9_Respiratory Virus

Question 1

Which viruses affect the UPPER respiratory tract?

Answer 1

Unique to Upper respiratory:

• Coxsackivirus
• Coronavirus
• Herpesvirus
• Rhinovirus

Others:

• Adenovirus
• Bocavirus
• Influenzairus
• Parainfluenza virus
• Respiratory syncytial virus

Question 2

list the viruses that infect the LOWER respiratory tract?

Answer 2

Unique: *Metapnuemovirus

• Adenovirus
• Bocavirus
• Influenzavirus
• Parainfluenza virus
• Respiratory syncytial virus

Question 3

What are the major viral respiratory pathogens?

Answer 3

Question 4

Parainfluenza viruses:

• family
• structure
• size
• serotypes

Answer 4

• Family: Paramyxoviridae
• Structure: enveloped, ss-RNA, negative, non-segmented
• size: pelomorphic (virions 150-300 nm diameter)
• 4 serotypes (1, 2, 3, 4)

Question 5

parainfluenza viral life cycle:

what is it?

Answer 5

1. HIV virion binds to cell –> fuses with cell
2. uncoats the virion
3. genome undergoes transcription, and replication, and translation
4. genome –> buds off
5. and is released from the cell

Question 6

parainfluenza viruses - epidemiology

• environmental
• season
• age

Answer 6

• environmental: parainfluenza type 3 is a serious nosocomial infxn
• season: parainfluenza 1& 2 infections occur in fall/winter, often in alternating years
• age:
  
  • 90-100% of children 5+ y/o, seropositive for parainfluenza type 3
  • 75% have Antibodies to parainfluenza types I & 2

Question 7

Parainfluenza:

• transmission
• pathogenesis
• clinical sxs

Answer 7

• transmission: close contact w/ infected persons or contaminated surfaces
  
  • through mucous membranes of eyes/mouth/nose
• pathogenesis:
  
  • site of replication: epithelial lining of upper respiratory tract
  • causes localized infection: no viremia occurs
  • incubation period: 2-3 days
  • virus is shed 8-10 days after infxn, up to 30 days
• clinical sxs
  
  • croup (parainfluenza 1& 2)
  • bronchiologitis (parainfluenza 3)
  • pneumonia (parainfluenza 3)

Question 8

Parainfluenza:

• immunology
• treatment

Answer 8

• immunology:
  
  • serum antibodies: questionable value since no viremia occurs
  • secretory antibodies: good correlation experimentally b/w IgA levels and protection against infxn, however protective levels not achieved in young children
    
    • passive immunity in breast fed children significant
• vaccine: no vaccine currently available

Question 9

Respiratory syncytial virus (RSV)

• epidemiology
• at risk populations

Answer 9

• primary cause of lower respiratory tract illness in young children
  
  • RSV infxn: 125,000 pediatric hospitalizations in the US
• at risk populations: children
  
  • generally resolves uneventfully
  • high risk populations may develop severe (sometimes fatal) illnesses
  • annual mortality to RSV in infants/children is 200-2,700

Question 10

Respiratory syncytial virus (RSV)

• structure
• environmental
• season
• age of at risk population

Answer 10

• structure:
  
  • family: paramyxoviridae
  • enveloped, (negative sense) single stranded, non-segmented RNA
  • pleopmorphic, 2 serotypes (A &B)
• environmental: hospitals ,day care, nursing homes
• season: annually every Nov-Mar, later in warmer climates
• age of at risk population: 50% of all children are seropositive by 1 yr of age, 85% by 4 years old

Question 11

Respiratory syncytial virus (RSV):

• morbidity and mortality
• factors contributing to inc. risk

Answer 11

• 100,000 hospitalizations; 4,500 deaths per year in US
• Factors contributing to increase risk:
  
  • premature infants, infants <6 weeks old
  • infants w/ congenital heart disease
  • infants w/ chronic lung conditions; cystic fibrosis
  • immunodeficiency
  • lower socioeonomic status/ crowded living conditions
  • attendance in day care setting
  • infants who are not breast fed
  • exposure to cigarette smoke

Question 12

Respiratory syncytial virus:

• transmission and
• immunology

Answer 12

• transmission: large aeorsolized respiratory droplets, generated by sneezing/coughing/through contact w/ nasal secretions/contaminated surfaces
  
  • enters through eyes/nose and infects epithelial cells of upper respiratory tract
  • incubation: 3-4 days
  • virus shedding 1-2 days prior to symptoms and can last up to 3 wekks
• immunology: virus transmitted cell-cell fusion
  
  • free virus is not present –> neutralizing antibodies are not formed
  • primary infection doesn’t prevent re-infection
  • passive immunity - maternal antibodies reduce severity of infxn
  • secretory IgA directed against F protein is effective neutralizing antibody

Question 13

Respiratory syncytial virus:

clinical symptoms (childhood infxns, adults)

Answer 13

• childhood infxn
  
  • lower respiratory illness
  • bronchiolitis - cough
  • pneumonia (crackles, repiratory distress)
• adult infections
  
  • upper respiratory infxn resembling the common cold

Question 14

key differences b/w URT and LRTs:

which is more severe?

which viruses start this?

how does infection spread?

