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Unifying Principles of All viruses |
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Definition
genomes packaged inside particles that mediate transmission genome contains information for initiating and completing infectious cycle in a susceptible, permissive cell able to establish themselves in a host population so that virus survival is ensured |
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types of viral genomes (understand requirements for each to be replicated and transcribed) |
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ds DNA ds RNA ss +RNA ss -RNA ss DNA |
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ALL RNA viruses must encode this for replication of their genome because there is not a host protein that can replicate RNA |
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type of virus genome that requires an encoded polymerase to make mRNA and to replicate the genome |
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+ sense RNA virus that requires a DNA intermediate for replication |
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DNA with full length but nicked + strand and pertial - strand. Requires DNA repair first and a viral reverse transcriptase |
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viral techniques for gene packing in genome |
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Polyprotein- one large protein cleaved to make many Leaky Scanning- different start sites yielding different reading frames Reinitiation- ribosomes chug along between genes Internal Ribosome Entry Sites- ribosomes can bind one of two different sites to yield different proteins |
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Viral genome secondary structure |
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Internal Ribosome Entry Site- efficient recognition of mRNA by ribosomes Packaging signals- promotes packaging for assembly into virio |
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"wimpy" virus because they don't survive for long periods outside fo their hosts. Membrane derived from host breaks down |
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viruses that are harder to destroy and that stick around longer because they survive better outside of their hosts |
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Uncoating of virus at plasma membrane |
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Definition
virus attaches to receptor AT NEUTRAL pH interaction induces conformational change in either viral ligand or fusion protein results in insertion of a fusion peptide this induces mixing of membranes virus is released into cytoplasm |
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uncoating of virus within endosome |
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Definition
virus attaches to receptor virus taken up by cell by CLATHRIN-DEPENDENT receptor mediated endocytosis pH becomes ACIDIC exposing fusion peptide membranes fuse and release virus into cytoplasm |
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Term
uncoating of virus at nuclear membrane |
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Definition
virus attaches to receptor internalized by endocytosis capsid protins are removed capsid is transproted in the cytoplasm along microtubules capsid docks into nuclear pore complex further disassembly and DNA injection into nucleus |
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virus cannot encode its own translational machinery this is always a good target for therapy because virus is dependent upon host's |
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1. Budding- leave membrane without destroying it 2. Lysis- destroy membrane |
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assay for detecting viruses clinical specimen examined for presence of virus EM, histological examination, antigen detection, PCR |
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Indirect detection (virus isolation) |
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Definition
assay for detecting viruses specimen is incubated in presence of cells that allow for virus growth - primary cells (noraml cells) -semi-continuous cells (embryonic kidney and skin cells) -continuous cells (immortalized) Presence of virus is detected by -cytopathic effect=degenerative changes in cells -haemadsorption=cells acquire the ability to stick to mammalian RBCs |
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assay for detecting viruses production of antibodies against the virus RISE in titer of IgG presence of IgM seroconversion extremely high titer of IgG (least reliable) |
