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42 Cards in this Set
- Front
- Back
Influenza is classified as what type of virus
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orthomyxovirus
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Major sx of influenza infection
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resp disease w/ fever and myalgia
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Mostclinically significant serotype of influenza
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Influenza A (cause epidemics and infect same host more than once in lifetime)
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Describe the ultrastructure of the Influenza A virus
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-enveloped
-very polymorphic particles -different shapes (spherical and others filamentous) -contain glycoprotein spike projections -helical Ribonucleoprotein assemblage |
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Describe the genome of the influenza A virus
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-RNA
-segmented -minus-strand (need to be made to mRNA first) |
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What proteins form the projecting spikes on the influenza envelope
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hemagluttin (HA)
and neuraminidase (NA) |
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Describe the oles of M1, M2, and Nucleoprotein (NP) for the flu virus
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-M1: under envelope and associates with NP
-NP: coats the RNA segment -M2: tetrameric membrane spanning complex |
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What is the roles of PB1, PB2, and PA enzymes for the flu virus?
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present in virion, bound to helical ribonucleoproteins
participate in viral RNA replication |
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What does HA bind to on cell surfaces?
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sialic acid
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Describe the synthesis of HA in virus infected cells
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cotranslational insertion into ER
protein folding and oligomerization 3 units are made (for a trimer) each monomeric unit is proteolytically cleaved (generates amino terminal and membrane anchored fragments) |
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General roles of HA and NA in influenza infection
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HA: promote virus binding
NA: promote virus release and dissemination |
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Describe general shape of NA
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four identical molecules form a box-shaped tetramer
box tetramer attaches to particle membrane by a slender stalk outer surface of NA tetramer recognizes sialic acid and cleaves it |
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Initial step in influenza infection
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HA attachment to sialic acid receptors
multiple trimers (up to 500) involved entire particles are internalized into endosome |
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Describe endosome acidification, and how this plays a role in influenza infection
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endosome pH is low (5-6)
acid environment alters flu particle in 2 ways: 1. protons bleed thorugh M2 pores = acidify virion interior. This frees ribonucleoprotein complexes and gets them ready for transport into the nucleus 2. alters charge of HA spike, changes their shape, and promotes fusion between flu and endosome membranes. End result = delivery of nucleocapsids into cell cytosol |
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Where are nucleocaspids targeted to in influenza infection? What is the goal of this?
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nucleus
for transcription to occur |
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What to PB2, PB1, and PA form at the cell nucleus?
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RNA transcriptase
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What is "cap-snatching"?
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virulent form of parasitism, involved in flu transcription
virus-encoded endonuclease cleaves 5' terminal 10-13 nucldotides from host transcript short RNAs used to prime viral transcription End result: promotes VIRAl transcription (and thus translation), but disables cellular protein synthesis |
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How do the newly synthesized HA, NA, and M2 get to the infected cell surface? where are the rest of the proteins targeted to?
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utilize the normal cellular exocytic pathway
rest- go back to the nucleus |
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Describe the replication of the virion genome
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late in infection
virion RNAs of flu serve as templates for synthesis of cRNA (templates for minus strand virion RNAs) |
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Describe packaging process of RNA virions during infection. Which proteins are involved?
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RNAs are packaged in conjunction with NP, transcriptase proteins, and M1.
Core migrates toward cell surface, acquire envelope, and later HA, NA, and M2. = BUDDING |
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BIG THREE important things regarding influenza epidemiology
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1. Influenza A infection prevented by antibody to HA protein. Lots of HA proteins however, so antibodies form prior infection is not always useful (in cases of novel influenza)
2. Broad range of hosts for influenza provides transmission from animals to humans 3. 2 flu viruses can infect the same cell, and RNA segments from parent viruses can reassert = novel gene constellations in progeny. |
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Mechanism responsible for influenza pandemics
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antigenic shift
flu antigen (HA) in one strain is shifted to a type not previously observed in human populations. shift is from reassotment of RNA segments = pathogenic assortment. |
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Mechanism responsible for influenza epidemics
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occur more frequently vs pandemics
results from ANTIGENIC DRIFT. Flu antigen (HA) drifts to a marginally altered form (due to inherently error prone flu replication) = escape immune surveilance |
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Mechanism responsible for influenza endemics
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infection of individuals who escaped infection during previous epidemics
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Major sx of influenza infection
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fever
sore throat nonproductive cough ha |
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where does the influenza virus replicate?
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ciliated columnar epithelium of resp tract
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describe major risk with influenza infection
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secondary pneumonia from bacterial infection (s. aureus) can occur
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Describe age group/risk factors for most influenza related deaths
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>65+ yo
risk increased in those suffering from chronic pulm or cardiac diseases |
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Lab diagnosis of influenza is made how?
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throat swabs by virus cultivation in cell lines
viral antigen identification in infected cells by EIA SEROLOGY NOT HELPFUL (PRIOR ANTIBODIES CONFUSING) |
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Major classifications of influenza
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1. Serotypes (A,B,C)
2. Host of origin 3. geographic location of isolate 4. strain number, yr of isolation 5. HA and NA subtypes |
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What is the critical immunogen for influenza vaccines?
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HA
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How are influenza vaccines made?
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virus is grown in embryonated chicken egg
purified and inactivated with formalin usually standarized for immunoreactive HA |
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Describe the concept of the live attenuated influenza vaccination
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administered via nasal spray
virus vaccine replicates enough to elicit powerful immune response does not replicate enough to cause disease |
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How does Amantadine work?
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antiviral against influanza A
blocks M2 protein ==> stops flow of protons into virion interior during penetration nucleocapsids are incompetent for migration due to this |
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How to oseltamivir and zanamizir work?
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block activity of NA, and limit dissemination of infection in resp tract
block influenza A and B |
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What type of virus is the rhinovirus?
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picornavirus
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Describe major sx and optimal conditions for the rhinovirus
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acute upper resp disease
particles = acid labile (no enteric infection), and growth os optimal in low temps found in nasopharynx |
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When do rhinovirus epidemics peak? incubation and sx duration?
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spring and fall peaks
incubation 2-3 days sx for 3-7 days |
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illnesses associated with adenovirus
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upper resp disease
conjunctivitis/pink eye |
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Adenovirus is what type of virus?
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non-enveloped
DNa virus lots of serotypic diversity |
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population most frequently infectd with adenovirus?
major spread routes? epidemic periods? |
infants
resp or fecal-oral late winter = epidemic time |
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Is there a vaccine for addenovirus?
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live attenuated vaccine against serotypes 4 and 7
only given to military recruits |