Answer 14

Question 15

Rhinovirus:

• family
• structure
• size
• causes what illness?

Answer 15

• family: Picornaviridae
• structure: positive, ss-RNA (non-segmented)
  
  • non-enveloped
  • icosahedral capsid
• size: 30 nM in diameter
  
  • hundreds of serotypes
• causes: “common cold”

Question 16

what are the two unique physical properties of Rhinovirus?

Answer 16

• Temperature stability
  
  • extremely stable at room temp;
  • can survive on surfaces at room temp for 18 hr or more
  • adapted to replicated better at 33 degrees celsius than 37 degrees
  • infect URT due to lower temp.
• pH lability
  
  • unlike other enteroviruses (+ssRNA viruses), rhinoviruses are not acid-stable
  • rhinoviruses are destroyed at low pH

Question 17

Rhinovirus:

epidemiology (Ages it affects, seasonal variations)

Answer 17

• age: children are most frequently infected and are major source of adult infections
• seasonal variations:
  
  • rhinoviruses –> cause colds in Fall and Spring
  • Coronavirus –> cause winter colds
  • (patterns may be due to changes in living w/ the seasons)

Question 18

Rhinovirus:

• transmission
• pathogenesis
• clinical symptoms

Answer 18

• transmission:
  
  • *direct contact w/ infectious nasal secretions on skin/contaminated surfaces
  • enters via eye or nasal pharynx and attaches via ICAM-1 or LDL receptor to epithelial cells in the posterior nasal pharynx and nasal passages
• pathogenesis
  
  • incubation: 2-3 days
  • sxs appear after 3-4 days
  • virus shedding begins 1-2 days prior to sxs –> continues for 1 week
  • infxn is self-limiting and localized to URT
• clinical symptoms
  
  • ST, stuffy nose, runny nose, sneezing, malaise

Question 19

Adenovirus:

• family
• structure
• sxs
• functions

Answer 19

• Family: Adenoviridae
• structure: non-enveloped viruses, icosahedral nucleocapsid, ds-DNA genome
  
  • medium-sized
  • *usually self-resolving, no anti-viral treatments available
• sxs:
  
  • causes URT in children, some adult infxns
  • eye infections (i.e. conjunctivitis)
  • GI distress
  • causes acute respiratory distress
• fxns:
  
  • viral vector used in gene therapy

Question 20

Coronavirus:

• family
• structure
• genome
• size
• causes what disease

Answer 20

• family: Coronaviridae
• structure: enveloped, derived from intracellular (not plasma) membrane
  
  • spike proteins on evelope resemble crown, corona = crown
• genome: positive, non-segmented single-stranded RNA; capped polyadenylated
• size: 100 nM in diameter
• causes what disease:
  
  • causes severe acute respiratory syndrome (SARS)

Question 21

list the viral proteins on the Coronavirus

Answer 21

• S (spike) protein (150 kD)
• HE protein (65 kD)
• M (membrane) protein
• E (envelope) protein (9-12 kD)
• N (nucleocapsid) protein (60 kD)

Question 22

Severe acute respiratory syndrome (SARS):

hx

Answer 22

Deadly virus, w/ 774 deatsh in November 2002- July 2003

Hx

• outbreak in China –> farmer w/ no definie diagnosis
• cluster of cases in hong kong
• hotel visitors –> traveled outside China causing local transmission in US, Canada, etc
• Last case of natural transmission from human-human was in June 2003

Question 23

Severe acute respiratory syndrome (SARS):

tx and vaccines

Answer 23

• tx
  
  • supportive therapy
  • anti-inflammatories (corticosteroids) controversial, can be immunosuppressive)
  • ribavirin (Efficacy not established)
  • coronavirus-specific drugs under development
• vaccine
  
  • vaccines under development
  • some early evidence that passive immunity and neutralizing antibodies are protective
  • strategry must be for multivariant strain vaccine

Question 24

Influenza:

• history
• cause
• transmission
• symptoms
• vaccine

Answer 24

• history: 1918 influenza epidemic; >20M people died during WWI
• cause: influenza A H1N1 virus
• transmission: from aerosols from coughing and sneezing
  
  • spread rapidly
• symptoms: highly lethal
• vaccine: new vaccine must be developed annually

Question 25

Influenza virus:

• structure
• types

Answer 25

• family: Orthomyxoviridae
• negative stranded ss-RNA virus
  
  • genome has 8 segments
  • enveloped virus, w/ haemagglutinin adn neuraminidase spikes
• 3 types based on serotype of ribonucleic protein
  
  • Type A: infects multiple species; undergoes antigenic shift and drift
  • Types B and C infects exclusively humans;
    
    • B: undergoes antigenic drift ONLY
    • C: relatively stable

Question 26

Influenza A Virus:

shifts and drifts?

which causes pandemics? what causes epidemics?

