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2014-11-14 00:13:13
virology fdn3 foundations tubberly

This is gonna be the death of us!
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  1. Tobacco Mosaic Virus (describe virion)
    naked helical capsid
  2. (Ortho)myxovirus
    • enveloped helix
    • causes influenza
    • single stranded antisense RNA
    • virion enzymes transcribe (sense) mRNA, translated to proteins, or it can be replicated again to viral RNA
    • drugs target trascription, replication, assembly
  3. Adenovirus
    • icosahedral
    • docking proteins at vertices
    • causes the common cold
    • can also be enteric (gastroenteritis, stomach flu)
  4. Picornavirus
    • poliovirus
    • complex icosahedral (naked)
    • endocytosis, makes pore and injects
    • ss RNA sense translated to a polyprotein that cleaves (2A pro and 3C pro) and replicated twice to make progeny RNA
    • drugs can target proteases, transcription and replication of RNA, assembly
    • 5’ end (left) structural and 3’ (right) viral
    • 2BC (2B + 2C) and 3AB and 3A reprogram the cell to disrupt golgi make vesicles
    • degrades protein kinase R (phosphorylates eIF2 so that does not unbind from eIF2B and do initiation)
    • also cleaves eIF4E cap binding protein (by 2A pro)
    • uses internal ribosomal entry sequence (IRES)
    • causes wave cycle of protein synthesis and less complexity (only cap independent)
    • 3B protects 5’ end from being recognized as viral
    • 3CD cleaves TATA and is primer
  5. Hepadnavirus
    • icosahedral with a tubelike envelope
    • infectious when it leaves the envelope
    • hepatitis B
    • ss RNA but in cell as partially dsDNA
    • most clear the virus
    • chronic with high risk for hepatocellular carcinoma after 30 years
    • probably through liver damage, chromosomal rearrangements and genomic instability
    • hepatitis C
    • persistent infection leads to cirrhosis and hepatocellular carcinoma after 20-30 years
    • 50% not cleared by immune system
    • ss sense RNA, making proteolytic polyprotein
    • no single transforming gene identified
    • blood blood transmission (IV drug use) and some through sexual intercourse
    • blood supply contaminant
    • ribavirin interferon treatment (gilead)
  6. Poxvirus (describe virion)
    • dumbell shape enveloped
    • fowlpox
  7. Retrovirus
    • triangular enveloped
    • HIV
    • virus RNA is reverse transcribed to ds DNA, which is used to make mRNA that can become virus polyprotine and cleaved or more virus RNA
    • drugs can target proteases, reverse transcriptase, or assembly
  8. Filoviridae
    • long enveloped
    • ebola and marbug from monkeys
    • each cell makes tons of viruses
    • can infect tons of cell types
    • then does a good job of killing cells and damaging tissues
    • fever, muscle weakness/pain, diarrhea, vomitting, rash with tons of viral particles
    • incubation 2-21 days
    • tests are through antibodies or PCR (fastest) but risk spreading infection
    • just give fluids and ZMapp is new and has potential, sera of survivors
    • largest at 1 µm
    • maybe seen with microscope
  9. Cell infection by HIV
    • gp120 on HIV envelope
    • targets macropahges and CD4 T
    • receptors CCR5 an CXCR4
    • release 2 RNA reverse transcribed and incorportaed
    • mutation in CCR5 receptor linked to immunity
  10. HIV genes and proteins
    • 5 and 3 prime long terminal repeats
    • gag does structural proteins
    • pol makes protease, reverse transcriptase and integrase
    • three open reading frames
    • vpr can have it hide, rev determines temporal transcription of structural proteins, and tat triggers making tons of viral mRNA
  11. HIV course of infection
    • CD4 T drops initially as virus disseminates and recovers when the virus goes latent
    • During clinical latency the virus slowly gains ground while CD4 slowly looses ground over 10 yrs
    • Once the CD4 is low enough the virus makes tons of copies and you get opportunistic diseases
    • Mediated by synthesis and HIV killing T cells (48 hours to kill)
