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The highly contagious avian influenza epidemic has spread from continent to continent since 2020. Avian influenza has killed hundreds of millions of wild birds and caused sporadic outbreaks among poultry. In recent months, the avian influenza strain (H5N1) that causes the disease has infected dairy cows, domestic cats, and even humans.
In one case this year, a patient in Missouri contracted the disease after apparently having no contact with infected animals. It is currently unknown how the patient contracted the virus. Some experts suggest it may be due to ingestion of raw milk, although traces of the virus have been found in samples of unpasteurized milk, but limited information is available. It’s difficult to determine whether raw milk is a potential source of infection (though you should be careful; pasteurized milk is completely safe to drink).
Transmission of avian influenza to humans is a cause for concern, but fortunately transmission remains rare. According to the World Health Organization (WHO), only 896 cases were reported worldwide from January 2003 to July 2024. However, if human bird flu cases continue to rise, it could mean the virus is becoming more contagious. In a recent study published in Nature Communications, researchers at the European Molecular Biology Laboratory (EMBL) show that allowing the mammalian ANP32 protein to be used more efficiently may give the virus this ability. discovered a mutation in the genome of avian influenza.
Virus on feathers (does not always stick)
Viruses cannot reproduce outside the host. To further multiply themselves, they must first invade the host cell and hijack its cellular machinery. In the case of the avian influenza virus, its polymerase (an enzyme that makes new copies of the viral genome) interacts with the ANP32 protein to form a structure called the replication complex. As the name suggests, this complex is required for viral replication. (In fact, in another study, scientists used CRISPR gene editing technology to genetically engineer chickens to be resistant to avian influenza. They )
However, differences between the avian and mammalian versions of this protein explain why avian influenza does not usually infect mammals. Specifically, avian ANP32 has an amino acid tail that human ANP32 does not have. Researchers have previously observed that virus particles can remain lodged in birds’ ANP32 as they pass from birds to mammals, which may explain some cases of avian influenza in mammals. There is a possibility that there are. Still, for this virus to be more successful in mammals, it must be able to utilize mammalian ANP32 as effectively as avian ANP32.
In a recent study, EMBL researchers used cryo-electron microscopy (cryo-EM), an advanced imaging technique with near-atomic resolution, to show that the viral polymerase of a human-adapted strain of avian influenza was detected in humans. We investigated the structure when interacting with. ANP32.
They discovered that the amino acid tail of ANP32 stabilizes the viral polymerase. In addition to replicating the viral genome, the polymerase encapsulates the genome into virus particles that then infect other cells. When performing its dual functions, polymerases adopt two tertiary structures called replicase and encapsidase. This study revealed that ANP32 forms a bridge between the two conformations, and this bridge facilitates the assembly of the replication complex.
A highly detailed cryo-electron microscopy structure of the replication complex reveals which individual amino acids are involved in the assembly of the replication complex. In other words, the researchers were able to figure out which amino acids in the replication complex are essential for virus replication. Mutations in these regions of the viral polymerase may cause it to bind more tightly to human ANP32, improving the ability of the virus to replicate in human cells.
Strengthen surveillance of avian influenza
To monitor the spread of avian influenza, the Centers for Disease Control and Prevention is sequencing the virus in samples taken from infected animals, in addition to tracking reports of illness and death. This is to track mutations in the virus population. EMBL studies have established a link between the structure of the replication complex and adaptive mutations in the viral polymerase. Researchers could use this insight to determine whether a particular strain of avian influenza virus is nearing the point where it gains the ability to infect humans.
As avian influenza continues to spread among birds and cows, there will be more opportunities for the virus to jump to humans who come into contact with birds and cows. For this reason, experts suggest that more animals and the people around them be tested for avian influenza, even if they are not showing symptoms. Avian influenza is still an unlikely scenario to become the next pandemic, as there is no evidence of human-to-human transmission of the virus.
But while avian influenza may not be widespread in humans, it is extremely deadly. Of the 896 cases reported between 2003 and 2024, 463 resulted in deaths. The high mortality rate is likely due in part to the fact that many human cases have no obvious symptoms and are underdiagnosed. In any case, treatments are urgently needed to treat cases of avian influenza in humans and to stop the spread of avian influenza epidemics among poultry and cattle.
Although there are many strains of the influenza virus, and new strains are emerging all the time, the replication complex is central to how the influenza virus infects and replicates within host cells. Future studies will need to investigate replication dynamics in more detail to make the replication complex an important target for anti-influenza drugs.
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