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287 Cards in this Set
- Front
- Back
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Where and when does HIV assembly take place?
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It occurs late in the HIV lifecycle - at the plasma membrane
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What is on either end of the HIV genome?
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LTR - long terminal repeat
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What are the three major structural proteins of HIV?
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Gag, Pol, and Env - found in all retroviruses
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Which protein is the major driving force for HIV assembly?
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Gag
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What is a key difference between immature and mature viral particles?
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In the immature particle, there is an electron dense ring and an electron-luscent center.
In the mature particle, there is a cone-shaped structure- the CORE |
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What viral proteins are key for this maturation process?
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Viral proteases
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is the HIV cone-shaped core open or closed?
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Closed
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What is the size of the HIV particle?
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100-120 nm in diameter
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Are HIV particles enveloped?
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Yes
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What forms this electrondense layer underneath the membrane of the immature viral particle?
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Gag
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What is inside the viral core?
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Viral genomic RNA, and viral enzymes (RT, IN etc)
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What is Gag translated as?
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A 55kDa precursor protein
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What is Gag processed into?
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Three proteins:
-Matrix (MA) -Capsid (CA) -Nucleocapsid (NC) |
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How is the Gag gene arranged?
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MA, CA, p2 spacer, NC, p1 spacer, p6 domain
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What are the four steps of Gag-mediated assembly?
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1) Gag is targeted to the membrane
2) Gag multimerizes 3) Gag forms a lattice 4) The viral particle buds and is released from the cell surface |
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What is the lattice structure like that Gag forms?
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Regular, hexamer
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Which domain is required for Gag membrane targeting and where is it located?
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M-domane, located at the N-terminus of MA protein
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What is contained in this M-domain that is crucial for Gag membrane targeting?
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Myristic acid attached to Gly2
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Which domain is important for Gag multimerization and where is itlocalized?
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The Gag-Gag interactionm domain (I-domain) which spans most of the NC protein
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Which domain is important for Gag lattice formation and where is it found?
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The lattice-bulding domain, is found within the capsid protein
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Which domain is important for budding? Where is it located?
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The Late-budding domain (L-domain), within the p6 domain
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How large is the L-domain?
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Only 4 aa P, S/T, A, P
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Besidse the hydrophobic myristic acid found in the M-domain, what else is required?
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A few basic AA (arginine, lysine) - positively charged willhelp stabilize the Gag proteins to the negatively charged survface membrane
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Where is Gag targeted to?
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Micro-domains on the PM- rich in sphingolipids, glycolipids, and cholesterol - RAFTS
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Can MA form a multimer?
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Yes, it can form a trimer
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What are some important components of the NC structure?
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-Two CCHC Zinc finger motifs
-Highly basic |
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What do these features of NC help?
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Helps NC bind to negatively charged viral RNA
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What is the structure of the CA protein?
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Two independently folding domains: N-terminal and C-terminal linked by a flexible peptide linker.
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Which component of CA can dimerize?
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The C-terminal
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Which components of HIV have the intrinsic property to form cone like structures?
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CA, NC and RNA
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What is required for the cone-shaped core to be a closed core?
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Pentamers in addition to the hexamers
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What is the L-domain responsible for?
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Reccruiting a CELLULAR factor TSG101
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What is TSG101?
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Tumor susceptibility gene 101, homolog of ubiqutin-conjugating enzyme (E2) enzyme
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How do Gag and TSG101 interact?
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Gag binds TSG101 on its UBC (ubiqutin-conjugating domaiN). Gag binds through the p6 domain (which contains the L-domain)
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What is TSG101 important for?
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Helping the virus close its membrane so that it can leave the cell surface
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What is the L-domain of RSV and MMLV?
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PxPY
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What does PxPY interact witH?
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Nedd4, a E3-ubiquitin ligase
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What is the L-domain of EIAV?
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YxxL
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What does YxxL interact witH?
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Ap2 adapter/AIP1
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How large is Gag-Pol?
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160 kDa
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Which enzymes are contained in Pol?
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Protease, Reverse transcriptase, Integrase
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What frequence is Gag:Pol produced over just Gag?
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1/20
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What is the mechanism that allows Gag to be produced sometimes, and Gag-POl at others?
