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What is a virus
- Packaged set of genes inert outside of cells
- Require cells for protein, nucleic acid synthesis, and energy
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Virion
- viral structure
- 20nm to 1 µm
- helix or icosahedron with few exceptions
- can be enveloped
- DNA or RNA, ds ss, + -
- DNA can be circular
- RNA can be segmented
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Susceptible cells
- have receptors for virus
- can be productively infected
- abortively infected
- latently infected (maintaining viral genome)
- non-permissive
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Attachment to cell
- protein receptor interaction
- electrostatic
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Penetration of cell
- sometimes receptor binding brings membranes close enough for fusion
- more commonly the binding recruits other receptors to form a coated pit vesicle
- lysosome fuses with phagosome and pH releases virus from vesicle
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Eclipse period
time between viral adsorption and rise in intracellular viral concentration
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Latent period
- time between viral adsorption and rise in extracellular viral concentration
- latent infections are usually through DNA
- no viral genome replication (except with cell division)
- few if any viral proteins expressed (non-immunogenic)
- compatible with cell survival
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ds DNA
- adenoviruses and herpesviruses
- virus DNA replicated to make progeny DNA as well as transcribed to mRNA
- mRNA makes immediate early proteins, early proteins, and then late proteins
- early proteins make viral proteins and late make capsule
- drugs can target transcription, replication, assembly
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Release from cell
- capsid can associate with membrane protein viral protein spikes, causing them to gather and bud
- usually lyse the cell
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Arboviruses
- bug borne
- eveloped RNA
- lots of them
- rapid onset fever, chills, aching
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Enteroviruses
- all start oral and go to stomach
- infects GI
- usually self limiting
- includes polio
- hand-foot-mouth disease
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Plaque Assay
- can detect viruses, titer them, and isolate
- dilution series and then plate onto cells
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Sabin Vaccine
OPV, live attenuated from chimps
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Accute infection
- Viral production increases with symptoms at peak
- After a short time the viral production decreases as do symptoms
- rhinovirus, rotavirus, influenze virus
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Persistent infection
- Viral production increases to high plateau without symptoms
- after a long time of sustained viral production symptoms appear
- lymphocytic chroiomeningitis virus, HBV, HCV
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Latent, reactivating infection
- Viral production increases and decreases over time
- Symptoms may or may not show depending on to what level the viral production reaches
- Herpex simplex virus
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Slow virus infection
- Initial viral production increase with symptoms at peak
- after a short time the viral production drops and levels off at a low level with no symptoms
- after a long time the viral production increases again, symptoms reappear and death often occurs
- measles subacute sclerosing panenchephalitis (SSPE), HIV
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Herpes classification
- classes I, II, and III are associated with different groups of animals
- class I is mammals (humans), reptiles and birds
- class II amphibians and fish
- class III bivalves
- within class I is alpha beta and gamma
- in humans alpha is always neuroinvasive with a short reproduction cycle HSV1, HSV2, VZV
- beta is cytomegalovirus mainly with long reproduction cycle CMV, HHV6, HHV7
- gamma is lymphotropic, oncogenic. EBV, KSHV
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Primary host v secondary host
- primary host maintains the virus in nature with mild/benign infections
- secondary host is a dead end host, causing a fatal infection
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Acyclovir
- related to valavyvlocir and gancyclovir
- GTP analog missing 2 and 3 positions of ribosome and phosphates
- cannot polymerize
- herpes thymidine kinase of herpes virus adds a phosphate
- cellular kinases continue adding kinases to make acycloguanosine-PPP
- does not work on TK mutant viruses of immunocompromised people
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Virally transformed cell characteristics
- itnegrated or episomal DNA sequences
- indefinite in vitro growth potential
- higher cloning efficiency
- anchorage independence
- chromosomal abnormalities
- virally expressed tumor antigens
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Gardasil
- inactivated fractional
- HPV 6, 11, 16, 18
- no effect on existing infection
- super effective (for specific types) with no known harmful effects
- not effective against ~30% of infections that can lead to cervical cancer
- expensive and social drama
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Pap smear
- looks for cells with aberrant morphology, koilocytes
- nucleus pushed to side (good sensitivity, not specific)
- further testing required to confirm cancer
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