Answer 26

• Antigenic SHIFTS of haemagglutinin –> pandemics
• Antigenic DRIFTS of H& N proteins –> epidemics

Question 27

Influenza: disease pathogenesis

Mild influenza

Severe influenza

Answer 27

• Mild: virus replication primarily restricted to upper respiratory tract
• Severe influenza: virus replicates extensively in lower respiratory tract, inhibiting gas exchange –> by damaging Type II pneumocytes and may disseminate further
  
  • excessive inflammatory respose
  • infxn and killing of pneumocytes
  • paralysis of cilia
  • severe hypoxemia
  • secondary infxns
  • multiorgan failure

Question 28

How does influenza look under an electron microscope?

Answer 28

Different shapes of the virus morphology –> polymorphic

Hemagglutinin (HA): seen on envelope as spikes; helps virus ENTER cell

Neuraminidase (NA): seen on envelope as rods; helps virus EXIT cell

Question 29

do type A, B, and C influenza virus vary based on the following criteria?

Answer 29

Question 30

Influenza virus:

pandemic

epidemics

Answer 30

Question 31

what are the antigenic changes of influenza A?

Answer 31

• viruses can undergo frequent changes due to recombination, reassortment, insertion, and point mutations
• antigenic drift
• antigenic shift – occurs every 8-10 years
• minor antigenic changes favor persistence of viruses in the population to eventually lead to severe epidemics and/or pandemics

Question 32

antigenic drift:

define

Answer 32

• gradual accumulation of mutations that allow the virus to escape neutralizing antibodies
  
  • can result from changes in amino acids
  • can involved any antigenic protein
  • can occur every year
• epidemic strains thought to have changes in 3 or more antigenic sites

Question 33

antigenic shift:

how does this occur w/ influenza virus?

Answer 33

• occurs every 8-10 yrs
• major antigenic change of either H or N antigens or both H & N
• occurs by gene re-assortment after simultaneous infxn of cell w/ 2 diff’t viruses
• 3 diff’t H proteins and 2 major N proteins have evolved

Question 34

Mechanisms of influenza virus antigenic “shift”?

Answer 34

• DIRECT: non-humans –> humans
• indirect:
  
  • non-human virus –> animal –> reassortment virus –> humans
  • human virus –> animal –> reassortment virus –> humans

Question 35

where does influenza come from?

Answer 35

• type A constantly circulates in natural reservoirs
• BIRDS are natural reservoirs of all subtupes of influenza A viruses
  
  • migratory waterfowl
  • chickens, turkeys, ducks, geese
• Humans
• pigs
• horses
• other

Question 36

why haven’t there been any Influenza B pandemics thus far?

Answer 36

• so far no shifts have been recorded
• no animal reservoir known

Question 37

symptoms of influenza virus?

Answer 37

Infxn may be mild, even asymptomatic, or very severe

• fever
• headache
• myalgia
• cough
• rhinitis
• ocular sxs
• chills and/or sweats

Question 38

clinical response for influenza

Answer 38

• acute symptoms last one week
  
  • abrupt onset of fever, myalgia, HA, and non-productive cough
• fatigue and weakness can last 2-3 weeks
• infected individual predisposed to bacterial infxns (staph, strep, and hemophilus)
• immunity dependent upon localized anti-viral secretory IgA (strain specific)
• develop long lasting circulating anti-viral IgG

Question 39

What is the immunity to influenza?

Answer 39

Question 40

laboratory diagnosis of influenza

Answer 40

• using respiratory secretions (direct aspirate, gargle, nasal washings)
• virus isolation and growth in embryonated eggs
• cell culture in primary monkey kidney or mandindarby canine kidney cells
• *hemagglutination inhibition: Gold standard for diagnosis and used to follow drift and shift
• ELISA and direct immunofluorescence

Question 41

how does diagnosis hemagglutination inhibition function?

Answer 41

and near patients or rapid tests which detects rise in antibodies to influenza or NA activity

Question 42

prophylaxis for influenza

Answer 42

• Prophylaxis:
  
  • Masks
    
    • effectiveness is not shown for influenza
    • can reduce transmission assoc. w/ large droplets
  • Handwashing
    
    • generally perceived to be useful
    • no studies specifically performed for influenza
    • easy to recommend

Question 43

describe the types of vaccines for influenza

Answer 43

Types of vaccines:

• Killed whole virus
• Live virus
• Virus subunit
• Synthetic

Question 44

which drugs are used for prevention and treatment of influenza?

how effective are they at preventing illness?

Answer 44

70-90% effective in preventing illness

• Rimantadine: blocks M2 ion channel
  
  • type A only, needs to be given early
• Amantadine: blocks M2 ion channel
  
  • type A only, needs to be given early
• Zanamivir: neuraminidase inhibitors (NA)
  
  • types A and B, needs to be give early
• Oseltamivir: neuraminidase inhibitors (NA)
  
  • types A and B, needs to be given early