More on influenza viruses

Image: CDC


Seasonal influenza viruses are a major healthcare problem in terms of disease burden.

They are highly infectious and are transmitted via contact with infected respiratory secretions. They infect the respiratory tract and cause fever and respiratory symptoms. Adults with normal immune systems normally recover from influenza infections without issue, but in high risk patients such as the elderly it can proceed to cause pneumonia which is a frequent cause of death in the elderly. Other high risk patients include the very young, patients with pre-existing respiratory conditions, patients with co-morbidities and patients who are hospitalised.


There are three main types of seasonal influenza viruses, labeled A, B, and C (related to their core proteins).

Only type A and B are problematic, and only type A, being the most pathogenic, is able to cause pandemics.

Influenza type A viruses can infect a variety of animal hosts, providing an extensive reservoir.

Influenza type B viruses usually infect only humans.

influenza type C causes milder infections and poses much less of a disease burden than A and B, so only A and B are included in seasonal influenza vaccines.

All influenza viruses bear two surface proteins, hemagglutinin (H) and neuraminidase (N), each of which there are several variations of.

So far there are 18 different types of H, and 11 different types of N identified. This makes it in theory possible to have 198 different H and N combinations. For example H1N1 to H18N11.

Type A influenza viruses are further divided into subtypes according to the combinations of H and N present (eg. H1N1 is a subtype). Type B viruses are not further subtyped in this way.

Type A H1N1 and H3N2 are the current circulating seasonal A viruses. The current seasonal H1N1 virus is the same virus that caused the 2009 influenza pandemic. (CDC 2017)

There are currently two type B viruses that are in circulation, Victoria lineage and Yamagata lineage (B/Yamagata and B/Victoria), named after the location where they were first identified.

All viruses are further identified by strain.

The WHO accepted naming convention of viruses is based on:

  • The antigenic type - A, B, C
  • The host of origin - swine, equine, chicken, etc. For human-origin viruses, no host of origin designation is given.
  • Geographical origin
  • Strain number
  • Year of isolation
  • For influenza A viruses, the hemagglutinin and neuraminidase antigen description in brackets eg (H1N1)


Examples:

A/duck/Alberta/35/76 (H1N1)

A/Michigan/45/2015 (H1N1)pdm09

B/Brisbane/60/2008



Hemagluttinin and Neuraminidase

These are enzyme proteins located on the surface of the virus. It is these which the immune system will use to identify the virus - in other words, they are antigens. Antigens stimulate the production of antibodies, which are specific to the antigen.

Variation of these proteins over time enables the virus to evade the immune response, necessitating the formulation of a new vaccine each year.

The neuraminidase protein is an enzyme which enables the release of new virus from infected cells. It is also the target molecule of the anti-flu neuraminidase inhibitors.


Cross-species infection

Most influenza viruses stay within their own species, and are often quite specific, for example will only circulate amongst ducks, or will only circulate amongst poultry. Only Type A viruses are known to rarely cross species. Of all the zoonotic viruses, humans seem to be most vulnerable to those which circulate amongst birds and pigs.

The recent avian influenza outbreak is a virulent strain of H5N1, which has caused an epidemic amongst birds of all species, as well as crossing species into other types of animals including humans. For the time being in cases where humans have been infected, although highly pathogenic, further person-to-person spread of this strain of H5N1 has not occurred.


Antigenic drift

Each type of Influenza A can undergo ‘antigenic drift’. This is the occurrence of natural mutations in viral RNA, and results in small changes to the shapes of H and N. The result is a new strain, but the subtype (e.g. H1N1) remains the same. If the changes are only small the immune system will still be able to recognise it. But if there are enough accumulated changes then the immune system may not recognise the virus anymore, or only be able to provide limited initial protection, enabling re-infection. This is why yearly vaccination is required.


Antigenic shift

This is associated with cross-species mutations and more dramatic and sudden changes in virus subtype.

If the host cell is infected with two different types of viruses, for example one from a human virus and the other from an animal virus, the two different virus strains may combine their genetic material to make a new sub-strain. This process is called ‘antigenic shift’, and is what led to the Swine Flu virus in 2009. In this case the flu virus crossed over from an animal source, then merged with a human virus, which was then was able to continue to spread via human to human transmission.

Cross-species infection only occurs with Type A viruses. Antigenic shift results in different subtypes with either different types or combinations of H and N, and are so different from the regular circulating viruses that the immune system is completely unable to provide any initial protection.


References

CDC Types of influenza virus

CDC drift and shift

Katzung

Microbe online blog