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Ribosome frameshift
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What brings Env to the assembly site?
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Interaction between cytoplasmic tail of the TM protein (gp41) and the MA sequence of Gag
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What is Env responsible for?
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binding to receptors and co-receptors to mediate viral entry
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What is Env composed of?
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Gp120 (binds to CD4)
Cp141 (important for fusion) |
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How is Vpr packaged into virus particles?
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Interaction with p6 sequence of Gag
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What is the role of Vpr?
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Part of pre-integration complex, important for transportation of PIC into nucleus
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How many molecules of Vpr per particle?
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100-200
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How many copies of the RNA genome do retroviral particles contain?
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2 copies of RNA genome/viral particle
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How are the copies of RNA genome arranged within the particle?
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They dimerize via sequences at the 5' end - via the SL1 structures
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How is viral mRNA incorporated into the viral particle?
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NC domain of Gag binds viral RNA via stem loop structures (SL1-SL4)
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What is the mechanism by which the SL1 of the HIV RNA form a dimer?
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Kissing-loop
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What is the sequence of SL1 that is part of the dimer?
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GCCGC
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What is t-RNAlys3?
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A CELLULAR FACTOR- serves as a primer for synthesis of minus-strand DNA (RT)
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What is tRNAlys3 incorporation mediated by?
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RT sequence in Pol
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How are cellular proteins generally incorporated into HIV particles?
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Through interacting with different domains of Gag
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What is APOBEC?
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Cytidine deaminase that is recruited in absence of HIV protein Vif
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What is TRim5alpha?
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From the old world monkey- inhibits RT step
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What is BST-2 (tethrin)?
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Blocks release of particles from the surface- counteracted by viral Vpu
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What does PA-457 do?
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Results in delayed cleavage of p25 and an abnormal HIV core structure - renders the particle uninfectious
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What happens if peptide inhibitors that lock the capsid conformation are administered?
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The capsid cannot build up teh core structure in the mature virus particle - thus, the mature virus particles are UNINFECTIOUS
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What is xenotransplantation?
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Transplantation of organs, tissues or cells between species
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What are some advantages of xenotransplantation?
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-Unlimited, predicatble organ supply
-Advanced planning, elective surgery -Immunological pre-treatment -Organs are harvested at time of requirement -Breeding specific pathogen free animals -Pre-screening organs for infection |
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What are some hindrances of using organs from non-human primates?
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-Slow to attain breeding maturity
-Long gestation period -One offspring/birth -Costly -Unethical |
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What are some advantages of using pigs as an organ source for xenotransplantation?
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-Short period to attain sexual maturity
-Short gestation period -Large scale breeding is feasible -No ethical issues -Can perform TRANSGENIC MANIPULATION |
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Are pigs and humans close in phylogeny? What does this mean for physiological compatibility?
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Not close- leads to difficulty in achieving physilogical compatibiltiy
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Why can hyperacute rejection of pig organs occur?
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Humans have natural antibodies against alpha1,3 galactose - which is expressed on the cell surface of lower mammals
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What are some strategies to reduce hyperacute rejection?
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Remove Ag, remove antibodies, block complement activation
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What is a concerning genetic barrier?
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Incompatibility of coagulation facots would lead to thrombosis
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What is zoonosis?
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Transmission of pathogens between species
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Why is there an increased risk of zoonosis in xenotransplantation?
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-Bypass skin and mucosal surfaces
-Use of immonsuppresive therapy -Genetic modification of source animals may HUMANIZE animal pathogens |
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What distinguishes retroviruses from other viruses?
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Reverse transcriptase
Integration into genome |
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Who won the nobel prize for finding RT?
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Howard Temin, David Baltimore
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What is the definition of an endogenous retrovirus?
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Results from ancestral retrovirus infection of germline cells and inherited by the host as Mendelian traits, replication incompetent
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Is HIV considered an endogenous retrovirus?
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No! HIV does not infect germline cells and thus cannot be passed down as a Mendelian train within the species
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Why do endogenous retroviruses pose a danger for xenotransplantation?
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In some animal species, live endogenous retroviruses can be found and can cause disease in the new host!
