Influenza A
Explain how mutation and reassortment can result in the emergence of Influenza A
viruses.
Describe and discuss the role of the Haemagglutinin in host adaptation, providing examples of host and virus determinants that are important in influenza host-switching.
Essay Plan:
Influenza A: The virus itneslt is a negative sense ssRNA with 8 segments: PB1, PB2, PA, HA, NP, HA, M, NS, translating to more than 14 proteins. With a viral coat having 2 major glycoprotiens the haemagglutinin (HA) - mediates cell entry through binding to sialic acid and is a host-range determinant, and is also the main target of neutralising antibodies neuraminidase (NA), there are currently known to be 18HA subtypes and 11NA subtypes.
Context of Influenza - Influenza A: It was the cause of the great Spanish Flu pandemic of 1918 causing the death of around 50 million individuals. The virus and its subtype H1N1 was established using reverse genetics using viral particles found from preserved samples from infected soldiers and origin has been hypothesised to be of avian origin due to similarity with avian viruses. Mortality resulted from secondary bacterial pneumonia.
Influenza is an RNA virus and RNA-dependant-RNA replication does not proof read so typically 1 mutation per 1000bp. Influenza genome in around 14kb.
ANTIGENIC DRIFT - non-synonymous mutations at the antigenic sites (HA/NA) - changing antigenicity. - SEASONAL epidemics.
Re-ASSORTMENT- ANTIGENIC SHIFT. When two subtypes of virus infect same cell, there is increased possibility of shift between the the antigenic site (NA/HA) and thus have a greater chance of evasion of immune response, due to naivety to the new virus - increased probability of pandemic,
Currently - seasonal epidemics/winter mortality - difficult to vaccinate against the correct strain. Expert committee in Geneva choose through studying the previous season epidemics.
The natural reservoirs of the Influenza is thought to be wild water fowl. 16 HA and 9NA isolated from wild water fowl.
Following the 1918-1919 pandemic there have been other less pervasive pandemics including the H5N1 pandemic coming from Avian origin and was a spillover event as so far is not transmittable between humans, though work has been carried out in ferrets (which are the gold standard of virological animal models) in which 5 mutations caused ferret-to-ferret transmission (Herfst et al., 2012)
1957- H2N2 - REASSORTMENT Atigenic Shift involving both antigenic glycoportien region of the genome.
1968 - H3N2 - Haemagglutanin antigenic shift
Pandemic of 2009 which saw H1N1 swine origin - pigs are intermediate hosts - RE-EMERGENCE
? Naive population as generation with H1N1 immunity has passed away
before the 2009 pandemic - the school of the thought had been new pandemic required new subtypes
H3N8 Canine influenza - equine virus which zoonotically jumped to dogs
Influenza infecting a new host species...possibility to become intermediate host - a stepping stone to infect another new species.
In the early 2000s an influenza-like virus was seen in dogs, and when particle were isolated and the genome was sequenced it was identical to the H3N8 equine influenza virus. I order to established whether ecology or evolution of EIV played a major role in this zoonotic incident.
Isolating the canine influenza virus and testing on canine bronchial explants was able to establish the pathophysiology of the infection. Using microbeads on the cilliated epithelial cell, and comparing between control and infected ex-vivo organ showed a loss of the cilliary sweeping action. Anti-NP (viral protein) showed viral infiltration with ex-plant infected with CIV, along with an increase of apoptosis visualised with anti-caspase. Once CIV infection pathology was established old EIV versus new EIV was tested on the ex-vivo organ sample, which clearly showed no significant difference between old EIV and the control explant. Which points towards an evolutionary basis for the cross-species jump between horses and dog, (Gonzalez, 2014).
Describe and discuss the role of the Haemagglutinin in host adaptation, providing examples of host and virus determinants that are important in influenza host-switching.
Essay Plan:
Influenza A: The virus itneslt is a negative sense ssRNA with 8 segments: PB1, PB2, PA, HA, NP, HA, M, NS, translating to more than 14 proteins. With a viral coat having 2 major glycoprotiens the haemagglutinin (HA) - mediates cell entry through binding to sialic acid and is a host-range determinant, and is also the main target of neutralising antibodies neuraminidase (NA), there are currently known to be 18HA subtypes and 11NA subtypes.
Context of Influenza - Influenza A: It was the cause of the great Spanish Flu pandemic of 1918 causing the death of around 50 million individuals. The virus and its subtype H1N1 was established using reverse genetics using viral particles found from preserved samples from infected soldiers and origin has been hypothesised to be of avian origin due to similarity with avian viruses. Mortality resulted from secondary bacterial pneumonia.
Influenza is an RNA virus and RNA-dependant-RNA replication does not proof read so typically 1 mutation per 1000bp. Influenza genome in around 14kb.
ANTIGENIC DRIFT - non-synonymous mutations at the antigenic sites (HA/NA) - changing antigenicity. - SEASONAL epidemics.
Re-ASSORTMENT- ANTIGENIC SHIFT. When two subtypes of virus infect same cell, there is increased possibility of shift between the the antigenic site (NA/HA) and thus have a greater chance of evasion of immune response, due to naivety to the new virus - increased probability of pandemic,
Currently - seasonal epidemics/winter mortality - difficult to vaccinate against the correct strain. Expert committee in Geneva choose through studying the previous season epidemics.
The natural reservoirs of the Influenza is thought to be wild water fowl. 16 HA and 9NA isolated from wild water fowl.
Following the 1918-1919 pandemic there have been other less pervasive pandemics including the H5N1 pandemic coming from Avian origin and was a spillover event as so far is not transmittable between humans, though work has been carried out in ferrets (which are the gold standard of virological animal models) in which 5 mutations caused ferret-to-ferret transmission (Herfst et al., 2012)
1957- H2N2 - REASSORTMENT Atigenic Shift involving both antigenic glycoportien region of the genome.
1968 - H3N2 - Haemagglutanin antigenic shift
Pandemic of 2009 which saw H1N1 swine origin - pigs are intermediate hosts - RE-EMERGENCE
? Naive population as generation with H1N1 immunity has passed away
before the 2009 pandemic - the school of the thought had been new pandemic required new subtypes
H3N8 Canine influenza - equine virus which zoonotically jumped to dogs
Influenza infecting a new host species...possibility to become intermediate host - a stepping stone to infect another new species.
In the early 2000s an influenza-like virus was seen in dogs, and when particle were isolated and the genome was sequenced it was identical to the H3N8 equine influenza virus. I order to established whether ecology or evolution of EIV played a major role in this zoonotic incident.
Isolating the canine influenza virus and testing on canine bronchial explants was able to establish the pathophysiology of the infection. Using microbeads on the cilliated epithelial cell, and comparing between control and infected ex-vivo organ showed a loss of the cilliary sweeping action. Anti-NP (viral protein) showed viral infiltration with ex-plant infected with CIV, along with an increase of apoptosis visualised with anti-caspase. Once CIV infection pathology was established old EIV versus new EIV was tested on the ex-vivo organ sample, which clearly showed no significant difference between old EIV and the control explant. Which points towards an evolutionary basis for the cross-species jump between horses and dog, (Gonzalez, 2014).
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