    • HIV kills immune system and changes antibodies
    • can cause other things like Karposi’s sarcoma
  12. HIV therapy
    • combination therapy of reverse trascriptase inhibitors and protease inhibitors
    • drug resistant mutations frequently arise
    • prophylactic treatment for and for opportunistic infections
    • no vaccine because no immune response and changes frequently and is inherently non immunogenic
  13. Togaviridae
    • includes alphavirus (all the equine encephalitis) and rubivirus (rubella)
    • icasohedral enveloped
    • ss sense RNA
    • arbovirus
  14. Flavaviridae
    • yellow fever, dengue, HCV, West nile, St Louis and Japanese encephatlitis
    • icosahedral enveloped
    • ss sense RNA coding polyprotein
    • arbovirus
  15. West Nile Virus,
    • fatal encephalitis or meningocephalitis
    • headahces, fever, rash, swollen lymph
  16. Coronoviridae
    • enveloped helix
    • single strand sense RNA
    • severe acute respiratory syndrome and MERS
    • SARS bat to civet to human then droplets
    • MERS bat to cammel to human or bat to human (droplets)
    • can also be enteric
  17. Norovirus
    • enterovirus
    • no envelope
    • very not labile
  18. Rotavirus
    • enterovirus
    • 3 capsid shells (no membrane!) so low pH resistant
    • secretes enterotoxin NSP4, only known viral secreted toxin causing diarrhea
    • non lytic
    • fecal oral infecting villi of small intestine
    • infection occurs at any age with diarrheal disease mostly in children
    • disease attenuates with each infection (multiple infections)
    • ds RNA (never leaves capsid)
    • outer capsule lost upon entry, causing squirting out of mRNA
    • processes and assembles in ER
    • picks up 3rd layer upon leaving ER and sheds the membrane part leaving proteins
  19. Common cold viruses
    • adenoviruses
    • coronaviruses
    • respiratory syncytial viruses
    • rhinoviruses
  20. Rhinovirus
    • respiratory
    • more than 100 serotypes
    • no durable protective immunity
  21. Respiratory Syncytial virus
    • respiratory
    • leading cause of bronchitis
  22. Parainfluenza
    • Respiratory
    • 4 strains and you get them all when you’re a kid
  23. Parovirus
    • Parovirus B19
    • respiratory
    • causes slapped cheek
    • some of the smallest known viruses
    • can cause miscarriage if mother never exposed as child
    • Human bocavirus 1 is a parovirus causing acute respiratory tract infection
    • common in developed countries with young children
    • new
  24. Measles, mumps and rubella
    • vaccines are good against these
    • limited cases drastically
  25. Herpes simplex virus infection and complications
    • HSV-1 mainly above the waist often to trigeminal ganglion
    • HSV-2 mainly below the waist often to sacral ganglion
    • exposure of mucosal epithelia/damaged skin to oral or genital secretions
    • replication exclusively deep to nerves, depositing genome into cell body genome
    • frequent severe recurrences
    • infection is for life
    • can rarely enter brain causing herpes sporadic encephalitis with CNS latency and recurrence, similar to stroke and highly fatal
    • herpes sporadic keratitis is leading cause of infectious blindness in US due to immune cell infiltrate and inflammation of cornea
    • neonatal herpes is mostly HSV-2 spread during birth causing localized mucocutaenous disease (recoverable), encephalitis (highest morbidity), or disseminated disease (highest lethality)
    • TK-null/TK mutant in AIDS patients is not neurotrophic or latent, lateral spread
  26. Herpesvirus structure and mechanics
    • enveloped icosahedral virion
    • linear dsDNA
    • tegument proteins between capsid and membrane
    • tegument and membrane shed upon fusion
    • some tegument remains and capsid can bind to dyenin, walking to nucleus (good for nerves)
    • some tegument is virion host shutoff protein, VP16 is transcription factor, US3 is antiapoptotic protein kinase
    • docks on nucleus dumping dsDNA, which becomes circular
    • can become latent or expressed
