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Flashcards in Respiratory Viruses Deck (121):
1

where are most respiratory infections acquired from?

people

2

how are most respiratory infections spread

from the afflicted respiratory tract by contact or droplets

3

animals are important in terms of respiratory symptoms because

they are a source of new types of respiratory viruses that are introduced into the human population (ie SARS coronavirus and influenza)

4

respiratory viruses usually invade and stay confined to...

the epithelial cells of the respiratory tract.

5

How do respiratory viruses spread within the host?

within the lumen of the respiratory tract by movement of respiratory secretions (mucus)

6

two ways that respiratory viruses escape host mechanisms?

1) "hit and run" strategy-- ifxn = shortlived and symptomatic < 1 wk
2) Respiratory viruses have evolved to escape the antibody response so they can infect repeatedly

7

what is important for the fast elimination of respiratory viruses?

Innate immune responses (interferons)

8

how do respiratory viruses damage the host?

1. the cytopathic effect of the virus on infected cells
2. host inflammatory response

9

3 components of the upper respiratory tract, and the manifestation of an infection in that area.

1) nasal cavity-- common cold
2) pharynx -- pharyngitis
3) larynx -- laryngitis, croup

10

4 components of the lower respiratory tract and the manifestation of an infection in that area

1) trachea -- tracheitis
2) bronchi -- bronchitis
3) bronchioles -- bronchiolitis
4) alveoli--pneumonia, influenza

11

the common cold is caused by...

a viral infection of the nasal mucosa

12

manifestations of the common cold

rhinorrhea, cough and sore throat, sneezing and mild (or no) fever

13

half common colds are caused by what virus?

rhinovirus

14

why do rhinvirus have tropism for the nasal mucoso?

bc they replicate best at the low temp of the nasal mucosa

15

how does rhinovirus evade the Ab response?

by having over 100 serotypes

16

why is the conserved receptor binding site of the virus (ICAM-1) not a good target for Abs?

because it's in a "canyon" on the viral surface so it's inaccessible to Abs

17

what is bronchiolitis?

inflammation of the bronchioles, usually associated with a viral ifxn

18

bronchiolitis is most common amongst people of what age?

children under 2

19

symptoms of bronchiolitis

fever and rhinorrhea, followed by cough and wheezing of 1-2 wk duration
severe cases include tachypnea, dyspnea, hypoxia and cyanosis

20

what is RSV?

Respiratory Syncytial Virus (RSV)-- an enveloped virus with a non-segmented, minus-strand RNA

21

what causes 80% of bronchiolitis?

RSV- which infects any part of the resp tract (URTI and LRTI)

22

infection of the bronchioles (like bronchiolitis) leads to

narrowing of the bronchiolar lumen, as the wall thickens and debris accumulates

23

what sound is suggestive of bronchiolitis and why?

wheezing-- upon exhalation the positive pressure in the lungs pushes the bronchioles shut, trapping air in alveolar spaces. Wheezing occurs as air moves through the narrow passage

24

what are the two surface proteins of RSV and how many serotypes are there for each?

F-protein (one serotype) and G protein (2 serotypes)-- so very little Antigenic variation compared to other viruses

25

does ifxn with RSV wane with frequency/severity over a person's life?

nope, noone knows why the ab response isn't completely protective since there are only 2 surface proteins (F and G) with 3 serotypes total

26

Symptoms of influenza?

mostly constitutional-- fever, chills, malaise, myalgias, headache, sore throat and a cough

27

in the us, how many people die of influenza on average

23,000

28

influenza viruses:
enveloped or not? what type of genome?

enveloped, segmented minus strand RNA genome

29

how is influenza A spread? How about B & C?

A is spread from person to person is respiratory droplets and from other mammals, mainly pigs, and domestic birds.

B and C just spread via droplets

30

when does influenza spread the most efficiently and why?

in the winter because absolute humidity is lowest and it facilitates the spread

31

hemagglutinin

protein on the surface of Influenza that binds to sialic acid on the host cell surface, leading to endocytosis of the virus

32

how is the viral ribonucleoprotein of influenza released into the cell

1. viral hemagglutinin binds to sialic acid on host cell and the virus is endocytosed
2. as the pH of the endosome drops, M2, an ion channel on the viral membrane opens and H+ enters the virus
3. the increase in H+ in the virus leads to the release of the ribonucleoprotein from the viral particle and to fusion of the viral and endosomal membranes
4. the RNP is then released into the host cell cytoplasm

33

what is M2?

an ion channel on the influenza viral membrane. When exposed to an acidic pH (like in an endosome) they open, H+ enters the virus and ribonucleoprotein is released from the viral particle into the cytoplasm

34

what is adamantase?

antiviral drugs that block the M2 ion channel and prevent release of RNP. It is only effective against influenza A

35

what happens after influenza RNP (ribonucleprotein) is released into the host cell cytoplasm?

