Lecture 16: Intracellular Pathogens, Influenza

Question 0

How often do new strains of viruses emerge through a major shift mutation to cause a worldwide pandemic?

Answer 0

every 25-40 years. \

Question 1

What do Influenza viruses cause?

Answer 1

• 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.

Question 2

In 2009 the swine flu (H1 N1) emerged where?

Answer 2

In Mexico

Question 3

The troublesome H5 N1 in Southeast Asia is called what?

Answer 3

Avian Influenza

Question 4

What viral family does Influenza belong to?

Answer 4

Belongs to (-) ssRNA called Orthomyxoviruses (Influenza)

Question 5

What is Influenza unique to the human RNA viruses?

Answer 5

• 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.

Question 6

What do segmented (influenza) genomes allow?

Answer 6

Segmented genome allow for infrequent, but potentially very serious shift mutations, where complete segments are exchanged between two different viruses infected the same cell.

Question 7

Describe the components within an Influenza virus?

Answer 7

8 Nucleocapsids inside a protein-reinforced envelope with spikes.

Question 8

What are H and N spikes for?

Answer 8

H (16 major ones known) spikes are important for targeting cells they infect.
N (9 major one) spikes release the virus from infectious cells

Question 9

What is Antigenic shift?

Answer 9

The genetic change that enables a flu strain to jump from one animal species to another, including humans.

Question 10

Point mutations in either of the 2 spikes (H or N) are called what ?

Answer 10

• Drift muations (minor) but can lead to epidemics.

- Happens often, most common

Question 11

What is an example of an intermediate host?

Answer 11

A pig (Which a new strain can spread from the intermediate host to humans)

Question 12

What are the H proteins called?

Answer 12

Hemagglutinin proteins

- They facilitate viral attachment and fusion with the cell membrane

Question 13

What are N proteins called?

Answer 13

Nuraminidase proteins that help viral release by cleaving neuraminic acid on the cell surface.

Question 14

What is a shift mutation?

Answer 14

*** Major changes, new subtype associated with pandemics.

-A complete exchange of spike proteins cause by co infection by 2 different strains.

Question 15

For the diagnosis of influenza what is a key technique ?

Answer 15

***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.

Question 16

What can adding the anti-hemagglutinin antibody do to influenza viruses?

Answer 16

It can inhibit this property of influenza viruses.

Question 17

Why are (-) ssRNA influenza strains more dangerous or prone to mutations?

Answer 17

• No 2nd strand in RNA
• Enzymes that spell-check are not present in RNA like DNA.
• Can mix 2 different viruses “segmented viruses”..

Question 18

What do viral infections of immune cells trigger that can inhibit effectiveness of viral replication?

Answer 18

IFN-alpha and IFN- beta which are pro-inflammatory all in innate immunity.

Question 19

How can interferons and other innate immune responses such as inflammation protect us?

Answer 19

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.

Question 20

How does the specific immune system work?

Answer 20

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.

Question 21

Temporary lack of innate epi barrier-protection leaves the lung susceptible to inhaled normal bacterial flora which can lead to what?

Answer 21

many deaths from influenza are often from secondary opportunist disease (Staph or Strep bacterial pneumonia)

Question 22

Shift mutation is only present in what type of Influenza?

Answer 22

Only type A

• This occurs when 2 different species (duck and pig) mix.
• Mallard duck can carry it :)

Question 23

What was the most recent Global Flu pandemic?

Answer 23

2009 Influenza A (H1N1) Not that severe

Question 24

What are the 3 types of influenza and which cause human disease?

Answer 24

• A, B, C.
• Only A(Pandemics caused by this) and B cause human disease.
• A and B cause Epidemics

Question 25

Flu vaccines are made up of which types?

Answer 25

They are trivalent which are pools of antigens from 3 different strains. (2 A and 1 B)

Question 26

What is a split vaccine?

Answer 26

The antigens are viral proteins usually with lipids removed

Question 27

Where are viruses used in vaccines grown?

Answer 27

In eggs usually but a new flu vaccine (2012) approved by the FDA are growing them in animal cells (dogs)

Question 28

What is the new method of administration of viruses since the 2003?

Answer 28

Intranasal rather than intramuscular route, mist flu vaccine were first marketed in the US. Almost 50 years after they were first used in Russia.

Question 29

What is the name of antiviral drugs with activity against influenza A viruses but not influenza B viruses.

Answer 29

Amantadine and Rimantadine are chemically related antiviral drugs known as adamantanes.

Question 30

How do these antiviral drugs, adamantanes act ?

Answer 30

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.

Question 31

How do antiviral drugs known as neuramindasae inhibitors work?

Answer 31

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

Question 32

What are two examples of neuraminidase inhibitors?

Answer 32

1) Oseltamivir (Tamiflu)

2) Zanamivir ( Relenza)

Question 33

What are characteristics for type A influenza virus strain?

Answer 33

• Causes epidemics and pandemics
• Moderate to severe illness
• Humans and animals affected
• all age groups

Question 34

What are characteristics for type B influenza virus strain?

Answer 34

• Milder epidemics
• Humans only
• Primary affects very young children and elderly

Question 35

What are characteristics for type C influenza virus strain?

Answer 35

• No epidemics

- Rarely reported in humans

Question 36

What are drift mutations?

Answer 36

Minor changes, same subtype associated with epidemics

Question 37

Influenza pathogenesis?

Answer 37

• Respiratory transmission
• viremia not demonstrable
• replication in respiratory epi. w/ subsequent destruction of cells
• viral shedding in respiratory secretions for 5-10 days!!!!!!!!!!!!!!!

Question 38

Influenza clinical features:

Answer 38

• 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

Question 39

Why is the flu more common in the winter (Temporal pattern)?

Answer 39

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 )…

Question 40

Influenza vaccine efficacy?

Answer 40

70-80% effective among persons < 65 years of age

30-40% for the frail elderly persons