9_Respiratory Virus Flashcards
1
Q
Which viruses affect the UPPER respiratory tract?
A
Unique to Upper respiratory:
- Coxsackivirus
- Coronavirus
- Herpesvirus
- Rhinovirus
Others:
- Adenovirus
- Bocavirus
- Influenzairus
- Parainfluenza virus
- Respiratory syncytial virus
2
Q
list the viruses that infect the LOWER respiratory tract?
A
Unique: *Metapnuemovirus
- Adenovirus
- Bocavirus
- Influenzavirus
- Parainfluenza virus
- Respiratory syncytial virus
3
Q
What are the major viral respiratory pathogens?
A
4
Q
Parainfluenza viruses:
- family
- structure
- size
- serotypes
A
- Family: Paramyxoviridae
- Structure: enveloped, ss-RNA, negative, non-segmented
- size: pelomorphic (virions 150-300 nm diameter)
- 4 serotypes (1, 2, 3, 4)
5
Q
parainfluenza viral life cycle:
what is it?
A
- HIV virion binds to cell –> fuses with cell
- uncoats the virion
- genome undergoes transcription, and replication, and translation
- genome –> buds off
- and is released from the cell
6
Q
parainfluenza viruses - epidemiology
- environmental
- season
- age
A
- 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
7
Q
Parainfluenza:
- transmission
- pathogenesis
- clinical sxs
A
- 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)
8
Q
Parainfluenza:
- immunology
- treatment
A
- 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
9
Q
Respiratory syncytial virus (RSV)
- epidemiology
- at risk populations
A
- 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
10
Q
Respiratory syncytial virus (RSV)
- structure
- environmental
- season
- age of at risk population
A
- 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
11
Q
Respiratory syncytial virus (RSV):
- morbidity and mortality
- factors contributing to inc. risk
A
- 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
12
Q
Respiratory syncytial virus:
- transmission and
- immunology
A
- 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
13
Q
Respiratory syncytial virus:
clinical symptoms (childhood infxns, adults)
A
- childhood infxn
- lower respiratory illness
- bronchiolitis - cough
- pneumonia (crackles, repiratory distress)
- adult infections
- upper respiratory infxn resembling the common cold
14
Q
key differences b/w URT and LRTs:
which is more severe?
which viruses start this?
how does infection spread?
A
15
Q
Rhinovirus:
- family
- structure
- size
- causes what illness?
A
- family: Picornaviridae
- structure: positive, ss-RNA (non-segmented)
- non-enveloped
- icosahedral capsid
- size: 30 nM in diameter
- hundreds of serotypes
- causes: “common cold”
16
Q
what are the two unique physical properties of Rhinovirus?
A
-
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
17
Q
Rhinovirus:
epidemiology (Ages it affects, seasonal variations)
A
- 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)
18
Q
Rhinovirus:
- transmission
- pathogenesis
- clinical symptoms
A
- 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
19
Q
Adenovirus:
- family
- structure
- sxs
- functions
A
- 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
20
Q
Coronavirus:
- family
- structure
- genome
- size
- causes what disease
A
- 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)
21
Q
list the viral proteins on the Coronavirus
A
- S (spike) protein (150 kD)
- HE protein (65 kD)
- M (membrane) protein
- E (envelope) protein (9-12 kD)
- N (nucleocapsid) protein (60 kD)
22
Q
Severe acute respiratory syndrome (SARS):
hx
A
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
23
Q
Severe acute respiratory syndrome (SARS):
tx and vaccines
A
- 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
24
Q
Influenza:
- history
- cause
- transmission
- symptoms
- vaccine
A
- 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
25
**Influenza virus:**
* structure
* types
* 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
26
**Influenza A Virus**:
shifts and drifts?
which causes pandemics? what causes epidemics?
* Antigenic SHIFTS of haemagglutinin --\> **pandemics**
* Antigenic **DRIFTS of H& N** proteins --\> **epidemics**
27
**Influenza**: disease pathogenesis
## Footnote
**Mild influenza**
**Severe influenza**
* **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
28
How does influenza look under an electron microscope?
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**
29
do type A, B, and C influenza virus vary based on the following criteria?
30
Influenza virus:
## Footnote
**pandemic**
**epidemics**
31
what are the antigenic changes of influenza A?
* 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
32
**antigenic drift:**
define
* 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
33
antigenic shift:
how does this occur w/ influenza virus?
* 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
34
Mechanisms of influenza virus antigenic "shift"?
* **DIRECT:** non-humans --\> humans
* indirect:
* non-human virus --\> animal --\> reassortment virus --\> humans
* human virus --\> animal --\> reassortment virus --\> humans
35
where does influenza come from?
* 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
36
why **haven't there been any Influenza B pandemics** thus far?
* so far no shifts have been recorded
* no animal reservoir known
37
symptoms of influenza virus?
Infxn may be mild, even asymptomatic, or very severe
* fever
* headache
* myalgia
* cough
* rhinitis
* ocular sxs
* chills and/or sweats
38
clinical response for influenza
* 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
39
What is the immunity to influenza?
40
laboratory diagnosis of influenza
* 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**
41
how does **diagnosis hemagglutination inhibition** function?
and near patients or rapid tests which detects rise in antibodies to influenza or NA activity
42
prophylaxis for influenza
* **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
43
describe the types of vaccines for influenza
Types of vaccines:
* Killed whole virus
* Live virus
* Virus subunit
* Synthetic
44
which drugs are used for prevention and treatment of influenza?
how effective are they at preventing illness?
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
