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Flashcards in M- Respiratory Viruses Deck (50):
1

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

2

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) :
1. attaches the virus to the target cell (respiratory epithelium)
2. 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

3

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.

4

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

5

What are the current circulating influenza strains?

H1N1 and H3N2

6

What is the pathogenesis of the influenza virus?

It is transmitted person-to-person by aerosol spread.

1. H binds to sialic acid and the virus is endocytosed in a clatharin coated vesicle
2. M2 proteins acidify the endosome exposing virus to hydrogen ions
3. acidification changes the HA1-HA2 conformation exposing the fusion domain and the virus uncoats
4. acidification also induces conformational change in M1 separating the nucleocapsid from the matrix and liberating it into the cytoplasm
5. Replication of the virus occurs in the cytoplasm using viral polymerase
6. During budding, neuraminidase cleaves sialic acid from the proteins on the viral envelope releasing it

7

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.

8

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

9

What are the 2 way influenza can cause pneumonia?

1. directly
2. by killing respiratory cells--> desquamation--> secondary infection --> pneumonia

10

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

11

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

12

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.

13

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

14

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

15

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

16

At Parkland, what is the point of ordering a respiratory viral panel DFA?

It can screen for:
1. influenza
2. RSV
3. parainfluenza
4. adenovirus

17

What are the 2 types of vaccines in current use for influenza?
What is the most commonly used?

1. Inactivated vaccines- most commonly used
2. Live virus vaccine

18

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

19

Describe inactivated vaccines
How are they made?
Who should NOT receive this vaccine?

They can be:
1. whole virion vaccines
2. sub-unit vaccines (split vaccines) - purified HA and NA segments

Viruses are cultivated on eggs- so someone allergic to eggs should not get it.

20

People who claim that they "get the flu" when they get the vaccine are most likely having what happen?

1. T cell response is making them feel icky
2. they are reacting to the egg component
3. cross-reaction with previous vaccine
4. supervening viral URI

21

Describe live virus vaccine.
How is it grown?
How is it administered?
Who is this contraindicated to use in?

It is called Flumist- it is cold adapted and grown at 25 degrees.
It is administered by intranasal inoculation to people between the age 2 and 49 and who are healthy (normal immune system)

Because it is live virus, immunosuppressed people cannot use it and people who LIVE or WORK with immunosuppressed people cannot use it

22

The current recommendations are to immunize all people over ___________ for the flu.

6 months

23

Who is considered to be at higher risk for getting the flu and thus should definitely be immunized?

1. pregnant women
2. asthma, diabetes, chronic lung disease
3. kids 65

Health care workers, household contacts, parents of small children

24

What are the treatments available if the person gets the flu?
What are the specificities for viral type?

1. M2 inhibitors - Amantadine, rimantadine which prevent penetration and uncoupling of the virus from the matrix so it cannot enter the cytoplasm to replicate. These only work on influenza A.

2. N inhibitors- Oseltamivir and zanamivir which prevent the release of flu from a cell preventing spread. Both A and B influenza

25

To be effective, when must patients take amantadine?

within 48 hours of illness OR during incubation period.

It CAN be taken prophylactically

26

What are the side effects of amantadine?
What can be used instead to avoid side effects?

Can cause confusion and changes in cognition especially in older people.

Rimantadine has less CNS effects

27

What is the difference between zanamivir and oseltamivir?

zanamivir- inhaled
oseltamivir- oral agent

28

What are complications of the flu?

1. pneumonia caused by superinfection **
2. exacerbation of asthma/COPD
3. myocarditis, pericarditis, rhabdomyolysis
4. DIC
5. acute renal failure
6. meningococcal carriage
7. Reyes syndrome**

28

What are complications of the flu?

1. pneumonia caused by superinfection **
2. exacerbation of asthma/COPD
3. myocarditis, pericarditis, rhabdomyolysis
4. DIC
5. acute renal failure
6. meningococcal carriage
7. Reyes syndrome**

29

An individual gets influenza, begins to recover, then develops fever, cough, chest pain, SOB and progresses to respiratory failure.
Why?
What are the likely agents at play?

This is pneumonia caused by superinfection:

1. S. pneumoniae
2. S. aureus (oxacillin sensitive AND MRSA)
3. H. influenza

29

An individual gets influenza, begins to recover, then develops fever, cough, chest pain, SOB and progresses to respiratory failure.
Why?
What are the likely agents at play?

This is pneumonia caused by superinfection:

1. S. pneumoniae
2. S. aureus (oxacillin sensitive AND MRSA)
3. H. influenza

30

What is Reyes syndrome?
Who does it commonly affect?
What is the major cause?

1. acute encephalopathy
2. Fatty infiltrate of the liver (occassionally with heart, pancreas, kidney, lymph nodes)

It affects children under 18 after a viral infection and is common if they take aspirin for the viral illness.

33

What is Reyes syndrome?
Who does it commonly affect?
What is the major cause?