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Enveloped, negative sense ssRNA, segmented 1. Virus life cycle -inhalation -attachment: HA protein, sialic acid, epithelial cells -endocytosis: M2 protein, acidificaiton -replication: ssRNA transproted into nucleus -assembly: at plasma membrane -budding: neuraminadase required to cleave 2. why the virus can cause such outbreaks -antigenetic drift: point mutations in type A or B causing epidemics -antigenetic shift: shuffling of RNA segments between virus types (A only) causing pandemics 3. how anti-viral drugs work -prevent entry -fusion -transcription/translation: Ribavirin prodrug resembling RNA neucleotide, very toxic -release: Nearaminidase inhibitors (Zanamivir [Relenza] and Oseltamivir [Tamiflu]) 4. how vaccines work -Seasonal: killed or inactivated, split virus vaccine (subvirion), live attenuated influenza nasal spray |
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Large, enveloped dsDNA encoding for thymidine kinase (activator) 1. principle of viral latency - dec gene expression -reduced recognition by immune response - persistence of intact viral genome - ability to re-enter productive phase 2. virus life cycle and "waves of gene expression" Active infection -Phase 1: fusion and DNA entry to nucleus, early gene expression using HOST RNA pol., induction of phase 2 -Phase 2: Immediate early proteins transactivate early gene expression which is REQUIRED FOR VIRUS REPLICATION, genome replicaiton initiated -Phase 3: DNA replication and early protein sstimulate expression of late genes, form many of teh viral structural proteins for capsid formation -Phase 4: Viral capsid assembly and progeny DNA encapsidatoin takes place in nucleus, virons egress form cell 3. Triggers that shift HSV from latency to lytic -repression by host cell factors -sensory neurons express low levelos of transcription factors -viral LAT transcripts inhibit viral lytic genes -inhibition by host immune response 4. Transition from latency to active -increased ICPO HSV gene/decreased ICP4 -local injury -stress, hyperthemia, UV light, Menstruation, hormone imbalance, immunocompromise 5. How anti-viral drugs work -act on thymidine kinase (which catalyzes the phosphorlyation of pyrimidines, purines and ribose analogs) -Acyclovir causes chain termination of viral DNA elongation inhibiting replication |
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1. Virus Life Cycle -Exposure via sexual contact -Attachment and entry: infection of the basal keratinocyte through wound or abrasion, entry via clathrin-dependent receptor mediated endocytosis -Viral transcription and viral protein production:E1 and E2 (viral helicase and master transcriptional regulator) recruit CELLULAR polymerases and accessory proteins to mediate replication -Assembly and budding: DOES NOT induce lysis, virion release is dependent on desquamation of the most stratified skin cells 2. Normal Coures of infection -In cervical cancer, viral DNA linearizes and integrates into host chromosome. If the break occurs in E2, viral regulation of E6 and E7 is lost leading to transformation of the infected cell 3. Why the virus promotes proliferation -interacts with p53 and Rb, tumor suppressor genes to promote proliferation 4. How the rial proteins E6 and E7 work -E6 interacts with E6AP to induce p53 degredation (tumor suppressor) and prevents stop at normal cellular checkpoints -E7 directly vinds ot the hypophosphorylated version of retionblastoma protein (pRb) leading to transcription of proteins of genes that are involve din DNA synthesis and cell cycle progression 5. Viral capsid structure and how the VLPs can be used for immunization -capsid formed by late genes L1 but not L2 can form a capsid without any DNA in it. This is used in the vaccine |
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Infects CD4+ T lymphocytes, encodes a reverse transcriptase, single stranded + sense RNA, encodes 3 major transcripts: Gag, Pol and Env. Gag: encodes major subunits Pol: produces enzymes (RT, integrase, protease) Env: precursor to the cleaved envelope proteins that serve as a receptor for HIV to CD4 (gp120 and gp41) 1. Virus Life cycle -acquisition: sexual contact -attachment and fusion: gp120 binds CD4, conformational change to bind to CCR5 or CXCR4 to mediate fusion of viral envelope with plasma membrane -RT: converts + sense RNA to dsDNA, no proofreading -Integration: integrase binds to ends of dsDNA and shuttles to nucleus, cleaves host DNA and catalyzes integration. Now called proviral DNA. copied by HOST DNA polymerase -Replication: HOST RNA polymerase II transcribes DNA into RNA. Can be 1. transpoted to cytoplasm for assembly 2. translated into three large polyproteins 3. spliced into smaller sequences for trsnslation -Assembly: the Env polyprotein is transported to the plasmama membrane where it is cleaved into gp120 and gp41. polyproteins associate at plasma membrane, when gp41 reaches threshold density virion initates budding -Budding and Maturation: protease must act on the polyproteins wihtin the virus in order fot eh virus to mature into an infectious particle. Virion mporpholgy is converted from doughnut-shaped center to an electorn dense, conical core 2. How drugs target HIV HAART: -Reverse transcriptase inhibitors -Protease inhibitors -Fusion inhibitors and early entry inhibitors -Integrase inhibitors 3. Why HIV quickly becomes drug resistant lots of mutations due to RT not having a proofreading mechanism. |
