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Flashcards in Respiratory Viral Infections Deck (109):
1

Why is there a global potential of new respiratory viral epidemics?

viruses mutate and evolve fast; respiratory viruses spread fast by bird or human flight; widely zoonotic; difficult to contain

2

How does the incidence of respiratory illnessses per person per year change with age?

declines over the course of a lifetime with a peak in the early 20s

3

What is the percentage of respiratory infections caused by viruses?

75%

4

What is the type of genetic info in RSV?

RNA

5

What protein in the virus determines the viral tropism?

viral coat

6

What is the suffix of all viral families?

viridae

7

What is the suffix of a viral genus?

virus

8

What type of virus has quasispecies?

RNA viruses

9

Give examples of DNA viruses?

poxviruses; herpesviruses

10

How are DNA viruses adapted to immune pressures?

mimicry

11

What is a quasispecies?

mutant viruses that develop as a virus replicates in a host

12

What is the envelope of virsues derived from?

host membrane- lipid

13

What is found on the outside of viruses that don't have an evelope?

symmetrical protein capsid

14

Why is it difficult to block the replicative processes of viruses?

use the host's biochemistry

15

Give an example of an infection which has acute viral infection then clearance?

flu

16

give an example of an infection which shows acute viral infection/clearance and re-infection?

RSV

17

Give an exmaple of a virus which shows slow chornic infection?

CMV

18

What is the general mechanism behind viral causes of oncogenesis?

an immune defense against viruses is apoptosis, thereofre viruses turn off this mechnism to survive, but this also results in cancer

19

What is viral culture?

growing virus in immortalised cell line

20

What family do the human rhinoviruses come under?

picornaviruses

21

What type of virus are the influenza viruses?

orthomyxoviruses

22

What are coronaviruses typically responsible for?

zoonotic transmission and epidemics

23

What viruses are paramyxoviruses?

RSV; parainfluenza

24

How many genes does RSV have?

10

25

What type of genome does RSV have?

ssRNA

26

Why is RSV able to reinfect?

stimulates poor immunological memory

27

What is the function of NS1 and NS2 in RSV?

non-structural proteins which have anti-interferon a and b activity

28

What is the function of N and P genes in RSV?

nucleoprotein and phosphoprotein- nucleocapsid proteins essential for transcriptional activity

29

What is the function of M gene in RSV?

matrix protein- viral assembly

30

What is the function of SH gene in RSV?

small hydrophobic protein- unkown function

31

What is the function of G gene in RSV?

glycoprotein- viral attachment to the cell

32

What is the function of F gene in RSV?

fusion protein- viral entry and syncytia formation

33

What is the function of M2 gene in RSV?

M2:1- transcription elongation factor; M2-2: regulation of viral transcription

34

What is the function of L gene?

nucleocapsid protein- RNA polymerase

35

How many strains of RSV are there?

2- A and B

36

What is RSV associated with in later life of infants it infects?

wheezing/astham (chicken and egg Q-- are children more ;ikely to get RSV is predisposed to asthma; or does RSV change lungs)

37

What is the largest single cause of hsopitalisaiotn in infancy?

RSV

38

What disease does RSV cause in infants?

bronchiolitis

39

What age is the highest risk for RSV bronchiolotis?

1-6months

40

What are the 2 forms of surface glycoproteins on influenza?

neuraminidase (N) and haemagglutinin (H)

41

What is unique about the genome of influenza viruses compared with otehr respiratory viruses?

have a segmented genome

42

What is antigenic drift?

minor changes caused by point mutations- slow process -- antibody no longer recognises

43

What is antigenic shift?

multiple alterations in antigenic makeup due to reassortment of genome segments; rapid process associated with pandemic outbreaks

44

Describe the pathogenicitiy of H5N1?

can replicate efficiently only in cells in the lower region of resp tract where the avianvirus receptor is prevalent- if gets into lower airways causes havoc but limited in its chances of getting there- mainly poultry workers

45

Where were >70s not affected by H1N1?

similar virus in the 1960s so immunological memory

46

Why is influenza difficult to prevent the transmission of?

very infecitous when asymptomatic

47

How amny serotypes are there of human rhinoviruses?