1. RNP is transported to host cell nucleus
2. the minus-strand RNAs are copied to plus strand RNAs
3. The plus strand DNAs are then 1. translated by the host cell to make new viral proteins and 2. used as templates for synthesis of more minus strand RNAs to be packaged in new virions

36

where does assembly of the influenza virus take place?

at the membrane of the host cell-- the new RNPs bind to the surface protein of the virus that are embedded in the host cell membrane, and the new viruses bud off.

37

what is neuraminidase?

a viral protein that cleaves sialic acid from the surface of host cells to prevent the influenza virus from reinfecting/getting stuck to a dying/previously infected host cell that was

38

neuraminidase inhibitors

antiviral drugs that block the action of neuraminidase, which inhibits the release of the virus. these are effective against both influenza A and B

39

what is the primary mechanism by which influenza viruses escape host defenses?

antigenic variation-- leads to repeated ifxns throughout life

40

in influenza, the Ab response is mounted against...

the 2 main surface proteins: hemagglutinin and neuraminadase. but each has several subtypes that don't cross react to Abs. (subtle variation in these prots can be cross reactive)

41

antigenic drift

accumulation of point mutations in neuraminidase and hemagglutinin that lead to the new serotypes of influenza virus that are associated with routine outbreaks of influenza

42

why is antigenic drift so common in influenza A and B?

because viral RNA polymerase is error-prone and lacks proof reading function

43

Antigenic shift

the introduction of a "new" serotype of influenza A from a pig or bird (or a mixture of both) to which the human population has little or no immunity. It only happens every 10-30 yrs and causes pandemics

44

the source of new influenza A virus during pandemic shift?

an animal, like a pig or bird

45

reassortment of influenza A-- what is it and why can it happen?

what: when 2 different influenza A viruses infect the same cell and the progeny viruses contain a mix of RNAs from two parental viruses
why: occurs readily because the viral RNA is segmented

46

why are pigs so problematic in terms of influenza A?

they are capable of housing human and bird influenza ---> increasing chance of reassortment between a human virus and a swine or avian virus which can generate an antigenic shift

47

after an antigenic shift occurs in influenza A, what happens to the virus

it generally persists in the human pop for several years. It will undergo antigenic drift and humans will develop increasing population immunity due to repeated exposure

48

how many influenza viruses are generally circulating in any given winter?

3: 2 A serotypes and 1 B serotype

49

how long does it usually take to recover from influenza?

2 wks

50

how does influenza damage the host?

1) kills ciliated epithelial cells that it infects, which weakens host mucociliary clearance (bacterial pneumonia can follow)

51

is bacterial or viral pneumonia more common?

bacterial (viral influenza, however, can kill cilated cells ---> weaken mucociliary clearance ---> increase bacterial ifxns)

52

how does viral pneumonia due to influenza present?

marked accumulation of fluid in the air spaces of the lung with hyaline membrane formation in the alveoli. Inflammation is scant.

53

how do you prevent influenza?

annual vaccination for people 6 mo or older

54

the 2 types of influenza vaccine available

1. inactivated (split) influenza is given intramuscularly
2. live attenuated virus is given intranasally
*both vaccines have similar efficacy

55

Natural hosts for influenza
A:
B:
C:

Natural hosts for influenza
A: mammals and birds
B: humans (and seals)
C: humans

56

virulence of influenza
A:
B:
C:

virulence of influenza
A: mild- severe
B: mild, rarely severe
C: very mild, children

57

antiviral medications for influenza
A
B:
C:

antiviral medications for influenza
A: adamantases and neuraminidase inhibitors
B: neuraminidase inhibitors
C: antivirals

58

source of antigenic variation, and the type of outbreak associated with influenza
A:
B:
C:

source of antigenic variation in influenza
A: antigenic shift (pandemic) and drift (endemic)
B: antigenic drift (endemic)
C: antigenic variation (outbreak)

