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This 12 page Study Guide was uploaded by Katy Cook on Thursday February 12, 2015. The Study Guide belongs to Bio 439 at Purdue University taught by Dr. Walter in Winter2015. Since its upload, it has received 159 views. For similar materials see Biology 439- Microbiology in Science at Purdue University.
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Date Created: 02/12/15
Lecture 8 6Q 1 What are the functions of virus structural proteins Protection of the genome Delivery of the genome other interactions with the host 2 What techniques are used to study virus structure and how do they differ Electron Miroscopy Cryoelectron Microscopy Xray Crystallography 3 Contrast common virus structures ie spherical helical tail head Helical These viruses are composed of a single type of capsomer stacked around a central axis to form a helical structure Spherical icosahedral or nearspherical with icosahedral symmetry A regular icosahedron is the optimum way of forming a closed shell from identical sub units Tail Head icosahedral head with helical tail tail attaches to host 4 Describe two approaches for building a bigger more genome icosahedral virus Quasiequivalence of subunits within the asymmetric units in larger particles increase number of subunits increase the triangulation number more structural units per face 5 In your own words explain quasiequivalence Any small nonrandom variation in a regular bonding pattern that leads to a more stable structure than does strictly equivalent bonding 6 How are morphological units of the virion used to determine triangulation number Th2hkk2 7 What are common features found in an enveloped virus What does the term envelope mean How would you determine if a virus has an envelope Lipid bilayer carrying viral glycoproteins to make a complete infectious virus particle Envelopes are essential to entry into the host cells proteins on surface serve to identify and bind to receptor sites Lecture 10 1 What is apoptosis and how might it be beneficial to the cell Nonpermissive infections are usually eliminated by the immune system killing the infected cell or by apoptosis programmed cell death Dead cells can t become tumors 2 How do viruses influence apoptosis RNAvirusesmechanismslargelyunknown may benefit virus replication or spread Cellstressinducedby Inhibition of cellular protein synthesis at multiple levels High level expression of exogenous viral proteins unfolded protein response DNAviruses Unscheduled cell division p53 Stabilization and Activation Many viruses encode apoptosis inhibitors 3 What are the common cellular targets that viruses target to affect the cell cycle Why do they do that Virusinduced transformation alters expression or function of protooncogenes tumor suppressors or both This immune suppression results in the inability to eliminate infected cells 4 How do retroviruses induce transformation and possibly tumors Transduce bring in a mutated copy of a cellular protooncogene Upregulate an endogenous cellular proto oncogene nontransducing lnactivate a cellular tumor suppressor 5 In your own words explain vSRC It is a captured cellular gene which is a constitutively active point mutation 6 Describe two DNA viruses that induce tumors defective adenovirus polyomavirus papillomavirus latent herpesvirus Lecture 11 1 What tools are used to study pathogenesis grow it in a pure culture count infectious units obtain or make mutants with altered biology study virusinduced disease in an appropriate animal model Embryonated eggs cytopathic effect plaque assay uorescent Viruses 2 What is the Iceberg Concept of Pathogenesis Severity of disease vs symptoms little sickdead clinical severe symptoms 3 Explain the theoretical basis of the plaque assay Does that inform how much virus is needed to infect a model organism No all of these variables affect how a virus infects an organism Viral genes Host genes nature and environmental history nurture Interaction between host and viral genes over time coevolution Spread from host to host 0 Interaction with secondary hosts in the environment Tropism in the host 0 Interaction with the host immune system 4 What factors control pathogenesis See question 3 5 Name the four forms of immunity Mechanical physical barrier between live cells and outside environment Intrinsic respond to cells tress by induction of cell death Innate slow pathogen replication and activate adaptive response Adaptive Generate pathogen specific response and clear infection 6 In humans what are the sites for viral entry Most need a moist warm surface mucosal membranes of the eye respiratory tract gastrointestinal tract and urogenital tract skin if not intact enter bloodstream directly insect or animal bites needles 7 Once inside the host how does a virus spread Localized infections celltocell spread systemic infections blood borne spread neural spread Lecture 12 amp 13 1 What is a PAMP Pathogen Associated Molecular Patterns dsRNA unmethylated DNA 2 What are the viral PAMPs recognized by the innate immune Toll Like Receptors TLRs Bacterial lipopeptide Viral dsRNA Lipopolysaccharide 3 What types of cells express TLR5 and in what subcellular locations Doublestranded viral RNAs can be recognized by TLRs in endosomes and by RIGl or MDA5 in the cytosol to induce the expression of interferons 4 How does expression of TLRs in these locations provide a reliable and rapid virus detection system Phagocytes that detect viral nucleic acid in their endosomes via TLRs express i cytokines ii chemokines and iii growth factors that i