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71 Cards in this Set
- Front
- Back
What kind of parasites are viruses?
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Obligate intracellular parasites
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Why are viruses parasites?
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They rely on the metabolic machinery and protein biosynthetic machinery of the host cells
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How can the structure of a virus vary?
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- Naked vs. enveloped
- RNA vs. DNA genome |
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What happens during the intracellular phase of a virus lifecycle?
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- Replication
- Transcription - Synthesis of proteins - Assembly of virions (All within infected cells) |
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What happens during the extracellular phase of a virus lifecycle?
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Particles must pass from cell to cell, throughout body, or between individuals
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What is the size range of viruses? Implications for type of microscope used?
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- Diameter from ~20 nM to ~300 nM
- Must be viewed with Electron Microscope |
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What type of taxonomic method is used for virology? What does this mean?
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"Polythetic" - any given virus group is described using a collection of individual properties - a class whose members always have several properties in common although no single common attribute is present in all of its members
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Why is the taxonomic classification of viruses important?
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- Diagnosis
- Identification of new viruses - Clarification of life cycle - Drug design |
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What are some possible properties that can be used for taxonomic classification of viruses?
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- Particle type
- Tissue tropism - Disease etiology - Serology - Genome type |
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How can viruses be classified based on particle type?
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- Icosahedral or Filamentous or Irregular
- Enveloped or Naked |
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How can viruses be classified based on tissue tropism?
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- Skin
- Respiratory Tract - Lymphoid Cells - Etc. |
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How can viruses be classified based on disease etiology?
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- Hepatitis
- Gastroenteritis - Encephalitis - Etc. |
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How can viruses be classified based on serology?
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E.g., cross-reacting epitopes
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How can viruses be classified based on genome?
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- RNA: + sense vs. - sense, ds, segmented
- DNA: ss vs. ds, linear vs. circular |
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What do +sense vs. -sense RNA viruses mean?
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+ sense --> same sense as mRNA
- sense --> needs to be copied to be inverse mRNA |
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What forms the structure of a viral capsid?
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One or a few proteins that have repeating protein-protein contacts
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What kind of viruses can have capsids?
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- Naked viruses
- Enveloped viruses (matrix protein lies under envelope) |
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What is the function of the capsid / envelope?
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- Packaging, protection, and delivery vehicle during transmission (designed to be stable until it contacts the next host)
- Exposed proteins are the targets of neutralizing antibodies |
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What is the Baltimore classification scheme?
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- Classifies viruses based on genome type (DNA/RNA and ss/ds and +/- sense)
- I: ± ds DNA - II: + ss DNA - III: ± ds RNA - IV: + ss RNA --> - ss RNA - V: - ss RNA - VI: + ss RNA --> - ss DNA |
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What happens in Baltimore classification scheme I?
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- Start as ± ds DNA
- Transcribed to + mRNA - Virus doesn't have to encode its own machinery because our cells have this transcription machinery (however viruses may also supply this for increased autonomy) |
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What happens in Baltimore classification scheme II?
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- Start as + ss DNA
- Need to synthesize complement strand (- DNA) --> machinery is unique to / encoded by virus - From there, - DNA is transcribed to + mRNA |
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What happens in Baltimore classification scheme III?
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- Start as ± ds RNA
- Replicates using host machinery to + mRNA, but can also use some of its own machinery - However there is never dsRNA in hosts, so the presence of it can activate interferon / immune system (need stealth mechanisms) |
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What happens in Baltimore classification scheme IV?
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- Start as + ssRNA
- Converted to - ss RNA so that it is the correct sense for making + mRNA - Also can be directly translated into proteins by host ribosomes |
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What happens in Baltimore classification scheme V?
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- Start as - ssRNA
- Converted to + mRNA - Also can be directly translated into proteins by host ribosomes |
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What happens in Baltimore classification scheme VI?
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- Start as + ssRNA
- Reverse transcribed by proteins provided by the virus to - ssDNA - -ssDNA is replicated to ± dsDNA - Host machinery transcribes into + mRNA |
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How does the size of RNA viruses compare to DNA viruses?
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- RNA viruses in general are smaller (7-27 kb)
- DNA viruses have a larger range and can be much larger (5-280 kb) - Although the RNA viruses are usually smaller, the smallest virus is a DNA virus (parvo virus) |
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What is the difference between a "virion" and a "virus"?
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- Virion is a viral particle (not all are infectious)
- Virus is an infectious particle |
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What is MOI?
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Multiplicity of Infectino
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What is CPE?
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Cytopathic Effect
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What is Viremia?
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Spread of virus throughout the body via the bloodstream
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What are some ways to quantify an infectious virus?
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- Plaque Assay
- Focus Forming Assay - Single-step Growth Curve |
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What happens in a "Plaque Assay"?
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- Tissue culture assay for quantitating infectious virus
- Titration of the number of infectious progeny (unit = plaque forming unit, pfu) - The plaque ("hole") reflects the zone of infection and spread initiated by a single infectious unit (pfu) |
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What happens in a "Focus Assay"?
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For viruses that induce cell proliferation rather than cell death
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What happens in a "Single-Step Growth Curve"?
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Provides quantitation of "burst size"
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What do naked capsid virions contain?
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- DNA or RNA
- Structural proteins - Enzymes and nucleic acid-binding proteins (= Nucleocapsid) |
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What is a Nucleocapsid?
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- DNA or RNA
- Structural proteins - Enzymes and nucleic acid-binding proteins |
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What do enveloped virions contain?
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- DNA or RNA
- Structural proteins (e.g., capsid), attachment and fusion proteins (for binding and entry), auxiliary proteins (aid in disassembly after entry) - Enzymes and nucleic acid-binding proteins (= Nucleocapsid) + Glycoproteins and membrane |
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The membrane of a virion is derived from what?
