VIRUS
Influenzavirus
Virus Disease Seroypes Lifelong immunity Length of infection
Influenza A Influenza (severe) Many No Acute disease ‘hit
and run’
Influenza B Influenza Many (less No
diverse)
Influenza C Influenza (mild) Many No
Adenovirus Pharyngitis/pneumonia Many No Acute disease and
(mild) latency/persistent
infection
• Influenza A and B are more severe, influenza C is mild
• Adenovirus focuses on upper respiratory tract, influenzavirus focuses on lower respiratory tract
• ‘Hit and run’ – influenzavirus, acute disease, virus used host to replicate then moves
• Adenovirus confers acute disease but persists in host (so not hit and run)
• Baltimore classification system
o Classification depends on how virus replicates
▪ (+) strand – RNA replicated directly
▪ (-) strand – RNA transcribed to (+) strand then replicated
o Influenzavirus is group 5 of Baltimore classification – (-) ssRNA
o Influenzavirus has a segmented genome
▪ Viruses with segmented genomes, viral RNA-dependant RNA polymerase produces
monocistronic mRNAs from each genome segment
▪ Cistron – segment of DNA that contains all information necessary to produce a single
polypeptide and included structural and regulatory sequences
• Orthomyxoviruses
o Influenzavirus is part of orthomyxovirus family
o Pleomorphic – spherical and filamentous forms
o Enveloped
o (-) strand segmented RNA genome
o 8 RNA molecules spanning 13.5 kb encoding 11 proteins
o RNA-dependant RNA polymerase does not have proof reading function – gives rise to
frequent mutations (in favour of virus survival)
o Febrile, respiratory illness with systemic symptoms
o Type A
▪ Birds, mammals, humans
▪ Larger mammals who live a long time
▪ Virus subtype jumps through species (bird → pig → human; bird → human)
o Type B, C – pigs, humans
• Structure
o Genus differentiation (A, B, C) – NP,
M1 protein
o Subtype differentiation (for type A) –
HA or NA protein
o Include other possible variations
affecting any genes (= increase
pathogenicity)
o Designation; Type, isolation, HA/NA
composition
, ▪ E.g., A/ Brisbane/ 59/ 2007 (H1N1)
o Heterogeneity driven by evolutionary pressures to avoid immune detection (proteins
change)
• Lifecycle
o Entry into host cell with receptor-mediated endocytosis
▪ Sialic acid glycosylates receptor to bind virus
▪ HA protein
▪ Endocytosis is active process
▪ Endosomal membrane fusion with viral lipid bilayer
o Virus genome released from endosome for transcription and replication in nucleus
without
o RNA dependant RNA polymerase with proofreading function = high mutation rate
o Non-structural viral proteins synthesised which influence host cell processes
▪ Degrade mRNA
▪ Inhibit translation of host mRNA
▪ Delay apoptosis of host cell
o Virus is bound on sialic acids on host proteins
o Release from host proteins requires NA which cleaves sialic acid
o Maturation (budding) – HA processing by trypsin-like proteases
▪ Proteases only found in respiratory tract of humans so Influenzavirus only replicates
here (droplet infection)
▪ In birds, proteases found in gut so Influenzavirus replicates there and infects gut of
birds (transmission through bird faeces)
• Function of HA protein
o Cell attachment, fusion
o Tissue specific processing – viral spread in respiratory epithelium
o Subtypes – H1-H15 (birds), H1-3, 5 (humans)
o Posttranslational modifications influence cell tropism and pathogenesis
▪ Cell tropism – where/what is infected
• Lower tract (alveoli epithelium)
• Upper tract (nose)
o Neutralisation prevents infection
o Variability to avoid antibodies – variability within strains due to mutations
o Human Influenzavirus infects lower respiratory tract due to tropism determined by changes
in HA proteins (posttranslational changes)
o Proteolytic cleavage of HA
▪ Processing of NA necessary for membrane fusion and IAV escape from endosome
HA
▪ Occurs in airways
• Function of NA protein
o Cellular release of virions
o An enzyme