    • gains envelop and tegument upon entering ER
    • transport between ER and golgi removes envelop
    • regains envelop upon entering golgi, which buds a vesicle for it to leave nonlyticly
    • in latency only makes latency associated transcript (LAT), which is never converted into protein but is sensing whether or not to reactivate, splices and intron is stable exon degraded
  27. Varicella zoster virus
    • inhalation to lylmphnodes, spleen, and liver where it replicates (primary viremia)
    • then to monocytes that go to skin and neurotropic transmission to most/all dorsal root ganglia (secondary viremia)
    • rarely causes encephalitis
    • dangerous in immunocompromised
    • vesicels on trunk then spread to extremities, turn to pustules then scabs
    • itchiness and can lead to scarring or damage if overitched
    • zoster (shingles) is reactivation
    • dermatome localized, painful which may never go away after clearance
  28. Cytomegalic virus
    • 90-95% of adults are infected in salivary glands, lungs and kidneys
    • shed in secretions and oral/respiratory route of infection
    • generally benign except immunocompromised (newborn, AIDS, organ transplant)
    • if mother has active infection give toxic, cancer-causing ganciclovir
    • acyclovir doesn’t work
  29. Kaposi’s sarcoma associated herpes virus
    • aka HHV-8
    • pre AIDS epidemic, mostly seen in old men
    • endothelial cells develop Kaposi’s sarcoma
    • epithelial cells develop squamous cell carcinoma
    • B cells develop B cell lymphoma
    • cell proliferation somehow caused through induction of cytokines
  30. Epstein-Barr virus
    • still in saliva of 10-20% of healthy adults
    • mononucleosis is common in children, lymph node swelling
    • Burkitt’s lymphoma (non-hodgkins) in African children, seems to be caused by 8,14 myc gene translocation to heavy chain enhancer due to viral damaging and malaria/dietary deficiency
    • Nasopharyngeal carcinoma (squamous) in China requiring environmental factor
    • Hodgkin’s lymphoma (B cell)
    • oral transmission
    • replicates in B cells, which replicate too, so even in latency it has to make proteins in order to not be lost
    • small portion gets in peripheral circulation and goes latent
    • back and forth infecting B cells and epithelial cells, changing tropism by glycoprotein switch
    • latency membrane protein 1 (LMP-1) is oncogene acting like CD40 (tells T lylmphocyte to keep replicating), and causes transient lymph node swelling counteracted by T cell response and causes NK/T-cell lymphoma
    • with AIDS it causes diffuse polyclonal lymphomas, lyphocytic interstitial pneumonitis and oral hairy leukoplakia of the tongue
  31. Human papillomaviruses
    • naked icosahedron
    • 200+ types
    • encodes very few proteins (host reliant)
    • infects basal epithelial cells of specific trophy (plantar warts, hand warts, genital)
    • 6 and 11 cause condyloma accuminata, benign genital warts
    • 16,18, 31 cause cervical carcinoma, anal, penile, vulva/vaginal, oropharynx
    • in cancer only two genes are expressed (no viral genes) just makes E6 and E7
    • E6 shuts down p53 (benign wart types lack this)
    • E7 degrades Rb
    • leads to unregulated growth, so further mutations
    • small lesions and slight growth can go away on its own
    • larger can be removed surgically
    • further mutations cause it to be invasive cancer (hysterectomy often required)
  32. Human T-cell leukemia virus
    • HTLV-1 and HTLV-2
    • human retrovirus that is not HIV related
    • 30-40 year incubation
    • problem with contaminated blood supply
    • transmission by blood and sexual contact
    • 1-4% risk of developing adult T-cell leukemia (ATL)
    • carribean, africa, and asia
    • demylination of motor neurons
    • long terminal repeats with tax (triggers event of making tons of copies) and rex (temporal transcription of proteins)
  33. Merkel cell carcinoma associated polyomavirus
    • MCPyV
    • merkel cells responsible for touch in skin
    • usually doesn’t cause cancer, but always seen in merkel cell carcinoma