Flashcards in Influenza and Cold Deck (31)
What are the general symptoms of the common cold?
(Diff. w/flu?) 16:49
- Affects the upper respiratory tract
- Sore throat
- Runny nose
- Nasal congestion
- Sneezing (TRANSMISSION)
- Muscle aches
>>> Mainly head symptoms
• High fever
• Joint pain
• Muscle ache
>>> Whole body symptoms
What are colds caused by?
- Rhinoviruses (main cause)
- Human coronaviruses (SARS/MERS)
- Human parainfluenza viruses, human respiratory syncytial virus (RSV), enteroviruses other than rhinovirus, metapneumovirus too
How does transmission of cold/flu virus occur?
Respiratory disease thus:
- Airborne droplets (aerosols; sneezing, coughing)
- Direct contact with infected nasal secretions
- Fomites (contaminated objects e.g. tissues)
- Hand-to-hand contact (handshake etc.; Contagion film)
- Hand-to-surface-to-hand contacts (e.g. door handles, lift buttons)
What are fomites?
Any object that can transmit pathogens/disease.
Explain the public health campaign: 'Catch it, bin it, kill it'
- Germs spread easily
- Always carry tissues and use them to catch cough/sneeze
- Germs can live for several hours on tissues
- Dispose of tissue soon as possible
- Hands transfer germs to every surface you touch
- Clean hands with soap + water ASAP
What do Rhinovirus, Influenza and Adenovirus have in common?
- ONLY their symptoms (overlapping); they are not related to each other
Describe the differences between Rhinovirus, Influenza and Adenovirus; some common causes of the common cold.
- Small (30 nm)
- ss(+)RNA virus (Baltimore IV)
- Large (80-120 nm)
- ss(-)RNA virus (Baltimore V)
- Large (100 nm)
- dsDNA virus (Baltimore I)
What is SARS and MERS respectively?
- Severe acute respiratory syndrome
- Middle East respiratory syndrome
What are the three genera (genus) of influenza viruses?
Influenza A (widest host spectrum), infects:
- Humans, horses, pigs, other (also marine e.g. seals) mammals and birds (birds more difficult to control)
- Humans, seals (less likely to catch as smaller host spectrum)
Influenza C (not thought to cause epidemics; only mild respiratory symptoms):
- Humans, pigs and dogs
What are the physical features of the influenza virus?
- ss(-)RNA; Baltimore Group V
• Haemagglutinin (HA)
• Neuraminidase (NA)
>>> Proteins on surface of envelope like GP120 in HIV (key role in invasion of cell)
Describe the influenza virus structure.
- Haemagglutinin (HA; Trimer)
- Neuraminidase (NA; Tetramer)
- Ion channel (M2; good drug target, goes right through to lumen: RNA)
- Lipid bilayer
- Matrix protein (M1, shell)
- Ribonucleoprotein (RNA, inside envelope)
Describe the influenza genome structure.
- Organised into 8 separate (-) ssRNA molecules
- 8 RNA non-identical strands, all encode different genes
E.g. one for NA, one for HA
• M1, M2
• NS1, NS2
What are the subtypes of Influenza A based on?
Based on the HA and NA proteins on their surface:
- 16 antigenically different HA subtypes (H1 to H16, like 16 different viruses; immunity to H1 does not protect against H11 etc.)
- 9 distinct NA subtypes
How are the subtypes of Influenza A differentiated?
- Subtypes distinguished serologically
>>> Antibodies to one virus subtype do not react with another
How do Influenza Subtypes occur?
In all manner of combinations:
E.g. H1NA (Bird flu), H5N1 (swine flu), H2N3 etc.
What are the nomenclature rules for the Influenza virus?
By the following rule:
- Influenza Type (A, B, or C)
- Species from which isolated (unless human)
- Place of isolation
- Strain designation
- Year isolation
- (HxNx) Subtype (for Influenza A only)
• A/seal/Massachusetts/1/80 (H7N7)
• A/duck/Hong Kong/960/1980 (H6N2)
• B/Yamagata/16/88 (Human)
• C/Mie/199/2012 (Human)
What are the common Zoonotic influenza strains?
