Influenza (flu) Virus: Introduction, Classification and Structure

Influenza commonly called “the flu”, is a contagious respiratory illness, a very important global public health problem. It causes seasonal flu epidemics every year and is an important disease responsible for school and job absenteeism, hospitalization and deaths. Flu pandemics has killed millions of people worldwide and another flu pandemic is looming in our future.

Influenz (flu) is caused by influenza viruses, a member of the orthomyxovirus family. Influenza viruses infect the respiratory tract (i.e.,nose, throat, lungs) and can cause mild to severe life-threatening illness. There are three types of influenza (flu) viruses: A, B and C. Antigenic differences exhibited by two of the internal structure proteins (NP and M), are used to divide influenza viruses into types A, B and C.

Influenza virus A and B cause seasonal epidemics whereas influenza type C causes mild respiratory illness. Currently circulating influenza B viruses are from one of two lineages: B/Yamagata and B/Victoria. There are no subtypes of influenza B virus.

Influenza A viruses has been further divided in to subtypes and strains. The mutability and high frequency of genetic reassortment in this virus results antigenic changes in viral surface glycoprotein which has made influenza type A antigenically highly variable and responsible for most cases of epidemic influenza.

Subtypes of Influenza A viruses

Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H) and the neuraminidase (N). There are 18 different hemagglutinin subtypes (H1 through H18) and 11 different neuraminidase (N1 through N11) subtypes.

Strains of Influenza A viruses

Influenza A viruses can be further broken down into different strains. Some of the  most successful and virulent strains of influenza are

  1. H5N1 Avian (bird) flu: caused outbreaks in domestic poultry in parts of Asia and the Middle East. Human infection with H5N1 is rare, nearly 650 cases of human cases of H5N1 have been reported from 15 countries since 2003.
  2. H1N1; originally referred as Swine flu: caused a world-wide pandemic in 2009.
  3. Influenza A H3N2 variant viruses

Nomenclature (naming) of Influenza Virus 

Internationally accepted naming convention is followed for the naming of influenza viruses. The approach uses the following components:

  • The antigenic type (e.g., A, B, C)
  • The host of origin (e.g., swine, chicken, duck etc. For human-origin viruses, no host of origin designation is given.)
  • Geographical origin (e.g., Hong Kong, Taiwan, etc.)

    Naming of influenza virus
    Fig: Naming of influenza virus
  • Strain number (e.g., 15, 7, etc.)
  • Year of isolation (e.g., 57, 2009, etc.)
  • For influenza A viruses, the hemagglutinin and neuraminidase antigen description in parentheses (e.g., (H1N1), (H5N1)

For example:

  • A/duck/Alberta/35/76 (H1N1) for a virus from duck origin
  • A/Perth/16/2009 (H3N2) for a virus from human origin

Structure of Influenza virus 

  • Influenza virion are usually spherical (diameter 80-110 nm).
  • An enveloped virus, the outer layer is a lipid membrane which is taken from the host cell.
  • Inserted into the lipid membrane are ‘spikes’, about 10 nm long, which are  glycoproteins, known as HA (hemagglutinin), and NA (neuraminidase).         # NA is a target of the antiviral drugs Tamiflu
  • HA and HA  are the important antigens that determine
    • antigenic variation of influenza viruses and host immunity.
    • subtype and strains of influenza virus (A/H1N1, for example).
  • Protection against re-infection is mainly due to development of antibodies to HA ( but antibodies to NA are also protective).
  • Influenza (flu) virus structure Image source: CDC
    Influenza (flu) virus structure
    Image source: CDC
  • M2 proteins are also embedded in the lipid membrane, which is the target of the antiviral adamantanes – amantadine and rimantadine.
  • Beneath the lipid membrane is a viral protein called M1, or matrix protein.
    • major component of the virion (about 40% of viral protein)
    • this protein forms a shell, gives strength and rigidity to the lipid envelope.
  • Within the interior of the virion are the viral single stranded, negative sense, viral RNAs
    • 8 of them for influenza A and B viruses; influenza C virus has only 7 segments; lacking a neuraminidase gene);
    • Genetic material of the virus
    • Most of the segments code for the single protein.
  • Each RNA segment consists of RNA joined with several proteins PB1, PB2, PA, NP (RNA Polymerase), 
    responsible for RNA transcription and replication.
  • The interior of the virion also contains another protein called NEP.

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