Flashcards in influenza and other enveloped viruses Deck (45)
characteristics of enveloped viruses
1: a nucleocapsid coated with a lipoprotein membrane
2: infectivity destroyed by treatment with ether
3: unstable so transmission requires close contact
4: more complicated pattern of assembly than that on nonenveloped
5: few cell-associated virions at any time
6: continuous release of virions without gross cellular damage
7: modified cellular membrane containing glycoproteins within the envelope membrane
8: released from infected cells by budding
9: antigens for neutralizing antibody are envelope glycoproteins
What are the features of viral envelopes... What are they composed of?
Can enveloped viruses be neutralized?
Are they sensitive to ether?
Are they stable?
Are infected cells killed? How does the virus leave the cell?
composed of lipid molecules and viral glycoprotein spikes
neuraminidase and hemagglutinin
antibodies can't neutralize because can't get to capsid - target antigens are on envelope
makes viruses sensitive to ether - can't bind to cells anymore because will dissolve the envelope
enveloped viruses usually unstable extracelluarly
virus doesn't have to kill cell to get out of it - just buds out
classes of enveloped viruses
budding of enveloped viruses
viral caspid attaches to transmembrane receptors on host plasma membrane - these receptors were made using viral genetic material
this membrane surrounds the viral caspid and buds off
orthomyxoviruses genetic material
aka influenza virus A, B, C
What is the structure of nucleotide?
Plus or minus strand?
contain 8 separate segments of single-stranded RNA - each segment has the genetic information to encode at least one unique viral protein
each RNA segment enclosed in separate helical nucleocapsid
RNA cannot function as mRNA because is minus strand
virion contains virus-specific RNA polymerase - makes mRNA from virion (-)-stranded RNA
replication cycle of influenza virus
1: attaches to cell membrane
2: endocytosis and acidification
3: fuses with endosome/lysosome membrane and releases genetic material into cell
4: genetic material moves to nucleus
5: converted to mRNA and translated
6: translated proteins move back to nucleus and others are post-translationally processed and inserted into the host cell plasma membrane
7: genetic material is moved from nucleus to cytoplasm and packaged in host cell membrane where the viral proteins have been inserted
buds off and is released
classes of viral antigens (2)
1: nucelocapsid proteins
2: envelope glycoproteins
How many nucleocapsids do orthomyxoviruses aka flu virus have?
Do antibodies to nucleocapsids have effect in enveloped viruses?
structure composed of caspid proteins and nucleic acid genome
antigens located on protein capsomers of helical nucleocapsids inside virion
orthomyxoviruses have eight separate helical nucleocapsids
antibodies to nucelocaspid proteins don't neutralize virions because don't penetrate past the envelope around the virions
protein coat that covers the nucleic acid genome
What are the two envelope glycoproteins that are antigens?
hemagglutinin and the enzyme neuraminidase
hemagglutinin (H or HA)
What does this glycoprotein do for the virus?
How effective are antibodies to this envelope protein?
required for adsorption of virions to cells - required for infection of susceptible cells
antibodies directed against it will neutralize orthomyxovirus virion - these antibodies are most important in controlling infection
binds to sialic acid molecules on host cells
What does this enzyme do for the virus?
enzyme that releases newly formed virions from their final point of attachment to the infected host cell by cutting sialic acid bonds
antibody to it slows release of newly formed virions and spread of infection to other individuals, reduces severity of disease but does not block infection of new cells or neutralize virions
What virus is this diagnostic for?
Does agglutination test for the whole virion?
process by which orthomyxoviruses agglutinate red cells
used to measure relative concentration of virions in a clinical sample
does not require that the virions be infectious - only that H-antigen present
since specific antiviral antibody directed against H-antigen inhibits hemagglutination can be used to titrate the relative concentration of antiviral antibodies in serum samples - if antibody present won't get glutination - RBCs will clump
when virus present, RBCs won't form clump at bottom of test tube - form sheet so still clump, but it looks clearish/light pink and is spread out
What is the definition of an epidemic?
pandemic (world-wide epidemic) of 1918-1919 caused millions of deaths (30-50 million)
epidemic detected/determined by calculation of how many people die over what's expected for that disease
types of influenza virus
three types: A, B, and C
each has its own specific nucleocapsid antigen (one for A, B, and C - called the S-antigen)
multiple strains of each type based on antigenic differences in hemagglutinin and neuraminidase and genetic variation in polymerase genes and other genes
influenza type B epidemics
How often do these occur?