59

is there a vaccine for influenza
A:
B:
C:

is there a vaccine for influenza
A: yes
B: yes
C: no

60

respiratory viruses often cause diseases in spite of the fact that they

1. infect the respiratory system but rarely invade

61

what are 3 examples of viruses that are mainly outside of the respiratory tract but are transmitted by the respiratory route

smallpox, varicella-zoster, measles

62

the source of many respiratory viruses are ... but a few like influenza are from... and others, like SARS, are from...

all: people
Influenza: birds (chickens), pigs, maybe seals?
SARS: palm civet cat

63

how are respiratory viruses transmitted? (3)

1. cough/sneeze- droplet
2. direct contact (from person ---> conjunctiva/respiratory mucosa)
3. indirect contact (person ---> fomite ----> conjunctiva/respiratory mucosa)

64

how can respiratory infections be spread through the eye?

1. there are small meibomian glands in the eyelids that add an outer lipid layer to the tears
2. tears come from the lacrimal gland, cross the eye and drain through the canaliculi into the tear sac ---> tear duct ---> nose ---> nasoharynx/oropharynx is now at risk

65

how do respiratory viruses enter the host?

respiratory mucosa/conjunctiva

66

how do respiratory viruses exit the host?

respiratory secretions

67

how are respiratory viruses transmitted?

contact with or inhalation of droplets

68

why is there seasonal occurence of resp. ifxns?

bc of transmission

69

resp. viruses adhere to... using

resp. epithelial cells using normal host cell-surface structures

70

respiratory viruses generally spread...

to adjacent or distant resp epithelial ells in EC mucus

71

invasion beyond resp. epithelium is rare and usually associated with...

severe ifxns (like SARS- severe acute resp syndrome) and viremia

72

why do we get so many resp virus ifxns?

1. many different species of resp viruses
2. they've all evolved to escape imm response (mainly by serotype variation)
3. imm resp to resp viruses is not long lasting

73

primary mech for resp viruses to evade imm resp

serotypic variation

74

Diversity of respiratory viruses (9 types)

1. rhinovirus
2. coxsackie virus A
3. Echovirus
4. coronovirus
5. Resp Syncytial virus
6. influenza virus
7. parainfluenza virus
8. human metapneumovirus
9. adenovirus

75

escaping the Ab response via serotypic variation allows...

the same species of resp virus to infect and ind repeatedly

76

new serotypes can be introduced into the human pop from

animal pops

77

the cytopahic effects of resp ifxns as well as the imm resp leads to

resp epithelium damage ---> 1) edema, increased mucus and necrosis ---> impaired resp func and 2) decreased mucociliary clearance ---> bacterial ifxns ---> impaired resp func/shock/DIC

78

rhinovirus mainly affects what part of the resp sys?

nasal cav, and a little pharynx (common cold/pharyngitis)

79

Parainfluenza mainly affects what part of resp sys?

larynx (laryngitis & Croup), pharynx (pharyngitis) and nasal cavity (common cold)

80

respiratory syncytial virus (RSV) mainly affects what part of the resp sys

bronchiloes (bronciolitis) and nasal cavity (common cold)

81

influenza primarily affects what part of the resp sys?

alveoli (pneumonia), bronchioles (bronchiolitis) and/or the nasal cavity (common cold)

82

what causes manifestations of the common cold/rhinovirus?

acute inflammation of nasal mucosa with cytokine production

83

rhinovirus is from what family? What are the features of this family?

Picornaviridae
-non enveloped
- icosahedral viruses
-non-segmented + strand RNA
- structure and replication = similar to polio virus

84

rhinovirus tropism for the nasal mucosa is NOT determined by receptors for the virus (ICAM-1 receptors) which are present on cells in many body sites, but rather...

the optimum temp of it's replication (33-34 degrees C)

85

what family is RSV (resp. syncytial virus) in? what are features of this family?

Paramyxoviridae
- enveloped
- helical
-non-segmented minus strand RNA
- structure and replication = similar to measles

86

features of normal bronchioles:

< 5mm
end in alveoli
lack cartilage rings in walls

87

syncytium

a multi-nucleated cell

88

in cases of RSV you can see what histologically?

multinucleated cell (Syncytium) and inclusion of RSV

89

the pathophysiology of bronchiolitis?

