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concepts of disease > Coronavirus Infection > Flashcards

Coronavirus Infection Flashcards

1
Q

What group of family does the coronavirus belong to?

A

Nidovirales - all have RNA dependent polymerase

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2
Q

What four families is coronavirus split up into?

A

alpha, beta, gamma and delta

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3
Q

What are other forms of nidoviruses and what do they infect?

A

Arterivirus - in mammals causes, respiratory sydromes, abortion or lethal hemorrhagic fever

Torovirus - infects animals to induce gastroenteritis

Coronavirus - alpha, beta and gamma infect mammals only and cause respiratory symptoms in humans and gastrointestinal symptoms in mammals

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4
Q

What is polycistronic RNA?

A

one mRNA that has a lot of the protein expressed

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5
Q

How can you end up with two products for a gene of a respiratory virus?

A

Can have the 1a part of the gene translated but the ribosome will skip over and miss it. So it will carry on to the end creating a 1b chain. This way you can end up with 2 gene products translated for it and one of them will be shorter

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6
Q

How many coding regions does COVID-19 have?

A

12 coding regions divided

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7
Q

What does the 1ab coding region of COVID-19 do and contain?

A

Divided into15/16 non-structural proteins and contains/ does:

  • RNA proofreading
  • replicases
  • RNA profiling
  • RNA modifying enzymes
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8
Q

What does the S (spike) region of COVID19 do and contain?

A

Has a homotrimeric class I fusion of glycoproteins. And it binds cell surface receptors and induces the fusion of viral and cellular membranes

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9
Q

What does the E (envelope) region of COVID19 do?

A

Controls virus morphogenesis, assembly and budding

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10
Q

What does the N (nucleocaspid) region of COVID19 do?

A

Binds RNA genome in a beads-on-a string fashion

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11
Q

What does the M stand for in one of the COIVD19 regions?

A

Membrane glycoprotein

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12
Q

What is the incubation period for Sars-Cov2?

A

2 - 14 days

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13
Q

What is Ro (naught)?

A

Indicates how contagious an infection is. defined by average number of secondary cases arising from typical primary case in entirely susceptible population of size.

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14
Q

What is the value for Ro of COVID?

A

4.5

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15
Q

What gene does COVID19 share 96% of similarity and what animal is it isolated from?

A

RaTG13 isolated from a bat

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16
Q

What specific sequence from the RaTG13 gene shows similarities in the binding region to COVID19?

A

MP789

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17
Q

Where does Sars-Cov2 replicate in abundance?

A

In upper respiratory epithelia where ACE2 is also expressed and efficiently transmitted

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18
Q

How does the S1 domain of COVID19 aid in its entrance to the host cell?

A

Cell surface exposed to S1 has a receptor binding domain that specifically binds to it. This engages the host cell receptor and determines viral cell tropism and pathogenicity

19
Q

Why are proteases vital for pathogenesis of the virus? And what are they?

A

Needed fro cleavage of spike protein - TMPRSS and cathespin B & L

20
Q

How does entry of coronavirus into the cell occur?

A
  1. Bind to ACE2 - proteases TMPRSS and Cat B&L used for cleavage of the spike protein
  2. Spike then induces fusion of protein with endosome
  3. mRNA will be released, and get immediate translation of positive RNA and of protein ORF 1ab
  4. ORF 1a and 1b are translated and this produces polyproteins pp1a and pp1ab.
  5. nsp12-16 or nsp1-10 are also translated from ORF 1a and 1b
  6. Cleavage is carried out by 2 cysteine proteases in between nsp3 and nsp5
21
Q

What does ‘nsp’ stand for?

A

Non structural protein

22
Q

Where does the ribosomal frameshift take place?

A

Between ORF 1a and ORF 1b and this is where you get the short overlap and formation of one shorter strand and longer strand.

23
Q

Where are transcription regulatory sequences (TRS) located?

A

Upstream to the ORFs in 3’ half of viral genome

24
Q

What does RTC stand for?

A

Replication and transcription complex

25
Q

How does regulation and discontinuous transcription occur in COVID19?

A
  1. RTC interrupts transcription after the encounter of TRS at TRS-B
  2. Synthesis of negative strand of RNA stops and is re-initiated at TRS adjacent to leader sequence
  3. Results in smaller piece of genome formed and the part that used to be a part of this smaller piece is no longer translated
  4. Therefore at the end you have 8 subgenomic mRNA produced
26
Q

What does DMV stand for?

A

Double Membrane Vesicles

27
Q

Outline the process of coronavirus lifecycle.

A
  1. Interaction of nsp proteins and host proteins forms replication organelles - are ER derives & interconnected perinuclear double membrane structures with DMVs and the site of RNA synthesis
  2. In cytoplasm of host cell, has sensors that recognise viral mRNA and soluble strand mRNA this causes inflammation and cell death
  3. Structural proteins start to accumulate to ER and move to Golgi and undergo exocytosis and virus is released
28
Q

Why is it important for the virus to exist as a DMV?

A

It’s trying to isolate its mRNA from the cytoplasm in the cytoplasm of the host cell to avoid recognition and cell death

29
Q

How comes people are symptomatic?

A

Because the virus is very good at blocking inflammation

30
Q

What is an advantage of existing as a DMV in terms of macromolecules?

A

Able to have macromolecules needed for mRNA double strand formation and transcription to be concentrated in a specific area

31
Q

What is a variant?

A

A virus that developed a specific group of mutations that causes variant to behave differently than that of the strain its originated from

32
Q

When does a variant become a new strain?

A

When it has acquired distinct properties and has a particular immune response

33
Q

What is the mutation rate of COIVD?

A

10^-6 which is therefore a 2 single letter mutations per month

34
Q

What are the main characteristics of the VUI 202012/01 strain?

A

23 mutations, 13 non-synonymous, 6 synonymous and 4 amino acid deletions

35
Q

Where do most of the VUI mutations occur?

A

In the spike protein

36
Q

What are some of the mutations that occur in spike in VUI?

A
  • Mutations N501Y - alters AA within 6 key residues in receptor binding domain
  • P861H has been found in RB
    Consequences:
  • Higher transmissibility
    Increase in R by 0.4 and shorter generation times
37
Q

What immune response occurs in response to the virus?

A

Pryoptosis - whole content of cytoplasm release and so is viral protein, mRNA and also cytokines. Macrophages will be picked up which will initiate an immune response

38
Q

What does the control of positive feedback cause?

A

Secretion of neutralising antibodies by B cells, CD8 and toxic components to kill the cells.
Antibody will then bind to virus and macrophage will phagocyte the virus

39
Q

What part of COVID19 do the antibodies target?

A

Spike protein and nucleocapsid. Antibody fro this is neutralising

40
Q

How does macrophages produce inflammation in respiratory distress syndrome?

A

Produces a higher amount of cytokines in genetically predisposed people, this will cause the cytokines to go everywhere and cause inflammation

41
Q

What are the characteristics of uncontrolled autoantibody production?

A

Some are anti-nuclear, antiphospholipid and anti IFN - so they stope type 1 IFNs to bock SARS-CoV-2

42
Q

What are some of the current treatments used to treat the symptoms of COVID-19?

A

Dexamethasone - corticosteroid that blocks inflammation.
Remdesivir - adenosine analogue that terminates viral replication. It blocks further addition to nucleotide by inhibiting viral mRNA replication

43
Q

What is convalescent plasma serum and how does it work for treating COVID patients?

A

Buys more time for patient to develop their immunity. Antibodies IgG and IgM from someone else are given to another person to protect them.

concepts of disease (20 decks)

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