By Dr Tomislav Meštrović, MD, PhD
Influenza is caused by three types of RNA viruses called influenza types A, B and C (considered different genera), which all belong to the family Orthomyxoviridae. The disease, colloquially called "flu" in humans, is generally caused by the viruses A and B, which are transmitted by aerosols from infected individuals or via close contact with infected animals.
Subtypes of influenza A and B viruses can be further characterized into strains. There is a plethora of different strains of influenza B viruses and of influenza A subtypes, and new strains of influenza viruses can appear and replace older strains. Such newly emerging viruses contain antigenic variations known as antigenic drift and shift. The clinical outcome of the disease depends on both the influenza virus and ensuing host defense.
Influenza type A viruses are known to infect people, birds, pigs, horses, whales, seals and other animals, but wild birds represent the natural hosts for these viruses. The enveloped influenza A virions contain three membrane proteins (HA, NA, M2), a matrix protein (M1) just below the lipid bilayer, a ribonucleoprotein core (consisting of 8 viral RNA segments and three proteins – PA, PB1, PB2), as well as the NEP protein.
Influenza type A viruses can be further divided into subtypes based on two membrane proteins on the surface of the virus. These proteins are called hemagglutinin (HA) and neuraminidase (NA). There are 18 different HA and 11 different NA subtypes (HA1 through HA18 and NA1 through NA11, respectively).
Although many different combinations of HA and NA proteins are possible, only a fraction influenza A subtypes (i.e. H1N1, H1N2 and H3N2) are currently in general circulation among people. Other subtypes are found in other animal species. For example, H7N7 cause illness in horses, and H3N8 has been shown to elicit the disease in dogs and seals.
Subtypes of influenza A virus are named in accordance to their HA and NA surface proteins. For example, an “H3N8 virus” designates an influenza A subtype that has an HA 3 protein and an NA 8 protein. Likewise, an “H5N1” virus has an HA 5 protein and an NA 1 protein.
An internationally accepted naming convention for influenza viruses also exists, accepted by WHO in 1979 and published in February 1980 in the Bulletin of the World Health Organization. This approach uses the components such as the antigenic type (A, B or C), the host of origin, geographical origin, strain number, year of isolation and, for influenza A viruses, the hemagglutinin and neuraminidase antigen description in parentheses.
Influenza B viruses are responsible the same spectrum of disease as influenza A; however, influenza B viruses do not cause pandemics. Such property may be a consequence of the limited host range of the virus (only humans and seals), which limits the occurrence of new strains by reassortment. In addition, they are not divided into subtypes, although can be broken down into lineages and strains. Currently circulating influenza B viruses belong to one of the two lineages: B/Victoria and B/Yamagata.
Influenza B virions contain four envelope proteins: HA, NA, NB, and BM2. The BM2 protein is a proton channel that is essential for the uncoating process (akin to the M2 protein of influenza A virus). The NB protein is thought to be an ion channel, not required for viral replication in cell culture.
This virus is responsible significant morbidity. For example, in the US in 2008, approximately one-third of all laboratory-confirmed cases of influenza were caused by influenza B. That is the reason why the seasonal trivalent influenza vaccine contains an influenza B virus component as its integral component.
Influenza C viruses are different in comparison to influenza A and B. The enveloped virions have hexagonal structures on the surface and form stretched cordlike structures (approximately 500 microns in length) as they bud from the cell. Analogous to the influenza A and B viruses, the core of influenza C viruses is composed of a ribonucleoprotein made up of viral RNA and four proteins.
The M1 protein lies just beneath the membrane, similar to influenza A and B virions. A minor viral envelope protein is CM2, which has a function of an ion channel. This virus does not contain separate HA and NA glycoproteins, yet their function is consolidated in one glycoprotein called HEF (hemagglutinin-esterase-fusion). Therefore the influenza virion contains 7 RNA segments, and not 8.
Influenza type C infections cause a mild respiratory illness (comparable to other common respiratory viruses) and are not thought to cause epidemics. According to the seroprevalence studies, nearly all adults have been infected with influenza C virus. Lower respiratory tract complications are rare, and vaccine against it is not available.
- Nicholson KG, Webster RG, Hay AJ. Textbook of Influenza. Blackwell Science, Oxford, 1998.
- Lamb RA, Krug RM. Orthomyxoviridae: The viruses and their Replication. In: Fields Virology fourth edition, Knipe DM, Howley PM eds, Lippincott, Philadelphia 2001, pp 1487-1531.
Last Updated: Nov 9, 2014