Influenza Flashcards
Payload of a virus
- contains the genome and enzymes necessary to initiate the first step in virus replication
Influenza overview
- Flu is an acute viral infection of the respiratory tract (nose, mouth, throat, bronchial tubes and lungs)
- 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
what type of viruses are influenza viruses
orthomyxoviruses
orthomyxoviruses
- Spherical
- Enveloped
- Segmented, negative strand RNA genome
influenza genes
negative strand RNA genome
8 genes encoding 11 proteins, including 11 proteins including 3 RNA polymerases (high error rates)
what are the two surface antigens
Haemagglutinin and Neuraminidase
Haemagglutinin (H)- 18 types
Binds to the cell of the infected person
Neuraminidase (N)
types of influenza
Influenza A virus
Influenza B virus
Influenza C virus
Influenza A viruses
- Causes outbreaks most years and are the usual cause of epidemics and pandemics
- Live and multiply in many different animals and may spread between them
Influenza A: Natural host range
- Birds particularly wildfowls
- Swine
- Equine
- Marine mammals
Influenza A: Epidemiology
Antigenic shift and drift
Influenza B viruses
Tends to cause less severe disease and smaller outbreaks
Influenza B: natural host
Predominantly found in humans
influenza B: burden of disease
mainly children
influenza B: epidemiology
- Antigenic drift only
- 2 lineages cocirculate
Influenzas C
Mild disease without seasonality
Influenza C: Natural host range
- Humans
- Swine
Influenza C: epidemiology
- Antigen drift only
- Multiple variants
replication of the influenza virus
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
- Small particle aerosols (<10um mass diameter)- remain suspended in air for many hours
- Larger particles or droplets will typically fall to the grounding within 3m of the infected persons- direct contact
- Viral particles could land on surfaces where influenzas viruses remain infectious- infect others through indirect contact
Barriers to entry via the respiratory route
- Respiratory epithelial cells are covered by a thick glycocalyx and tracheobronchial mucus that can trap particles
- Ciliated resp epithelial cells continually sweep mucus up from the lower resp tract into the upper respiratory tract where it is swallowed
- In the lung- immunologic defences
- Include secretory igA
- NK cells
- macrophages
So how does the virus enter cells?
Haemaglutinin binds to Neu5Ac (NANA) residues – sialic acid on a glycoprotein/glycolipid which acts as a receptor for influenza virus
entry via receptor mediated endocytosis
So how does the virus leave the cell?
Neuraminidase comes along and cleaves sialic acidà then able to leave the cell and infect cell
MSK symptoms of influenza
- Myalgia- muscle ache
- fatigues
neurological symptoms of influenza
- Fever
- Confusion
- Serious: meningitis- rare
respiratory symptoms
- Dry cough
- Sore throat
- Nasal congestion
- Serious: otitis media and croup
GI symptoms
- Nausea
- Vomiting
- Diarrhoea
overview of symptoms fo influenza
diagnostic test?
Mostly done on history and not formal test (bar those in hospital)
- Antigen detection- rapid diagnostic test
- RT-PCR
treatment
- antivirals
- neurominidase inhibitors
antivirals
-
Antivirals (used less now)
- E.g. rimantadine and amantadine
- Which inhibit viral uncoating after uptake probably through M2 protein influenzas A
- E.g. rimantadine and amantadine
Neuraminidase inhibitors
- Oseltamivir (Tamiflu), Zanamivir (relenza)
- Inhibits viral release from infected cells and cause aggregation of viral particles
prevention
- Formalin-inactivated vaccine (quadrivalent/ trivalent) by injection of influenza A and B
- Live, attenuated, cold-adapted vaccine (quadrivalent) by nasal spray influenza A and B (children)
Time course of influenza A virus infection
- Incubation period of 1-5 days (average 2-3 days)
- Sudden onset of fever, chills, headache, muscle/joint paint, extreme fatigue, dry clough sore throat and stuffy nose
Risk factors for complications of influenza
- Child under 6 months
- Older people
- Those with underlying health conditions such as resp, cardiac diseases and long term neurological conditions or immune suppression
- Pregnant women
- Morbid obesity (BMI >40)
Genetic changes in the influenzas virus
- Viral RNA polymerases have a high error rate
- High error rate and lack of proofreading ability ability leads to mutations
- Genetic variation and resistance
- Surface antigens haemagglutinin and neuraminidase
- antigenic drigt and shift
Antigenic drift
involves point mutation in the hemagglutinin and/or neuraminidase genes- encoding envelope glycoproteins, thus reducing the binding affinity of antibodies raised against previous strains. This is why individuals can become reinfected with influenza and why the content of seasonal vaccines must be altered annually.
Antigenic shift
is the genetic reassortment of genome segments between animal and human strains leading to the expression of novel hemagglutinin subtypes- essentially creating new virus’ to which pre-existing immunity exists e.g. Spanish flu.
Dramatic changes in antigenic properties of the H and/or N proteins
- Occurs infrequently – maybe every 10 or 20 year
- Only influenza type A show antigenic shift
explain antigenic shift
- influenza type A viruses in many animals, including horses, pigs, and wild migrating waterfowl.
- 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
- In environments where pigs, birds and humans coexist, it is possible for a pig to be simultaneously infected with multiple influenza subtypes.
- “Reassortants” can, therefore, be produced within one host animal (the pig), in which the mRNAs encoding the H and N antigens have been reassorted into unique combinations.
- The reassortant virus then has the potential to spread among humans, birds, and pigs.
Consequence of antigenic shift
- New subtype of influenza virus
- May not have been seen in circulation in population for many year
- Immune systems of many indiivduals 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 – often the world
Occurrence of major outbreaks of type A influenza
4 pandemics in past 100 years:
- 1918 H1N1, from seasonal human and avian (bird) flu
- 1957 H2N2, from human and avian reassortment
- 1968 H3N2 human and avian components
- 2009 novel H1N1 contains genes from a combination of human, swine, and avian reassortment.
key characteristic of a pandemic e.g. the spanish flu
waves
How does the flu actually kill people
Symptoms= the body’s immune response to viral invasion
- Antibodies triggered and immune cells move to site of infection
- Release of cytokines leading to local inflammation
HOWEVER..
- The immune system may ‘overreact’- T cells attack and destroy the tissues in which the virus is replicating- particularly the lungs
- There is an opportunistic secondary infection i.e. bacterial (streptococcus or staphylococcus species)- usually in the lungs
