virus 5

• Influenza - • Respiratory disease - Enteric disease in birds
• Influenza =  Replicates in upper respiratory tract in humans 
• Influenza = • Replicates in the intestines and respiratory tract in birds
• Influenza

   Reservoir host is in birds 

  • Human, horses, dogs and swine (and bats)

   • Newly pathogenic strains emerge (increased tropism and jump species)
• Influenza virus structure:

  Membrane/Lipid Bilayer: Surrounding the virus particle, composed of lipids with embedded proteins

  Haemagglutinin (HA) and Neuraminidase (NA) Spikes: viral entry

  Matrix Layer: m protein

  Ion Channel Protein

  Nucleic Acids: Located within the virus particle, comprising RNA segments.

  Nucleocapsid Proteins: Surrounding each RNA segment, protecting and stabilizing the genetic material.
• Influenza viruses

  • Segmented RNA genome (8) 

  • Helical nucleocapsid capsid

   • Most segments codes for a single protein (mostly!) 

  • Haemagglutinin (HA) spike

  • Neuraminidase (NA) spike
• influenza = enveloped ad negative sense and ss RNA
• So the HAEMAGGLUTININ protein and the new neuraminidase protein contain type specific antigens.
• HAEMAGGLUTININ protein = 8 H types
• neuraminidase protein= 11 N types
• spike proteins on influenza = type specific antigens. 18 H types and 11 N types
• Birds have all...influenza subtypes
• H5& 7 = can become highly pathogenic
• • The virus attaches to host cells via the Haemagglutinin (H) protein, binding to sialic acid receptors.
  • Entry occurs through receptor-mediated endocytosis.
• • Within the endosome, the low pH triggers a conformational change in the H protein, facilitating fusion with the endosomal membrane.
  • This allows the release of viral nucleocapsids into the cytoplasm.
• Replication in the Nucleus:

  • Viral nucleic acids enter the nucleus for replication.
  • In the nucleus, the virus utilizes host cell machinery for transcription and replication.
  • It requires specific nuclear components like the five prime cap and splicing enzymes for mRNA production.
• Protein Synthesis:

  • Newly synthesized mRNA migrates to the cytoplasm and undergoes translation at ribosomes.
  • Protein synthesis occurs, leading to the production of viral proteins.
• Assembly and Budding:

  • Viral proteins and nucleocapsids migrate to the cell surface.
  • Nuclear capsids are recognized by envelope proteins embedded in the cell membrane.
  • Budding of new virus particles occurs, where the viral envelope fuses with the cell membrane, releasing mature virions.
• Neuraminidase-Mediated Release:

  • Neuraminidase (NA) cleaves sialic acid residues on the host cell surface.
  • This cleavage facilitates the efficient release of newly formed virus particles from the host cell.
• life cycle = enters via receptor mediated endocytosis. virus replication occurs in nucleus using 5' cap and splicing enzymes. Neuraminidase aids release of virus from cell so it can spread to other cells
• h to get into the cell and N to get out of the cell
• influenza changes genomes / evolve via two mechanism

  • Antigenic shift
  • Antigenic drift
• − Antigenic shift 

  • Complete change in subtype of HA or NA - virus can reassortant and swap genes

  • Change in HA can result in pandemics 
•  Antigenic drift 

  • Variation within the HA or NA subtype - error rna polymerase / mutations

  • Drift in HA or NA results in epidemics

   • Can also allow influenza to “jump” species 

  • Can cause changes in virulence /tissue tropism
• influence evolves to allows change speeises and virulence
• Reassortment / Antigenic Shift

  • Complete change in HA type 

  • different HA type from a different species as a result of re - assortment of the viral segments

   • Pigs generally act as mixing vessels as they can be infected with both human and avian viruses 

  • Causes Pandemics

   • immunologically “naïve” 

  • No protection
• pandemics happen because..due to antigenic shift our bodies do not have existing immunity against the new strains allowing it to spread rapidly.
• pandemics happen because..due to antigenic shift our bodies do not have existing immunity against the new strains allowing it to spread rapidly.
• antigenic shift = complete change in subtype of HA or NA. change in HA can cause pandemics. cells affected with 2 different strains yield a new strain (normally in swine as they can get human and avian types). reassortment of viral segments
• Antigenic Drift

  • Minor variations in the sequence of HA and NA genes 

  • Caused by mutation 

  • Causes epidemics
• Antigenic Drift often causes variation in spike proteins present of the viral surface
• Antigenic Drift often

   Produce viruses with slightly different amino acid compositions: 

  • Some may grow better in a particular host than others

   • Gradual accumulation of antigenic mutations 
• haemagglutination protein = most abundant protein on virus surface. binds to sialic acid on host cells. cleavage site- cleaves HA into 2 units to allow virus release from endosome and aids fusion of virus with membrane of vesicle.
•  Cleavage site 

  • Cellular proteases cleave HA into two subunits (HA1 and HA2) to allow virus release from the endosome 

   Cleavage aids fusion of the virus membrane with membrane of the vesicle

  antigenic drift = Changes in the sequence at these two sites can allow influenza viruses to change species specificity and cell tropism
• Entry of Influenza

  1. Attachment: HA binds to sialic acid groups on membrane bound proteins on the cell surface 
  2. Entry Virus enters by receptor mediated endocytosis
  3. Release from endosome a) Acidic pH inside the endosome, causes a conformational change in HA which exposes a fusion domain which promotes fusion of viral and endosomal membranes b) Viral nucleocapsids to be released into the cytoplasm
• Amino acid changes caused by Antigenic Drift Changes can lead to:

   • Change in host (species specificity) 

  • Change in tropism
• Low Pathogenic Avian Influenza 

  • Causes a wide range of symptoms in wild birds

   • Generally a mild illness

   • If the virus infects domestic birds, it can occasionally develop into a highly rapidly fatal disease or High Pathogenic Avian Influenza
• Highly pathogenic Avian influenza (fowl plague) 

  • Results in severe epidemics

   • Severe illness

   • Rapid death

  • Mortality can be up to 100% 

  • All pathogenic forms are caused by H5 and H7

   • infects every cell in the bird’s body
• → low pathogenic avian influenza

   HA1 and HA2 Cleaved by a few cellular proteases found in a limited subset of cells therefore limited spread
• Highly Pathogenic avian influenza

  → • Insertional mutations add basic residues at HA cleavage site

  HA1 and HA2

  Cleaved by all expressed cellular proteases cleaved by more protease all around the body accesses to very cell