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89 Cards in this Set
- Front
- Back
GIT barriers |
pH bile prevents enveloped virues villi mononuclear cells survey gut (macro) M cells deliver antigens via transcytosis |
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Norovirus characters, genome |
Caliciviridae ssRNA, non env single capsid prot |
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Norovirus is easily transmissible |
contagious rapid and prolifically shed constant evolve limited immunity moderately virulent - maintain pool of susceptible hosts - symbiosis of gut flora may faciliate persistence |
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Norovirus RdRp |
contributes to evolution error prone may change structure of VP1 recomb during coinfection for reassortment |
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Norovirus Spread |
spread by contaminated food and water worldwide distribution |
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MNV |
cannot culture human tissue, use a mouse model MNV
transient expression of CD300lf receptor may sustain infection |
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Norovirus IR |
dsRNA > MDA5 on mito > IRF > T1 IFN T1 IFN > JAKSTAT path > ISG |
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Rotavirus |
Reoviridae segmented dsRNA multilayer capsid
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Rota VP |
VP4 - spiked for recepter interaction, cleaved by trypsan into VP5/8 to increase infectivity. VP4 (P sero) and 7 (G sero) elicit netralising ab VP6 - elicit ab inhibibting infection during IgA transcytosis |
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Detect Rota |
ELISA w mab to det sero nested RTPCR to det geno EM seroconversion IgA conversion in stool |
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Rota symptoms |
Severe dehydration due to blunting of villi, decrease absorbative capacity Base of villi contain IgA producing cells |
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Rota diversity |
gene reassortment fro coinfection |
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Rota infection cofacters |
cofacters = pH, ionic strength binding is low aff, high av binding to terminal SA = susceptible to sialidase. resistance by binding branched SA. VP8 structural change can change glycan class, |
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Rota binding |
binds glycans and integrins
Upon binding, struct change to adapt to diff viral receptors |
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Rotavirus and diabetes |
increase of ab ass with diabetes progression beta cells prod insulin in pancreas. virus taken up by DC, produce type 1 IFN and activates bystander autoreactive islet sp CD8 cells to kill the beta cells. |
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Rota vaccine |
live vaccines atten through passage monovalent human strain bovine reassortment vaccine |
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Bats |
only flying mammals variable thermoregulation low rate of tumorogenesis long life span |
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Hendra |
paramyxo - ssRNA, non segmented encodes fusion and attachment prot, matrix, NC bat-horse-human, no HH |
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Nipah |
related to hendra bat-pig-human - high PP Bangldesh has yearly emergence w no intermediate host and HH specific due to conserved surface recept |
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SARS |
+RNA spike prot used for both fusion and att. human spike binds ACE2, bats doesnt MERS = Sars like, high mortality low transmission. uses diff receptor, true reservoir unknown |
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Melaka |
reoviridae, dsRNA has envelope and fusogenic in human not bats
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Why bats? |
flying = high metab = ox stress = efficient DNA repair systems = no cancer, harbour virus w/o disease high basal expression of IFNa MHC1 groove is varied, flexible binding No M2 macro different post-transl mod of NLRP3/caspase |
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Epidemiology |
study of distribution and determinants of health related states or evens and its application to the control of diseases and other health problems |
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Endemic |
present at all times at low frequency, ongoing age incidence is det by duration of immunity, Whooping cough - IR drops off w age |
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Epidemic |
sudden severe outbreak of a region or group |
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Pandemic |
widespread epidemic may be novel, highly susceptible, must be highly transmissable |
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Cross over events |
spread of dieases from animals, ranked by degree of severity |
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The SIR paradigm |
susceptible - infected - recovered recovery leads to removal of virus from pop rate of infection det by number of infected = the transmission parameters x prevalence |
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Host determinants of susceptibility |
age immune status - naive, vaccinated, prior inf underlying risk pregnancy ethnicity |
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Virus determinants of natural history |
latency infectiousness - sympt, duration, shed/spread induction of IR - temporary, strain sp |
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Population determinants of spread |
birth rate household size crowding population density connectedness mobility |
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Environmental risk factors |
season sanitation proximity to vector/reservoirs natural disaster |
