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MIMM 324 > 27. Coronavirus 1 > Flashcards

27. Coronavirus 1 Flashcards

1
Q

what organisms are coronaviruses pathogenic in?

A
  1. humans
  2. animals
  3. birds
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2
Q

which 4 coronaviruses cause the common cold?

A
  1. 229E
  2. OC43
  3. ML63
  4. HKU1
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3
Q

is coronavirus enveloped?

A

yes

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4
Q

3 proteins on virus surface

A
  1. spike protein (S)
  2. membrane protein (M)
  3. envelope protein (E)
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5
Q

What is inside the coronavirus particle?

A

long +RNA coated by viral nucleocapsid protein arranged in specific conformation

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6
Q

2 conformations of spike proteins

A
  1. down
  2. up –> receptor binding domain is able to interact with ACE2 for entry
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7
Q

is coronavirus genome relatively long or short?

A

long

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8
Q

what is a consequence of having a long genome and how does coronavirus prevent this?

A

longer genome = more errors can be introduced, therefore has proofreading mechanism

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9
Q

how many total proteins in coronavirus?

A

26

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10
Q

what makes up about 2/3 of the coronavirus genome? what proteins do they encode for?

A

ORF1a and ORF1b

encodes for NON-STRUCTURAL proteins for replication, translation, and packaging

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11
Q

are non-structural proteins found in the viral particle?

A

no

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12
Q

what comes after the non-structural ORFs in the genome?

A

structural proteins

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13
Q

what comes after the structural proteins in the genome? 3 functions

A

ORF3A-10 –> accessory proteins to promote replication, counter immune response, and promote pathogenesis

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14
Q

how does the protein composition differ btwn coronaviruses?

A

structural and non-structural proteins are conserved but the accessory proteins differ

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15
Q

which proteins use subgenomic RNA?

A

structural and accessory proteins

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16
Q

order, family, subfamily, and genera of coronaviruses

A

order: nidovirales
family: coronaviridae
subfamily: coronavirinae
genera: alpha, beta, gamma, delta

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17
Q

coronaviruses that affect humans are part of which genra?

A

alpha or beta

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18
Q

are alpha or beta coronaviruses more pathogenic?

A

highly pathogenic ones are beta

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19
Q

how are beta coronaviruses separated?

A

separated into lineage A, B, and C

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20
Q

which 2 coronaviruses are alpha?

original host
secondary host

A

229E and NL63

original host: bat
secondary host: camel

21
Q

which 2 coronaviruses are beta lineage A?

A

HKU1 and OC43

22
Q

original and intermediate host of HKU1

A

original: rodents
intermediate: rodents

23
Q

original and intermediate host of OC43

A

original: rodents
intermediate: cattle

24
Q

which coronavirus is part of beta lineage B?

original host

A

SARS-CoV

original host: bats

25
Q

which coronavirus is part of beta lineage C?

original host
intermediate host

A

MERS-CoV

original host: bats
intermediate host: camel

26
Q

what animal is the original host of most coronaviruses

A

bats

27
Q

5 most important steps in coronavirus life cycle

A
  1. virus entry
  2. translation
  3. viral RNA replication/transcription
  4. viral gene expression
  5. virus assembly/egress
28
Q

describe coronavirus lifecycle in more detail (6 steps)

A
  1. spike protein binds ACE2, triggering fusion of viral and cell membranes
  2. viral RNA is delivered into the cell
  3. non-structural proteins made first
  4. ER is remodeled to form double membrane vesicles where replication and transcription can take place
  5. structural and accessory proteins made into subgenomic RNA
  6. virus assembles and exits
29
Q

is coronavirus efficient at producing progeny?

A

yes, can produce a lot of new particles very quickly

30
Q

2 domains of spike protein

A

S1 and S2

31
Q

another name for S1 domain, why?

A

S1 aka attachment domain bc interacts with ACE2

32
Q

prefusion spike

A

S1 and S2 together, allows binding at ACE2

33
Q

postfusion spike

A

only S2 domain once membranes have fused

34
Q

how do vaccines relate to prefusion spike?

A

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

35
Q

how does spike differ btwn coronaviruses

A

diff coronaviruses have diff domains to bind their receptor

36
Q

stability of prefusion vs postfusion

A

prefusion –> metastable
postfusion –> stable

37
Q

can coronaviruses recognize protein or carbohydrate receptors?

A

either one!

there are only 4 protein receptors, the rest are carbohydrate

38
Q

3 main domains of spike

A
  1. N-terminal domain
  2. receptor binding domain
  3. C-terminal domain
39
Q

how do coronaviruses develop resistance?

A

change aa in spikes to change recognition by Ab

40
Q

describe S1/S2 cleavage

A

S1/S2 boundary has ARGININE that is cleaved by host protease FURIN in golgi

41
Q

which is the only bat coronavirus with furin cleavage site?

A

SARS-CoV

42
Q

why is furin cleavage site important for coronavirus evolution?

A

allows it to adapt to new hosts

43
Q

which other 3 coronaviruses have furin cleavage site?

A
  1. MERS
  2. OC43
  3. HKU1
44
Q

why is furin cleavage site important for coronavirus entrance?

A

S1/S2 cleavage by furin allows for fusion which allows for infection –> “stronger” fusion = more damage

45
Q

what happens after receptor binding and furin cleavage?

A

virus particle can enter

46
Q

2 molecules that allow for virus entry?

A
  1. TMPRSS2
  2. cathepsins
47
Q

how does entry via TMPRSS2 work? (3 steps)

A
  1. TMPRSS2 cleaves S2
  2. exposes fusion peptide so it can anchor into target membrane
  3. triggers fusion
48
Q

how does entry via cathepsins work?

A
  1. virus particle endocytosed
  2. enters lysosomes with many proteases that cleave S2
49
Q

describe the 5 steps of viral membrane fusion

A
  1. RBD in up conformation binds ACE2
  2. fusion protein can be inserted into membrane
  3. S1 dissociates and causes conformational change in S2
  4. folds back and creates 6-helix bundle
  5. forms fusion pore to allow genome release into cell

MIMM 324 (37 decks)

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