Lecture 16: Intracellular Pathogens, Influenza Flashcards
How often do new strains of viruses emerge through a major shift mutation to cause a worldwide pandemic?
every 25-40 years. \
What do Influenza viruses cause?
- Major cause of these lung infections
- Can directly cause death through viral pneumonia, or more commonly weaken the innate immune system (e.g breach in the barrier lung epithelial) leading to secondary bacterial pneumonias.
In 2009 the swine flu (H1 N1) emerged where?
In Mexico
The troublesome H5 N1 in Southeast Asia is called what?
Avian Influenza
What viral family does Influenza belong to?
Belongs to (-) ssRNA called Orthomyxoviruses (Influenza)
What is Influenza unique to the human RNA viruses?
- It replicates in the nucleus of the cell (Segmented genome=Influenza)
- While The ssRNA genome makes point mutations common (Drift mutations) while the segmented(influenza) genome allow for infrequent, but potentially very serious, shift mutations.
What do segmented (influenza) genomes allow?
Segmented genome allow for infrequent, but potentially very serious shift mutations, where complete segments are exchanged between two different viruses infected the same cell.
Describe the components within an Influenza virus?
8 Nucleocapsids inside a protein-reinforced envelope with spikes.
What are H and N spikes for?
H (16 major ones known) spikes are important for targeting cells they infect.
N (9 major one) spikes release the virus from infectious cells
What is Antigenic shift?
The genetic change that enables a flu strain to jump from one animal species to another, including humans.
Point mutations in either of the 2 spikes (H or N) are called what ?
- Drift muations (minor) but can lead to epidemics.
- Happens often, most common
What is an example of an intermediate host?
A pig (Which a new strain can spread from the intermediate host to humans)
What are the H proteins called?
Hemagglutinin proteins
- They facilitate viral attachment and fusion with the cell membrane
What are N proteins called?
Nuraminidase proteins that help viral release by cleaving neuraminic acid on the cell surface.
What is a shift mutation?
*** Major changes, new subtype associated with pandemics.
-A complete exchange of spike proteins cause by co infection by 2 different strains.
For the diagnosis of influenza what is a key technique ?
***Influenza viruses agglutinate RBCs so a Hemagglutination inhibition assay is a fast way to determine if a patient has developed neutralizing antibodies to a certain influenza strain.
Note: It is based on the fact that influenza viruses can grow in eggs and that they bind sialic acids, which are found on some RBC.
What can adding the anti-hemagglutinin antibody do to influenza viruses?
It can inhibit this property of influenza viruses.
Why are (-) ssRNA influenza strains more dangerous or prone to mutations?
- No 2nd strand in RNA
- Enzymes that spell-check are not present in RNA like DNA.
- Can mix 2 different viruses “segmented viruses”..
What do viral infections of immune cells trigger that can inhibit effectiveness of viral replication?
IFN-alpha and IFN- beta which are pro-inflammatory all in innate immunity.
How can interferons and other innate immune responses such as inflammation protect us?
They hold and fort until influenza specific lymphocytes can clone.
Note: In cases where the virus replicates TOO FAST or host immunity is inadequate host may die from viral pneumonia.
How does the specific immune system work?
With Abs neutralizing the free viruses and Tc cells destroying infected cells (viral factories).
Note: If so many ling epi cells become infected that Tc cell killing of infected lung epi cells can leave the lung significantly “ denuded” (bare) —>leads to many deaths due to secondary infections.
Temporary lack of innate epi barrier-protection leaves the lung susceptible to inhaled normal bacterial flora which can lead to what?
many deaths from influenza are often from secondary opportunist disease (Staph or Strep bacterial pneumonia)
Shift mutation is only present in what type of Influenza?
Only type A
- This occurs when 2 different species (duck and pig) mix.
- Mallard duck can carry it :)
What was the most recent Global Flu pandemic?
2009 Influenza A (H1N1) Not that severe
What are the 3 types of influenza and which cause human disease?
- A, B, C.
- Only A(Pandemics caused by this) and B cause human disease.
- A and B cause Epidemics
Flu vaccines are made up of which types?
They are trivalent which are pools of antigens from 3 different strains. (2 A and 1 B)
What is a split vaccine?
The antigens are viral proteins usually with lipids removed
Where are viruses used in vaccines grown?
In eggs usually but a new flu vaccine (2012) approved by the FDA are growing them in animal cells (dogs)
What is the new method of administration of viruses since the 2003?
Intranasal rather than intramuscular route, mist flu vaccine were first marketed in the US. Almost 50 years after they were first used in Russia.
What is the name of antiviral drugs with activity against influenza A viruses but not influenza B viruses.
Amantadine and Rimantadine are chemically related antiviral drugs known as adamantanes.
How do these antiviral drugs, adamantanes act ?
They appear to act by blocking uncoating and thus viral infection and can be used to stop infection before vaccines have had enough time to work.
How do antiviral drugs known as neuramindasae inhibitors work?
They inhibit neuraminidase and this viral release and have acitivity against both influenza A and B.
Downfalls:
- They are expensive
- and drug resistance can develop quickly
- not enough doses to treat a pandemic
What are two examples of neuraminidase inhibitors?
1) Oseltamivir (Tamiflu)
2) Zanamivir ( Relenza)
What are characteristics for type A influenza virus strain?
- Causes epidemics and pandemics
- Moderate to severe illness
- Humans and animals affected
- all age groups
What are characteristics for type B influenza virus strain?
- Milder epidemics
- Humans only
- Primary affects very young children and elderly
What are characteristics for type C influenza virus strain?
- No epidemics
- Rarely reported in humans
What are drift mutations?
Minor changes, same subtype associated with epidemics
Influenza pathogenesis?
- Respiratory transmission
- viremia not demonstrable
- replication in respiratory epi. w/ subsequent destruction of cells
- viral shedding in respiratory secretions for 5-10 days!!!!!!!!!!!!!!!
Influenza clinical features:
- incubation period 1-4 days
- abrupt onset of fever, myalgia, sore throat, nonproductive cough, headache, shortness of breath
- case fatality 0.5-1 per 1000 cases
Why is the flu more common in the winter (Temporal pattern)?
Some studies have shown that vitamin D is needed for optimal immune response. Or humidity could explain seasonality of influenza by controlling the ability of viruses to remain infectious while they are in droplets or aerosols. Viruses survived best at low humidity due to composition of fluids (salts, and proteins in respiratory droplets )…
Influenza vaccine efficacy?
70-80% effective among persons < 65 years of age
30-40% for the frail elderly persons
