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The Influenza Virus: Structure and Replication

Inflenza viruses are enveloped RNA viruses, belonging to the family Orthomyxoviridae. 1 x RA Lamb, RM Krug. Orthomyxoviridae: the viruses and their replication. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1487 - 1531) There are three influenza virus genera, or virus types, within this family, influenza A, B and C, distinguishable on the basis of antigenic differences between their matrix and nucleoproteins (M and NP). Influenza A, B and C viruses also differ with respect to host range, variability of the surface glycoproteins, genome organization and morphology. 1 x RA Lamb, RM Krug. Orthomyxoviridae: the viruses and their replication. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1487 - 1531) The influenza A viruses are responsible for pandemic outbreaks of influenza and for most of the well-known annual flu epidemics. 2 x PF Wright, RG Webster. Orthomyxoviruses. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1533 - 1579) Therefore, the discussion here will be limited primarily to influenza A viruses, only referring to influenza B where appropriate. Influenza C virus, which is substantially different from the A and B viruses, is of little importance for human influenza infections, causing only a mild common-cold-like disease; it will not be further discussed in this book.

The A and B viruses contain two major envelope glycoproteins, haemagglutinin (HA) and neuraminidase (NA). 1 x RA Lamb, RM Krug. Orthomyxoviridae: the viruses and their replication. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1487 - 1531) An important feature of influenza viruses is their segmented genome, containing eight independent RNA strands of negative polarity. The RNA segments are packaged in the viral core. The core is surrounded by a lipid membrane, or “envelope”, derived from the plasma membrane of the infected host cell during the process of budding of progeny virus from the cell's surface. 1 x RA Lamb, RM Krug. Orthomyxoviridae: the viruses and their replication. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1487 - 1531)

Human-to-human transmission of influenza occurs through aerosols or droplets, spread into the environment by a sneezing or coughing infected individual. 3 x MR Moser, TR Bender, HS Margolis, et al.. An outbreak of influenza aboard a commercial airliner. Am J Epidemiol 110 (1979) (1 - 6) The virus attacks primarily epithelial cells of the upper and lower respiratory tract. 2 x PF Wright, RG Webster. Orthomyxoviruses. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1533 - 1579) Infection occurs by binding of the viral HA to sialic acid receptors on the target cell surface and subsequent fusion of the viral envelope with the host cell membrane. 1 x RA Lamb, RM Krug. Orthomyxoviridae: the viruses and their replication. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1487 - 1531) It is through this fusion process that the viral RNA gains access to the cytosol of the host cell. The RNA then enters the nucleus of the cell, where it is replicated. Viral proteins are being synthesized in the cytosol, ultimately resulting in production of many new virus particles. During the production of progeny virus, the host cell's own protein synthesis is effectively shut down. Finally, having produced many thousands of new virus particles, the cell lyses and dies as a result of the infection. 1 x RA Lamb, RM Krug. Orthomyxoviridae: the viruses and their replication. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1487 - 1531)

Key Messages

  • There are three types of influenza virus: A, B and C. Influenza A viruses are responsible for all pandemic and most epidemic outbreaks, influenza B viruses also cause human disease, but influenza C virus is of little clinical importance.
  • Influenza A and B viruses have two major envelope glycoproteins, haemagglutinin (HA) and neuraminidase (NA). HA is responsible for infectious entry of the virus into cells; it is also the virus’ most important surface antigen, against which virus-neutralizing antibodies are directed.
  • Influenza virus enters cells through receptor-mediated endocytosis and low-pH-induced fusion from within acidic endosomes.
  • Cleavage into two subunits is essential for HA to mediate entry of influenza virus into cells. The HA1 subunit is involved in receptor binding, HA2 has membrane fusion activity.
  • The receptor for HA is sialic acid bound to glycolipids or glycoproteins on the host cell surface. Avian and human influenza A viruses have a different receptor specificity; pigs have receptors for both avian and human viruses.
  • NA cleaves the sialic acid receptor, thus releasing progeny virus from the infected cell surface. It is the target for the antiviral drugs zanamivir and oseltamivir, which are sialic acid analogues and inhibit release of progeny virus from infected cells.
  • Influenza viruses have a segmented RNA genome of negative polarity. Mixed infection of a single cell with two different influenza viruses may lead to genetic reassortment between the two viruses.

References

Label Authors Title Source Year
1

References in context


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  • Influenza A, B and C viruses also differ with respect to host range, variability of the surface glycoproteins, genome organization and morphology.1 The influenza A viruses are responsible for pandemic outbreaks of influenza and for most of the well-known annual flu epidemics.2 Therefore, the discussion here will be limited primarily to influenza A viruses, only referring to influenza B where appropriate.
    Go to context

  • Influenza A, B and C viruses also differ with respect to host range, variability of the surface glycoproteins, genome organization and morphology.1 The influenza A viruses are responsible for pandemic outbreaks of influenza and for most of the well-known annual flu epidemics.2 Therefore, the discussion here will be limited primarily to influenza A viruses, only referring to influenza B where appropriate.
    Go to context

  • The A and B viruses contain two major envelope glycoproteins, haemagglutinin (HA) and neuraminidase (NA).1 An important feature of influenza viruses is their segmented genome, containing eight independent RNA strands of negative polarity.
    Go to context

  • The A and B viruses contain two major envelope glycoproteins, haemagglutinin (HA) and neuraminidase (NA).1 An important feature of influenza viruses is their segmented genome, containing eight independent RNA strands of negative polarity.
    Go to context

