Viruses respiratory Flashcards
how many people in the US become infected with influenza?
29-59 million
36,000 die
give 2 examples of negative strand RNA viruses?
- respiratory syncytical virus (RSV)
- influenza virus (IV)
herpes virus and adenovirus B, C and E are examples of what kind of virus?
Double stranded DNA virus
giva an example of a positive strand RNA virus?
Coronavirus (CoV)
what can cause the common cold?
RHINOVIRUS, RSV, PIV (parainfluenza virus), flu, adeno, coronaviruses
what can cause Tonsilopharyngitis?
RHINOVIRUS, RSV, PIV (parainfluenza virus), flu, adeno, coronaviruses, HSV, CMV (Cytomegalovirus), EBV (Epstein–Barr virus)
what can cause bronchitis?
RSV, PIV, Adeno, HSV
what can cause Pneumonia?
Adeno, PIV, RSV, VZV, Measles, CMV, HSV, Hantavirus
are there vaccines against viral resp infections?
trials are currently in progress
what family of viruses is influenza from?
Orthomyoxviridae
what is the shape of influenza?
pleomorphic
how is RNA packaged in influenza?
what is found on the envelope of influenza?
- individual segments of RNA packaged as separate NUCLEOCAPSIDS
- PROMINENT PEPLOMERS
what does Type A influenza cause? who does it affect?
causes WORLDWIDE PANDEMICS
infects man and animals
what does Type B influenza cause? who does it affect?
localised outbreaks
infects man
who does Type C influenza affect? what type of symptoms?
infects HUMANS AND PIGS
mainly asymptomatic
what is classification of the influenza virus based on?
antigenic properties of surface glycoproteins: Haemagglutinin and Neuraminidase
what recognises N-acetyl neuraminic acid?
carbohydrate binding proteins
Alpha linked terminal carbohydrate of upper respiratory tract and lung associated glycoconjugate
what is the role of Neuraminidase (NA)?
Tetramer-Particle dispersal: assist movement along the upper respiratory tract and virus release
what is the role of Haemagglutinin (HA)?
Trimer-Attachment and fusion: initial point of contact by binding cell glycoconjugates
where is the receptor binding site located on influenza?
on top of haemagglutinin (HA)
HA binds sialic acid
- the TYPE of sialic acid bound is key to determine virus tropism
describe antigenic drift as a factor of evolution?
- accumulation of aa changes that result in subtle changes in ANTIGENS and infections where host immunity is INCOMPLETE
describe antigenic shift as a factor of evolution?
- reassortant viruses (segmented genome) resulting in novel antigenic virus stains
(this commonly occurs with human and avian viruses)
in influenza, where can antigenic changes occur?
where can aa changes occur?
how can this lead to drift?
- antigenic changes cluster in 5 highly variable regions surrounding the RECEPTOR BINDING POCKET
- aa changes occur at other sites in HA1 molecule
- ->DRIFT when mutations ACCUMULATE in 2 or more of the antigenic domains
how are variants in influenza different?
how does spread of the virus occur?
they have REDUCED SUSCEPTIBILITY to PRE-EXISTING immunity in the infectable population (i.e they are more likely to infect)
- spread occurs because of the large numbers of SUSCEPTIBLE HOSTS and the increased liklihood of the virus causing symptomatic infection
why are pigs an important mixing vessel for influenza?
they can be infected by HUMAN AND AVIAN viruses
in human lungs, what is the dominant receptor used in influenza?
α(2,6)
in bird intestine (enteric inf), what is the dominant receptor used in influenza?
α(2,3)
in swine lungs (respiratory inf), what is the dominant receptor used in influenza?
α(2,6) and α(2,3) abundant
what causes antigenic shift in influenza?
sult of reassorting between segments of different Influenza, can occur between different human viruses or between human and animal viruses
what are the 2 features of an antigenic shift in influenza?
- sudden appearance
- antigenically distinct from Influenza currently circulating in humans
what was the cause of the Spanish flu? how many did it kill?
H1N1 infection, killed 50m
how does neurominidase work?
NEUROMINIDASE (enzyme) cleaves SIALIC ACID off, means that virus DOES NOT AGGREGATE and can leave the HOST CELL
name 2 drugs used against influenza, how do they work? how are they administered|?
1) Zanamivir (Relenza) (inhaled)
2) Oseltamavir(Tamiflu) (oral)
- sits in the binding site of
neurominidase, stops it working, causes clumping of virus
when do drugs against influenza oseltamavir and Zanamavir need to be deployed?
what other situations canthey be used in?
what is a concern abut oseltamavir?
quickly!