What do the vaccines include?
occur every 3-6 years
vaccine usually contains one B strain that's anticipated to represent the predominant H-antigen and N-antigen types for the future flu season
killed flu vaccine contents
Why are killed flu vaccines suboptimal?
vaccine usually contains one B strain and two A strains that are anticipated to represent the predominant H-antigen and N-antigen types for the future flu season
influenza type C has minor clinical significance
new virus isolates added each year
more than 70% effective when vaccine is well-matched to predominant viruses
suboptimal in protection because does not efficiently induce secreted IgA - primarily induces IgG response and IgG antibodies
recommended for everyone over the age of 6 months, special risk groups, and medical personnel
about 65% effective - but likely to be less severe illness if vaccinated even if you do get sick
live flu vaccine contents
What are the benefits?
What age groups are recommended?
approved in 2012
has two influenza A and two B strains or several of each
administered by intra-nasal spray
selected for optimal growth at low temperature - so ideal for upper respiratory tract and nasal cavity but does't grow well deeper in the respiratory tract
approved for use in ages 2-49
may give 30-50% greater efficacy than killed (at least in preschool-age children)
get more IgA response with this than with the killed vaccine
epidemics of influenza type A
How often do epidemics occur? Minor? Major?
minor epidemics occur every 2-3 years
major ones every 10-30 years
Which flu antigen is affected?
Do prior antibodies provide any protec
explanation for minor epidemics
minor variation within existing RNA segments in the gene for H-antigen due to mistakes made by viral RNA polymerase, spontaneous mutations, and other mechanisms
results in different minor antigenic variant of H-antigen
existing antibody from previous epidemics confers partial immunity
Which antigens shift?
What are possible causes?
explanation for major pandemics
happens when existing antibody from previous epidemics fails to confer immunity
result of major antigenic variation
strains of influenza A can have same N glycoprotein antigen, but the H glycoprotein antigen is always antigenically shifted (sometimes both shift - results in worse pandemic)
major mechanism = introduction of a major H-antigen variant directly from swine or avian influenza A - this genetic reassortment between species is frequent because the viral genome is segmented
can also occur by direct transmission of a animal flu to humans, though less likely to cause an instant pandemic because would be unlikely to propagate well in humans but if minor mutations accumulate the virus may become well adapted to humans and cause a pandemic
influenza (disease characteristics)
How is it diagnosed in the lab?
What is transmission?
What cells in the respiratory tract are damaged by flu?
What affect does that have on other infectious agents?
subclinical infections common
laboratory diagnosis by virus isolation in embryonated eggs or tissue cultures or by comparison of acute and convalescent sera (anti-HA assay or hemagglutination inhibition assay)
transmitted person to person by coughs and sneezes
droplets initially infect upper respiratory tract then extend to lower
infects ciliated cells best - damages cilia
increases risk of other infections.
Is viremia involved?
fever, chills, aches
destruction of ciliated epithelium in respiratory tract
viremia not common
systemic symptoms (headache, muscle pains) caused by pro-inflammatory mediators released from sites of local growth in the respiratory tract
in severe cases contributes to lung disease
most common complication = pneumonia
From what virus is this a common complication from?
most common complication due to influenza
sometimes with secondary bacterial infection from pneumococcus or staphylococcus - occurs because of destroyed ciliated epithelium and malfunctioning infected alveolar macrophages
deaths due to influenza
Why did the 1918-1919 flu kill 20 to 40 year olds more than other age groups?
deaths usually occur in elderly and infants (though in the 1918-1919 pandemic deaths in very young and people very old but mostly in people from 20ish to 40ish)
death usually due to underlying respiratory insufficiency
20 to 40 year olds were killed do to immune response to flu (they had a stronger immune response than other age groups.
immunity to influenza
no obligatory viremia so incubation period short (days)
attacks mucosal surface of respiratory tract so immunity largely dependent on IgA
immunity may only be short term (3-10 years)
treatment of influenza
What drugs are used to treat?
What is their mechanism?
When does treatment need to be employed to be effective?
drugs = oseltamivir (tamiflu) and zanamivir (relenza)
both neuraminidase inhibitors - prevent neuraminidase from cleaving sialic acids on particles, which would allow them to be released - if cleavage is prevented, the newly budded virus remains stuck on the host cell
active against A and B viruses
slows release of virus from infected cells and slows spread from cell to cell
reduce symptomatic period by a day or two
only effective if treated early in infection period though
some H1N1 strains have resistance to tamiflu, others resistant to relenza
Why is this drug no longer used?
older family of anti-influenza drugs
no longer really used because most type A flu strains have acquired immunity to it and it doesn't treat type B
but still inhibits H1N1
tricyclic amine that likely blocks late phase of adsorption-penetration-uncoating process - mechanism not established
more effective if given before infection
paramyxovirus genetic material
What kind of nucleotide? positive or neg?
Can recombination occur?
one piece of single-stranded RNA within helical nucleocapsid - therefore recombination by reassortment can't occur and marked antigenic variation not observed
information first transcribed into mRNA by polymerase present in the virion