>100

48

What is the second main cause of hospitalisation in children under 5 years?

parainfluenza

49

What disease is parainfluenza assocaited with ?

croup

50

What is the evidence that RSV disease isn't caused by virus directly but immunopathology?

illness is after the peak viral load, SCID mice do not get normal RSV pathology, instead are overwhelmed by virus after WT mice have cleared infection

51

What form does prophylaxis of viral infection take?

passive transfer of antibody to block disease

52

When are antivirals particularly effective?

when viral pathogenesis/persistence is the problem

53

Why would anti-RSV drug not work in acute infection?

by the time giving antivirals in response to symptosm , too late as viral peak has already happened, symptoms happeneing as result

54

What is hte problem with tinkering with inflammation e.g anti-TNF?

very dependent upon timing as during peak viral load need to boost inflam whereas need to dampen inflammation during actual disease after viral peak

55

What is the most common lab abnormality detected in viral infection?

hypoxamia

56

What are the absolute indications for hospital referrals for acute bronchiolotis?

cyanosis or severe respiratory distress (RR>70; nasa flaring; grunting; chest wall recession); marked lethargy-poor feeding; respiratory distress preventing feeding (<50% usual intake in past 24 hours); apnoeic epsidoes; diagnostic uncertainty

57

What pulse ox says a baby should be admitted?

<=92

58

What is the first choice in control of viruses?

vaccination

59

What is the treatment for bronchiolitis?

supportive- oxygen (intubation; CPAP; head box)'; fluids; +/- antibiotics; vasodilators and CS

60

How many respiratory infections do children get per year on avergae?

5-6

61

How many infants with respiratory viral infections will develop lower respiratory tract symptoms ?

1/3rd

62

give examples of extrapulmonary manifestations of RSV infection?

seizures; hyponatraemia; cardiac arrhythmias; cardiac failure and hepatitis

63

Which infants are at risk of severe LRTI?

premature and infants with congenital heart disease

64

Give examples of neuraminidase inhibitors?

oseltamivir and zanamivir

65

What is the benefit of neuraminidase inhibitors?

shortens symptoms by about 1 day and may reduce disease severity

66

When are neuraminidase inhibitors helpful?

wihtin 48h of exposure or 36h after first symptoms- not in established influenza infection or sever LRTI

67

Who should get neuraminidase inhibitors?

for children with chronic morbidity who are at an increased risk of sever influenza-induced disease

68

What is ribavirin licensed for?

inhalation for severe RSV bronchiolitis

69

What is a problem with ribavirin?

teratogenic

70

Why has ribavirin provided little or no benefit?

once developed, the severe inflammation in RSV bronchioloitis may be maintained independetly of the presence of live RSV virions

71

Which respiratory infections are cosrticosteroids helpful in?

croup

72

What are the 4 main ways in which respiratory viruses are diagnosed?

virus culture; serology; immunofluorescen/antigen detection and nucleic acid/PCR based test

73

What is serology?

blood is tested for either virus-specific antibodies or viral antigen by a functional assay

74

What is the disadantage of both viral culture and serology?

cultures can take upto 10 days and the antibody response to viral infection can take 2 weeks (infection is often resolved before the infecitous agent is defined)-- more useful in epidemiological studies

75

Whati s the basis of antigen detection?

use of virus-specfic monoclonal antibodies

76

Which viruses cause bronchiolotis?

influenza; adenovirus; human metapenumovirus; parainfluenza; rhinovirus and RSV

77

What is the role of viral coinfection in bronchiolitis?

common-20% of cases; depends on whcih viruses coinfect together- increase in severesity with hMPV and RSV but not with RSV+ adenovirus/rhinovirus

78

What is the benefit of knowledge of the infecting agent?

doesnt alter treatment but will reduce inappropriate antiboitic use and may allow cohorting of patients to reduce nosocomial infection

79

What are the factors involvedi n likelihood of a respiratory tract infection?

age and exposure to infection

80

What are the risk factors for severe RSV infection?

age when infected; increased exposure to an infectious agent; decreased body size; protection against virus due to breastfeeding and amount of IgG in breast milke; factors affecting lung function eg smoke and air pollution

81

What are the factors related to increased exposure to an infectious agen?

siblin order; daycare attendance; birth season; hospitalisation and socioeconomic status

82

Why does young age act as a metafactor?

age has an effect on the size of hte child- esp airway size; transmission dynamics; immune experience ; have smaller energy reserves and more likely to get exhausted by effort of breathing

83

What is the ultimate cause of mortality in acute bronchiolitis?

exhuastion due to effort of breathing

84

Polymrophisms in which genes of the innate immune system result in higher RSV susceptbility?

transcriptional regulator Jun; IFNa; nitric oxide synthase and the vitamin D receptor

85

What are the 2 groups of genes important for changing the outcome following respiratory viral infection?

first group- involved in the magnitude and type of immune response e.g IL-4 or IL13; second- genes involved in control of viral load e.g TLR4; IL6; CD14

86

Which TLRs detect viruses extracellularly?

