Flashcards in Respiratory Viruses Deck (121):
where are most respiratory infections acquired from?
how are most respiratory infections spread
from the afflicted respiratory tract by contact or droplets
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)
respiratory viruses usually invade and stay confined to...
the epithelial cells of the respiratory tract.
How do respiratory viruses spread within the host?
within the lumen of the respiratory tract by movement of respiratory secretions (mucus)
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
what is important for the fast elimination of respiratory viruses?
Innate immune responses (interferons)
how do respiratory viruses damage the host?
1. the cytopathic effect of the virus on infected cells
2. host inflammatory response
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
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
the common cold is caused by...
a viral infection of the nasal mucosa
manifestations of the common cold
rhinorrhea, cough and sore throat, sneezing and mild (or no) fever
half common colds are caused by what virus?
why do rhinvirus have tropism for the nasal mucoso?
bc they replicate best at the low temp of the nasal mucosa
how does rhinovirus evade the Ab response?
by having over 100 serotypes
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
what is bronchiolitis?
inflammation of the bronchioles, usually associated with a viral ifxn
bronchiolitis is most common amongst people of what age?
children under 2
symptoms of bronchiolitis
fever and rhinorrhea, followed by cough and wheezing of 1-2 wk duration
severe cases include tachypnea, dyspnea, hypoxia and cyanosis
what is RSV?
Respiratory Syncytial Virus (RSV)-- an enveloped virus with a non-segmented, minus-strand RNA
what causes 80% of bronchiolitis?
RSV- which infects any part of the resp tract (URTI and LRTI)
infection of the bronchioles (like bronchiolitis) leads to
narrowing of the bronchiolar lumen, as the wall thickens and debris accumulates
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
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
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
Symptoms of influenza?
mostly constitutional-- fever, chills, malaise, myalgias, headache, sore throat and a cough
in the us, how many people die of influenza on average
enveloped or not? what type of genome?
enveloped, segmented minus strand RNA genome
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
when does influenza spread the most efficiently and why?
in the winter because absolute humidity is lowest and it facilitates the spread
protein on the surface of Influenza that binds to sialic acid on the host cell surface, leading to endocytosis of the virus
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
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
what is adamantase?
antiviral drugs that block the M2 ion channel and prevent release of RNP. It is only effective against influenza A
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
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.
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
antiviral drugs that block the action of neuraminidase, which inhibits the release of the virus. these are effective against both influenza A and B
what is the primary mechanism by which influenza viruses escape host defenses?
antigenic variation-- leads to repeated ifxns throughout life
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)
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
why is antigenic drift so common in influenza A and B?
because viral RNA polymerase is error-prone and lacks proof reading function
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
the source of new influenza A virus during pandemic shift?
an animal, like a pig or bird
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
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
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
how many influenza viruses are generally circulating in any given winter?
3: 2 A serotypes and 1 B serotype
how long does it usually take to recover from influenza?
how does influenza damage the host?
1) kills ciliated epithelial cells that it infects, which weakens host mucociliary clearance (bacterial pneumonia can follow)
is bacterial or viral pneumonia more common?
bacterial (viral influenza, however, can kill cilated cells ---> weaken mucociliary clearance ---> increase bacterial ifxns)
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.
how do you prevent influenza?
annual vaccination for people 6 mo or older
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
Natural hosts for influenza
Natural hosts for influenza
A: mammals and birds
B: humans (and seals)
virulence of influenza
virulence of influenza
A: mild- severe
B: mild, rarely severe
C: very mild, children
antiviral medications for influenza
antiviral medications for influenza
A: adamantases and neuraminidase inhibitors
B: neuraminidase inhibitors
source of antigenic variation, and the type of outbreak associated with influenza
source of antigenic variation in influenza
A: antigenic shift (pandemic) and drift (endemic)
B: antigenic drift (endemic)
C: antigenic variation (outbreak)
is there a vaccine for influenza
is there a vaccine for influenza
respiratory viruses often cause diseases in spite of the fact that they
1. infect the respiratory system but rarely invade
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
the source of many respiratory viruses are ... but a few like influenza are from... and others, like SARS, are from...
Influenza: birds (chickens), pigs, maybe seals?
