T A REVIEW NOTES Cryro EM means ultra low temp It freezes like the virus so it preserves it EM tomography sample is tilted but the microscope stays stationary Transmembrane protein page 18 21 goes through membrane 4 routes of viral entry Membrane pores at the cell surface and endosomes and membrane fu sion at the cell surface and endosomes Membrane fusion will only happen if the virus is a envelope virus Virus entry at the endosomes requires PH drop to 5 or 6 Viral receptor cell surface molecule bound by a virus Virion is a virus particle basically part of the virus Same thing Endocytosis page 25 Cellular uptake of extracellular space Tropism page 18 Species specific receptors specific HIV receptors 2 coreceptors what are they 1 CCR5 maraviroc in HIV cocktail therapy which blocks the receptor and prevents the HIV cells from infecting the cells 2 CV4 primary receptor which infect the T cells Why is this drug affective Nucleic acid polymer made up of repeating nucleotides Nucleotides are made up of pentose sugar nitrogenous base and phosphate groups Proteins made up of amino acids The DNA double helix 2 chains run in opposite directions or in anitparallell fashion Adenine pairs with thymine Cytosine pairs with guanine DNA vs RNA DNA has 4 basis and RNA has 3 plus uracil Base pairing is called complementary base pairing Central Dogma DNA to MRNA to proteins All roads lead to MRNA Reverse transcription DNA to RNA to proteins back to DNA RNA is the genome but DNA integration Reverse transcriptase enzyme that uses RNA template to produce DNA RNA dependent RNA polymerase uses RNA template to produce RNA Why do RNA virus have a much higher mutation rate They have low fidelity makes more mistakes PAGE 32 What is the difference between positive sense and negative sense RNA Negative can be con verted back to pos before it can be translated into protein Page 48 49 50 Difference that virus have two common shapes Bugs life overview Genomes uses host ribosome to make it s own copy Late gene expression uses other parts of it s genome to make structural proteins Page 63 and beyond Signal transduction Change in gene expression Interferons use this What is a receptor mediated endocytosis What are the steps of this pathway Receptor binding pit formation membrane pinches off proton pumps ph drops viruses enter acidification of the endosome page 65 How do viruses enter using this pathway proton pumps which delivers protons into endo some PH drops lower which triggers Cytoskeleton page 65 structures are microfilament intermediate filament and microtubule provides support and structure Physical defenses skin Chemical defenses tears PAMP pathogen associated molecular patterns when a virus enters the host cell recogniz ing if the cell is infected of not Part of the defense Part of the Intrinsic Cell response Example of PAMP double stranded RNA because our cells DONT have this PRR Activate cellular response Interferons are an example of a cytokine Cytokines are part of the intrinsic defense primary produced by infected cells they produce an anti viral state Apoptosis cell suicide last resort of defense LAST RESORT What is a consequence of a virus suppressing apoptosis Cancer Methods of apoptosis blebbing DNA lattering capsize cascade CLASS REVIEW NOTES Topic 1 Overview of viruses and virology Viruses are measured in a nanometer 10 20 Micron Also a name for a micrometer A virus with a diameter of 100nm is smaller that a virus with 1 2 microns but larger that 700 angstroms 0 2 microns can not remove a virus with 150nm but can with 750nm Electron Microscopy Uses light beam 100 times higher resolution can see interior structures of cells and viruses can only look at dead specimen specialty EM cry and tomography Topic 2 Life cycle of a virus Entry Which of the following does not belong in the group A viral receptor B viral tropism C nucleic acid D cell surface E CCRS C Membrane fusion and pore formation at the cell surface and at the endosomes interior At surface occur at neutral PH interior occurs at low PH Proton pumps lower the PH by moving H ions into endosomes Topic 3 Life cycle of a virus Replication DNA double helix 2 strands spiraling around axis The double helix strands run in a way called antiparallel 3 parts to a nucleotide sugar base and phosphate DNA Polymerase Uses DNA as a template to make more DNA Reverse Transcriptase Uses RNA template to make DNA then uses DNA to make copies or original RNA low fidelity don t copy accurately make more mistakes mutations RNA Dependent RNA polymerase Uses RNA template to make more RNA low fidelity Hepatitis uses DSDNA double stranded DNA DNA can go through a replication and make mRNA which is the final template Topic 4 Life cycle of a virus Assembly and exit Structural proteins make up the physical entry of virus called virion Structural proteins usually shaped 5 or 6 sides Viral genome gets packaged Cell becomes enveloped Exit from host cell lysis virus when cell breaks and it exits Budding cell uses virus out Ex ocytosis exit of virus through body Helical rod shaped Icosahedron is 20 faced 3 methods of virion assembly Self assembly capsid protein does it all by itself Assisted as sembly chaperone proteins Assembly followed by maturation maturation process of HIV is a target of the cocktail therapy Why do viruses need to use repeating units for building visions virion is many many times larger that a single protein The small size of the viral genome Topic 5 Virus host interaction virus hijacks a cell Primary cells versus cell lines primary cells are more relevant but they don t grow as well and harder to come by because you have to get them from patients Cell lines can be grown in labs but are cancer Endocytosis uptake of cholesterol entry Exocytosis Mucus production exit Transcription process of using DNA to make RNA and produce proteins Normal functions of viral receptors Signaling transmitting signals from outside of the cell to the inside Adhesion allow cells to attach to surfaces Cell junction formation sealing off space between cells can create barrier Uptake of extracellular nutrients Immunity Summary primary barrier skin tears Intrinsic cellular defense interferon innate immunity macrophages dendritic cells NK cells Acquired Immunity immune memory and vaccines body will have faster response PAMPs non self molecules PRR host proteins that detect PAMPS and activate cellular responses signal for PAMPS Death Pathway for viruses Topic 6 Virus host
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