- can be used prophylactically
- natural polymorphisms can lead to drug resistance against oseltamavir
describe the two influenza vaccines
what are the 3 types of trivalent flu vaccine?
who are they used in
1) TRIVALENT vaccine
- STANDARD :made using virus grown in eggs
- RECOMBINANT: egg free, used in 18+ inc pregnant women
- made with ADJUVANT (creates stronger immune response in body) for 65+
2) QUADRIVALENT
RSV stands for what?
respiratory syncytial virus
when was RSV discovered?
1956
how many deaths p/a caused by RSV?
200,000
what does RSV cause?
acute disease, leads to longer term respiratory conditions
describe the seasonal nature of RSV?
in temperate zones: late autumn, winter spring
tropical/Arctic: all year round
Europe: winter
what is the structure of genetic info in RSV?
- single stranded
- non segmented NEGATIVE SENSE RNA genome
- has ‘G’ attachment protein (imp for receptor binding and vaccine development, site of genetic variation)
- ‘F’ fusion protein
- 2 subgroups A and B
describe the pathogenesis of RSV? how does it infect? incubation period?
initial infection: contact of particles w/ nose/eyes
incubation period: 2-8 days
- initial infection of epithelial cells/ upper or lower RT
- extensive inflammation, monocyte and T cell infiltration
- overproduction of mucus
- HIGH virus load associated with more symptoms
what are risk factors for severe infection of RSV?
- premature birth
- co morbidities (cardiac/respiratory disease)
- genetic predisposition affecting T cell responses
what kind of environmental factors are important in RSV?
smoke, pollution, crowding
if initial exposure to RSV is 6wks – 9 months of age, what happens?
if severe?
if underlying cardiac or respiratory disease?
causes mild/ asymptomatic upper resp tract inf
(25-40% involves lower resp tract)
- most cases: recovery after 7-12 days after initial illness
- if severe: coughing and wheezing causes respiratory failure
- if underlying cardiac or respiratory disease, progression can be rapid and fatal
what characterises acute RSV inf in nromal adults?
how long does it last?
what about if older patients?
- rhinorrhea
- pharyngitis (sore throat)
- cough, fever
- lasts ~5 days
- older patients= inf = severe
describe the epidemiology of RSV?
- worldwide
- major paediatric inf esp infants 6 wk-9 months more likely to have LRT inf (esp boys)
- RE inf = common & ASYMPTOMATIC
how is RSV transmitted?
via large droplets or fomite contamination and spread requires close contact or contamination of hands between contaminated areas and nasal or conjunctival mucosa
how is RSV controlled?
- hand washing
- gloves and gowns
what did the early vaccine for RSV cause? how?
- more SEVERE disease on re-exposure to community RSV
Caused by:
-Inadequate serum neutralising antibodies - Lack of local immunity
- Excessive induction of Th2 responses with pulmonary eosinophilia and increased production of IL-4 and IL-5
how are newborns protected from RSV?
Passive immunisation (via placenta) with IgG protects newborns against infection/disease
is there a current vaccine for RSV?
ongoing study
- study shows purified F protein = safe and immunogenic
- 4x inc in RSV neutralising Ab
how are RSV inf treated?
how is treatment administered?
how does it work?
infant? considerable supportive care
- only RIBAVIRIN (nucleoside analogue)
- administered by SMALL PARTICLE AEROSOL (no systemic toxicity)
- drug causes DEC VIRAL SHEDDING and INC level of oxygenation
but ribavarin may not affect mortality rates
give an example of a corona virus?
SARS
corona viruses cause what?
URTI and GI inf infections of mammals and birds
what was the major global outbreak of SARS in China in 2002 exacerbated by?
extensive global human travel
how did SARS-CoV emerge?
RECOMBINATION between 2 bat CoVs
what % of bats are CoV positive in China?
6%
how did CoV go from bats to humans?
bats transmitted to PALM CIVETS–> humans via live animal markets in China
what in CoV increased transmission?
rapid adaptation of VIRUS SPIKE PROTEIN
what is MERS-CoV?
middle east resp syndrome associated coronavirus
what does MERS-CoV use as a receptor?
dipeptidy peptidase
where did MERS orginiate?
zoonotic- bats. camel inf (URT) = closest link w/ human infections
how is MERS transmitted?
through contact with camels, BUT human cases have been reproted where there is no contact with camels
what specimens are used to make diagnosis?
using specimens:
- nasopharyngeal aspirate/swab
- throat sawb
- endo-tracheal aspirate
- broncho-alveolar lavage
