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The Influenza Virus: Structure and Replication

Classification and nomenclature of influenza viruses

Influenza A viruses are divided into subtypes, based on the nature of their surface glycoproteins, HA and 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) There are 16 different HAs and nine NAs which are distinguishable serologically, i.e. antibodies to one virus subtype do not react with another. All virus subtypes appear to circulate in aquatic birds. 4 x VS Hinshaw, RG Webster, WJ Bean, G Sriram. The ecology of influenza viruses in ducks and analysis of influenza viruses with monoclonal antibodies. Comp Immunol Microbiol Infect Dis 3 (1980) (155 - 164) Crossref. Only some of these subtypes have been identified in humans ( Table 1 ), specifically the H1N1, H2N2 and H3N2 viruses, corresponding to the three major pandemics of the last century. During recent outbreaks of highly pathogenic avian influenza (HPAI), there have been occasional transmissions of H5N1, H7N7 and H9N2 viruses to humans (see Chapter 3). 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, 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) 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) 4 x VS Hinshaw, RG Webster, WJ Bean, G Sriram. The ecology of influenza viruses in ducks and analysis of influenza viruses with monoclonal antibodies. Comp Immunol Microbiol Infect Dis 3 (1980) (155 - 164) Crossref. There are no influenza B virus subtypes. The B virus primarily infects humans, although it has also been isolated from seals. 5 x ADME Osterhaus, GF Rimmelzwaan, BE Martina, TM Bestebroer, RAM Fouchier. Influenza B virus in seals. Science 288 (2000) (1051 - 1053) Crossref.

Table 1 Natural hosts of influenza A viruses. The table indicates the subtypes of haemagglutinin (HA) and neuraminidase (NA), and the hosts in which they have been identified. source: Adapted from Lamb RA, Krug RM. Orthomyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM, Griffin DE et al., editors. Fields Virology, 4th edn. Lippincott Williams & Wilkins, 2001; pp. 1487–1531 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) with permission from Lippincott Williams & Wilkins.

Natural hosts of influenza A viruses
Haemagglutinin Neuraminidase
Subtype Predominant hosts Subtype Predominant hosts
H1 Human, pig, birds N1 Human, pig, birds
H2 Human, pig, birds N2 Human, pig, birds
H3 Birds, human, pig, horse N3 Birds
H4 Birds N4 Birds
H5 Birds, (human) N5 Birds
H6 Birds N6 Birds
H7 Birds, horse, (human) N7 Horse, birds
H8 Birds N8 Horse, birds
H9 Birds, (human) N9 Birds
H10 Birds
H11 Birds
H12 Birds
H13 Birds
H14 Birds
H15 Birds
H16 Birds

References in 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

  • 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

The current nomenclature system for influenza A viruses includes the host of origin, geographic location of first isolation, strain number and year of isolation. 6 x WHO Memorandum. A revised system for nomenclature of influenza viruses. Bull World Health Org 58 (1980) (585 - 591) The HA and NA subtype of influenza A viruses is specified in parentheses, e.g. A/Swine/Iowa/15/30 (H1N1). By convention, the host of origin of human strains is omitted, e.g. A/Puerto Rico/8/34 (H1N1). Since there are no subtypes of influenza B virus, no parenthetical specification is given in this case and, as the B viruses primarily infect humans, the host of origin is not mentioned in the influenza B virus nomenclature, e.g. B/Yamagata/16/88.

 
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Table 1 Natural hosts of influenza A viruses. The table indicates the subtypes of haemagglutinin (HA) and neuraminidase (NA), and the hosts in which they have been identified. source: Adapted from Lamb RA, Krug RM. Orthomyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM, Griffin DE et al., editors. Fields Virology, 4th edn. Lippincott Williams & Wilkins, 2001; pp. 1487–1531 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) with permission from Lippincott Williams & Wilkins.

Natural hosts of influenza A viruses
Haemagglutinin Neuraminidase
Subtype Predominant hosts Subtype Predominant hosts
H1 Human, pig, birds N1 Human, pig, birds
H2 Human, pig, birds N2 Human, pig, birds
H3 Birds, human, pig, horse N3 Birds
H4 Birds N4 Birds
H5 Birds, (human) N5 Birds
H6 Birds N6 Birds
H7 Birds, horse, (human) N7 Horse, birds
H8 Birds N8 Horse, birds
H9 Birds, (human) N9 Birds
H10 Birds
H11 Birds
H12 Birds
H13 Birds
H14 Birds
H15 Birds
H16 Birds

References in 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

  • 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

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.
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  • 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.
    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 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.
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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
4

References in 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

  • 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

VS Hinshaw, RG Webster, WJ Bean, G Sriram. The ecology of influenza viruses in ducks and analysis of influenza viruses with monoclonal antibodies. Crossref. Comp Immunol Microbiol Infect Dis 3 (1980) (155 - 164) 1980
5

References in context

  • Influenza A viruses are divided into subtypes, based on the nature of their surface glycoproteins, HA and NA.1 There are 16 different HAs and nine NAs which are distinguishable serologically, i.e. antibodies to one virus subtype do not react with another.
    Go to context

ADME Osterhaus, GF Rimmelzwaan, BE Martina, TM Bestebroer, RAM Fouchier. Influenza B virus in seals. Crossref. Science 288 (2000) (1051 - 1053) 2000
6

References in context

  • The current nomenclature system for influenza A viruses includes the host of origin, geographic location of first isolation, strain number and year of isolation.6 The HA and NA subtype of influenza A viruses is specified in parentheses, e.g.
    Go to context

WHO Memorandum. A revised system for nomenclature of influenza viruses. Bull World Health Org 58 (1980) (585 - 591) 1980

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