Influenza And Virology Flashcards
viruses
Viruses are simple structures consisting of a delivery system and a payload.
The delivery system of a virus protects it against degradation in the environment and contains structures used to bind to target cells in the host.
The payload of a virus contains the genome and enzymes necessary to initiate the first steps in virus replication
Influenza overview
flu is an acute viral infection of the respiratory tract (nose, mouth, throat, bronchial tubes and
lungs)
it is a highly infectious illness which spreads rapidly in closed communities
even people with mild or no symptoms can infect others
most cases in the UK occur during an 8 to 10 week period during the winter
Structure of the influenza virus
Orthomyxoviruses are spherical, enveloped viruses containing a segmented, negative strand RNA genome
Genetic material:
negative sense single stranded RNA (ssRNA)
Types of influenza viruses
Antigenic drift - essentially the 2 surface antigens can undergo small mutations but this means that our antigens in the body don’t recognise them as well
C virus - not seasonal but not potent - not too worried about it
A virus - cause outbreaks most years and are the usually cause of epidemics and pandemics - live and multiply in many different animals and may spread between them - birds particularly wildfowl, are the main animal reservoir (can fly to other countries)
B virus - tend to cause less severe disease and smaller outbreaks - predominantly found in humans - burden of disease is mostly in children
Replication of the influenza virus
A single stranded piece of RNA
It’s negative sense which means when it gets into the human host - on its own its not infective
It’s needs to be transcribed into positive sense RNA - which can then be translated into more negative ssRNA
At the same time the original ssRNA is going to be generating mRNAs
Both actions are done via a RNA-dependent RNA polymerase (provided by the infecting virus) (RdRp)
Some of the mRNA will be converted into viral proteins - this plus
the newly produced -ve ssRNA will be assembled together to produce nucleocapsids
These can leave the host cell and spread to other host cells or be spread to another person
Transmission of the influenza virus
Influenza viruses are transmitted from person to person via the respiratory route (coughing, sneezing, inhaling)
Three potential modes of transmission:
1) small-particle aerosols (<10 μm mass diameter) - remain suspended in air for many hours
2) larger particles or droplets will typically fall to the ground within 3 m of the infected person - infect individuals in direct contact.
3) viral particles could land on surfaces, where influenza viruses remain infectious - infect others through indirect contact.
Barriers to entry via the respiratory route:
1) Respiratory epithelial cells are covered by a thick glycocalyx and tracheobronchial mucus that can trap virus particles.
2) Ciliated respiratory epithelial cells continually sweep mucus up from the lower respiratory tract into the upper respiratory tract, where it is usually swallowed.
3) In the lung, immunologic defenses include secretory IgA, natural killer (NK) cells, and macrophages.
How does virus enter cells
How does the virus leave the cells
Influenza virus particle has its Hemagglutinin protein on the surface
Senses on a cell that it has a host glycoproteins/glycolipid receptor - which can act as a receptor for this flu virus
Then entry occurs via receptor mediated endocytosis, so entering the cell
When a vesicle is budding off an infected cell it still contains on the outside of it the Hemagglutinin and the Neuraminidase
Hemagglutinin binds to the glycoproteins on the cell surface preventing the newly budded off cell from leaving
Neuraminidase cleaves between skaldic acid and galactose on the glycoprotein that is bound to the Hemagglutinin allowing the newly produced virus cell to leave and infect another cell
Symptoms and complications of influenza
Neurological symptoms - Fever, headache and confusion
Respiratory symptoms - dry cough, sore throat and nasal congestion
GI symptoms - nausea, vomiting and diarrhoea
MSK symptoms - fatigue and myalgia
Commonly in kids complications could be - Otitis media and croup in lungs and febrile convulsions and Reye’s syndrome in the brain
Time course of influenza A virus infection
incubation period 1-5 days (average 2-3 days)
people with mild or no symptoms can still infect others
sudden onset of fever, chills, headache, muscle/joint pain, extreme fatigue, dry cough, sore throat, stuffy nose
Possible complications of influenza
Risk of most serious complications is higher in:
Diagnosis and treatment of influenza
Just need to know that there are different types of test that can be done: - usually don’t do a test - do it by analysing symptoms and clinical assessment
Sample from a nasopharyngeal swab - from this can do anyone of the following - rapid influenza diagnostic test, a rapid molecular assay, immunofluoresence, PCT, rapid cell culture and viral tissue culture
Treatments for influenza:
1) Anti virals - e.g. rimantadine and amantadine - which inhibit viral uncoating after uptake through the M2 protein - e.g. in influenza A- not really used much due to resistance
2) Neuraminidase inhibitors - e.g. Oseltamivir (Tamiflu), and Relenza - which inhibit viral realise from the infected cell an cause aggregation of viral particles - treats influenza A and B
3) Prevention -
a. formalin-inactivated vaccine (quadrivalent/trivalent) by injection influenza A & B
b. live, attenuated, cold-adapted vaccine (quadrivalent) by nasal spray influenza A & B
Neuraminidase inhibitors - The virus can no longer cleave sialic acid from the glycoprotein receptor present on the host cell, therefore the new budding virus cell cant leave the host cell, therefore cant spread to other people or other cells in the host - the infected cell ends up being destroyed by bodies immune system
Genetic changes in the influenza virus
The flu virus is constantly replicating
Life cycle of approximately 6 hours
Viral RNA polymerases have a high error rate
High error rate & lack of proofreading ability leads to mutations + accumulation of mutations
This can lead to genetic variation and resistance
Surface antigens hemagglutinin & neuraminidase are key as its what the immune system sees - its what we raise our antibodies against
This is called antigenic drift
These changes are only seen in the influenza A virus - Dramatic changes in the antigenic properties of the H and/or N proteins
Occurs infrequently - maybe every 10 or 20 years
Only influenza type A viruses show antigenic shift
Change in subtype, e.g., from H1N1 to H3N2
Surface antigens hemagglutinin & neuraminidase from different species (pigs birds etc)
Anti genetic drift
minor changes (natural mutations) in the genes of flu viruses that occur gradually over time -
How does this major anti genetic drift (reassortment) occur?
a) influenza type A viruses in many animals, including horses, pigs, and wild migrating waterfowl.
b) reassortment can occur between influenza A viruses that infect different animal and avian species, e.g., pigs can be infected by human- and avian-specific influenza viruses
c) In environments where pigs, birds and humans coexist, it is possible for a pig to be simultaneously infected with multiple influenza subtypes.
d)
Consequences of antigenetic shift
Antigenic shift leads to a new subtype of influenza virus
May not have been seen in circulation in population for many years
Immune systems of many individuals have no defence against this new subtype
Epidemic - Prevalent among a people or a community at a special time, and produced by some special causes not generally present in the affected locality
Pandemic - epidemic over a very large area; affecting a large proportion of - a population
