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83 Cards in this Set
- Front
- Back
Orthomyxoviridae classification
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(-) sense RNA
segmented genome must enter nucleus requires host functions in nucleus enveloped |
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"myxa"
"ortho" |
mucous
standard/true |
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Orthomyxoviridae generates _____, and has a ______infection.
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Lots of mucous
lytic |
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Influenza produces fever lasting _______, and symptoms lasting ________.
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4 - 5 days
3 weeks |
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Influenza "H" designation
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hemagglutanin - antireceptor
allows for centers of infection More H than N |
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Influenza "N" designation
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neuraminidase
More H than N |
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Thogotovirus
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helical RNP's
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Influenza _ has greatest disease impact
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A
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Influenza M2
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viroporin - ion channel- necessary for entry
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Influenza M1
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Helical RNP's coated with M1
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RNP's associate with
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multisubunit polymer PB1, PB2, PA holoenzyme
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Phospholipid bilayer sensitive to
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non ionic and lipid solvents
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Influenza NP
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Nucleoprotein
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HA is
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cleaved into HA1 and HA2
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HA 1
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binds the receptor
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Influenza NS1
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inhibits host RNA splicing and polyadenlyation
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Influenza NEP
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is a viral adaptor to help export unspliced viral mRNAs from nucleus to cytoplasm
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Influenza segments 1 - 6 encode ______RNAs, where Influenza segment 7 & 8 encode ______RNAs
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one each
multiple |
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ds viral influenza RNA
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inhibits interfuron
shuts off protein syn |
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Influenza adsorption depends on
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cell receptors containing neuraminic acid
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Mucoproteins
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have neuraminic acid-abundant in respiratory tract
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HA
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Antireceptor - protrudes as globular molecule from surfaces of flu virions
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Adsorptive endocytosis needs
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low pH for uncoating
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low pH during adsorptive endocytosis causes
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major rearrangement of HA2 portion allowing extension toward cell membrane from envelope
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Receptor/antireceptor carry out
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docking
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M2 ion channel
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allows penetration of protons from endosome into core of virus
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M1 protein must be released from ______ before ______occurs
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RNPs
uncoating |
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Partial uncoating
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release of M1 but not NP from viral RNA
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Influenza entry requires 2 steps
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1)adsorptive endocytosis-low pH
2)activation of M2 ion channel to allow release of M1 |
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Amantidine
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ion channel blocker
prevents uncoating of M1 side effects caused by other ion channel blocking |
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Amantidine resistance from
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mutants of M2 - keeps ion channel open
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RNPs have proteins with____________signals
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nuclear localization
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NA
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neuraminidase
envelope protein that cleaves neuraminic acid |
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NA allows spread of virus by
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by preventing released virus from staying attached to viral producing cells
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NA facilitiates spread by
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cleaving neuraminic acid on mucoproteins that are abundant in the respiratory tract
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Influenza replication:
RNP's move into ______ and stay attached to ______ |
nucleus
RNA pol, PA, PB PB2 |
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PA
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protein acidic
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PB
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protein basic
PB1 -protein basic 1 PB2 protein basic 2 |
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Actinomycin inhibits
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DNA dependent RNA polymerase
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Influenza is inhibited by actinomycin suggesting a
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DNA dependent event - cap snatching
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PB1 cleaves
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cap from nascent cellular mRNA 10 - 13 nucleotides downstream from cap
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PB2 binds
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binds cap of cell mRNA
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PB1 polymerizes
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RNA cynthesis using cell (cap) RNA as primer
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PA has ______ role
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structural role in polymerization, assembly, and elongation of viral mRNA
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Influenza mRNA gain poly A tail at 3' end by
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reiterative copying
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Orthomyxo mRNAs are/are not exact copies of viral genome
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are not
5' end snatched 3' end poly A |
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Influenza polymerase associates with cell
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RNA pol II
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Flu needs
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m7G mRNA that has A or G 10 - 13 bases dowstream of cap
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Flu replication prerequiste events
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Pol bind viral segment
PB 2 binds cap on cell mRNA Then PB1 activates cleavage event |
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Each segment of flu mRNA has ______ sequence ______ so PA, PB1, PB2 can
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same sequence at 3' end
recognize them |
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Influenza PB1 is a
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polymerase
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synthesis of flu proteins requires
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full length mRNA synthesis
continuous supply of NP protein for encapsidation |
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Influenza segments 7 and 8 require
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splicing
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Most abundant proteins (M1 and NS1 are translated from
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unspliced mRNA
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advantage of 2 proteins from 1 unspliced mRNA is
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regulation of ratio of those 2 proteins
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During switch from mRNA polymerization to antigenomic
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polymerase composistion changes
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PB2 binding cap is ________ in replcation
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unneccesary
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Role of PA is
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critical for replication to begin
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Genome and antigenome remain associated with
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NP during replication
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Antigenome is an
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exact copy of genomic - no 5' cap or poly a tail
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secondary transcription
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transcription off of newly transcribed- amplifies amount of mRNA available for translation
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NS1
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accumulates late in IC
promotes ribosome/vRNA assoc interferes with host mRNA splicing and poly adenylation |
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NS1 also shuts off cell
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host protein synthesis
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NS2
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nuclear export protein
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Host cell mRNA splicing is coupled with
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export from nucleus
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Cleavage of HA occurs by
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cell enzyme
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Ability of HA to be cleaved by ubiquitous enzymes allows
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influenza to extend its tissue range
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NA must be
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packaged to allw spread of virus
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NA allows
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release of virus from cell that produced it
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packaging requires incorporation
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of all 8 segments
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Random incorporation model
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more than 8 segments are packaged
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Selective model
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Presence of PA and Pol help to slect all 8 segments for each particle
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Cleavage of _______ of _________ is key to infectivity
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precursor for HA
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HA1 and HA2 ________ is required to allow the formation of an ____________ particle
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cleavage
infectious |
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Influenza infection leads to a _________immune response
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strong immune response - flooding of blood and lymph into the lungs
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Antigenic drift
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Natural mutant selection in infected particle-mistakes by pol
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61 % difference in HA1 and HA2 is _____ _____ ____ _____ for just __________mistakes
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too big a difference
polymerase |
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Antigenic shifts
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reassortments of HA or N or both
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epidemic
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increase in frequency or severity of disease over that in normal pop
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Pandemic
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world wide increase in frequency or severity of disease
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Amantidine/rimantidine
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drug that blocks the M2 channel. Also causes premature triggering of fusion peptide of HA2
can cause seizures/dizziness |
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Tamiflu/Ralenza
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neuraminidase inhibitor
bloacks active site for neuramic acid limited efficacy in late infection |
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Potential target of influenza virus
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cap snatching
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