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What percentage do human ERVs acount for? Are they active?
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Human ERVS are inactive and account for 7% of our total genome!
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What is another name for endogenous retroviruses?
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LTR retrotransposons
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What are the three classfications of transposons?
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RNA transposons or retrotransposons
DNA transposons HElitrons |
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What are the two types of retrotransposon?
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Autonomous:LTR (8%) and non-LTR (non-LTR compose 20% of our genome)
Nonautonomous: Need help to move |
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What is a key example of a non-LTR retrotransposon?
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LINE1- ORF2 of RT encodes for RT
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What are some mechanisms by which endogenous retroviruses are controlled?
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-Accumulation of inactivating mutations
-Promoter CpG methylation -Small-RNA mediated silencing |
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Where is PERV Rna found?
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Several porcine tissues: kidney, lung, skin, liver, heart, etc..
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What are the three groups of PERV isolates?
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A, B and C
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What family does PERV A-C belong to?
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Gammaretrovirus
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What family does PERV-L belong to?
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Spumavirus
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What do PERVs encode for?
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Only Gag, Pol and Env (they are simple retroviruses!)
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Which PERVs are infecitous to human cells in vitro?
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PERV-A and PERV-B but not C
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What are the identified PERV-A receptors?
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HuPAR-1 and HuPAR-2
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What are some transgenic pigs used to prevent pig organ rejection?
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HDAF-Tg (prevents complement activation)
A1,3galactosyltransferase knockout |
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What are other names for viral diarrhea?
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Viral gastroenteritis, Stomach flu
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What are two major viruses that cause viral diarrhea?
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Rotavirus
Norovirus |
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What is gastroenteritis?
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Acute infection of the stomach lining and intestine (gut)
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What do syndromes associated with gastroenteritis include?
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Diarrhea, vomiting, abdominal pain, nausea, fever and chills
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What are the two major mechanisms by which viruses cause diarrhea?
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1) toxins
2) Pathogen invastion of gut |
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How do virus toxins cause diarrhea?
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Cause excessive water and electrolyte loss
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How does pathogen invasion of the gut cause viral diarrhea?
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Inflammation (immune response targeted to invading virus)
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How are viruses that cause viral diarrhea transmitted?
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Oral-fecal route
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How many deaths annually can be attributed to diarrhea?
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>2 million
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What are the four viruses that cause most cases of viral diarrhea?
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Rotavirus
Adenovirus Calciviruses Astrovirus |
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Which family does Rotavirus belong to?
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Reoviridae
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What is the genome of rotavirus like?
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11 segments of ds RNA per virus particle
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Are rotaviruses enveloped?
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NO
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Describe the capsid of Rotaviruses
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Icosahedral (T=13) with 2 layers (inner + outer)
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Which Rotavirus species causes the majority of infections?
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Rotavirus A species
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What is the tissue tropism of Rotavirus?
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Small intestinal enterocytes (first layer of cells within the inner gut)
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Who does Rotavirus mostly infect?
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Children
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Which Rotavirus protein serves as the enterotoxin?
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NSP4
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What was the first Rotavirus vaccine?
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Rotashield
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Why was Rtoashield withdrawn?
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Risk for intussusception
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What are two current rotavirus vaccines?
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Rotarix, RotaTeq
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What does each Rotavirus genome segment encode?
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A single proteni
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What is the exception to this?
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Segment 9 and 11 encode two proteins - the two proteins differ by their N terminus
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What is the mechanism by which Rotavirus genome segments 9 and 11 encode two different proteins?
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Alternative initiation
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How many layers of proteins are in the Rotavirus particle?
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Three
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What forms the outer layer of Rotavirus particle?
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VP4 and VP7
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How is VP4 arranged in the particle?
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VP4 protrudes away - binds viral receptors on target cell surfaces
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What forms the middle layer of the virus particle?
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VP6
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How is VP6 arranged?
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As hexamers
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What forms the inner layer of the Rotavirus particle?
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VP2
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What does VP1 encode?
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Rna-dependent RNA polymerase
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What does VP3 encode?
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Capping enzyme -adds the 5' cap to the viral mRNA
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How do VP1 and VP3 interact?
