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41 Cards in this Set

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