SARS: palm civet cat
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)
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
how do respiratory viruses enter the host?
how do respiratory viruses exit the host?
how are respiratory viruses transmitted?
contact with or inhalation of droplets
why is there seasonal occurence of resp. ifxns?
bc of transmission
resp. viruses adhere to... using
resp. epithelial cells using normal host cell-surface structures
respiratory viruses generally spread...
to adjacent or distant resp epithelial ells in EC mucus
invasion beyond resp. epithelium is rare and usually associated with...
severe ifxns (like SARS- severe acute resp syndrome) and viremia
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
primary mech for resp viruses to evade imm resp
Diversity of respiratory viruses (9 types)
2. coxsackie virus A
5. Resp Syncytial virus
6. influenza virus
7. parainfluenza virus
8. human metapneumovirus
escaping the Ab response via serotypic variation allows...
the same species of resp virus to infect and ind repeatedly
new serotypes can be introduced into the human pop from
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
rhinovirus mainly affects what part of the resp sys?
nasal cav, and a little pharynx (common cold/pharyngitis)
Parainfluenza mainly affects what part of resp sys?
larynx (laryngitis & Croup), pharynx (pharyngitis) and nasal cavity (common cold)
respiratory syncytial virus (RSV) mainly affects what part of the resp sys
bronchiloes (bronciolitis) and nasal cavity (common cold)
influenza primarily affects what part of the resp sys?
alveoli (pneumonia), bronchioles (bronchiolitis) and/or the nasal cavity (common cold)
what causes manifestations of the common cold/rhinovirus?
acute inflammation of nasal mucosa with cytokine production
rhinovirus is from what family? What are the features of this family?
- icosahedral viruses
-non-segmented + strand RNA
- structure and replication = similar to polio virus
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)
what family is RSV (resp. syncytial virus) in? what are features of this family?
-non-segmented minus strand RNA
- structure and replication = similar to measles
features of normal bronchioles:
end in alveoli
lack cartilage rings in walls
a multi-nucleated cell
in cases of RSV you can see what histologically?
multinucleated cell (Syncytium) and inclusion of RSV
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
on xray, what happens to the lungs in bronchiolitis?
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!
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)
how do Abs respond to RSV?
neutralizing IgG response wanes quickly
IgA response is weak/absent in infants
Th2 response to RSV
might be associated with increased pathology (wheezing)
- most = mild- treated at home for fever/hydration
- severe cases require O2, role of steroids/bronchodilators is unclear
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
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
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
peak month of influenza ifxn?
explosive, world-wide outbreak
RNA segments in Influenza
RNA segments in Influenza
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
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
coughing up blood
influenza A subtypes are defined by
serotypes of hemagglutinin (H 1-16) and neuraminidase (N 1-9)
influenza A serotypes are defined by
lack of Ab cross-reactivity
viruses are names for:
type/site of isolation/ isolate number and year (A/California/7/2009)
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)
Antigenic shift occurs when
an influenza A virus, for which there is no pop immunity infects humans
the segmented genome of influenza A allows ready...
reassortment in doubly infected cells
the H sequence of influenza A determines
affinity for forms of sialic acid
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
3 outcomes of influenza A
1. uncomplicated inf ---> recovery = very common
2. bacterial pneumonia ---> moderate mortality = uncommon
3. viral pneumonia ---> high mortality = rare
common bacterial pneumonias that infect post viral resp tract ifxn (3)
S. pneumoniae, S. aureus and H. influenzae
manifestations of influenza followed by viral pneumonia
severe influenza ---> hemorrhagin pneumonia, hyaline membranes line alveoli and scant inflammation --> fluid accumulation ---> decreased gas exchange ---> death
the inactivated influenza vaccine is administered...
comments: 1) inexpensive, 2) > 6 mo old, 3) high dose avb for >65yo, 4) egg allergy = contraindication
live attenuated inf vaccine is administered...?
comments: expensive, ages 2-49, eg allergy, pregnancy and immunocompromise are contra indications
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
which resp. tract infection (RTI) evades the imm response by hiding its conserved Ag?
rhinovirus (ICAM-1 receptor)
which RTI evade imm resp by stimulating a partially effective response?