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They form a protein COMPLEX
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What happens once viral mRNA is formed?
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It leaves the particle through a channel made up of VP2 and VP6
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What is VP4 cleaved into?
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VP5 and VP8
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What does VP5 interact witH?
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integrins
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What does VP8 interact with?
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Sialic acid
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What happens to the three layered particle upon entry into the target cell?
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Loss of outer layer- release of DLP into cytoplasm
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How can one recapitulate this uncoating process in the lab?
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Using calcium chelators such as EDTA
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How many channels are there that the mRNA can exit from?
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132
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How many molecules of VP2 form the inner shell?
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60 dimers - 12- five fold acis
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How are the 11 RNA segments arranged in the viral particle?
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Each segment is coiled tightly and oritened towards one of the vertices of the capsid
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What cofnormation does the VP1 polymerase domain assume?
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Right-handed structure
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What are the four channels in the VP1 protein?
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1) Entry for viral RNA template
2) Entry site for NTPs 3) exit of template (- strand mRNA) 4) exit of + strand RNA (mRNA) |
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What is an important site located on VP1?
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Cap binding site
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What is the difference between who Rotavirus and Norovirus infects?
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Rotavirus mainly infects the young population, while norovirus infects all ages
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How common is norovirus-associated viral diarrhea?
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Very common - infact norovirus accounts for ~90% of non-bacterial outbreaks of gastroenteritis
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What family does Norovirus belong to?
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Calciviridae
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Describe the norovirus particle
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non-enveloped, icosahedral, 38 nm in size
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Describe the norovirus genome
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+ strand, single-stranded RNA
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How many genogroups are there of norovirus?
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5:G1-GV
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How many genotypes does G1 have?
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8
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How many genotypes does G2 have?
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17
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Which genogroup + genotype accounts for the majority of Norovirus outbreaks?
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Genogroups 2, genotype 4
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What is Norwalk virus?
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Prototypical norovirus, genogroup 1 and genotype 1 - first isolated viral agent that causes viral diarrhea!
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What is the hallmark of norovirus infection?
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Sudden onset of vomiting and diarrhea
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What are some key features of norovirus infection?
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-Highly contagious
-Viral shedding precedes onset of symptoms and can occur even 2 months following infection -Withstand wide range of temperatures -Great diversity (high mutation rate) - leads to lack of cross-protection and long term immunity |
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How many ORFs are locate din the norovirus RNA and what do they encode for?
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ORF1: enzymes for replication
ORF2: VP1 ORF3: VP2 |
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What do VP1 and VP2 do?
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Build the virus particle
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What are the domains of VP1?
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P1, P2 and S
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What does S do?
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Form the capsid
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What is the role of P2?
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P2 (protruding) - binds the cellular receptor
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What are the receptors for Noroviruses?
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Histo-blood group Ag
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What do nonsecretors lack?
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A functional fucosyltransferase 2 gene
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What are histoblood group Ags?
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A family of complex glycans expressed on the surfaces of RBCs, gut and respiratory epithelia
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What are the three major groups of histo blood group Ags?
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ABO, Lewis, and secretor
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What is the T number of the norovirus capsid?
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3
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What is common within a Norovirus genogroup?
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Consensus binding sequence for HGBA
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Why are there no norovirus vaccines or antivirals available?
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-Lack of info about how the virus grows or replicates in cells
-No cell lines that can grow the virus, no small animal models in which we can study the pathogenesis |
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What are the two major classes of symptoms of viral respiratory disease?
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Upper respiratory tract infection
Lower respirator tract infection |
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Which is more severe?
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Usually LOWER respiratory tract
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What are the symptoms of upper RI infection?
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Congestion (Coryza), cogh, horseness, rhinitis, pharyngitis, fever,poor feeding
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What are the symptoms of a lower respiratory tract infection?
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Tachypnea (rapid breathing), wheeze, severe cough, breathlessness, respiratory distress
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What are four factors that influence susceptibility to and severity of viral respiratory disease?
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-Genetic factors
-Immune factors -Viral factors -Physical factors |
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What are the two mechanisms by which viruses induce disease?
