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Tobacco Mosaic Virus (describe virion)
naked helical capsid
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(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
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Adenovirus
- icosahedral
- docking proteins at vertices
- causes the common cold
- can also be enteric (gastroenteritis, stomach flu)
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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
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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)
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Poxvirus (describe virion)
- dumbell shape enveloped
- fowlpox
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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
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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
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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
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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
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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
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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
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Togaviridae
- includes alphavirus (all the equine encephalitis) and rubivirus (rubella)
- icasohedral enveloped
- ss sense RNA
- arbovirus
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Flavaviridae
- yellow fever, dengue, HCV, West nile, St Louis and Japanese encephatlitis
- icosahedral enveloped
- ss sense RNA coding polyprotein
- arbovirus
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West Nile Virus,
- fatal encephalitis or meningocephalitis
- headahces, fever, rash, swollen lymph
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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
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Norovirus
- enterovirus
- no envelope
- very not labile
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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
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Common cold viruses
- adenoviruses
- coronaviruses
- respiratory syncytial viruses
- rhinoviruses
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Rhinovirus
- respiratory
- more than 100 serotypes
- no durable protective immunity
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Respiratory Syncytial virus
- respiratory
- leading cause of bronchitis
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Parainfluenza
- Respiratory
- 4 strains and you get them all when you’re a kid
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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
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Measles, mumps and rubella
- vaccines are good against these
- limited cases drastically
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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
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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
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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
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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
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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
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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
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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)
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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)
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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
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