open the endothelium of the infected tissue capillary bed ii attract immune cells and iii induce immune cell production in bone marrow respectively 5 What cytoplasmic sensors of virus infection exist and how do they work RIGl PKR OAS DAI induce expression of interferons 6 What is the role of dendritic cells Migrate to infection site Phagocytose viral proteins antigens Migrate to lymph node Antigen presentation Immune synapse with CD4 T cells helper T cells to initiate a specific adaptive response against the virus Lecture 14 1 What are the signals required to initially activate a CTL and enable it to kill and where are these signals delivered Respond to antigen presented by class I MHC molecules by means of a Tcell receptor that they express on their surface Activation requires exposure to cognate antigen and a second signal usually supplied by Thelper cells 2 What types of MHC molecules are found and what cell types What is their function How are they different T helper cells express CD4 and recognize antigen presented by Class II MHC whereas MHC class I is expressed by most cells in the body class II is expressed primarily by Tcells Bcells and other cells of the immune system 3 What are the differences between the T cell receptor and the B cell receptor T cell receptors recognize linear amino acid epitopes in conjunction with MHC B cell receptors bind cytokines 4 How is diversity achieved in B and T cell receptors The variable region is unique for every B or T cell binds to antigen Receptor recombination is mediated by the RAG recombinase system Recognizes small recombination sequence signals RSS anking each V D or segment 5 What are the cellular targets cleaved by granzyme B and why do these cleavage events induce cell death What does perforin do They cleave lytic granules that trigger caspase cascade l substrate proteolysis and cell death Granzyme B is a protease that is found in the granules of cytotoxic lymphocytes CTLs natural killer cells and cytotoxic T cells It is secreted by these cells along with the pore forming protein perforin to mediate apoptosis 6 How are peptides processed for presentation in most cells MHCl Cytosolic proteins degraded to peptide fragments by the proteosome a large multicatalytic protease TAP delivers a peptide that binds to the MHC class I molecule and completes its folding The fully loaded MHC class I molecule is released from the TAP complex and exported MHCll Antigen is taken up into intracellular vesicles In early endosomes of neutral pH endosomal proteases are inactive Acidi cation of vesicles activates proteases to degrade antigen into peptide fragments Vesicles containing peptides fuse with fesicles containing MHC class II molecules Lecture 15 1 What does it mean to neutralize a virus particle How would you measure neutralization To eliminate virus infected cells and to eliminate free virus particles in solution measured by a plaque assay 2 What differences exist between the types of epitopes recognized between T cell and B cell receptors The epitopes recognized by Tcell receptors are often buried so the antigen must rst be broken down into peptide fragments A B cell binds virus through viral coat protein which is internalized and degraded 3 How does the structure of an antibody potentially enable virus neutralization The variable end is unique to each B cell which makes it speci c to an an gen 4 What happens during Bcell activation and what cell types and products are produced When rst activated B cells secrete low af nity lgM Upon exposure of the cell to an antigen recognized by the antibody the cell can divide and produce plasma cells that secrete antibody Activation requires second signal supplied by helperT cells After activation memory cells are formed that persist 5 What is meant by somatic hypermutation B cells can generated higheraf nity antibodies by introducing small numbers of mutations into the DNA encoding their V domains 6 What are mechanisms by which antibodies neutralize viruses aggregation phagocytes prefer large particles phagocytes have receptors for the Fc portion of lg destabilization of metastable virion structures 0 mimics natural uncoating trigger blocking attachment 0 director stearic hindrance need no tachieve full saturation of all epitopes since multiple sideby side virusreceptor interactions are required to trigger entry blocking fusionentry may access an inducible normally hidden epitope stabilize the metastable entry machinery and prevent rearrangements blocking uncoating block new virion assembly at cell surface Lecture 16 1 What is meant by virulence and what are the key determinants Virulence is the capacity of a virus to induce disease The key determinants are 0 Tropism and invasiveness primary site of infection Capacity to invade secondary tissues 0 Cytopathicity the capacity of a virus to induce cell death in vitro or in vivo 0 Host response is it protective or damaging 2 How does immune memory protect you from a secondary infection The ability of the immune system to respond more rapidly and more effectively to pathogens that have been encountered previously due to the preexistence of a of a clonally expanded population of antigen specific cells 3 What are some characteristics of memory B cells Memory T cells B Cells Increased frequency of Agspecific clones higher antibody cocentration Higher affinity antibody lgG vs igM more MHC Class II costimulatory molecules longlived T cells Increased frequency of Agspecific clones preformed perforingranzyme B some located in tissues some located in LN longlived 4 What are the major