Influenza virus Flashcards
What is influenza?
- Respiratory disease in humans, horses and swine (and other mammals)
- Enteric disease in birds
Location: - Replicates in upper respiratory tract in humans
- Replicates in the intestines and respiratory tract in birds
Host: - Reservoir host is in birds
- Human, horses, dogs and swine (and bats)
- Newly pathogenic strains emerge (increased tropism and jump species)
What type of genome does influenza have?
Member of the Orthomyxoviridae family
Enveloped virus (80-120 nm)
Negative-sense, ss, RNA genome
Segmented RNA genome (8)
* Helical nucleocapsid
* Most segments codes for a single protein (mostly!)
* Haemagglutinin (HA) spike
* Neuraminidase (NA) spike
Describe influenza’s life cycle?
Virus replication occurs in the nucleus:
* Viral mRNA need to be capped at
their 5’ end (5’C)
* Some viral mRNAs are spliced
- Neuraminidase aids release of the virus from the cell
- Spreads to other cells in the upper respiratory tract
- Virus normally remains localised in the respiratory tract
Steps of influenza life cycle?
(1) virus attachment to sialic acid receptor via HA; (2) entry of the virus into the host cell via endocytosis; (3) fusion and uncoating of virus particle; (4) Viral ribonucleoproteins (vRNPs) entry into the nucleus followed by transcription and replication of the viral RNA genome and then export of vRNPs from the nucleus; (5) assembly of viral components and budding at the host cell membrane; (6) new virion release from the host cell.
How are influenza viruses able to evolve so rapidly?
− Antigenic shift
* Complete change in subtype of HA or NA
* Change in HA can result in pandemics
− Antigenic drift
* Variation within the HA or NA subtype
* Drift in HA or NA results in epidemics and more rarely pandemics
* Can also allow influenza to “jump” species
* Can cause changes in virulence /tissue tropism (as seen with Avian influenza H5 and H7 subtypes)
This allows the virus to change species specificity and change virulence.
What is reassortment/antigenic shift?
- Complete change in HA type
- Virus acquires a 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
- Population are immunologically “naïve”
- Host immune system has not seen this
gene before - No protection
What is antigenic drift?
- Minor variations in the sequence of HA and NA genes
- Caused by mutation
- Causes epidemics
- Produce viruses with slightly different amino acid compositions
- Some may grow better in a particular host than others
- Gradual accumulation of antigenic mutations
What can antigenic drift cause?
-changes in host (species specificity)
-change in tropism
What is the haemagglutinin protein?
Most abundant protein on the viral surface and is the main target of immune response
- Receptor binding site:
* Allows virus to bind to sialic acid on host cells
* Enables virus internalisation (within endosome)
- 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
* How well HA is cleaved by cellular proteases facilitates virus entry
What happens when HA protein changes sequence?
Changes in sequence at the receptor binding site and cleavage sites can allow influenza viruses to change species specificity and cell tropism
How does influenza enter?
- HA binds to sialic acid groups on membrane bound proteins on the cell surface
- Virus enters by receptor mediated endocytosis
- Acidic pH inside the endosome, causes a conformational change in HA which exposes a fusion domain which promotes fusion of viral and endosomal membranes
- Viral nucleocapsids to be released into the cytoplasm
High vs low pathogenic avian influenza?
Mutations that lead to changes in cell tropism leads to increase pathogenicity.
If virus infects domestic birds, it can occasionally develop into a highly rapidly fatal disease or High Pathogenic Avian
Influenza.
All pathogenic forms are caused by H5 and H7. Goes from being an enteric virus to affecting every cell in the body.
How can HA protein cleavage by cellular proteases lead to changes in cell tropism?
Low pathogenic: HA1 and HA2 linked by single arginine residue; cleaved by few cellular proteases in small number of cell types -> influenza can only replicate in a few cell types
High pathogenic: insertional mutations add basic residues at HA cleavage site; HA1 and HA2 linked by several aa residues -> cleaved by proteases in all cell types so virus can replicate throughout birds body
Sialic acid receptor types?
Siaα2,6Gal: Recognised by HA of avian influenza. Present in the human upper respiratory tract, therefore human viruses can enter and cause infection
Siaα2,3Gal: Recognised by HA of human influenza. Present in the human lower respiratory tract, therefore avian viruses can enter and cause infection (but only when in close contact with avian viruses)
What are the differences in pathogenicity of H1 and H5 types?
H1N1: easily spread and rarely fatal
H5N1: spreads slowly and often fatal
