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41 Cards in this Set
- Front
- Back
Which country was most severely affected by the SARS epidemic?
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China
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Where did SARS originate from?
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Zootransmission from animals (civet or racoon dogs) to humans
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Why did SARS cross over to infect humans?
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Mutation in spike protein - favored interaction with human ACE (angiotensin-converting enzyme)
This was only a 29 nt change |
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How is SARS transmitted between humans?
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Respiratory route
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Descibe the SARS particle:
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Enveloped with spike proteins
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Describe the SAR genome
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Large (one of largest) RNA genome
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How does SARS enter the cell?
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Via endocytosis - RNA is exposed to the cytoplasmic milieu
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Where is the SARS RNA replicated?
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In the cytoplasm, by the RNA dep RNA pol
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What is pp1a and pp1b?
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Large precursor proteins
-Pp1b is synthesized as a result of a FRAMESHIFT |
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What are the SARS precursor proteins cleaved by?
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3CL proteinase- self-mediated cleavage
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What are some proteins produced as a result of this cleavage?
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Replicases proteins (Helicase, RNA pol, papain-like protease) and RNA processing enzymes(endonuclease, methylase) etc..
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How are multiple RNAs generated?
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Discontinous transcription
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How is SARS transmitted?
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Respiratory, droplet, and inoculation transmission
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What type of disease does SARS cause?
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Severe progressive pulmonary disease
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Does SARS cause a local or systemic infectioN?
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Systemic
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How is SARS pathogenesis mediated?
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Direct epithelial destruction + immune mediated damage
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What are some clinical presentations of SARS?
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=Abnormal chest radiograph
-Bronchopneumonia (shadow) -Diffuse alveolar damage -Cytological changes of type II pneumocytes -Interstitial infiltrates on mononuclear cells -Edema |
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What other cells does SARS show tropism for?
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Kidney cells!
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Is the tropism of SARS limited to lung cells, renal cells?
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No!!
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Can SARS be transmitted from cell-cell?
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Yes -likely via a virological synapse
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How is this cell-cell transmission achieved/
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Likely a tight junction between cells- results in formation of virological synapse - seems to be receptor-dependent
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What are the steps of cell-cell transmission?
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-Recruitment of membrane receptors
-Reorganization of cytoskeleton -Recruitment of MTOC to site of cell-cell contact -Viral protein + genome trafficking -Recruitment of membrane receptors -Formation of virological synapse -Transmission |
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What are the benefits of cell-cell transmission for the virus?
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-Means to evade host immune response
-Enhances rate of infection (100x!) |
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Where does assembly and budding occur?
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Rough ER!
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What is NSP1?
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Sars protein that inhibits translation
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How does NSP1 inhibit translation?
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1) binds to 40S subunit, preventing formation of 80S ribosome
2) Induces modification of 5' capped mRNAs -> removal of 5' region from mRNA 3) Induces cleaveage of IRES containing transcripts - > leads to their degradation |
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How does NSP1 inhibit the immnue response?
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Decreases phosphorylation of STAT1, and thus inhibiting IFN expression
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What does TMPRSS2 stand for?
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Transmembrane protease serine 2
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What role does TMPRSS2 have?
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Cleaves spike
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What does spike cleavage result in?
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1) Activates SARS-Cov -allownig it to better penetrate the cell
2) Makes virus less sensitive to neutralizing Abs |
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How would host genome expression be altered upon SARS infection?
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-Decrease host transcription
-Divert host resources to viral replication -Avoid immune surveillance -Increase pathogenicity -Increase cell survival by decreasing apoptosis -Avoid hot negative regulators |
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What are some potential negative regulators of SARS?
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C11orf59
GLG1 |
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Which host compartments are depleted to benefit the virus?
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Golgi, ER, lysosome
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Which host compartments are enriched to benefit the virus?
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Ribosome
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Where was the CoV strain NL-63 discovered?
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New Haven
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Where was the strain HKU1 found?
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Hong Kong
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In which population is NL-63 prevalent?
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Children and immunocompromised adults
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What is a key difference that might explain the lack of pathogenticity in comparison to Sars-CoV?
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Has only 1 accessory protein vs. SARS which has 9!
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What is increased S. pneumoniae adhereance associated with?
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Increaded expression of platelet activating factor receptor during NL-63 infection
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What are current treatments of SARS=CoV?
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Protease inhibitors (Lopinavir and Ritonavir)
IFN treatment Abs to block spike |
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What are some good targets to treat SARS?
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3CLpro and PL2pro
nsP13 (helicase0 NSP1 (blocking this would elminate the block on the IFN response) |