Discussion of avian flu

 

Discussion of avian flu by Yoshihiro Kawaoka

In the New England Journal of Medicine 2025

 

Bottom line:  More mutations will be needed for avian flu viruses to be highly transmissible in humans. But, for now, pasteurize milk and thoroughly cook poultry and meat. 

 

We are dealing with an H5N1 virus, a subtype of influenza A virus known for primarily infecting birds.

It’s called H5N1 because of two surface glycoproteins on the virus.

Hemagglutinin — H, and neuraminidase — N. Avian flu refers to influenza viruses that circulate among birds.

There are 19 H types and 11 N types. H5N1 is just one of them.

They can sometimes cross species barriers and infect mammals, including humans, but are considered avian because birds are their natural host where they replicate most efficiently.

When we say highly pathogenic avian influenza viruses,that means highly pathogenic for poultry.

There are two kinds of avian influenza viruses in terms of pathogenicity:

One group kills poultry, like chickens and turkeys, a hundred percent experimentally.

The other group, in fact, replicates in chickens and turkeys, but they do not die. So there are low pathogenic avian influenza viruses.

The highly pathogenic avian influenza virus infects wild waterfowl, so the virus is transmitted from wild waterfowl and migratory birds to poultry, and then chickens and turkeys get infected and die.

Currently, there are at least two different H5N1 strains circulating in the United States.

Their genetic makeup is slightly different. Some emerged in the previous outbreaks and others like the 2344B clade started circulating more recently, often with broader geographic spread.

Within the 2344B clade, two genetically slightly different viruses — genotype D11 and B313 — are present in the United States. D11 viruses are mainly in birds, and B313 viruses are mainly in U.S. cattle.

Domestic poultry like chickens and turkeys are at high risk because they are highly susceptible. A hundred percent of experimentally infected poultry die.

Another notable animal species we need to consider is cattle. The avian flu virus outbreak in dairy cattle was identified at the beginning of 2024 in Texas. The virus spread from birds to cattle and then among cattle in 17 states, and it continues to circulate among cattle. This outbreak was caused by genotype B313 avian flu virus.

Two separate introductions or transmissions from birds to cattle of genotype D11 viruses occurred recently, one in Nevada and the other in Arizona. The sheer number of avian flu–infected cows also creates more opportunities for the virus to mutate and adapt in mammals. Also, the spread of avian flu virus to cats that are exposed to virus-containing milk and uncooked pet food is worrying.

The concern with cat infection is that they’re close to humans.

So cats are highly susceptible. Usually the virus replicates among systemic organs and the virus goes to the brain and usually they show neurologic symptoms.

Virus-infected chickens have been fed to lions and other large animals, and cats.  In the past they got infected and died. 

We do not completely understand what is needed for avian flu viruses to circulate efficiently in humans.

Mutations in the hemagglutinin, a protein on the surface of virus particles, need to be acquired by avian flu viruses for them to simply bind to receptors present on the surface of human respiratory organs.

Additional mutations in the viral polymerase proteins, which make copies of the viral genome, also help avian flu viruses to grow better in human cells.

Yet more mutations will be needed for avian flu viruses to be highly transmissible in humans.

 

Once the avian influenza viruses are introduced into mammalian species like cattle, then they acquire mutations in the PB2 proteins that make the virus replicate better in mammalian species.

There have been some reports describing infection of cattle with avian influenza viruses, but there have been no sustained transmissions of influenza viruses in cattle in the past.

There have been 70, 80 documented episodes of human infection in the U.S., most of which have been conjunctivitis or mild illness.

However, at least two cases were quite severe, with one being a fatality. My understanding is those two cases were the D11 variant.  This genotype makes it more pathogenic potentially.

Standard pasteurization is sufficient to inactivate influenza viruses, including H5N1 virus, in milk or other dairy products.

Proper cooking of poultry and eggs also inactivates the virus. These findings emphasize how important food safety practices are in reducing exposure to virus, especially when outbreaks are ongoing in animal populations.

So pasteurizing dairy products, cooking poultry thoroughly, and maintaining good hygiene, are important for minimizing the risk of virus transmission to humans.

In the cattle cases, in the infection of humans in cattle farms, they usually get the exposure to eyes, so they get conjunctivitis. Not many humans who got infected with cattle viruses show respiratory symptoms.

Drinking contaminated milk is a real risk. 

I think the oral ingestion will expose the back of the throat, and of course that is sufficient to initiate the virus infection.

The culling the infected poultry eliminates the source of the infection and therefore you reduce the risk of spread of the virus.

But there’s some cost.

The vaccine for poultry highly pathogenic influenza virus has been approved, but that does not mean the use of that vaccine is approved, so that needs to be further discussed.

In other countries like China, they have used poultry vaccines for highly pathogenic avian influenza viruses effectively. They had major outbreaks of highly pathogenic H7 and 9 viruses, and they used the vaccine and they controlled and reduced the human infections. So there is some precedent, but there is a cost because you may not be able to export your poultry product.

The vaccine for cattle is being developed and it’s been reported that the vaccine induces good immune responses.

The virus can live in chickens for 60 days.