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Virus-induced disease
Immunopathology |
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What are some ways to clinically manage viral respiratory disease?
|
-Target the virus
-Bronchodilators -Corticosteroids -Oxygen supplementation -Hypertonic saline inhalation |
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Wha tis the main cause of hospitalization due to bronchiolitis?
|
Respiratory syncytial virus (RSV)
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What family does Rhinovirus belong to?
|
Picornaviridae
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Describe the rhinovirus particle
|
Nonenveloped, 30 nm
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What type of genome does rhinovirus have?
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Single stranded, + sense RNA genome
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How many serotypes does Rhinovirus have?
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99 (Rhinovirus A (76), Rhinovirus B (23))
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What are the rhinovirus receptors?
|
ICAM-1 (majority)
LDLR (minor) |
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What is the tissue tropism ofd rhinovirus?
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respiratory epithelium
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What life cycle is rhinovirus similar to?
|
Poliovirus
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What family do Coronaviruses belong to?
|
Coronaviridae
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Describe the Coronavirus particle
|
Enveloped, 80-200 nm in diameter
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Describe the Coronavirus genome
|
SIngle + strand RNA
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What is unique about Coronavirus assembly?
|
Occurs at the GOLGI
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What is another member of the Coronaviridae family that causes severe respiratory disease?
|
SARS
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Where does Coronavirus infect?
|
upper respiratory tract
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What family do Adenoviruses belong to?
|
Adenoviridae
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Describe the Adenoviridae particle
|
Non-enveloped, icosahedral, 80-100 nm in diameter
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Describe the adenovirus genome
|
Linear, dsDNA genome
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How many serotypes are there of Adenovirus?
|
More than 50!
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What family does Reovirus belong to?
|
Reoviridae
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What is the genome of Reovirus like?
|
10 segments of dsRNA
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What is the particle of Reovirus like?
|
Non-enveloped, icosahedral, 65-70
|
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What family does Parainfluenza virus belong to?
|
Paramyxoviridae
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|
|
Desribe the parainfluenza virus particle
|
Enveloped, pleomorphic morphology (some spherical, some filamentous), 150-200 nm in diameter
|
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What is the genome like?
|
one linear ss negative RNA
|
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What is similar between parainfluenza virus and influenza in regards to surface proteins?
|
Parainfluenza also carries surface HA and NA
|
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Which disease is Parainfluenza strongly associated with?
|
Croups (causes 75% of cases)
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What is the main target and prevalence of RSV?
|
Children - 90% are infected by 2 years of age
Also infects elderly and immune compromised individuals |
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Which family does RSV belong to?
|
Paramyxoviridae
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Which subfamily does RSV belong to?
|
Pneumovirinae subfamily, Pneumovirus genus
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Which sub family does parainfluenza virus belong to?
|
Paramyxovirinae
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What is the route of RSV infectioN?
|
Aerosol + direct contact
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What are the inoculation sites of RSV?
|
Nose and eyes
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What is the primary infection site?
|
Nasopharynx
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What are the symptoms of RSV infection?
|
Rhinorrhea, cough, fever, bronchiolitis, air trapping, wheezing, pneumonia
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What are the serious symptoms of RSV that require hospitalizatioN?
|
Bronchiolitis and pneumonia
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How does RSV induce its pathology?
|
-Necrosis of epithelial cells
-infiltrates of monocytes, T cells, neutrophils -Mucous secretion |
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What is unique about RSV diversity?
|
RSV has limited antigenic and strain diversity, it has only ONE serotype
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What are the target cells of RSV?
|
Superficial cells of the respiratory epithelium
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What is a unique feature of RSV infection?
|
It can cause a fusion of neighbouring cells - forming a giant, multinucleated cell
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What is the word for this giant nucleated cell formed by RSV infection?
|
Syncytium
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Why, if RSV has limited antigenic variation, does a person infected with RSV have a chance to get re-infected and does not develop immunity against this?
|
-Surface G protein (heavily glycosylated)
-Secreted G protein neutralizes antibodies |
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What is the difference between the secreted G protein and the Surface G protein?
|
The secreted G protein is translated from the SECOND methionine of the coding sequence. As a result, this protien lacks the anchor domain
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Why does the tissue tropism of RSV reduce the effect of host immunity?
