M- Respiratory Viruses Flashcards
Influenza is a member of what viral family?
Describe the structure (envelope? capsule? ss or ds? DNA or RNA?).
What does the genome look like?
Influenza is a member of the orthomyxovirus family. It is: -enveloped -negative strand sSRNA - capsule (with helical symmetry)
The genome is 8 segments of RNA encoding 10 proteins
What are the 2 envelope proteins on influenza virus?
What are the functions of each?
How many varieties of each are there?
Which envelope protein do we have drugs against?
Hemagglutinin (HA or H) :
- attaches the virus to the target cell (respiratory epithelium)
- fusion site at the HA1-HA2 clearvage site to allow it to undergo conformational change in acidified endosome to enter the cytoplasm
There are 15 H and no drugs yet
Neuraminidase (NA or N):
1. separates bound virus from sialic acid on the host membrane glycoproteins allowing it to spread and infect new cells
There are 9 N and drugs like zanamivir and oseltamivir are neuraminidase inhibitors
In addition to the envelope proteins, what other protein is crucial for viral replication and spread?
Where is it located?
Are there drug targets against it?
M proteins are in the matrix of the virus and help attach the envelope and envelope proteins to the nucleocapsid.
M1 is necessary for viral assemble and to stabilize the nucleocapsid.
M2 is an ion channel that allows hydrogen ions to enter the virion while in the endocytic vacuole to allow viral RNA release into the cytoplasm to allow for replication.
Amantadine and rimantadine inhibit M2 proteins preventing acidification and preventing dissociation of the nucleocapsid from the matrix. This stops replication of the virus.
What are the 3 main types of influenza? Which affect humans?
Types A, B and C.
Only types A and B cause disease in humans
What are the current circulating influenza strains?
H1N1 and H3N2
What is the pathogenesis of the influenza virus?
It is transmitted person-to-person by aerosol spread.
- H binds to sialic acid and the virus is endocytosed in a clatharin coated vesicle
- M2 proteins acidify the endosome exposing virus to hydrogen ions
- acidification changes the HA1-HA2 conformation exposing the fusion domain and the virus uncoats
- acidification also induces conformational change in M1 separating the nucleocapsid from the matrix and liberating it into the cytoplasm
- Replication of the virus occurs in the cytoplasm using viral polymerase
- During budding, neuraminidase cleaves sialic acid from the proteins on the viral envelope releasing it
The influenza virus initially multiplies in the cells of the ___________________. After intracellular multiplication, they can cause ___________ and death of these cells. This leads to ___________ which can lead to ________________________/
Initially multiply in cells of the upper respiratory tract.
After intracellular multiplication, they cause ciliary dysfunction and death of the cells.
This leads to desquamation which leads to secondary colonization by bacteria and secondary infection/superinfection.
What is the incubation time of influenza? What is the prodrome? After this what symptoms develop? What is duration of illness? What symptom can persist for longer?
It incubates 1-4 days. Prodrome : malaise and headache -acute onset of fever (39-40) - severe sore throat - headache, malalgia, arthralgia -prostration, rhinorrhea -nonproductive cough, NO nasal stuffiness/sinus disease
Illness lasts about a week
Fatigue can last for months
What are the 2 way influenza can cause pneumonia?
- directly
2. by killing respiratory cells–> desquamation–> secondary infection –> pneumonia
A patient comes in to see you. They felt fine at breakfast and then BOOM. They feel like shit. Headache, muscles ache, joints ache. They have a high fever and dry cough. They have a severe sore throat.
What is your suspicion?
influenza
What type of mutation is associated with antigenic drift? What kind of flu does it cause?
It is a point mutation leads to the generation of random mutants that have new epitopes on the surface proteins. (new H and N)
This causes the yearly epidemics of flu
What is antigenic shift? What kind of flu is it associated with?
It is when two or more viruses infect the same cell and genetic reassortment takes place.
This creates a new progeny virus (not just new H and N surface proteins)
This can involve non-human hosts: bird flu, swine flu, etc
Antigenic SHIFT accounts for pandemics of influenza.
Why do antigenic drifts cause yearly epidemics while antigenic shifts cause huge pandemic strains?
Drift- changes the surface antigen proteins but there is still some cross-reactivlty if the strain is still closely related
Shift- all new viral progeny so there will be no cross-reactive immunity
In inter-pandemic influenza, there is a yearly periodicity of influenza epidemics due to ______ and a 2-3 year periodicity of influenza due to _________.
yearly - H and N
2-3 years - influenza B epidemics
How can influenza be diagnosed during and epidemic period?
How is it diagnosed during non-epidemic periods?
During an epidemic, it can be diagnosed on clinical grounds alone.
During non-epidemic times or for definitive diagnosis:
1. viral culture from respiratory secretions
2. DFA test on the respiratory secretions
3. PCR
At Parkland, what is the point of ordering a respiratory viral panel DFA?
It can screen for:
- influenza
- RSV
- parainfluenza
- adenovirus
What are the 2 types of vaccines in current use for influenza?
What is the most commonly used?
- Inactivated vaccines- most commonly used
2. Live virus vaccine
Vaccines for influenza stimulate the production of _________ which confers protection. This is in distinction to the clearance of infection which requires _______________.
Vaccine makes antibodies to confer protection.
Clearance of the infection requires CMI
Describe inactivated vaccines
How are they made?
Who should NOT receive this vaccine?
They can be:
- whole virion vaccines
- sub-unit vaccines (split vaccines) - purified HA and NA segments
Viruses are cultivated on eggs- so someone allergic to eggs should not get it.
People who claim that they “get the flu” when they get the vaccine are most likely having what happen?
- T cell response is making them feel icky
- they are reacting to the egg component
- cross-reaction with previous vaccine
- supervening viral URI