Influenza

What the different types of Influenza and what do they infect?

Influenza A → Humans and animals (e.g. birds, pigs)

Influenza B → Humans only

Influenza C → Humans and pigs

Which Influenza has pandemic potential?

Influenza A

Which Influenza causes seasonal epidemics?

Influenza A

Influenza B

Which Infleunza undergoes Antigenic shift and drift?

• Influenza A

Which influenza undergoes drift?

Influenza B and C

What type of virus is Influenza?

• (-) ssRNA Segmented

• Enveloped

• HA and NA

What cells does Influenza infect?

• Ciliated epithelial cells

• Goblet cells

• Alveolar cells (Lower respiratory tract)

What receptors do different Influenza strains target?

Human strains → alpha-2,6-linked sialic acid

Avian strains → alpha-2,3- linked sialic acid

What are more severe cases of Influenza due to?

• Infection of the lower respiratory tract

What are milder cases of Influenza linked to?

• Infection of upper respiratory tract

What is the role of Hemagglutinin?

• Binds to host sialic acid residues

• Mediates cell entry and endosomal fusion, releasing viral RNA

What is the role of Neuraminidase?

Cleaves sialic acid residues allowing viral release

What drug can block Neurimindase?

Tamiflu

What viral proteins contribute to pathogenicity?

• NS1

• PB1-F2

What does NS1 do?

Impairs host antiviral/IFN responses

• Prevents dsRNA-mediated activation of NF-kB and IRF 3 activation

• Binds to viral sensors RIG-I

• Binds to dsRNA, preventing detection

What does PB1-F2 do?

Induces apoptosis and enhance inflammation

What strains are of concern?

Highly pathogenic avian influenza virus

• H5N1 and H7N9

What sort of immune response correlates with protection?

Early activation of innate immunity

• Detection via TLRs 7/8, RIG-I and NLRP3

• Secretion of IFNs and proinflammatory cytokines

• NLRP3 induces pyroptosis in infected cells

What greatly influences the severity of Influenza

Hyperactive dysregulated prolonged pro-inflamation

• High viral load due to inadequate initial control and replication leads to hyperactive inflammatory responses

• Excessive levels of IL-6, TNF-a, IL-1b and IFN-g (cytokine storm)

• Greater M1 polariziation and less M2 macrophage to terminate inflammation

• Overreactive Cd8+ T cells

How did the 2009 swine flu pandemic strain arise?

Genetic reassortment/Antigenic shift → Quadrouple reassortment of 8 gene segments

• North American Swine

• North American Avian

• Human Influenza

• Eurasian swine

How is Influenza survaillance?

• Next generation sequencing of genomes

• Phylogenetic tracking

Importance of Influenza survaillance?

• Detection of pandemic strains - live poultry surviallance via PCR, detecting presence before human cases

• Monitor viral evolution

• Monitoring avian flu outbreaks - H5N1, H7N9

• inform vaccine strain design

• Antiviral resistance markers

How did genomics aid in understanding the emergence of HPAI in China?

• Viral genomic surviallance Found HPAI (H7N9) spread from poultry markets in china and where the main source of H7N9 infection in 2013

• They found the H7N9 virus originated in wild waterbirds, that were transmitted to domestcic ducks → Chickens that acquired new genes

• The H7N9 strain spread rapidly in China and spilled over into human pop.

• Resulting H7N9 outbreaks in china have shown the virus to increasingly be genetically diverse due to viral mutations and reassortment → H7N9 & H9N2 co-circulating in live poultry markets

How many cases are there of seasonal Influenza?

1 Billion

How many cases of Influenza are severe and lead to death?

• 3-6mill cases per year

• 300,000-650,000 deaths per year

What is the mortality rate of HPAI?

50%