1. acute encephalopathy
2. Fatty infiltrate of the liver (occassionally with heart, pancreas, kidney, lymph nodes)

It affects children under 18 after a viral infection and is common if they take aspirin for the viral illness

34

Describe the structure of parainfluenza virus.
Describe the genome.

It is an enveloped, negative strand ssRNA virus
All the genes are encoded on one genomic segment

35

What are the 3 main groups of paramyxoviruses?
What proteins are on the envelope of each?

1. morbillovirus- Measles - only hemagluttinin
2. parainfluenza- mumps and parainfluenza - 4 serologies- protein AND H and N
3. pneumovirus- RSV- metapneumovirus- fusion proteins for direct cell-to-cell spread

36

How is parainfluenza transmitted?
What is the incubation time?
What cells are infected?

They are transmitted in large respiratory droplets. Contact must be closer than with influenza
Incubation is 1-4 days and the virus replicates in teh respiratory epithelium

37

What season are people most likely to get parainfluenza?
What are the presenting symptoms?

There is an autumn peak.
They present with symptoms similar to influenza but the fever is LESS high and the illness is LESS severe
-common cold
-bronchitis
-bronchiolitis
-pneumonia

38

An infant presents to the office with hoarseness, a seal bark, cough, tachypnea, tachycardia and retractions. What is the MOST likely disease? What is the organism responsible?

What other organism should be on the differential?

It is croup- a swelling below the glottis which can potentially close the airway

Parainfluenza is most likely to blame

The other differential would be epiglottitis by H. flu

39

What is the most important respiratory viral pathogen in infancy?
What does it cause?
How long does it typically take children to recover from infection?

RSV-
1. bronchiolitis
2. pneumonia

It takes children 8-15 days to recover

40

What group of viruses does RSV belong to?
What is the structure?

It is a paramyxovirus that is ssRNA, negative sense with an envelope (that has ONLY fusion proteins, no H or N)

41

The presence of what on RSV determines pathogenicity?

fusion protein which allows direct cell-to-cell spread without the need for an extra step.
Adjacent cells fuse to form syncitia and giant cells.

42

What inactivates RSV?

Soap and water and disinfectants

43

For RSV, transmission is usually by ____________ and requires ________ and often can be transitted by _______________.

What is the seasonal peak for RSV?

Usually by respiratory secretions and requires close proximity.
It can be transmitted by unwashed hands

Seasonal peak - winter

44

How is RSV diagnosed?
What is treatment?
Describe the vaccine.

Diagnosis:
1. viral culture (RARE)
2. immunofluorescence/ enzyme-linked immunoassay
3. PCR

Treatment:
-symptoms of pneumonia/bronchiolitis (bronchodilators, O2, corticosteroids)

- Ribavirin is an aerosol guanine nucleoside analog that chain terminates - high concentrations of drug get to the lung

- monoclonal antibody directed against F protein of RSV is available for passive immunization

The vaccine was ineffective and may have even made the disease more severe.

45

Describe the structure of adenovirus.
How does it attach to host cells?
How many serogroups and serotypes are there?
Describe the genome.

Large dsDNA, NO envelope, icosahedral symmetry
Has spikes to attach to host cells. 6 serogroups, 100 serotypes
Genome encodes 40 genes

46

As a naked virus, adenoviruses are resistant to ___________, _________, _______, ______ and ________.
This allows them to be spread in what way?
Epidemics occur in what locations?

Resistant to:
1. GI secretions
2. Bile salts
3. drying
4. detergent
5. chlorine

They spread:
1. fecal-oral
2. respiratory secretions on fingers/fomites
3. medical instruments
4. water

Epidemics occur in:
military barracks
schools
other closed environments

47

Describe the pathogenesis of the adenovirus. How does it attach to the host?
Where does it replicate in the host cell?
What are the two major sets of genes?

1. Attaches to host by spike-like projections
2. endocytosis into clatherin-coated vesicles
3. viral DNA is released to cytoplasm and transported to the nucleus where it replicates
4. adenovirus replicates : EARLY GENES (expressed for replication and include polymerase) and LATE GENES (structural to package virion)

48

Adenoviruses can cause lytic, latent and transforming infections. Describe each.

Lytic- acute infection with death of epithelial cell

Latent- long term infection in lymphoid cells (tonsils/adenoids). Disemmination usually only occurs in immunocompromised and goes to liver.

Transformation- of cell types into immortalized cell lines that can cause tumors in rodents (not found in humans yet)

49

What are the 6 major problems caused by adenovirus?

1. pharyngitis- with or without exudates
2. Pharyngoconjunctival fever- sore throat and pink eye (associated with teens/pools)
3. epidemic conjuctivitis- pink eye WITHOUT sore throat. Usually unilateral but transmissible on hands
4. Pneumonia/ARDS- military recruits, only serotypes 4 and 7
5. immunosuppressed get pneumonia, liver disease, renal disease
6. Diarrhea in infants/young children

50

How is adenovirus diagnosed?
What is treatment?

Diagnosis by:
1. PCR
2. culture
3. immunological techniques

Treatment:
-live oral vaccine for serotypes 4 and 7 ONLY given to military