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56 Cards in this Set
- Front
- Back
what occurs during viral biosynthesis?
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generate mRNA, translate mRNA to generate protein, replicate viral nucleic acid
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what does the term 'replicate' mean in terms of viral nucleic acid?
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exact copies of viral genomes (directly or through intermediate copy)
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what do DNA viruses use to replicate?
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most use viral and cell factors
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what do RNA viruses use to replicate?
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all use viral polymerase, some use additional cell factors
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why do RNA viruses all use viral polymerase?
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there are no cellular RNA-dependent RNA polymerase or general RNA-dependent DNA polymerase (telomerase is a special case)
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what types of antiviral agents would affect viral replication?
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nucleotide analogs that inhibit viral component (but inhibit cell component minimally or not at all), non-nucleoside reverse transcriptase inhibitors
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how are retroviruses a special case in replication?
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use reverse transcriptase to copy genome to DNA, then integrase to insert DNA into cell's chormosomes, creating a permanent viral DNA copy in genome, so cell RNA polymerases transcribe integrated DNA just like cell DNA, cells can't be cured of these viruses
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what is reverse transcriptase?
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Viral RNA-dependent DNA polymerase
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what does reverse transcriptase do?
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copies RNA genome into DNA copy
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what is integrase?
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viral enzyme that cuts cell DNA and inserts viral DNA into cell chromosome
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what does integrase do?
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cuts cell DNA and inserts viral DNA into cell chromosome
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how do we cure retrovirus infected cells?
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can't, so focus on inhibitors of polymerase first
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what do nucleoside analogs do?
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inhibit polymerase
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nucleoside analogs inhibit polymerase by what mechanisms?
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chain terminators & polymerase inactivators
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what are examples of chain terminators?
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Azidothymidine (AZT) and Acyclovir
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what does AZT stand for?
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Azidothymidine
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what does AZT treat?
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HIV
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what does Acyclovir treat?
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genital herpes simplex virus (HSV) and varicella zoster (chicken pox/shingles)
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what mechanism, besides chain termination, does acyclovir work via?
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polymerase inactivator
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how do chain terminators work?
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DNA polymerase insterts nucleoside analog in growing DNA chain, but then that chain can't accept any more nucleotides (terminated)
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what is a nucleoside analog?
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ddNTP (dideoxyNTP)
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what is one problem with chain terminators?
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must insert early enough that functional mRNA isn't made (excess DNA is already trimmed off)
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how does AZT work?
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high affinity for HIV reverse transcriptase causing premature termination of HIV DNA chain while having a low affinity for cell DNA polymerase so low toxisty for cell DNA synthesis
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how do polymerase inactivators work?
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nucleoside analog is phosphorylated (by kinase) to generate NMP-analog which is phosphorylated to an NDP-analog, which is phosphorylated to an NTP-analog, which binds DNA polymerase irreversibly and therefore inactivates it
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what are the types of polymerase inactivators?
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cell kinase & viral kinase (which phosphorylate nucleoside analogs to nucleotide monophosphate (NMP)
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what is an example of a cell kinase chain terminator?
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Vidarabine (secondary to acyclovir) to treat HSV
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what is the problem of a cell kinase chain terminator?
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nucleoside analog will be converted to NTP in uninfected cells, which is toxic to the cell
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how do cell kinase chain terminators work for viral infections (vs cell damage?)
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the NTP-analog has a higher affinity for viral polymerase than cell polymerase, so better inactivator of viral polymerase
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what is an example of a viral kinase chain terminator?
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acyclovir (treat HSV, varicella zoster) & ganciclovir (cytomegalovirus)
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what is the advantage to viral kinase chain terminators over cell kinase chain terminators?
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nucleoside analog will be converted t oNTP only in infected cells
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how do viral kinase chain terminators work for viral infections (vs cell damage?)
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the NTP-analog has a higher affinity for viral polymerase than cell polymerase, so better inactivator of viral polymerase
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viral kinase chain terminators are describes as BLANK specific for viruses:
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doubly specific (viral kinase and viral polymerase)
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how can retrovirus replication be inhibited?
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inhibit viral polymerate using nucleoside analogs (chain terminators like AZT) & Non-nucleoside reverse transcriptase inhibitors (which binds RT and inhibits it) and inhibit viral integrase (Isentress-HIV integrase inhibitor which prevents integration of HIV DNA)
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what occurs in viral maturation & assembly?
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virion or nucleocapsid (if enveloped virus) is assembled from proteins and nucleic acid, and the envelope is genereally acquired during release
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what are the three mechanisms for viral release?
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cytolysis, budding, extrusion
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what occurs in cytolysis?
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cell dies & virus is released
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what are the types of cytolysis?
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necrosis and apoptosis
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what is necrosis?
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release of cell lysosomal enzymes (due to infection)
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what is apoptosis?
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activation of specific cell signal transduction pathway, for 'cell suicide'
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what type of viruses is budding restricted to?
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enveloped viruses only!
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what occurs during budding?
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nucleocapsid acquires envelope by budding through cell membrane (picks up viral proteins there); the location is virus specific (plasma membrane, nuclear membrane, golgi membrane) and then final release, it can pick up some cell proteins too, and does not necessarily kill the cell
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what common virus undergoes budding?
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influenza
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how does influenza undergo budding?
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viral hemagglutin (viral attachment protein) binds sialic acid (cell receptor), then viral neuraminidase cleaves sialic acid, freeing virus from cell membrane (critical for entry/exit)
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what occurs during extrusion?
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nonenveloped viruses extrude through membrane, but it is poorly understood
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how does a multinucleate syncytia form?
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newly synthesized viral fusion proteins at cell surface cause fusion of infected cell with neighboring uninfected cells
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what does a multinucleate syncytia allow?
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viruses to spread to other cells iwthout ever exposing themselves extracellularly
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what are the experimental and current anti-HIV strategies?
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block attachment (soluble CD4; not being done), block fusion (Fuzeon [v], Maraviroc [c]), inhibit RT (nucleoside analogs, NNRTI), inhibit integrase (Isentress), inhibit assembly
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what does HAART stand for?
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highly active antiretroviral therapy
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what does HAART mean?
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several drugs (typically 3-4) are taken in combination because simultaneous mutation in many viral genes is rare
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if an antiviral targets cellular paths/proteins, what are the affects on viruses and cells?
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viruses have a low frequency of mutation to drug resistance while cells may have normal funcitons intered with
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what is the cell response to viral replication?
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viral replication in cell induces immediate cell response (first defence, before immune response) and infection induces synthesis of interferon in cell (does nothing to virus, but induces other antiviral events)
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what does interferon do?
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induces antiviral events (does not directly do anything to virus)
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what types of interferon are there?
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alpha ('leukocyte' made in lymphoid cells), beta ('fibroblast' made in virtually all cells), and gamma ('immune' made in T & NK cells, potentiates alpha & beta interferons)
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what does interferon gamma do?
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potentiates alpha & beta interferons
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what does interferon beta do?
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protects neighboring cells by binding receptors on neighboring cells and inducing the cell to synthesize antiviral proteins which serves as a 'red flag' to warn surrounding cells (after production and secretion from infected cell)
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how do viruses inhibit the interferon system?
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inhibit the cell factors involved in making IFN and the cell factors involved in IFN making antivirals
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