RSV attacks the bronchiole--- > inflammation, epithelial death, increased mucus production ---> thickening of bronchiole wall plus necrotic debris ---> narrowing of airway. On inhalation, the bronchioles expand and air gets in, but on exhalation the pressure closes the bronchioles, leading to: wheezing, less O2 exchange, and gas trapping

90

on xray, what happens to the lungs in bronchiolitis?

hyperinflation

91

does RSV infection efficiently prevent re-infection?

no! 75% of those with 1st exposure get it again, and 65% of those with 2nd exposure get it a 3rd time!

92

How does previous infection by RSV affect the severity of the infection?

the severity of RSV infection is reduced by previous infection (ie. first time ifxn is usually associated with fever and LRTI, well as 2nd and 3rd exposure have less fever and are more commonly assoc with being well/URTI)

93

how do Abs respond to RSV?

neutralizing IgG response wanes quickly
IgA response is weak/absent in infants

94

Th2 response to RSV

might be associated with increased pathology (wheezing)

95

RSV txt

- most = mild- treated at home for fever/hydration
- severe cases require O2, role of steroids/bronchodilators is unclear

96

preventing RSV (2 hings)

1. exclusive breast feeding reduces risk of LRTI by 40-50% in infants
2. susceptible children get prophylaxis with monoclonal Ab agst F-prot

97

64 yo woman in Jan presents with:
abrupt onset of headache, fever, chills, myalgia, cough, sore throat and malaise, fever (39.7) and 99% O2 sat, cervical lymphadenopathy, lungs clear, flushed

influenza

98

can influenza be diagnosed with certainty on history/PE?

no-- but it's more likely with: severe constitutional symptoms (fever/chills), severe headaches and myalgias

99

peak month of influenza ifxn?

february

100

pandemic

explosive, world-wide outbreak

101

RNA segments in Influenza
A:
B:
C:

RNA segments in Influenza
A:8
B:8
C: 7

102

why is seasonality important for the spread of influenza?

-- most common in seasons with low absolute humidity
- influenza drops during school vacations because less contact

103

Abs target what two things in Influenza A viruses and provide what?

Abs target Hemagglutinin and neuraminidase and provide protection from subsequent ifxn with same subtype influenza A virus

104

hemoptysis

coughing up blood

105

influenza A subtypes are defined by

serotypes of hemagglutinin (H 1-16) and neuraminidase (N 1-9)

106

influenza A serotypes are defined by

lack of Ab cross-reactivity

107

viruses are names for:

type/site of isolation/ isolate number and year (A/California/7/2009)

108

annual influenza A and B epidemics are caused by

unchanged strains or by strains generated by Antigenic drift (viral RNA polymerase makes a mistake 1/10,000 bases)

109

Antigenic shift occurs when

an influenza A virus, for which there is no pop immunity infects humans

110

the segmented genome of influenza A allows ready...

reassortment in doubly infected cells

111

the H sequence of influenza A determines

affinity for forms of sialic acid

112

how does influenza ifxn damage the host?

1. ciliated columnar epithelial cells are primary cells infected and killed
2. host mRNA = degraded/production = blocked ---> prot synth = blocked
3. apoptosis = induced

113

3 outcomes of influenza A

1. uncomplicated inf ---> recovery = very common
2. bacterial pneumonia ---> moderate mortality = uncommon
3. viral pneumonia ---> high mortality = rare

114

common bacterial pneumonias that infect post viral resp tract ifxn (3)

S. pneumoniae, S. aureus and H. influenzae

115

manifestations of influenza followed by viral pneumonia

severe influenza ---> hemorrhagin pneumonia, hyaline membranes line alveoli and scant inflammation --> fluid accumulation ---> decreased gas exchange ---> death

116

the inactivated influenza vaccine is administered...
comments (4)

intramuscularly.
comments: 1) inexpensive, 2) > 6 mo old, 3) high dose avb for >65yo, 4) egg allergy = contraindication

117

live attenuated inf vaccine is administered...?
comments (3)

intranasal
comments: expensive, ages 2-49, eg allergy, pregnancy and immunocompromise are contra indications

118

which type of inf vaccine is least expensive? which can you give to children older than 6 months, but younger than 2 and/or people 50 and older?

inactivated influenza vaccine

119

which resp. tract infection (RTI) evades the imm response by hiding its conserved Ag?

rhinovirus (ICAM-1 receptor)

120

which RTI evade imm resp by stimulating a partially effective response?

RSV

121

which RTI evades imm resp by varying Ags?

rhinovirus and influenza