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Nucleus, ER, Golgi, vesicles, plasma membranes
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How do viruses replicate?
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"Xeroxing" - make many copies at once
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What are the steps in a viral lifecycle?
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1. Attachment
2. Penetration 3. Uncoating 4. Synthesis of components (synthesis of viral mRNA, translation of viral proteins, genome replication) 5. Assembly of viral components 6. Exit/maturation |
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How does a virus mediate attachment (step 1)?
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- For both naked and enveloped viruses, a viral surface protein recognizes a receptor on the target cell
- Cell surface receptors (proteins or carbohydrates) can often determine species or tissue tropism - Antibodies that interfere with this interaction "neutralize" viral infectivity |
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What is the virus recognition of its receptor important for?
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- Host range (human vs. other hosts)
- Cell tropism (location of infection in the body) |
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What is the receptor for HIV?
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Human CD4 on T cells
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What is the receptor for Epstein-Barr Virus?
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Human Complement receptor CD21
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What is the receptor for Rhinovirus?
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Human ICAM-1
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What is the receptor for Influenza Virus?
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Sialic Acid
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How does a virus mediate entry (step 2)?
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- Naked virus enters the cell via endocytosis and is surrounded by endosomal membrane
- Some enveloped viruses use their glycoprotein to induce fusion of virus and cell membranes; fusion releases capsid into the cytoplasm, leaving traces of viral protein in the plasma membrane - Some enveloped viruses are taken up by endocytsois and fusion of their membrane with the membrane of an acidic endosomal compartment releases the capsid into the cytoplasm |
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How does a virus mediate genome replication and transcription (step 4)?
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- The replicative pathway a virus is reflected in, and depends upon, the enzymes it encodes
- Cells do not have enzymes that copy RNA --> RNA, or RNA --> DNA |
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Where does viral replication and transcription take place?
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In the nucleus or in the cytoplasm, using cellular or viral enzymes
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What must all viruses synthesize to make proteins?
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+ sense mRNA
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What is used by viruses to synthesize viral proteins?
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All viruses use host ribosomes to synthesize viral proteins, although viral proteins may modify their translational specificity
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What is used by viruses to modify proteins?
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Host or viral machinery (e.g., phosphorylate)
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How do viruses affect the cellular membranes?
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Use, divert, or modify cellular membranes for replication and assembly
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How do viruses affect the host macromolecular synthesis?
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Many viruses "shut-off" host macromolecular synthesis; others manipulate the cell cycle of the host to provide the best replicative environment
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How does a virus mediate assembly (step 5)?
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- Proteins sorted to nuclear or cytoplasmic location
- Capsid proteins assemble - Viral genome selectively encapsidated - Viral membrane proteins synthesized (translation in ER), modified (glycosylated in Golgi), and trafficked to correct membrane (internal or plasma by vesicular transport) |
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How does a virus mediate exit (step 6)?
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- Most enveloped viruses bud from the plasma membrane (also from nuclear membrane or into compartments of secretory pathway) and acquire the lipid envelope and viral membrane proteins
- Many naked viruses rely on cell lysis for release |
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What kind of viruses can acquire a membrane in the cytoplasm?
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Poxvirus
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What are the possible outcome of infection at the cellular level?
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- Productive infection
- Latent infection - Persistent infection - Abortive infection |
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What happens in a productive infection?
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Generally leads to cytopathic effect with a burst of virus production
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What happens in a latent infection?
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No production of infectious virus particles, but genetic information of the virus remains
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What happens in a persistent infection?
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Chronic virus production
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What happens in a abortive infection?
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Virus life cycle incomplete and virus lost
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How does a virus affect the host cell?
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Acute Cytopathic Effects:
- Membrane fusion of adjacent cells to form giant, multi-nucleate cells called syncytia - Shuts off host metabolism - Induces apoptosis - Leads to cell death and necrosis Cell transformation: loss of normal growth control, "oncogenic potential" Or no apparent effect |
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What factors influence the species/organ/tissue for disease by virus?
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- Tropism: receptor, tissue-specific cellular components required for infection, tissue-specific restriction factors that abort infection, temperature or pH or activating proteases
- Transmission: respiratory, fecal/oral, direct contact (sexually, or parenteral - blood), indirect (fomites or vectors) |
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How do viruses cause disease?
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- Virus destruction of infected cells
- Viral modification of infected cell function - Immune and inflammatory responses to viral infection (fever, rash, myalgia, immune-mediated damage or destruction of cells or tissues) - Combination |
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What are the components of the host defenses to viruses?
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- Innate response (soluble mediators and/or apoptosis)
- Adaptive response (humoral) - Adaptive response (cell-mediated) - Memory response (B and T cells) |
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What soluble mediators (innate response) are part of the host defenses to viruses? How do they function?
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- Interferons (IFNs)
- Cytokines - Chemokines - Antiviral response within infected cell --> make surrounding cells resistant to infection --> recruit effector cells (NK cells and macrophages) |
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How does apoptosis (innate response) play a part in the host defense to viruses?
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Programmed cell death to avoid release of infectious virus
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What are the components of the humoral adaptive response to viruses?
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- Neutralizing antibodies - block attachment or entry
- Complement fixing antibody - lyse virions or infected cells |
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How does the cell-mediated adaptive response help the host defend against viruses?
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MHC presentation of viral peptides --> killing of virus-infected cells by cytotoxic T cells
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What are the targets for antiviral therapy?
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The basic steps in a viral life cycle
1. Attachment 2. Penetration 3. Uncoating 4. Synthesis of components 5. Assembly of viral compoennts 6. Exit / maturation |