Influenza World Health Care Professionals

The influenza viruses belong to the family Orthomyxoviridae, from the Greek myxa meaning mucus, a reference to the special association of the virus with mucosal surfaces. They are unique amongst respiratory viruses with respect to their segmented genome and great antigenic diversity (through antigenic drift and/or shift) and are classified into three distinct types (A, B and C) according to the proteins situated on the outer membrane.

• Influenza A infections can cause potentially severe illness in both humans and animals. The virus can change rapidly and is responsible for both epidemics and pandemics [1]
• Influenza B infections only affect humans (mostly children). [2] The virus has caused epidemics that have been associated with widespread hospitalisation and death. [1]
• Influenza C infections are usually associated with mild respiratory illness and are more common in children. [3] The virus is not thought to cause epidemics.

Structure of the virus

Influenza A and B are spherical (80–120 nm in diameter), negative-strand RNA viruses with a segmented genome. [4] Influenza A and B viruses contain eight RNA segments – each segment is encapsulated by viral nucleoprotein and associated with a polymerase complex. [4] Together the RNA segments, nucleoprotein, and polymerase complex are known as ribonucleoprotein particles and are contained within a lipid membrane lined with M1 protein.

Embedded in the membrane are two spike proteins that protrude outwards and are essential for viral replication:

• haemagglutinin (rod shaped) is involved in the attachment of the influenza virus to the host cell and triggers internalisation [4]
• neuraminidase (mushroom shaped) facilitates release of the newly-produced virus particles from the host cell. [4]

The lipid membrane of influenza A and B viruses also contain membrane-spanning ion channels: the M2 protein for influenza A and the NB protein for influenza B.

Neuraminidase inhibitors can be used to prevent newly formed virus particles from being released from the host cell and therefore limit the spread of infection. More information about the mode of action of neuraminidase inhibitors and how they can be used to treat influenza, can be found here.

Mutation of influenza viruses

Influenza viruses, particularly influenza A, exhibit a unique ability to undergo antigenic variation. Minor antigenic changes to influenza A and B viruses are known as antigenic drift, and major changes – which only occur with influenza A – are known as antigenic shift.

Antigenic drift is the accumulation of point mutations, and which may result in amino acid substitutions within the antibody-binding sites of the haemagglutinin and/or neuraminidase proteins. [5, 6] These mutations, which can occur naturally or under pressure from antiviral antibodies, produce new virus strains that may not be recognised by the body’s immune system. [5] The novel virus strain can therefore be transmitted more easily through a partially immune population, causing the annual influenza epidemics.

• Both influenza A and B undergo antigenic drift
• Cause of seasonal / interpandemic influenza

Antigenic shift  occurs less frequently than antigenic drift. It is the result of replacement of entire gene segments (including the haemagglutinin or neuraminidase proteins), with subtypes that have not been present in human viruses for some time. [6] The most plausible explanation is a genetic reassortment as a result of interactions between human and animal influenza A viruses. Antigenic shift can result in a worldwide pandemic as most people have little or no immunity to the new influenza strain.

• Only influenza A undergoes antigenic shift
• Cause of pandemic influenza

More information about pandemics and avian influenza, can be found here.

To view a short film about the adaptability of influenza viruses, follow the link.

1. Laver WG, Bischofberger N, Webster RG. Disarming flu viruses. Sci Am 1999; 280: 78–87.
2. Nicholson K. Human influenza. In: Nicholson K, Webster RG, Hay A, eds. Textbook of influenza. Oxford, UK: Blackwell Science, 1998: 219–64.
3. Matsuzaki Y, Katsushima N, Nagai Y, et al. Clinical features of influenza C virus infection in children. J Infect Dis 2006; 193: 1229–35.
4. Ruigrok R. Structure of influenza A, B and C viruses. In: Nicholson K, Webster RG, Hay A, eds. Textbook of influenza. Oxford, UK: Blackwell Science, 1998:
   29–42.
5. Moorman JP. Viral characteristics of influenza. South Med J 2003; 96: 758–61.
6. Treanor J. Influenza vaccine – outmaneuvering antigenic shift and drift. N Engl J Med 2004; 350: 218–20.