Influenza Virus Infections
28 December 2020 13:40
Influenza Viruses:
• Orthomyxoviridae family
• Pleiomorphic
• Individual segments of RNA packaged as separate nucleocapsids
• Prominent peplomers
Types of Influenza:
• Type A: infects man and animals - worldwide pandemics
• Type B: Infecting man - localised outbreaks
• Type C: humans and pigs - mainly asymptomatic
• Type D: pigs and cattle - mainly asymptomatic or mild
Classification based on antigenic properties of surface glycoproteins: Haemagglutinin (HA) and
Neuraminidase (NA).
Both HA and NA are carbohydrate binding proteins:
Recognise sialic acid (N-Acetyl) neuraminic acid (Neu4Ac), and alpha-linked terminal carbohydrate of
the upper respiratory tract.
Influenza bears two types of surface protein
Neuraminidase (NA) Tetramer-Particle dispersal:
Assist movement along the upper respiratory tract and virus release
Haemagglutinin (HA) Trimer - Attachment and fusion:
Initial point of contact by binding cell glycoconjugates (sialic acid)
There is a receptor binding site located on the top of haemagglutinin. HA binds sialic acid and the
type of sialic acid bound is key determinant of virus tropism.
Important factors in Influenza virus evolution
Antigenic Drift:
• Accumulation of amino acid changes that result in subtle changes in antigens and infections
where host immunity is incomplete.
Antigenic Shift:
• Reassortant viruses (segmented genome) resulting in novel antigenic virus strains
• Where do viruses reassort?
Mixing of avian and human viruses most common
B-cell immune responses and antigenic drift
• Antigenic changes cluster in 5 highly variable regions surrounding the receptor binding pocket
• Amino acid changes also occur at other sites in the HA1 molecule
• Drift occurs when mutation accumulate in two or more of the antigenic domains
• These variants have a reduced susceptibility to pre-existing immunity in the population
• Spread occurs because of the large number of susceptible hosts and the increased likelihood
of the virus causing symptomatic infection.
Pigs are important mixing vessel for influenza
Pigs have the high capability of receiving large number of influenza strains. The other hosts like
chicken that associate with the pigs then mix and reassort their genes and give rise to novel viruses
which can infect humans who live at close proximity to those animals.
Dominant receptor usage in different species:
Human - respiratory infection - alpha (2,6) receptor abundant in human lungs
Bird (avian) - enteric infection - alpha (2,3) receptor abundant in bird intestine
Swine (pigs)- respiratory infection - Both forms are abundant in swine lungs
Influenza virus Page 1
28 December 2020 13:40
Influenza Viruses:
• Orthomyxoviridae family
• Pleiomorphic
• Individual segments of RNA packaged as separate nucleocapsids
• Prominent peplomers
Types of Influenza:
• Type A: infects man and animals - worldwide pandemics
• Type B: Infecting man - localised outbreaks
• Type C: humans and pigs - mainly asymptomatic
• Type D: pigs and cattle - mainly asymptomatic or mild
Classification based on antigenic properties of surface glycoproteins: Haemagglutinin (HA) and
Neuraminidase (NA).
Both HA and NA are carbohydrate binding proteins:
Recognise sialic acid (N-Acetyl) neuraminic acid (Neu4Ac), and alpha-linked terminal carbohydrate of
the upper respiratory tract.
Influenza bears two types of surface protein
Neuraminidase (NA) Tetramer-Particle dispersal:
Assist movement along the upper respiratory tract and virus release
Haemagglutinin (HA) Trimer - Attachment and fusion:
Initial point of contact by binding cell glycoconjugates (sialic acid)
There is a receptor binding site located on the top of haemagglutinin. HA binds sialic acid and the
type of sialic acid bound is key determinant of virus tropism.
Important factors in Influenza virus evolution
Antigenic Drift:
• Accumulation of amino acid changes that result in subtle changes in antigens and infections
where host immunity is incomplete.
Antigenic Shift:
• Reassortant viruses (segmented genome) resulting in novel antigenic virus strains
• Where do viruses reassort?
Mixing of avian and human viruses most common
B-cell immune responses and antigenic drift
• Antigenic changes cluster in 5 highly variable regions surrounding the receptor binding pocket
• Amino acid changes also occur at other sites in the HA1 molecule
• Drift occurs when mutation accumulate in two or more of the antigenic domains
• These variants have a reduced susceptibility to pre-existing immunity in the population
• Spread occurs because of the large number of susceptible hosts and the increased likelihood
of the virus causing symptomatic infection.
Pigs are important mixing vessel for influenza
Pigs have the high capability of receiving large number of influenza strains. The other hosts like
chicken that associate with the pigs then mix and reassort their genes and give rise to novel viruses
which can infect humans who live at close proximity to those animals.
Dominant receptor usage in different species:
Human - respiratory infection - alpha (2,6) receptor abundant in human lungs
Bird (avian) - enteric infection - alpha (2,3) receptor abundant in bird intestine
Swine (pigs)- respiratory infection - Both forms are abundant in swine lungs
Influenza virus Page 1
