-mediating amino acids. The study and findings The present study investigated whether MxA restricts zoonotic infections with mammalian H5N1 clade 2.3.4.4b isolate
Avian Influenza H5N1 Virus Evolution Zoonotic Threat Human Immunity
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