Lec 25 Resp Viruses Flashcards

1
Q

What does palivizumab treat?

A

RSV infections

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2
Q

What does ribavirin treat?

A

RSV infections

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3
Q

What does cidofivir treat?

A

adenovirus infection

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4
Q

What are the respiratory viruses we are responsible for?

A
Parainfluenza (hPIV)
Respiratory Syncytial Virus (RSV) 
Metapneumovirus (hMPV)
Influenza
Coronavirus (hCoV)
Adenovirus
Rhinovirus
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5
Q

What type of virus is measles?

A

morbillivirus

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6
Q

what type of virus is parainfluenza?

A

paramyxovirus

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7
Q

What type of virus is respiratory syncytial virus [RSV]?

A

pneumovirus

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8
Q

What type of virus is metapneumovirus?

A

pneumovirus

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9
Q

Paramyxoviruses: what sense, strandedness, DNA/RNA?

A
  • negative sense
  • single stranded
  • non-segmented RNA
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10
Q

What are the 3 proteins of paramyxovirus nucleocapsid?

A

helical nucleocapsid with 3 proteins

  • nucleoprotein [NP]
  • polymerase phosphoprotein [P]
  • large protein [L]
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11
Q

What are the glycoproteins in the lipid bilayer of paramyxoviruses?

A
  • fusion protein [F]

- attachment proteins [HN, H, G]

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12
Q

How do paramyxoviruses replicate?

A
  • attachment proteins bind to sialic acid on cell surfaces
  • genome transcribed into individual mRNAs and full-length + RNA template
  • nucleoplasmid associated with matrix and plasma membranes and leaves by cell budding
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13
Q

What are the clinical symptoms of parainfluenza virus?

A
  • primarily in young children get upper and lower respiratory tract infections
  • –> croup, common cold, bronchiolitis, pneumonia
  • community acquired resp tract infection in adults
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14
Q

What are the types of parainfluenza virus that most commonly cause croup?

A

HPIV-1, HPIV-2

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15
Q

What is pathogenesis of parainfluenza?

A
  • infects nasal and pharyngeal mucosal epithelia

- spread locally along respiratory epithelium to larynx and trachea

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16
Q

What is the steeple sign?

A

narrowing of trachea in subglottic region

= sign of croup

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17
Q

How is parainfluenza transmitted?

A

respiratory droplets or direct person-person contact

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18
Q

When do serotypes 1-4 infections occur primarily

A

HPIV-1 and HPIV-2: fall
HPIV-3: through year, peak in spring
HPIV-4: no well-defined infection pattern

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19
Q

How is parainfluenza diagnosed?

A
  • antigen detection: direct fluorescent antibodies [DFA] or ELISA
  • cell culture
  • PCR
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20
Q

What is treatment for parainfluenza?

A

normally self-limited, give supportive treatment

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21
Q

What is treatment for croup?

A
  • IV/IM/oral dexamethasone [steroid]

- for more serious: nebulized racemic epinephrine

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22
Q

What are clinical syndromes of RSV virus?

A
  • bronchiolitis or pneumonia [most common cause of bronchiolitis in kids < 2 yrs old]
  • usually upper respiratory tract disease
  • lower respiratory diseases in older children and adults
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23
Q

Who is at increased risk for severe RSV?

A
  • preterm birth
  • congenital heart diseases
  • chornic lung disease of prematurity
  • immunodeficiency
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24
Q

How is RSV transmitted?

A
  • by direct contact with contaminated secretion or fomite, persist on environmental surfaces/hands for hours
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25
Q

When are RSV outbreak?

A
  • winter and early spring in temperate climates
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26
Q

How is RSV diagnosed?

A

rapid antigen test [fast but not that sensitive]

also: DFA, cell culture, PCR

27
Q

What is treatment for RSV? for not severe? for severe?

A

if not severe: supportive

if severe/immunocompromised: ribavirin [oral, IV, aerosolized forms]

28
Q

What is ribavirin? mech of action? what is downside?

A
  • nucleoside analog that inhibits nucleic acid synthesis
  • used to treat RSV
  • comes in oral/IV/aerosolized form
  • its a teratogen so can’t be administered near pregnant women in aersolized form
29
Q

What are ways to prevent RSV?

A
  • give palivizumab = monoclonal antibody against RSV F protein
  • infection control = use contact precautions
30
Q

What is palivizumab?

A
  • monoclonal antibody against F protein of RSV
  • gives passive immunity to high risk infants
  • reduces hospitilization rates
  • give monthly IM during peak season [nov - march]
31
Q

What is pathogenesis of RSV?

A
  • replicates in nasopharynx then infects bronchiolar epithelium
  • extends to alveolar pneumocytes by cell-cell spread, aspiration of secretions, formation of syncytia!!!
  • necrosis of bronchi and bronchioles causes mucus plugs to form
32
Q

What are the first and second leading cause of bronchiolits in infants?

