Bird flu is spreading: Here’s what you should know about avian influenza, H5N1

An outbreak of avian influenza in the U.S. has affected wild water and shorebirds, commercial poultry, and common backyard birds. More than 55 million birds have been infected with the virus since January 2022, according to the Centers for Disease Control and Prevention, and it has spread to some mammals. (iStock)

Microbiologist John Lednicky, Ph.D., came to the University of Florida in 2010 to study how avian influenza, also known as bird flu, is transmitted through the air. At the time, few people knew how to safely work with what is typically the most dangerous version of the bird flu, called H5N1. Working with H5N1 influenza viruses often requires growing them in chicken or duck eggs in secure facilities. Studies of airborne H5N1 require advanced knowledge and experience, all of which Lednicky was familiar with.

Bird flu, as its name implies, primarily infects birds. But just as Lednicky’s H5N1 studies were about to take wing, global events shut down H5N1 research. In 2011, investigators at the University of Wisconsin and Japan, and investigators in the Netherlands, learned how to engineer the H5N1 virus to move between mammals. This kind of change is called gain-of-function because it allows the virus to do things it could not before. While the research widened our understanding of bird flu, it could also potentially be used for bioweapons; hence, the temporary moratorium. Lednicky’s avian influenza research was shelved, and his focus changed to other viruses.

His past bird flu research includes:

  • How to prepare for pandemic bird flu
  • How mammals became infected with bird flu through airborne virus particles spread by aerosols
  • The most appropriate cells to use in a laboratory to study how H5N1 infects and causes disease

But now that H5N1 bird flu is causing an avian pandemic and has naturally spilled over into some mammals, Lednicky’s phone keeps ringing with people needing information. A research professor in the UF College of Public Health and Health Professions department of environmental and global health, Lednicky is also a member of the UF Emerging Pathogens Institute.

We’ve seen bird flu outbreaks before, but what is different now, globally?

One thing that is different now is that we are seeing H5N1 in birds in the mainland of the U.S., and the number of affected birds is great. This did not happen to a great extent in prior years when we would read about it causing infection on chicken or duck farms in other countries. Here in Florida, we have had a mass kill off of vultures, eagles, and shorebirds. And it has affected the poultry industry. On recent trips outside of Gainesville, I’ve noticed a lot of dead buzzards and crows, and I suspect it’s avian influenza.

But we need to understand what that term means. Because almost all influenza is in fact bird flu. It’s just that some of them cause high mortality events only in poultry flocks or birds, while others can cause illness in people.

Where does bird flu fall in terms of influenza types?

The influenza viruses that cause bird flu are type A flu viruses. There are other flu viruses: types B, C, and D. Influenza A viruses are divided into subtypes based on two proteins found on the virus’s surface, hemagglutinin (H) and neuraminidase (N). Different combinations of H and N occur; there are 18 H subtypes and 11 N subtypes among the known flu A viruses. In birds, 16 H and 9 N subtypes have been identified. For example, A(H5N2), A(H6N1), and A(H7N3) are among the influenza A virus strains that have been found in birds. A(H5N1) and A(H7N9) viruses have caused most avian influenza A virus infections reported in people.

Is there a relationship between bird flu strains that causes illness and death in birds and what may cause severe illness and death in people?

This is where it gets complicated. A lot of birds will get bird flu and not much will happen. Those are what is called low pathogenicity avian influenza virus, or LPAIV. And then we talk about highly pathogenic avian influenza virus, HPAIV. But when we say highly pathogenic avian influenza, it really means highly pathogenic in birds. Not necessarily in people. It just so happens that some of those that are highly pathogenic in birds are also highly pathogenic in humans. But not all. I, for example, worked on some H5N1 strains that killed birds like crazy but caused barely anything in humans. One of the H5N1 strains was from a child with an illness It was less severe than common flu. In contrast, the most dangerous H5N1 strain I worked with was associated with about 50% mortality in humans.

How is bird flu being transmitted from birds to mammals to people?

Microscope image of avian influenza virus particles
Colorized transmission electron microscopic image of avian influenza type A(H5N1). Virus particles are shown in gold and were grown in laboratory cells shown in green. (CDC)

In birds, it is mostly oral-to-fecal routes. Ducks for example shed a lot of virus into water when they poop, and other ducks may be feeding near them. And that is likely how it mostly gets transmitted between ducks and other waterbirds. In poultry flocks, oral-fecal transmission occurs, but the birds also shed the virus in oral, nasal, and eye secretions, and may transmit the virus animal-to-animal when there is close contact between a sick and healthy animal. Predatory birds and scavenging birds can acquire an H5N1 infection when they eat an infected bird or the carcass of a bird that died of H5N1 infection.

But between mammals is different. In Asia, people buy live birds at markets where they are plucked. The plucking has been shown to aerosolize virus from the feathers. Or birds poop in crowded markets. And there may be fans or air currents in the markets that move that airborne virus around. People may breathe it in.

We also think that mammals can get the virus from eating infected birds. There is evidence from studies of zoo animals such as tigers that were fed H5N1-infected chicken meat. These animals typically developed severe pneumonia, but mammals infected with H5N1 can develop brain disease. This should not be surprising, as many birds affected with H5N1 display signs of brain disease and succumb to it. In mammals, I suspect it may enter the body through the olfactory bulb, either after inhaling virus or when eating infected meat. But there may be other ways. It should be noted that H5N1 can cause systemic disease; it can adversely affect the kidneys, brain, liver, and intestinal tract, for example, and should not be considered just a pathogen of the lungs.

How much of a threat is bird flu to people right now?

It is not easily transmitted between people right now. Think about how many birds have died, but only a few people have been infected. Here in the U.S., the threat is still low.

But what we are most worried about is where the virus binds. The H5N1 viruses typically bind to cell receptors that are in the lower lungs where they interact with what are called alpha-2,3 receptors. These are found on bird cells. Whereas human influenza viruses typically interact with alpha-2,6 receptors that are found in the upper respiratory tract. Your upper lungs, your nasal passages. There are some influenza viruses that can infect multiple receptors, both alpha-2,3 and alpha-2,6. Now, if we have H5N1 that can now interact equally well with both, we would be in big trouble.

But the good news is that we have a medication called tamiflu (oseltamivir) that works well. It’s an antiviral for flu. It does not prevent infection, but once the virus makes copies of itself inside a cell, it prevents those copies from getting out. This allows the immune system to sweep up the infected cells and it shortens the length and severity of infection.

Is there a threat from bird flu in Gainesville to either people or birds?

Our birds are just like the birds elsewhere, they will get sick. My own cat brings me birds almost every night during the summer. I don’t know if he has caught them or if he found them dead. Chances are if it’s dead, he won’t pick them up. But the fact that he’s catching so many may mean that the birds are on the ground, they are not feeling very alert, then he pounces on them. Is it easier for him to catch sick birds? I imagine. The risk is probably lower though because we don’t have a lot of shorebirds or buzzards or eagles. Birds you would find in more rural areas. But this is a complex question because in the rural areas you may encounter more virus-infected birds, but there are fewer people. Here in town, there might be less virus, but more people.

Any closing thoughts on bird flu?

Work with H5N1 is very expensive. It must be performed in a high-containment laboratory, BSL3 or BSL4, and researchers require special skills such as knowing how to grow the virus in chicken eggs when standard methods don’t work. But if we want to proactively develop new pharmaceuticals before it’s a pandemic in people, this research is also very necessary. There is a need for this work without doing gain-of-function research.

By: DeLene Beeland