TLR2,6 and 4 (mice deficient in TLR2/6 have increased RSV virla load)

87

How does RSV interact with TLR4?

via its F protein

88

What is the function of hte influenza virus NS1 protein?

concelas the viral genome from deetection

89

How does RSV prevent RIG-I detection?

binds La antigen

90

What is the effect of RSV on downstream signalling from PRRs?

inhibits IFN production; IRF3 activation is inhibited; although NF-kB increases following RSV (prevent apoptosis); IFNa receptor signalling by the JAK-STAT pathway

91

How is the adaptive immune repsonse evaded by respiratory viruses priamrily?

mutation of viral proteins

92

Which is the main respiratory virus that does not have an RNA genome?

adenovirus

93

What effect does increasing glyosylation of the coat proteins of a virus have?

increased immune evasion

94

What does influenza use to inhibit DC function?

haemagglutinin and NS1 proteins

95

What suggests that lung damage caused by the virus is a key factor in pathology?

correlation bewteen viral load and disease severity; RSV cause inhibit cilia movement leading to airway blockade; study of infants who died of RSV showed presence of virus but not lymphocytes- however this might be due to immunodeficiency; RV causes cytotoxicity in vitro; inhibiting cytokein response had not effect on H5N1 pathogeneisis; IL-1 deficiency mice had worse pathology with influenza

96

What evidence suggests that immunopathology is responsible for lung damage with respiratory infectiosn?

RSV-child who ided in crash had lots of lymphocytosis; RSV-infected HIV pos infants had icnreased viral shedding but decreased bronchiolitis; data shows patietns who died of SARS or H5N1 had cleared the virus; antiviral drugs did not alter disease outcome; RSV and RV are characterised by neutrophil infiltrate; IL-8 is upregulated in RSV bronchiolitis and asthmatics with RV

97

What is the function of IL-8

main neutrophil chemosttractant

98

What are the 2 main methods by which viral infection enhances bacterial infections?

altering physical barriers and altering immune system barriers

99

How does the viral infection alter the physical barriers ?

may damage lung epithelia (virus and immune response); neuraminidase thins mucus and exposes receptors onf epithelial cells- increased bacterial infectivity

100

How does influenza alter the immune response?

inhibit neutrophilia

101

When does bacterial coinfection tend to happen with viral infections?

later stages of viral infection- during dampening of immune repsonse e.g IL10 upregulation can lead to increased bacterial infection; general downregulation of pathogen sensing following viral infection

102

Why do infants have a tendency towards hyporesponsive immune responses?

critical to survive exposure to previously unseen nonpathogenic antigens of both self and foregin origins

103

what type of Th response are infant immune responses skewed towards and why?

Th2- reflection of pregnancy- to avoid rejection, Th1 in pregnnacy is associated with preeclampsia, infections eg chlamydia which stimualte Th1 assoc. with abortion

104

Which respiratory viruses have an associated with later-life wheezing?

hMPV; RV and RSV

105

What virus is ribavirin used for?

RSV

106

What is the problem with antivirals in general?

very prone to inducing viral escape mutatns eg oseltamivir resistnace only requires a single point mutation

107

Give an example of passive immunisation?

palivizumab- monoclonal antibody against RSV

108

If infants have immune hyporesponsiveness, how is there a problem with immunopathology?

have reduced IFN and th1 responses; with increased IL23 and Th17; reduced immunoregulation(IFN increases IDO); lack of previous exposure to virus- increased viral load--resulting response is greater

109

What should be considered with the possiblity of vaccinating against viral infections early in life?

infection is important in the development of normal immune responses thereofre vaccination coverage may have an impact on immunity development and more severe infection/asthma later in life