outcomes of virus infection Death Survival complete elimination of virus clearance memory and immunity memory and enhanced disease on second infection rapidly fading memory and transient immunity to second infection chronic infection elimination of replicating virus but viral genome remains latency potential for reactivation of infection and disease 0 same disease as first infection or different 0 can be associated with cancer or autoimmune disease continued replication of virus persistence immune response ineffective at clearance HIV HCV 5 How might the activity of the immune system result in an enhanced disease relative to the activity of the virus alone Disease caused by antibody mediated immune pathology large aggregates of antibody and antigen are impossible for phagocytes to engulf these aggregates can get stuck in capillary beds in the kidneys causing tissue damage Viral disease caused by inflammationinduced genotoxicity and tumorigenesis the immune response to a noncytopathic virus may be a cofactor cell death without clearance of infection continuous production of inflammatory cytokines in the liver Lecture 17 1 What is the difference between variolation and vaccination Variolation is inoculation using live virus rst used to immunize against smallpox with material taken from a patient or recently infected individual scabs blown in nose inoculate pus onto scratch Vaccination is inoculation using less dangerous attenuated virus 2 What was the source of the original smallpox vaccine Cowpox virus 3 What are the advantagesdisadvantages to a killed vaccine A live virus vaccine Killed vaccine disadvantages no replication few PAMPs produced must use adjuvants to stimulate Few MHCl and MHCll peptides presented must do booster vaccines immune response will be almost entirely B cell driven Live attenuated vaccine disadvantages Low level replication tropism may be altered response to secondary natural infection may not be protective reversion to virulence spread to unvaccinated atrisk individuals can t be administered to immune compromised patients 4 What are the characteristics of an ideal virus vaccine For each of the points be prepared to expand on them Effective with a single dose oral needles are expensive and spread disease Cheap lt 1 per person stable without refrigeration safe low risk of complications Lecture 18 1 What is the difference between vaccines and antivirals Antivirals can stop an infection once it has started Vaccines have no therapeutic effect for individuals who are already infected 2 What are potential targets for antivirals Peptide analogues fusion inhibitors entry inhibitors interferons 3 How does the duration of a virus infection in uence the utility of an antiviral By the time the patient feels ill the virus is no longer replicating in the patient the symptoms are due to the immune response the antiviral drug is of no use The antivirals must be given early in infection 4 Why is drug resistance such a problem and what are strategies to reduce this problem Resistance to any antiviral drug must be anticipated when one applies compounds that inhibit viral growth viruses replicate so efficiently have modest to high mutation frequencies Mutation rate is more than one million times greater than for a host DNA genome 5 Why is drug development so an expensive and timeconsuming process What are the three basic stages of drug development 1 Basic research Target ID understand disease mechanism identify a relevant target for drug action Assay develop a reliable assay for drug activity at target Hit ID Screen chemical compounds for activity in the assay 2 Translational Lead ID make chemical analogs to improve activity potency and selectivity con rm activity in vitro and in vivo select scaffolds for optimization Lead optimization make chemical analogs to improve druglike properties potency ef cacy safety pharmaceutics ADME intellectual property 3 Clinical candidate selection select best compounds based on a battery of biological and pharmacological tests preclinical toxicology GMP and stability standard toxicology studies required by FDA for human testing Review Session Killed vaccine only stimulates B cell response M o quot may not get into cell no T cell response 0 quot quot only structural proteins are presented Germ linechromosomal DNA l series recombination this region comprises the antigen binding site 0 quotquot why do we do this RII is a sensor for dsRNA in every cell TLR is only in antigen presenting cells 0 number of TLRs in the endosome that will recognize viral nucleic acid 0 Know structure for multilayered viruses 0 Understand icosahedral nature 0 Calculate triangulation number with just a visual picture as well 0 P53 when activated causes caspase activation which being proteolytic events which lead to apoptosis 0 Th cell becomes activated when bound to the presented peptide then secretes cytokines such that interaction with a B cell will happen if they have same recognition 0 CD4 helper does not kill cells identi es peptides which is a stimulatory event Intrinsic immune response independent of pathogen surveys state of cell could induce death of cell if it is in bad shape pathogen or mechanical Cytotoxic T cell does nothing unless activated by a helper Know few steps of antiviral need target do assay hit compound lead compound research on lead compound bring to animal studies ef cacy studies in animal then clinical trials Know pyramids and virus examples Transducing ability to introduce genetic info into germline retroviruses
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