A

first: RSV
second: human metapneumovirus

33
Q

What are clinical syndromes associated with human metpneumovirus?

A
  • bronchiolitis in infants
  • 15% of common colds in children
  • pneumonia, croup, URIs
34
Q

Who is at risk for severe hMPV?

A
  • immunocompromised
  • preterm birth
  • transplant
  • cardiopulmonary disease
35
Q

How is human metapneumovirus [hMPV] transmitted?

A
  • direct or close contact with contaminated secretions

- some health-care associated infections

36
Q

When do hMPV infections occur?

A

late winter/early spring in temperate climates

37
Q

how is hMPV diagnosed?

A

PCR
antigen detection
cell culture [but difficult to grow and requires long incubation]

38
Q

What is structure of coronavirus?

A
  • enveloped
  • single strand
  • positive sense
  • RNA
  • glycoproteins form halo-like projections that surround envelope = corona
  • RNA genome plus N protein form helical nucleocapsid
39
Q

How if hMPV treated?

A

supportive

40
Q

How is coronavirus replicated?

A
  • uses E1/E2 attachment proteins to bind cell
  • virus fuses with cell and genome is released in cytoplasm
  • translation of genome in two phases
  • —- early phase: produces RNA polymerase
  • —- late phase: negative sense RNA yields struct and non struct protein
  • forms into vesicle at RER
  • released by exocytosis
41
Q

What clinical syndromes associated with coronavirus?

A
  • common cold and other resp infections
  • gastroenteritis
  • SARS
42
Q

What are signs of SARS? possible cause?

A
  • can be due to coronavirus
  • fever, pneumonia/resp distress, diarrhea, leukopenia
  • 10% mortality
43
Q

How is coronavirus transmitted?

A
  • reservoir may be in animals

- transmitted by resp tract secretions via person to person contact or fomites

44
Q

When do coronavirus infections occur?

A
  • some sporatic

- outbreaks in winter/spring

45
Q

What is MERS?

A
  • middle east respiratory syndrome
  • newly recognized pathogenic coronavirus
  • no treatment currently
46
Q

How is coronavirus diagnosed?

A
  • PCR [respiratory, stool]
  • antibody assays
  • electron microscopy
47
Q

What is treatment for coronavirus?

A
  • supportive care
  • steroids used to treat SARS-CoV associated respiratory distress syndrome [ARDS]
  • no treatment for SARS
48
Q

Where does transcription/translation occur in DNA viruses?

A

in nucleus

49
Q

What is structure of adenovirus?

A
  • linear
  • double stranded
  • DNA
  • non-enveloped
  • icosadeltahedron shape
50
Q

How does adenovirus replicate?

A
  • viral fibers attach glycoprotein member of Ig superfamily
  • penton base interacts with integrin on host cell [helps endocytosis]
  • DNA genome goes to nucleus
  • transcription of mRNA in two phases
  • capside proteins produced in cyto and transported to nucleus for viral assembly
  • virus remains in cell and released when cell degenerated and lyses

short form: everything happens in the nucleus

51
Q

What clinical syndromes associated with adenovirus

A

immunocompetent: pharyngitis + conjuctivitis [pink eye]
also: URI/LRI, gastroenteritis, cysitis

imunocompromised = more severe disease: pneumonia + respiratory failure, meningitis, encephalitis

52
Q

How is adenovirus transmitted?

A
  • by aerosol, close person-person contact, fecal-oral, fomites
  • very contagious!
53
Q

what is pathogenesis of adenovirus infection?

A
  • virus establishes pharyngeal infection
  • infects mucoepithelial cells in respiratory tract, GI, conjunctiva/cornea
  • virus persists in lymphoid tissue
  • viremia can occur if local replication
  • then spreads to visceral organs
54
Q

Where and when do adenovirus outbreaks occur?

A

in congregate settings –> military

no seasonality [all year round]

55
Q

How is adenovirus diagnosed?

A

DFA
culture [for some serotypes]
PCR

56
Q

How is adenovirus treated?

A
  • usually supportive

- cidofovir for some immunocompromised

57
Q

What is cidofovir? mech? type of administration? side effects?

A
  • cytosine analog
  • serves as substrate and inhibits viral DNA synthesis
  • used to treat adenovirus in immunocompromised patients
  • clear benefit has not been demonstrated
  • IV administration
  • side effect: nephrotoxic
58
Q

What are clinical syndromes associated with rhinovirus?

A
  • most frequent cause of common cold
  • pharyngitis
  • otitis media
  • less commonly: bronchiolitis, pneumonia
59
Q

what is the most frequent cause of common cold?

A

rhinovirus

60
Q

How is rhinovirus transmitted?

A

aerool/droplets, fomites

hands are major vector!!

61
Q

When do rhinovirus infections primarily occur? in which patients?

A
  • in autum and late spring

- highest in infants and children

62
Q

How is rhinovirus treated?

A

supportive

63
Q

how can rhinovirus be prevented?

A

hand washing, disinfection contaminated objects