Influenza Flashcards
What are viruses?
Simple structures
Delivery and Payload system
Delivery system protects virus and binds to target cells
Payload contains genome and enzymes needed to initiate replication
Influenza summary
Infection of respiratory tract (nose, mouth, throat, bronchial tubes and lungs) Highly infectious (closed communities especially) Most 8-10 week period in winter
Structure influenza
Orthomyxovirus - spherical
enveloped
segmented -ve ssRNA
- 3 RNA polymerases (high error rate)
Outside structure influenza
Haemagglutinin (H) antigen - binds to cells of infected person
Neuraminidase (N) antigen - releases virus from host cell surface
1 segment of influenza =
1 polypeptide
Types of influenza and what species
A - humans, swine, equine, birds, marine mammals
B - humans
C - humans and swine
Influenza A involves
Antigenic shift AND drift
May cause large pandemics
Significant mortality for young people
Influenza B involves
Antigenic drift ONLY
Severe disease = old adults or high risk (no pandemics)
Influenza C involves
Antigenic drift ONLY
Mild disease, no seasonality
Most concern influenza type
Influenza A -
outbreaks most years
epidemics and pandemics
live and multiply in many animals (wildfowl in particular)
Second concern influenza type
Influenza B
Smaller outbreaks, less disease
Humans only
Mostly children affected
How does influenza replicate
-ve ssRNA –> +ve ssRNA
via RNA dependent RNA polymerase
–>
this produce mRNA which can make viral proteins
-ve —> +ve —> -ve produces multiple -ve ssRNA copies
these then assemble in nucleocapsid = replicated
How is influenza virus transmitted? 3 modes
Respiratory route (cough sneeze inhale)
- small particle aerosols <10micrometre (remain in air)
- larger particle/droplets
- viral particles (land on surface, indirect)
Barriers to influenza
Resp epithelium = thick glycocalyx and mucus
Trap virus particles
Ciliated epithelium sweep mucus up to be swallowed (mucociliary escalator)
Immunological defences lung
Secretory IgA
Natural killer cells
Macrophages
How does virus enter cell?
Neu5Ac (NANA) residues act as receptor for Hemagglutinin antigen on virus
Invagination of virus
into Endocytosis vesicle
release virion into cytoplasm
(RECEPTOR MEDIATED ENDOCYTOSIS)
What is a NANA residue?
Sialic acid on glycoprotein/glycolipid which acts as receptor for influenza virus
How does virus leave cells?
Hemogglutinin is already attached to NANA sialic acid receptor
Neuraminidase cleaves glycoprotein + sialic receptor NANA off and allows virus to leave
Complications of influenza
Meningitis/encephalitis
Otitis media (ear infection)
Croup (young children usually)
Pneumonia
Time course influenza
Incubation - 1-5 days
Recovery time - 2-7 days
When can virus be found in resp secretions after initial infection?
As soon as 24 hours after infection
Those at risk of serious influenza complications
Children under 6 months Older people (65+) Underlying health conditions (resp, cardiac) Pregnant women Obesity (morbid >40BMI)
Flu during pregnancy
Perinatal mortality
Prematurity
Smaller neonatal size/lower birth weight
Diagnosing infuenza
usually from symptoms and clinical assessment
BUT can do:
Rapid influenza diagnostic tests
PCR
Treatments influenza
Antivirals
Neuraminidase inhibitors
prevention: Vaccines
Antivirals example and explain
Rimantadine & Amantadine
Inhibit viral uncoating after uptake through M2 protein
for Influenza A
Neuraminidase inhibitors example and explain
Oseltamivir (Tamiflu) & Zanamivir (Relenza)
Inhibit viral release from cells (cant cleave off) and cause aggregation of particles
for influenza A AND B
Vaccines for flu
Both for Influenza A AND B:
Formalin inactivated vaccine injection (quadri/trivalent)
Live, attenuated, cold adapted vaccine NASAL SPRAY (quadrivalent, for children)
What does cold-adapted vaccine mean?
Will only stay in upper resp tract
Cannot survive in lungs as too warm
What does trivalent and quadrivalent mean?
Trivalent - contains 2 Influenza A strains and 1 B strain
Quadrivalent - contains 2 influenza A strains and 2 influenza B strains
Neuraminidase inhibitors (TAMIFLU) come from
Chinese Star anise:
Shikimic acid
Genetic changes influenza (antigenic drift)
Life cycle = 6 hours
Constantly replicating
Viral RNA polymerase =
high error rate, lack of proofreading = mutations
What happens as a result of these mutations?
Genetic resistance and variation
What is antigenic drift?
Minor changes (natural mutations) in genes of flu virus that occur gradually over time Minor antigenic changes in H and N Cause seasonal epidemics
NO VIRAL SUBTYPE CHANGE
How does antigenic drift affect vaccines?
WHO monitors epidemiology and makes recommendations about strains likely to be circulating
Results in composition of virus vaccines
How do PHE help with flu?
Send letters to GP’s with updates (strains, no. of cases) and details of WHO recommendations
Other genetic changes influenza (antigenic shift)
Dramatic changes in antigenic H and N properties Infrequent (10-20 years) ONLY Influenza A Change subtype (H1N1 --> H3N2) Surface antigens from different species
Antigenic shift defined
Major changes in genes that occur suddenly when two or more different strains combine
This results in NEW subtype
= widespread epidemics/pandemics
How can antigenic shift happen?
Influenza viruses from different species combine in same host at same time
Reassortment of RNA segments from each species into new capsid
Why can antigenic shift occur in Influenza A?
Can infect many animals - horses, pigs, waterfowl
Host infected with two different subtypes influenza (eg pig can be infected by human and avian specific viruses)
Reassortment of 2 different specie virus in one host
Has potential to spread among humans, birds and pigs
Consequences antigenic shift
New subtype not seen before
= no immunity defence
Pandemics and epidemics
Epidemic
Widespread occurrence of infectious disease in a community at particular time
Pandemic
Epidemic over a very large area; populations all over the world
Major Influenza type A outbreaks
Spanish influenza (1918 - human and avian H1N1)
Asian influenza (1957 - human and avian reassortment H2N2)
Hong kong influenza (1968 - human and avian components H3N2)
2009 Novel H1N1 (human swine and avian reassortment)
Spanish influenza truth
Was actually from Kansas
But spain only place neutral in WW1 and was able to report news on flu and not on war
Spanish flu size
50 million
more people died (1 year) than in 4 years of black death
How does flu kill people? (2 methods)
1:
Immune system overreacts
T cells attack and destroy tissue of virus - particularly lungs
2: Opportunistic secondary infection (eg streptococcus/staphylococcus) in lungs usually
Why do we get symptoms?
body’s immune response to viral invasion
Antibodies triggered and immune cells move to site of infection
Release cytokines = local inflammation
What can occur when encountering new subtype of infleunza?
Cytokine storm (bird flu jumped species)
Who does WHO recommend flu vaccine for?
Pregnant women children 6months - 5 years elderly (>65) people with chronic medical condition healthcare workers