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Surveillance |
layers of severity = diff burdens for intervention year by year comparisons threshold detection algorithms serosurveillance to determine at risk |
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Intervention |
non pharma pharma vaccines, antivirals mitigate severe outcomes by ID vulnerable groups to reduce risk of critical care requirements |
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RNA structure |
complex, can self anneal and pair noncoding RNA contains sequenc sepcific structural info
dsRNA/shRNA initiate plants silencing, cleaved into siRNA pre miRNA initiates mammalian silencing |
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Plants RNA silencing |
- long dsRNA from infection or exp intrinsically -processed by Dicer/RNAse3 into siRNA w overhangs - RISC produced targets complementary mRNA and cleaves into fragments |
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siRNA |
short dsRNA important for genetic immunity 21nt, perfectly duplexed double helix with 3' overhangs |
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Dicer |
processed long dsRNA, seperate strands guide strans is incorp into RISC, has less tightly paired 5' |
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RISC |
RNA induced silencing complex has argonaut proteins to inhib gene exp argo1 = silencer, binds NA argo2 = endonucl, cleaves target RNA |
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Human RNA silencing - PKR |
long dsRNA causes the ISG PKR to autophos, leading to phos of ELF2a to block protein synth |
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miRNA for silencing |
in humans not perfectly duplex, has sequence mismatches |
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Human silencing - RISC |
triggered by small 21nt RNA DNAP produces pre miRNA shRNA enters nucleus, interact with DICER RISC represses translation |
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cellular miRNA silences exp of viral RNA |
- primate foamy virus - huan miRNA inhib replication by binding to complementary sequence - Hep C requires miRNA expressed in hepatocytes for replication = tropism
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Viral miRNA inhibits host mRNA |
- Adeno Pol3 can bind to inhib PKR and dicer - Herpes LATS prod miRNA = targets apoptosis and CTL killing - HIV Tat suppresses prod of miRNA, supports persistance and latency |
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viral miRNA can inhibit viral mRNA |
- Adeno SV40 late genes prod miRNA that degrades early gene = reduces susceptibility to LT specific CTL |
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miRNA for therapeutic approaches |
make lentivirus vector to produce miRNA and target specfic genes to alter expression
embed miRNA sequence into an intron on a plasmid |
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Cellular restriction factors |
intrinsic antiviral proteins that block RT, uncoating or budding Tetherin prevents enveloped virus from budding APOBEC3 induces lethal G-A hypermutations on ssDNA |
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cancerous agents
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chemical carcinogens UV and ionising radiation viruses |
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Tumour |
growth produced by abnormal cell proliferation. Leukemia = circulating cells Lymphoma = solid cells |
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Transformation |
introduction of inheritable change to a cell that causes a change in growth phenotype and immortalisation |
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cell cycle |
G1 = synth proteins required for DNA prod S = replication M = mitosis controlled by cyclans that stim/inhib |
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Tumour stimulation genes |
c-onc aka protooncogenes = genes encoding proteins that give GO sigals for exp of proteins. normal products of a cell v-onc - viral version of the c-onc, may be slightly diff |
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Tumour suppressor genes |
give stop signals for negative regulation of growth |
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classes of oncogene |
growth factors for prolif eg. IL2 growth factor receptors intracellular signal transducers TF e.g. NFkb |
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RNA tumour viruses |
non lytic, do not lead to cell death integration is essential v-onc is not unique, there is a c-onc counterpart stimulate activators |
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Classes of retrovirus oncogenesis |
-endogenous - transmitted in germline
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retrovirus classes of tumour prod |
transducing - introduce v-onc cis activating - insertional mutagenesis trans activating - gene regulation |
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Transducing retroviruses |
most are rep defective except Rous sarcoma introduce v-onc gene under LTR transcriptional control into host genome |
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Cis activating retroviruses |
have no v-onc, but may insert at particular location upstream of oncogene - its LTR may allow for transcription of downstream oncogene - provirus may contain enhancer that amplifies production of nearby genes |
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Trans activating retroviruses |
In humans - aboriginal populations HTLV-1 associated with adult T cell leukemia-lymphoma (ATLL), high persistence. spread across placenta, breastfeeding, sex |
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HTLV-1 |
infects CD4 Tc exp gag, pol, env, tax and rex tax = TF upreg exp of other genes as well as c-onc IL2/IL2R = uncontrolled Tc prolif. prolif maintained by HBZ when tax downreg |
