Bird flu? Swine flu? A guide to H5N1 viruses and beyond

Avid virus-watchers will know that influenza viruses that make the news often feature the letters "H" and "N" in their names, such as H5N1 or H9N2.

Those are examples of "Type A" influenza viruses — classed as highly infectious pathogens and a significant threat to influenza viruses that make the news.

But there are B, C and D types as well, with various sub-types and lineages, many colloquially known as avian/bird, cow and swine flues.

You can forgive yourself for feeling confused — because it is confusing: And it's not immediately clear which types of flu risk public health to the extent of the Spanish flu of 1918 or a COVID-style pandemic. 

So, here's DW's guide to help you navigate the maze of influenza code. We'll start with those four types of the virus.

The four types of influenza

As mentioned above, there are four types of influenza: A, B, C and D.

Types A and B cause seasonal, epidemic outbreaks of influenza among humans during winter months. But only type A is known to cause pandemics.

Type A influenza viruses often originate in aquatic birds and spread among bird species — that's then known as avian influenza or bird flu. But they can also spread to other mammals if the virus has the right mutations.

Some strains of the Type A virus H1N1 are endemic (consistently present) in humans, bird, and pigs. Annual flu vaccines help protect us against strains of H1N1 viruses, among others.

The A(H1N1)pdm09 viruses, adapted from H1N1, caused the Spanish Flu pandemic of 1918, which killed between 20-50 million people. The variant has been genetically traced to flu outbreaks in swine populations (swine flu) as recently as 2009.

At the time of writing in June 2024, only two subtypes of influenza A — A(H1N1)pdm09, and A(H3N2) — were co-circulating (at the same time) among humans.

A major outbreak of H5N1 is currently ongoing in birds and cattle in the US, but there is no evidence yet it's spreading in humans.

The so-called Spanish Flu pandemic killed millions over a two year period from 1918-1919 — although it may not have originated in Spain Image: picture alliance / AP Photo

Type C influenza viruses can infect humans and other mammals like pigs, but cause mild illnesses in people. Flu due to Type C viruses are rare compared to type A viruses.

And Type D influenza viruses primarily affect cattle. They can spread to other animals, but no human infections have been observed. 

The subtypes of influenza A viruses

Now let's unpack the those "HxNy" codes. We'll stick to Type A influenzas because those are the ones that use this specific denomination and pose the greatest threat to human public health.

Type A influenza viruses are classified according to two types of proteins found on the surface of the virus:

• Hemagglutinin (H or HA)
• Neuraminidase (N or NA)

Hemagglutinin and neuraminidase are found in all types of influenza and they work as a viral team: The hemagglutinin helps the virus attach itself to a cell to infect it, and the neuraminidase releases the virus to allow it infect other cells — that, in the simplest of terms, is how the virus spreads in your body.

These two proteins determine the "infectivity" and "pathogenicity" of the virus — essentially, how dangerous they are for your health.

There are 130 known H + N combinations. But since viruses are good at "reassortment" — a process by which viruses swap genetic information — there is the potential for many more. Reassortment in viruses can happen when, for example, two subtypes of a virus infect the same host (a person or non-human animal) at the same time.

Add to that the fact that new H + N subtypes do emerge in the wild. Until recently, for instance, researchers spoke of 16 hemagglutinin subtypes in influenza, but now two further subtypes are known to exist: H17 and H18 found in two species of bats.

When the H and N numbers are unknown, H takes the variable "x" and N takes the variable "y". 

Type B influenza denominations

Type B influenza viruses are named according to their lineage. And there are two: Yamagata and Victoria.

The names for Type B influenza viruses aren't as varied as those for Type A because the H + N subtypes in Type B influenza viruses don't appear to vary within their lineage.

However, they can be further defined into clades and subclades, or groups and sub-groups.

B/Victoria influenza viruses, for example, include the V1A clade and sub-clades V1A.1, V1A.2 and V1A.3. B/Yamagata include Y1, Y2 and Y3 clades but no known sub-clades.

Types of influenza to watch out for (if you are human)

Influenza viruses originating in animals don't aften affect humans, but when it does, we speak of zoonotic transmission. That's the same for any disease where there is a transmission from animal to human-animal or the other way around.

Five subtypes of avian influenza A viruses do caused human infections — H5, H6, H7, H9, and H10 viruses.

Most of the zoonotic forms of influenza — from birds to humans — are A(H5N1) and A(H7N9).

A(H5N6) — known as a Highly Pathogenic Avian Influenza (HPAI) — and A(H9N2) — a Low Pathogenic Avian Influenza (LPAI) — have also caused human infections.

As mentioned above, Type C influenza viruses tend only to cause mild illnesses and Type D influenza viruses are not known to affect humans at all.

Edited by: Fred Schwaller

Sources:

Types of Influenza Viruses. US Centers for Disease Control and Prevention, accessed June 13, 2024 https://www.cdc.gov/flu/about/viruses/types.htm

Influenza hemagglutinin and neuraminidase: Yin–Yang proteins coevolving to thwart immunity. Published in the journal Virus, 2019 https://doi.org/10.3390/v11040346

Avian Influenza Type A Viruses. US Centers for Disease Control and Prevention, accessed June 14, 2024 https://www.cdc.gov/bird-flu/about/?CDC_AAref_Val=https://www.cdc.gov/flu/avianflu/influenza-a-virus-subtypes.htm

Genetic characterization of a new candidate hemagglutinin subtype of influenza A viruses. Published in the journal Emerging Microbes and Infections, June 2023 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10308872/pdf/TEMI_12_2225645.pdf

Emerging HxNy Influenza A Viruses. Published in Cold Spring Harbor Perspectives in Medicine, February 2022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805644/pdf/cshperspectmed-INF-a038406.pdf