27. Coronavirus 1 Flashcards
what organisms are coronaviruses pathogenic in?
- humans
- animals
- birds
which 4 coronaviruses cause the common cold?
- 229E
- OC43
- ML63
- HKU1
is coronavirus enveloped?
yes
3 proteins on virus surface
- spike protein (S)
- membrane protein (M)
- envelope protein (E)
What is inside the coronavirus particle?
long +RNA coated by viral nucleocapsid protein arranged in specific conformation
2 conformations of spike proteins
- down
- up –> receptor binding domain is able to interact with ACE2 for entry
is coronavirus genome relatively long or short?
long
what is a consequence of having a long genome and how does coronavirus prevent this?
longer genome = more errors can be introduced, therefore has proofreading mechanism
how many total proteins in coronavirus?
26
what makes up about 2/3 of the coronavirus genome? what proteins do they encode for?
ORF1a and ORF1b
encodes for NON-STRUCTURAL proteins for replication, translation, and packaging
are non-structural proteins found in the viral particle?
no
what comes after the non-structural ORFs in the genome?
structural proteins
what comes after the structural proteins in the genome? 3 functions
ORF3A-10 –> accessory proteins to promote replication, counter immune response, and promote pathogenesis
how does the protein composition differ btwn coronaviruses?
structural and non-structural proteins are conserved but the accessory proteins differ
which proteins use subgenomic RNA?
structural and accessory proteins
order, family, subfamily, and genera of coronaviruses
order: nidovirales
family: coronaviridae
subfamily: coronavirinae
genera: alpha, beta, gamma, delta
coronaviruses that affect humans are part of which genra?
alpha or beta
are alpha or beta coronaviruses more pathogenic?
highly pathogenic ones are beta
how are beta coronaviruses separated?
separated into lineage A, B, and C
which 2 coronaviruses are alpha?
original host
secondary host
229E and NL63
original host: bat
secondary host: camel
which 2 coronaviruses are beta lineage A?
HKU1 and OC43
original and intermediate host of HKU1
original: rodents
intermediate: rodents
original and intermediate host of OC43
original: rodents
intermediate: cattle
which coronavirus is part of beta lineage B?
original host
SARS-CoV
original host: bats
which coronavirus is part of beta lineage C?
original host
intermediate host
MERS-CoV
original host: bats
intermediate host: camel
what animal is the original host of most coronaviruses
bats
5 most important steps in coronavirus life cycle
- virus entry
- translation
- viral RNA replication/transcription
- viral gene expression
- virus assembly/egress
describe coronavirus lifecycle in more detail (6 steps)
- spike protein binds ACE2, triggering fusion of viral and cell membranes
- viral RNA is delivered into the cell
- non-structural proteins made first
- ER is remodeled to form double membrane vesicles where replication and transcription can take place
- structural and accessory proteins made into subgenomic RNA
- virus assembles and exits
is coronavirus efficient at producing progeny?
yes, can produce a lot of new particles very quickly
2 domains of spike protein
S1 and S2
another name for S1 domain, why?
S1 aka attachment domain bc interacts with ACE2
prefusion spike
S1 and S2 together, allows binding at ACE2
postfusion spike
only S2 domain once membranes have fused
how do vaccines relate to prefusion spike?
immune system recognizes the prefusion spike to make Ab so vaccines must be able to stabilize the spikes on the surface to induce Ab production
how does spike differ btwn coronaviruses
diff coronaviruses have diff domains to bind their receptor
stability of prefusion vs postfusion
prefusion –> metastable
postfusion –> stable
can coronaviruses recognize protein or carbohydrate receptors?
either one!
there are only 4 protein receptors, the rest are carbohydrate
3 main domains of spike
- N-terminal domain
- receptor binding domain
- C-terminal domain
how do coronaviruses develop resistance?
change aa in spikes to change recognition by Ab
describe S1/S2 cleavage
S1/S2 boundary has ARGININE that is cleaved by host protease FURIN in golgi
which is the only bat coronavirus with furin cleavage site?
SARS-CoV
why is furin cleavage site important for coronavirus evolution?
allows it to adapt to new hosts
which other 3 coronaviruses have furin cleavage site?
- MERS
- OC43
- HKU1
why is furin cleavage site important for coronavirus entrance?
S1/S2 cleavage by furin allows for fusion which allows for infection –> “stronger” fusion = more damage
what happens after receptor binding and furin cleavage?
virus particle can enter
2 molecules that allow for virus entry?
- TMPRSS2
- cathepsins
how does entry via TMPRSS2 work? (3 steps)
- TMPRSS2 cleaves S2
- exposes fusion peptide so it can anchor into target membrane
- triggers fusion
how does entry via cathepsins work?
- virus particle endocytosed
- enters lysosomes with many proteases that cleave S2
describe the 5 steps of viral membrane fusion
- RBD in up conformation binds ACE2
- fusion protein can be inserted into membrane
- S1 dissociates and causes conformational change in S2
- folds back and creates 6-helix bundle
- forms fusion pore to allow genome release into cell
