Influenza Flashcards
Symptoms of influenza
Cough, fever, chills, muscle aches, headache, normal chest X-ray
Duration of acute infection
Seven days or longer. Weakness and cough might persist for several weeks
Incubation period
1 - 5 days
Infectious period
5-6 days
At-risk groups
Young, elderly, people with underlying chronic heart, lung, renal, metabolic condition
Receptor bound by flu
Sialic acid-containing receptor on non-ciliated respiratory epithelium.
Configuration of sialic acid
Bound by alpha-2-6 linkage to galactose
Place in airways where flu particularly replicates
Large airways
Factor contributing to fever
IL1
Factor contributing to muscle aches
Interferon alpha
Where later infection can occur
Ciliated epithelium of trachea and bronchi
Bacterial pneumonia pathogenesis
1) Late-stage flu replicates in ciliated epithelium, deciliates it
2) Bacterial species colonise airways
- H. influenzae, staph. aureus, strep. pneumoniae
How closely related are influenza types A, B and C?
Not closely related.
Role of M1 protein
Capsid stability (matrix)
Role of M2 protein
Ion channel.
Allows H+ into virus, causing matrix conformation change, RNPs can exit capsid
Location of RNA-dependent RNA polymerase
Attached to ribonucleoprotein
Number of ribonucleoproteins
Eight
Genes encoded
Ten
Total number of HA and NA subtypes
17HA, 10NA
Type of genome
ssRNA, segmented into eight ribonucleoproteins
Number of RNA polymerase subunits
Three
Number of silalic acid receptors on HA
Three
Number of sialic acid receptors on NA
Four
Area of influenza replication
Nucleus of host cell (despite being RNA virus)
Reason for replication in the nucleus
Spliceosome needed to separate gene products of RNPs with two genes
Tryptase Clara origin
Clara cells, limited to respiratory tract
Tryptase Clara role
Removes lysine from HA cleavage site.
Allows HA to change conformation at pH 5 in endosome, escape endosome
Mannose-binding lectin
Looks just like C1a.
Can take role of C1a in complement cascade
Role of innate immune system in influenza infection
Slow virus until adaptive immune system is ready
Role of CD8+ in influenza immunity
1)
2)
1) Not long-lived
2) Recognise peptides from internal antigens of virus. These peptides are broadly cross-reactive between type A subtypes
(NOT between A and B)
Role of antibodies in influenza immunity 1) 2) 3) 4)
1) LIfelong response
2) Bind HA, NA, prevent attachment/release
3) Ab+C’ lysis of infected cells
4) Preexisting antibodies neutralise input virus
Antigenic drift
Formation of new strains within a subtype because of accumulated missense mutations
Reason for greater number of mutations in RNA genomes
RNA genomes no more error-prone than others.
RNA-dependent RNA polymerase lacks proofreading system
Effect of antigenic drift affecting HA/NA antibody-binding site
Antibodies can no longer bind/lower affinity binding. These mutations are selected FOR by natural selection
Number of antibody-binding sites on HA
Five
Duration of reverse-transcriptase PCR diagnosis
Hours - 1 day
Duration of culture diagnosis (determine subtype)
Days
Reverse-transcriptase PCR diagnosis:
1)
2)
1) RT-PCR sample
2) Antibody strip captures nucleoprotein in lysed virus sample
Culture diagnosis:
1)
2)
3)
1) 10-days eggs with embryo infected with virus
2) Allantoic fluid is sampled
3) Allantoic fluid haemagglutination tested
Definition of seroconversion
Four-fold titre increase in antibodies
Haemagglutination test
1) Influenza virus can bind sialic acid on red blood cells, causing them to agglutinate
2) Chicken RBCs have sample added. If virus is not present, cells sink.
Reason for use of chicken RBCs in haemagglutination tests
RBCs are nucleated, so sink if there is no agglutination (as they are heavy)
Haemagglutination-inhibition test
1) Antibody added to haemagglutination test.
2) If antibody can bind to flu, no haemagglutionation.
Used to determine specific subtype of flu
Influenza vaccine:
1)
2)
3)
1) Inactivated trivalent vaccine
2) H1N1, H3N2, influenza B strains
3) Intramuscular injection
Influenza vaccine manufacture:
1)
2)
3)
1) Viruses grown in chicken eggs
2) Viruses purified from allantoic fluid
3) Virus chemically inactivated, detergent-disrupted
Influenza vaccine effect on the immune system:
1)
2)
3)
1) Induces AB, not CD8+ response
2) 70% seroconversion in the healthy
3) After strains are selected, takes ~6 months to make vaccine
Types of antiviral drugs for influenza:
1)
2)
1) Ion channel blockers
2) NA inhibitors
Ion channel blocker action:
1)
2)
1) Inhibit M2 channel function in the endosome
2) H+ from pH drop cant enter virus, prevents endosomal escape
Limitations of ion channel blockers
Only effective for type A influenza
NA inhibitor action
1) Mimic sialic acid
Zanamivir - (+)’ve guanidine binds bottom of NA pocket.
Ostelamivir - Hydrophobic group fits into hydrophobic pocket in NA pocket.
NA inhibitor limitations
Only effective if given within 2 days of symptoms
NA inhibitor advantages
Effective for influenza types A and B