  • Human-to-human transmission of influenza occurs through aerosols or droplets, spread into the environment by a sneezing or coughing infected individual.3 The virus attacks primarily epithelial cells of the upper and lower respiratory tract.2 Infection occurs by binding of the viral HA to sialic acid receptors on the target cell surface and subsequent fusion of the viral envelope with the host cell membrane.1 It is through this fusion process that the viral RNA gains access to the cytosol of the host cell.
    Go to context

  • Human-to-human transmission of influenza occurs through aerosols or droplets, spread into the environment by a sneezing or coughing infected individual.3 The virus attacks primarily epithelial cells of the upper and lower respiratory tract.2 Infection occurs by binding of the viral HA to sialic acid receptors on the target cell surface and subsequent fusion of the viral envelope with the host cell membrane.1 It is through this fusion process that the viral RNA gains access to the cytosol of the host cell.
    Go to context

  • Influenza A viruses are known to also infect a variety of other mammals, including non-human primates, pigs, horses, cats, seals, whales and mink (Table 1).1,2,4 There are no influenza B virus subtypes.
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  • Influenza A viruses are known to also infect a variety of other mammals, including non-human primates, pigs, horses, cats, seals, whales and mink (Table 1).1,2,4 There are no influenza B virus subtypes.
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  • Influenza viruses are roughly spherical, although somewhat pleomorphic, particles, ranging from 80 to 120 nm in diameter.1,7 Figure 5 presents a model of the overall structure of the influenza virus.
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  • The major envelope glycoprotein HA is synthesized in the infected cell as a single polypeptide chain (HA0) with a length of approximately 560 amino acid residues, which is subsequently cleaved into two subunits, HA1 and HA2.1,8 These subunits remain covalently linked to one another through disulphide bonds.
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  • The influenza A or B virus genome consists of eight segments of negative-sense single-stranded RNA.1 Each RNA segment is associated with multiple copies of NP and with the viral transcriptase consisting of RNA polymerase components PB1, PB2 and PA, thus forming the RNP complex.21 The RNPs are surrounded by a layer of the matrix protein, M1.
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  • The influenza A or B virus genome consists of eight segments of negative-sense single-stranded RNA.1 Each RNA segment is associated with multiple copies of NP and with the viral transcriptase consisting of RNA polymerase components PB1, PB2 and PA, thus forming the RNP complex.21 The RNPs are surrounded by a layer of the matrix protein, M1.
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  • RNA segments 1–6 of influenza A viruses encode a single protein each.1 For example, segment 4 encodes the HA, segment 5 NP and segment 6 the NA protein.
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  • Here, the negative-sense viral RNAs are transcribed to positive-sense messenger RNAs (mRNAs) by the transcriptase (consisting of PB1, PB2 and PA) carried with the RNPs.1 The transcriptase, in a process referred to as “cap snatching”, steals short cap regions from cellular mRNAs as primers for initiation of viral mRNA synthesis.
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  • Thus, cleavage of HA0 is essential for viral infectivity.1,11,12,28,29 In human influenza viruses, cleavage is thought to occur extracellularly, at a single arginine residue, after HA0 has been incorporated in virus particles.37 The enzyme responsible for cleavage, a trypsin-like protease, is probably released from Clara cells in the respiratory epithelium.
    Go to context

RA Lamb, RM Krug. Orthomyxoviridae: the viruses and their replication. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1487 - 1531) 2001
2

References in context

  • Influenza A, B and C viruses also differ with respect to host range, variability of the surface glycoproteins, genome organization and morphology.1 The influenza A viruses are responsible for pandemic outbreaks of influenza and for most of the well-known annual flu epidemics.2 Therefore, the discussion here will be limited primarily to influenza A viruses, only referring to influenza B where appropriate.
    Go to context

  • Human-to-human transmission of influenza occurs through aerosols or droplets, spread into the environment by a sneezing or coughing infected individual.3 The virus attacks primarily epithelial cells of the upper and lower respiratory tract.2 Infection occurs by binding of the viral HA to sialic acid receptors on the target cell surface and subsequent fusion of the viral envelope with the host cell membrane.1 It is through this fusion process that the viral RNA gains access to the cytosol of the host cell.
    Go to context

  • Influenza A viruses are known to also infect a variety of other mammals, including non-human primates, pigs, horses, cats, seals, whales and mink (Table 1).1,2,4 There are no influenza B virus subtypes.
    Go to context

PF Wright, RG Webster. Orthomyxoviruses. DM Knipe, PM Howley, DE Griffin (Eds.) et al. Fields Virology 4th edn. (Lippincott Williams & Wilkins, 2001) (1533 - 1579) 2001
3

References in context

  • Human-to-human transmission of influenza occurs through aerosols or droplets, spread into the environment by a sneezing or coughing infected individual.3 The virus attacks primarily epithelial cells of the upper and lower respiratory tract.2 Infection occurs by binding of the viral HA to sialic acid receptors on the target cell surface and subsequent fusion of the viral envelope with the host cell membrane.1 It is through this fusion process that the viral RNA gains access to the cytosol of the host cell.
    Go to context

MR Moser, TR Bender, HS Margolis, et al.. An outbreak of influenza aboard a commercial airliner. Am J Epidemiol 110 (1979) (1 - 6) 1979

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