Influenzavirus
Virus Disease Seroypes Lifelong immunity Length of infection
Influenza A Influenza (severe) Many No Acute disease ‘hit
and run’
Influenza B Influenza Many (less No
diverse)
Influenza C Influenza (mild) Many No
Adenovirus Pharyngitis/pneumonia Many No Acute disease and
(mild) latency/persistent
infection
• Influenza A and B are more severe, influenza C is mild
• Adenovirus focuses on upper respiratory tract, influenzavirus focuses on lower respiratory tract
• ‘Hit and run’ – influenzavirus, acute disease, virus used host to replicate then moves
• Adenovirus confers acute disease but persists in host (so not hit and run)
• Baltimore classification system
o Classification depends on how virus replicates
▪ (+) strand – RNA replicated directly
▪ (-) strand – RNA transcribed to (+) strand then replicated
o Influenzavirus is group 5 of Baltimore classification – (-) ssRNA
o Influenzavirus has a segmented genome
▪ Viruses with segmented genomes, viral RNA-dependant RNA polymerase produces
monocistronic mRNAs from each genome segment
▪ Cistron – segment of DNA that contains all information necessary to produce a single
polypeptide and included structural and regulatory sequences
• Orthomyxoviruses
o Influenzavirus is part of orthomyxovirus family
o Pleomorphic – spherical and filamentous forms
o Enveloped
o (-) strand segmented RNA genome
o 8 RNA molecules spanning 13.5 kb encoding 11 proteins
o RNA-dependant RNA polymerase does not have proof reading function – gives rise to
frequent mutations (in favour of virus survival)
o Febrile, respiratory illness with systemic symptoms
o Type A
▪ Birds, mammals, humans
▪ Larger mammals who live a long time
▪ Virus subtype jumps through species (bird → pig → human; bird → human)
o Type B, C – pigs, humans
• Structure
o Genus differentiation (A, B, C) – NP,
M1 protein
o Subtype differentiation (for type A) –
HA or NA protein
o Include other possible variations
affecting any genes (= increase
pathogenicity)
o Designation; Type, isolation, HA/NA
composition
, ▪ E.g., A/ Brisbane/ 59/ 2007 (H1N1)
o Heterogeneity driven by evolutionary pressures to avoid immune detection (proteins
change)
• Lifecycle
o Entry into host cell with receptor-mediated endocytosis
▪ Sialic acid glycosylates receptor to bind virus
▪ HA protein
▪ Endocytosis is active process
▪ Endosomal membrane fusion with viral lipid bilayer
o Virus genome released from endosome for transcription and replication in nucleus
without
o RNA dependant RNA polymerase with proofreading function = high mutation rate
o Non-structural viral proteins synthesised which influence host cell processes
▪ Degrade mRNA
▪ Inhibit translation of host mRNA
▪ Delay apoptosis of host cell
o Virus is bound on sialic acids on host proteins
o Release from host proteins requires NA which cleaves sialic acid
o Maturation (budding) – HA processing by trypsin-like proteases
▪ Proteases only found in respiratory tract of humans so Influenzavirus only replicates
here (droplet infection)
▪ In birds, proteases found in gut so Influenzavirus replicates there and infects gut of
birds (transmission through bird faeces)
• Function of HA protein
o Cell attachment, fusion
o Tissue specific processing – viral spread in respiratory epithelium
o Subtypes – H1-H15 (birds), H1-3, 5 (humans)
o Posttranslational modifications influence cell tropism and pathogenesis
▪ Cell tropism – where/what is infected
• Lower tract (alveoli epithelium)
• Upper tract (nose)
o Neutralisation prevents infection
o Variability to avoid antibodies – variability within strains due to mutations
o Human Influenzavirus infects lower respiratory tract due to tropism determined by changes
in HA proteins (posttranslational changes)
o Proteolytic cleavage of HA
▪ Processing of NA necessary for membrane fusion and IAV escape from endosome
HA
▪ Occurs in airways
• Function of NA protein
o Cellular release of virions
o An enzyme
