Mcim lecture 12 Flashcards
Influenza virus and the two types of spike proteins?
Enveloped RNA virus with a “segmented” genome (8 separate & distinct pieces of nucleic acid
Two types of “spike” proteins on envelope:
1) neuaminidase (N)
- -> degrades mucus that lines epithelial cells of respiratory tract( allows virus to reach cell surface)
- -> also req. for release of mature virus from the host cell ( helps virus separate from host cell envelope)
2) hemagglutinin(H)
- ->for attachment to respiratory epithelial cells
Viruses of the respiratory tract
Viruses which replicate in cells of any part of the respiratory tract(upper airways, nasal passages–> lower bronchioles in lungs
Includes more than 200 different viruses, ranging in severity;
- mild “rhinitis”(cough, congestion, runny nose)–> rhinoviruses (common cold) + many others
- mild to moderate–> respiratory syncytial virus( RSV)–> most common respiratory infection in newborns
- severe respiratory distress(pneumonia)–> SARS virus, hantavirus, influenza
Share common modes of transmission:
- Indirect contact( breathing in aerosolized droplets)
- Physical hand to nose contact
Three major types of influenza virus?
1) influenza type A
- -> most common type( responsible for global pandemics)
- -> broad host range(humans, birds? Pigs)
- -> numerous strains(sub-types) which differ in amino acid structure of the H and N spike proteins: designated as H1/N1, H2/N1, etc and presently 13 different H types + 9 different N types
2+3) influenza types B and C
- -> less common( small, localized outbreaks only)
- -> restricted host range(humans only)
- -> generally gives much milder symptoms vs type A
- -> only a small number of different strains
How do different type A influenza strains arise? (2)
- Antigenic drift
- -> during virus replication, spontaneous mutations occur in H or N genes which result in minor changes in H or N proteins
- -> new progeny virus only slightly different from parent - Antigenic shift- intermixing of genes for H and N proteins
- -> b/c of segmented genomes, H and N genes can re assort (mix) if two different flu strains(ex animal + human stain) infect the same host cell at the same time
- -> new progeny virus is completely different from either parent
Note: shifting is facilitated in geographic areas where farming practices involve close humananimal bird contact(eg. Asia)
End result of shifting & drifting is the continual creation of new or variant flu strains to which humans have been exposed–> new flu stains cause new localized or global outbreaks
Influenza- clinical features: transmission via aerosols or hand to nose contact?
Transmission via aerosols( ex. Sneeze) or hand to nose contact
–> flu virus can survive up to 48 hours on dry surfaces
Influenza- clinical features: life cycle?
- -> replication in nasopharyngeal epithelial cells( upper resp. Tract)
- -> spread to lower resp. Tract (ciliated cells in the lungs)
- -> damaged ciliated cells are sloughed off- inflammation
- -> fluid build up in lungs- difficulty breathing
Compromised lung defences ex. Lost of ciliated cells means that host becomes susceptible to secondary bacterial infections
Symptoms appear 36-48 hours after infection( although transmission possible before symptoms appear)–> death may result from influenza alone, or secondary bacterial infection, or combination of both
Laboratory diagnosis( influenza)
Nasopharyngeal swab
- -> best results if collected within 5 days of onset of symptoms
- -> proper specimen collection is critical
- get back far enough to sample the nasopharyngeal area
- vigorous enough to remove infected cells
- lab tests include microscopy for infected cells(DFA) &/or molecular test for viral nucleic acid
Treatment/prevention: influenza
Anti viral agents
- oseltamivir( tamiflu), zanamivir (refenza)
- -> block neuraminidase activity
- -> most effective if given soon after infection ( reduces severity & duration of symptoms
- -> generally indicated if patient is hospitalized and/or is at risk of developing severe complications(eg. Resp. Failure, pneumonia, etc)
Amantadine
- -> blocks virus un-coating after entry
- -> limited clinical use- most influenza strains are resistant
Limited the risk of infection–> hand hygiene, cover your sneeze, avoid close etc
Vaccination–> highly effective prevention strategy
Influenza- vaccination and immunity
- full immunity to influenza requires that you produce antibodies against both the H and the N virus proteins( either via a natural infection or vaccination)
- but immunity is “stain specific”- antibodies against one H or N type will not cross protect against a different H or N type. Ex) recovery from flu does not prevent later re infection with a different flu strain (only protected against same strain)
- flu vaccine- killed whole virus or purified H & N proteins( therefore will not cause flu)
- antibodies against H&N proteins arise 2 weeks after vaccination
- -> 60% effective at protecting vs influenza( OK, but not ideal)
- -> antibody levels decline after= 1 yr (need to be re-vaccinated)
Influenza vaccine formulation
B/c of numerous influenza sub types, the vaccine must be reformulated each year to incorporate the H&N types which are expected to be circulating:
2013/14 seasonal flu vaccine: flu A- H1/N1(original 09)
Flu A- H3/N2 strain
Flu B- common seasonal strain
why do I need to get a flu shot again this year (2)?
- the antibodies you developed last year are now mostly gone
- there may be new influenza strains that will circulate this year that were not included in lady years vaccine formulation
Illustration: how new human viral diseases emerge: Ebola
- enveloped RNA virus with a “pleomorphic” morphology
- only found in naturally on the African continent
- broad hose range( bats, monkeys, human, others??)
- an ex. Of a “hemorrhagic fever virus” = a family of related viruses( Marburg virus, Lassa fever, etc) which all cause diseases characterized by bleeding, high fever >70% mortality
Mechanism of disease: Ebola virus
- most common transmission via contact with blood/ body fluids
- symptoms appear within 2 days of becoming infected: High fever, headache, nausea, bloody diarrhea
- severity of symptoms increases after 7-10 days:
- -> internal bleeding , shock
- -> organ failure leading to death
Virus replicates in different tissues, incl. capillary epithelial cells
- -> capillary damage- blood loss through damaged vessels
- -> immune system response- fever shock
Large numbers or virus appear in blood, lungs, nasal secretions and are sources for further transmission
What does the history of Ebola tell u about it’s transmission? (3)
- Starts as a “zoonotic” disease
- animal to human transmission following encroachment of humans into animal ecosystems (primates? Others?) - Human to human transmission
- via physical contact with secretions, blood of patients
- airborne spread? (Experimentally shown in primates)
- medical personnel at high risk - International outbreaks (beyond Africa) are possible
- air travel& the world wide shipment of biological specimens
Why study a virus that has thus far killed only 1500 people worldwide? We a way of preparing for more dangerous viruses yet to come and as a concern as a possible agent of bio-terrorism
What makes Ebola (and other hemorrhagic fever viruses) a bio-terrorism threat?
- they can(possibly) be disseminated through aerosols
- they have a low infectious dose
- they can cause high rates of mortality
- they cause fear and panic in the general public
- effective vaccines are not available or supplies are limited
Centres for disease controls "category A " agents ( those most likely to cause mass casualties if deliberately released) - anthrax(bacillus anthracis) - botulism (C. Botulinum toxin) -plague (yersinia pestis) - tularaemia (fracisella tularensis) Viruses: - smallpox Hemorrhagic fever viruses( Ebola, Marburg, Lassa fever)