- Swine flu (H1N1)
- Avian (bird) flu (H5N1)
>>> Transmitted by animals
Does immunity against one influenza subtype confer immunity to another?
- Immunity acquired against any particular strain by infection or vaccination confers little or no cross-protective immunity against other subtypes
How does the influenza virus attach and enter the host cell?
- HA protein mediates attachments to sialic acid on epithelial cell surface
- Uptake by endosomes follows (vesicle; but with a membrane too, additional to just an envelope)
>>> HIV (envelope virus too) enters host cell via membrane fusion; influenza is an exception
Where is sialic acid on the host cell?
- Sialic acid are the terminal parts of transmembrane glycoproteins
- Act as attachment sites for influenza viruses
Explain the selectivity of influenza viruses.
Human influenza viruses:
- Preferentially bind in the α-2, 6 configuration with galactose (glycosidic bond)
Avian influenza viruses:
- Preference for α-2, 3 configuration
>>> Hence why avian flu is not very infectious for humans
Why are pigs influenza sluts? (selectivity)
- Have either type of glycosidic linkage between galactose and sialic acid; α-2, 6 or α-2, 3(human vs. avian)
- Thus makes them susceptible to both human and avian flu viruses
>>> Pigs can be infected with different strains at the same time; co-infection means genes get mixed up, results in avian flu being able to infect humans (gaining α-2, 6 activity)
How does influenza strain mixing occur?
- Pigs are susceptible to infection from strains with α-2,6 or α-2,3
- Genetic exchange between influenza viruses from different hosts can occur in pigs as a result, creating new subtypes
- Genetic exchange involves random packaging of 8 RNA genes from different subtypes infected
- Copies of the viral genes from different strains get mixed up inside the host cell and are packaged into new viral particles without regard to their original make up
Why does avian flu normally not infect humans?
- Human influenza binds preferentially bind in α-2, 6 configuration with galactose (glycosidic bond)
- Avian influenza preference for α-2, 3 configuration
>>> Haemagglutinin protein (galactose?) on the outside of the virus has trouble hooking up to the receptor (sialic acid)
How does influenza virus uptake by the nucleus occur once the virion is already in the cell?
- Endosome (has lipid bilayer) contains protein pumps which gradually decrease endosomal lumen pH from 7 to 5
- M2 ion channel (from lumen endosome into viral lumen) is also a protein pump which channels the protons from the endosomal lumen into the virion, lowering the pH
- Results in FUSION of the viral envelope with the endosomal membrane, and subsequent release of the viral genome (8 x RNA) into the cytoplasm
- Matrix disassembles, RNA released
- This occurs via HA (haemagglutinin) fusion peptide (trimer); normally hidden at neutral pH, conformational change of HA at low pH exposes peptide at tops of trimer, inserts into endosomal membrane
>>> Influenza uses its envelope to fuse with endosomal envelope, unlike HIV which fuses with the cell surface membrane
Amantadine is a drug used for Parkinson's. How is it also efficacious for influenza?
- Can be used for influenza as it blocks the M2 ion channel; blocking pump blocks virus release from endosome = blocks virus release from endosome
- Interferes with the influenza life cycle
What is the function of HA (haemagglutinin) of influenza?
- Mediates access to host cell (initial adhesion)
- Trimer mediates attachment to sialic acid and fusion with the endosome (fusion peptide at low pH)
What is the function of neuraminidase (NA) of influenza?
- Enables viral release from host cell by cleaving sialic acid on host cell and from mucin to allow access to new target cells
- Virus reinfects old cell as sialic acid closer, but cell is now dead thus NA cleaves glycosidic bond between sialic acid and galactose for release
How do neuraminidase (NA) inhibitors work? Give examples.
- Sialic acid-mimic drugs
- Designed to mimic the NA natural ligand, sialic acid
- Blocks viral escape from infected cells; virus doesn't get released from old sialic acid on old cells
• Oseltamivir (Tamiflu)
• Zanamivir (Relenza)