|
Since RSV infects the epithelial cells of the RT, the local IgA responses are short-lived in comparison to IGm and IgG that occur elsewhere
-IgG has pooor access to respiratory limen |
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|
What are some other immunological barriers assocaited with RSV infection?
|
-Functionalyl impaired RSV-specific CD8 cells
-Delayed Ag presentation of RSV to immune system (since RSV infects inner part of RT) -Immunological immaturity at infancy |
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|
What is one the surface of RSV envelope?
|
F- fusion proteins
G- proteins - mediate attachement |
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What is underneath the RSV envelope?
|
A layer of M protein (matrix protein)
|
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|
What is also on the RSV surface?
|
SH - a viroporin and inhibits apoptosis
|
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What is bound to the viral genomic RNA?
|
Viral nucleoprotein (N protein)
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What encodes the RSV polymerase?
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L protein
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Where is viral RSV RNA replicated?
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In the cytoplasm
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Which RSV proteins function to produce the syncytia seen in RSV infection?
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G and F proteins
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What is the RSV receptor?
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Heparin or proteoglycans
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What is the receptor for Parainfluenza virus?
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Sialic acid
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What is the receptor for Measles virus?
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CD46/SLAM
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What is the receptor for Hendravirus?
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Ephrin B2 and B3
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Why does the virus carry a viral polymerase in the particle?
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Viral genome is negative strand and therefore need to convert to + strand before it can make any viral proteins
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How does the RSV polymerase work?
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-Transcribes the viral RNA into multiple fragments of mRNA - each encoding a protein
-At a certain point it switches to make the full length antigenome to be packaged |
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How does RSV polymerase know where to make the fragments?
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Synthesizes + strand mRNA until it reaches a GE sequence, slides a bit until the GS sequence, and starts synthesizing RNA again
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What is the one exception to this method of RSV polymerase action?
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The M2/L overlap: GS precedes GE (reversed). The polymerase goes until the GE, making the M2 protein, then slides back to the GS and then makes the L protein!
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Why is there a greater abundance of viral proteins near the 3' end?
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The polymerase falls off alot before it reaches the 5' end
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What is the leader sequence?
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Located at the 3' end of RSV genome -This is wher the viral RNA pol binds and starts transcription
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What is the trailing sequence?
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Located at the 5' of RSV genome - this is where RNA polymerase will stop
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How does RSV evade detection of virus infection?
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NS2 protein inhibits RIG-I, inhibits MDa-5, targets NF-KB, targets IRF-3
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Which family does influenza belong to?
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Orthomyxovirus family
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What are the five members of the Orthomyxovirus family?
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Influenza A
Influenza B Influenza C Isavirus Thogotovirus |
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What is the host tropism of Influenza A?
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Human, pig, bird, horse
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What is the host tropism of Influenza B?
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Human, seal
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What is the host tropism of Influenza C?
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Human, pig
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What is the host tropism of Isavirus?
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Salmon
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What is the host tropism of Thogotovirus?
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Mosquito, mammals
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What is the natural influenza reservoir?
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Wild water fowl (pond birds)
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What is an important feature concerning the influenza genome?
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Fragmented, - strand, RNA
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Which influenza viruses cause human pandemics?
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Influenza A and Influenza B
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What is the morphology of Influenza A?
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Pleomorphic - sphere or filament
Enveloped |
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How many segments of RNA are in the Influenza A, B, C particles?
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INfluenza A and B: 8
Influenza C: 7 |
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What are the three proteins on the surface of Influenza A?
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-Hemagluttinin (HA)
-Neuraminidase (NA) -M2 ion channel |
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What are vaccines againt influenza based on?
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THe types of HA and NA antigens circulating in the current population - these are the neutralization antigens which host Abs recognize
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How many subtypes of HA are there?
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16
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How many subtypes of NA are there?
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9
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What are the current dominant subtypes in the human population?
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H3N2 and H1N1
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What is antigenic drift?
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A result of viral error-prone polymerase (high mutation rate) - changes antigenic profile of virus
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What is antigenic shift?
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Emergence of a new virus strain, a result of either:
1) Interspecies transmission or 2) Reassortment of genomic RNA fragments |
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Why do pigs play such an important role in the interspecies transmission of influenza virus?