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Cestode egg has striations Proglottid has many uterine lines Scolex has 4 suckers COWS eat embryonated eggs, migrate to tissues, eat undercooked beef, stomach acids release cysticerci, scolex attaches to intestine, proglottids passed in feces |
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Cestode football shaped egg Proglottid has rose shaped blotch Eats lots of B12-pernicious anemia, occulocysterocosis and neurocysticerosis Scolex has longitudinal grooves without hooks Larvae hatch in water, multiple FISH cycle, eat infected fish, scolex attaches to mucosa, grows and proglottid breaks up in colon, EGGS present in feces |
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Cestode egg has striations Proglottid has many uterine lines Scolex has 4 suckers and hooklets PIGS eats embryonated eggs, migrate to tissues, eat undercooked pork, stomach acids release cysticerci, scolex attaches to intestine, proglottids passed in feces |
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Term
Enterobius Vermicularis (Pinworm) |
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Definition
Cestode oval and elongated eggs transmitted fecal oral route, larvae hatch in small intestine, migrate to colon, mature, release of eggs at perineum, eggs embryonate->itching diagnosed by tape test (NIH Swab) |
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Trichuris Trichuria (whipworm) |
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Definition
Cestode barrel shaped, yellow-brown with bipolar prominences on egg Ingestion of eggs from soil, hatch in small intestine, migrate to colon, unembryonated eggs in feces, embryonate in soil In south east US Dysentery in heavy infestations, anemia, rectal prolapse diagnose by ova in stools |
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giant intestinal round worm eggs have hard shell infective eggs containing larvae ingested, penetrate small intestine and enter blood, migrate to liver, lung, then coughed up and swallowed to intestine, mature and eggs passed in feces hepatic and lung damage diagnose by chest x-ray, sputum, eosinophilia or ovas/adult in feces |
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Necator Americanus, Ancylostoma Duodenale |
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Definition
Hookworms filariform larva develop in soil, penetrate through skin, follow lymphatics, migrate to heart and lungs, up trachea and swallowed, mature in intestine, unembryonated eggs pass in feces |
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Strongloidiasis stercocalis |
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Definition
similar to hookworm prevalent in institutionalized persons filariform larva develop in soil, penetrate through skin, follow lymphatics, migrate to heart and lungs, up trachea and swallowed, mature in intestine, can penetrate back into blood and reinfect, unembryonated eggs pass in feces intestine damage, dysentery like syndrome diagnose by larvae in stool or sputum Creeping eruptions |
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Definition
Protozoan parasite amoebic dysentery, disseminated amoebiasis (encephalitis, hepatitis) trophozoite form: active and vegetative amoebic form in colon, eats RBC, amoebic abcesses in colon and liver, flask shaped ulcers cyst form: spore-like form for transmission/infection ingested as cyst, excysts in small intestine, trophs live in colon and invade by releaseing proteases, may disseminate, cysts form in dried feces diagnose by exam of feces 3 times or serology by elisa or IHA |
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Flagellage protozoa parasite DOES NOT invade causes lawnmower effect and villous atrophy in colon, malabsorption, diarrhea Trophozoite: spook appearance Cyst: triggered by dehydration in colon diagnosis by 3 stool exams, tissue endoscopy, enterotest |
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sporozoan parasite very small intracellular protozoan stains with Giemsa or H & E acid-fast affects jejunum causing explosive, profuse diarrhea Diagnosis: detection of oocytes in stools, acid-fast stain, or immunofluorescence |
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microsporidia obligate intracellular pathogen that injects spore contents via coiled polar tubule diagnosis: microscopic exam for ova and parasites X 3, fluorescence microscopy (NOT acid-fast) |
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sexually transmitted protozoan flagellate prefers basic envrionment readily visible on wet mount |
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Amoeboid flagellate causes encephalitis and keratitis found in warm ponds enters nares of nose and is fatal similar to Acanthamoeba spp. (keratitis) |
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