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DNA tumour viruses |
lytic integration non essential v-onc are unique - inactivate inhibitors requires S phase enzymes to replicate DNA, therefore exp early prot to stimulate entry into S phase |
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DNA tumours |
limites viral protein expression show integration of viral genome/episome |
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Rb protein |
tumour suppressor gene controls transition of G1 to S gets hypophos, bind E2F TF to stop cell cycle |
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P53 |
tumour suppressor gene TF, promotes expression of genes that stop cell growth and initiates apoptosis Hep C binds p53 |
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Papilloma virus tumour virus |
DNA tumour virus -cutaneous skin (warts) - episome -cervix mucosa (cervical carcinoma) - random integration, loss of E2 gene that controls E6 and E7 E6 and E7 suppress p53 and Rb |
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Hep B tumour virus |
genome randomly integrates into cell chromo
protein X encodes transactivating gene that deregulate c-onc. destroys regeneration of cells leading to chromo mt |
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Herpes tumour virus |
solid tumours. EBV (herpes) transforms B cells causing clonal expansion of a single B cell Cofactors - malaria expands B cells |
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Flavivirus |
ssRNA arthopod vector, no HH nonsp entry w promiscuous receptor |
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Dengue - mosquitos |
transmission req moq w inf salivary glands period of asymp viremia - still spread to mosq females feed a lot during embryogenesis extrinsic inc period: 7-14 days to be inf |
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Dengue 2nd infection
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increased chance of complications = ab dependent enhancement non neautralising ab from 1st inf bind, Dengue uses Fc to infect macro/mono |
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Dengue vaccine |
4 types, ag Xreactive, vacc based on YF vacc, uses Prm and env for each of the 4 types pretty meh efficacy, ~55% in Asia |
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Yellow Fever |
20% fatality, due to spillover evens from tropical sylvatic cycle Aedes aegypti - SE Asia, US, upper AUS |
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Yellow Fever vaccine |
well characterised 1 dose gives 10y immunity low production, low dist |
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Issues for detecting emergence |
silent incubation asymptomatic/mild infections nonsp syndromes e.g. flu low frequency devastating complications |
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Ebola outbreaks and host |
70s - outbreak outside of known geographic range, poor detection 2014 - Guinea, 80% mortality, spread to HCW maintained by bats, spillo ver to apes and deer things |
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Ebola infection and shed |
enters via muc mem or broken barriers high blood titre low ID shed in blood, saliva, tears, milk, semen, faeces, urine |
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Ebola diagnosis |
acute viremia culture, RTPCR, sequence serology - cannot do, people die before detectable IR, access to samples is limited |
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Zika outbreaks |
Africa via sylvatic cycle, Aedes africans Asia, spread from Africa, Aedes aegypti |
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Zika and Wolbachia |
coinfection with Wolbachia in mosq = compete for resources and replication, prevents growth of Zika |
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Zika transmission and shed |
transmission mosquito, perinatal, sexual, transfusion, direct contact shed blood, saliva, urine, semen |
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Zika diagnosis |
short viremia PCR, serology limited to expert labs |
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surveillance and outcomes |
outcomes det by surveillance, diagnosis, contact tracing and isolation incidences in smaller pop harder to detect than larger pop, even if its at the same freq |
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What is an emerging Infectious disease? |
disease whose incidence has increased in the past 20 years and threatens to increase in the near future |
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How do you get emerging viruses? |
emerging viruses are the causative agent of new or previously unrecognised infection expanded host range, zoonoses, cross species infection, globalisation, climate change, viral mt |
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Emerging virus contributing factors |
-access to susceptible/permissive cells -population density and health -human demographic change (expansion to new areas means new sources of inf) -economic development -behaviour change (child car facilities, sex, drugs) -zoonotic transsmission |
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Climate change and emerging viruses |
- less predators, more food supply - temp can affect rodent breeding patterns - prolong the time vector can transmit disease - drought = resurgence of mosq disease as they move towards urban areas of water storage |
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Evolution and emerging viruses |
biodiversity of pathogens produces quasispecies
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zoonosis |
enzootic = endemic - virus continually circulated between animal hosts
epizootic - epidemic - occurs in animal host sparodically to cause epidemic disease in humans |