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-Express both human and avian influenza receptors on their tracheal epithelial cells
-Thus, they become mixing vessels for human and avian inflluenza viruses |
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Which viral proteins contributed to the pathogenesis of the Spanish Influenza H1N1?
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HA and PB2
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What strain caused the Asian influenza in 1957?
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H2N2
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What strain caused the Hong Kong outbreak in 1968?
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H3N2
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What strain caused the Russian influenza outbreak in 1977?
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H1N1
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How did the 2009 H1N1 strain arise?
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Two combinations
1) Classical swine + North American avian + Human H3N2 2) This combination then recombined with a Eurasion avian-like swine to get the H1N1 |
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What is an important determinant of pathogenicity on the PB2 protein?
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At position 627, pathogenic viruses have a Lys, whereas low pathogenic viruses have a Glu
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Why can asian influenza viruses infect systemically, while humans are limited to the respiratory tract?
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The HA of humans has a single basic aa, but avian HA has has multiple basic aa. HA can therefore be matured by proteases present in many host cells whereas human strains can only be processed by proteases found in tracheal epithelial cells
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How is entry accomplished for influenza ?
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Internalization into an endosome
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Where does influenza RNA replication occur?
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Nucleus
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What triggers the release of Influenza RNA segments into the cytoplasm?
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Drop in pH causes a conformational change in HA and fusion with the membrane of the late endosome
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Where does assembly + budding of influenza occur?
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At the cell membrane
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What is required for the virus to leave th ecell surface?
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Neuraminiadse needs to cleave sialic acid in order to allow HA to dissocaite and the particle to leave
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What needs to happen to HA to be functional?
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Cleaved into two domains, HA1 and HA2 (linked by a disulfide bond)
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Which sialic acid is the receptor in avian cells?
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SAalpha2,3, Gal
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Which sialic acid is the human receptor?
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SAalpha2,6Gal
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What is the role of HA1?
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Binding pocket for sialic acid
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What is the structure of HA1?
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Beta sheet
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What is the role of HA2?
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Helicase, fusion peptide
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What is the structure of HA2?
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Helical
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Where is the HA0 protein cleaved?
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At the basic amino acid
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What are common features between Paramyxovirus F protein, influenza HA protein, and HIV env protein?
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-All processed into two subunits
-Fusion peptide (FP) -Heptad repeat (HR) -TM domain (TM) |
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What is the structure of influenza HA?
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Helical bundle and globular head (globular head binds receptors)
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What is the difference between class I and II fusion proteins?
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Class II dont have helical structures, but fold mainly into Beta sheets, but following entry they assume a similar structure as Class I
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Which viral protein constitutes a possible third class of fusion protein?
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VSV G protein (Both helical structures and beta sheets)
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What are the 5' and 3' ends of viral RNA normally like?
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Bound by viral RNA polymerase
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What are the three subunits of influenza RNA pol?
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PA1
PB1 PB2 |
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What is the role of PB2?
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Binds to the cap of cellular mRNA
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What is the role of PA?
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After binding, it cuts the cellular mRNA into a short fragment
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What is the role of PB1?
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PB1 used the short RNA fragment as aprimer to initiate transcription of viral RNA
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How many proteins are encoded by Influenza A? C?
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11
9 |
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How does NS1 help influenza to evade the host response?
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-Limits IFN by blocking RIG-I and OAS
-Limits antiviral state -Blocks cellular mRNA translation -Limiting apoptosis through viral protein -Enhancing viral mRNA translation |
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What does Zanamivir and Olsetamivir target?
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The neuraminidase protein
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What is the normal function of NA and why is blocking this good to treat influenza?
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Cleave sialic acid on infected cells so HA can be released
-Blocking this limits virus propagation |
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What does Amantadine target?
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M2- the ion channel required for fusion of influenza and release of genome into cytoplasm
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How does amantidine work?
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Goes into the channel and blocks its function
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What are the benefits of using live, attenuated vaccines?
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Elicits a stronger humoral and cellular immune response
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What is a potential universal target to ALL influenzas?
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The highly conserved ectodomain of M2 protein
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