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Imperial Y2 - Genes & Genomics > Tristem & Curry > Flashcards

Tristem & Curry Flashcards

1
Q

What is a virus?

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2
Q

How do viruses differ from other life forms?

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3
Q

What are different types of genome diversity that exist in viruses?

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4
Q

Distinction between Virus and Virion particle?

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5
Q

How do DNA and RNA viruses differ? Why might these differences arise?

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6
Q

Do viruses with small genomes often have overlapping genes?

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7
Q

What is the correlation between double and single stranded genomes between RNA and DNA viruses?

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8
Q

What is more common Circular or Linear DNA in viruses?

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9
Q

What is one crucial difference between -ive sense and +ive sense viruses?

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10
Q

What is meant segmented and non-segmented genomes?

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11
Q

How does the evolution of segmented vs. non-segmented genomes differ?

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12
Q

Can viruses be visualized using a light microscope?

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13
Q

What is the simplest virus particle structure?

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14
Q

Are capsids commonly found in viruses? How do they assemble if the virus has no metabolism?

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15
Q

Apart from spherical sturctures, what other shapes do Capsid protein auto-assemble into|?

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16
Q

What are envelopes? Give an example of a virus surrounded by an envelope?

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17
Q

Summary - genomics and morphology

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18
Q

Can viruses have more than one host? If so, is there a way to classify the different stages of transmission?

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19
Q

What are Zoonotic viruses?

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20
Q

Using Ebola as an example explain how researchers can find out what is the reservoir species?

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21
Q

What is an example of a extreme boundaries that is blurring the lines on whether viruses are alive or not?

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22
Q

What are the main steps in the Viral life cycle in a cell?

A

Steps in viral replication:

  1. Infection and disassembly of the infectious virion particle
  2. Replication of the viral genome
  3. Synthesis of viral proteins by host cell machinery
  4. Reassembly into progeny virus particles  may be followed by a maturation step
  5. A viral life-cycle in relation to its genome (Not covered)
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23
Q

What is a generic example of a virus life cycle in a host cell?

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24
Q

How does a plot of Viral growth look like?

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25
Q

Generally speaking, how does Viral-Host cell attachment take place?

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26
Q

Why is HIV-1 unusual when it comes to virus host cell attachment?

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27
Q

What are two common themes that prevail in host cell infection and disassembly of viruses?

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28
Q

Outline what is happening following viral infections and dissaembly.

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29
Q

What Generalizations can be made Viral genome replication?

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30
Q

Outline how RNA viruses with ssRNA + replicate in a host cell.

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31
Q

Outline how RNA viruses with ssRNA - replicate in a host cell.

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32
Q

Outline how DNA viruses and retroviruses replicate in a host cell.

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33
Q

Are host proteins highly involved in viral replication?

A

YEAHHHHH BUDDYYYYYY

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34
Q

What are some generalizations that can be made about Virus assembly & cell exiting?

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35
Q

Outline how surface assembly of an envelope virus + capsid takes place?

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36
Q

Outline how the small pox virus undergoes subsurface assembly.

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37
Q

Define the following terms/concepts?

Permissive Cell

Non-permissive cell

Productive infection

Persistant infection

Transform Cells

A

Cytocidal = Cytopathic

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38
Q

What are some morphological effects one can observe when a virus infects a cell?

A

Inclusion body formation - due to overproduction of viral proteins which end up aggregating together?

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39
Q

What are some effects on cell biochemistry and physiology when CMV infects a cells?

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40
Q

What are some genetic effects commonly observed when a virus infects a host cell?

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41
Q

How and why do we get giant cells when viruses infect cells?

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42
Q

What are the two main ways cells defend themselves against virusus?

Discuss about interferon example

A
43
Q

Outline how Inteferon activates TIP as well as virus counteract this defence action?

A
44
Q

Outline why and how RSV (virus) is an example of a transforming virus?

A
45
Q

What is the morphology of the SARS coronavirus?

A
46
Q

What order and subfamily do coronaviruses fall under?

A
47
Q

What is the main reservoir species for coronavirus’s? What is the reservoir and intermediate for MERs, SARs-1 and SARs-2?

A
48
Q

Genomic organisation of coronaviruses?

A

Genomic organisation between human and non-human coronaviruses is significantly different

but

SARS-1 and SARS-2 very similar – 1 gene difference

49
Q

Outline the life cycle of SARS-1 (most likely very similar to SARS-2)

A
50
Q

Where did SARS-1 orginate? Differences with SARS-2? Possible reason why there was such a different outcome?

A
51
Q

SARS-2 origin? Symptoms?

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52
Q

What are the infectious Routes of SARS-CoV2?

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53
Q

Surivial rates of SARS-CoV on different surfaces?

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54
Q

Prospects of controlling SARS-CoV2? Weather? Vaccines? Anti-viral?

A
55
Q

Out of Lockdown, Pop. density and climate - which one has the biggest impact on SARS-Cov2 reproductive number?

A
56
Q

Briefly outline the different vaccine approaches

  1. DNA & RNA
  2. Live attenuated
  3. Inactivated
  4. Subunit
  5. Viral Vector
A
57
Q

Do other organisms other than viruses ever use RNA as their genomes?

A
58
Q

Can RNA of retrovirus get translated directly?

A
59
Q

Why do some viruses bother using minus sense RNAs when it just sounds like a hassle?

A

No reason, just reflects origins of viruses - just started of like that and remained like that during evolution

60
Q

How does the virion “know” which mRNA to pack into the core? For example, if we have a +RNA virus how does it know not to pack the intermediate (minus)RNA and vice versa?

A
61
Q

Since RNA is less stable than DNA, and RNA polymerase has lower ability of proof reading, why would some virus use RNA as their genetic material? What evolutionary advantages does RNA give these virus?

A
62
Q

Could you explain how a multinucleated syncytical cell (giant cell) can be used to test whether a cell line has certain type of virus in it?

A

Does not tell you the type of virus per se just that it indicates the likelihood of an envelope virus present

63
Q

Is protein protein crystallography often used to study viral proteins?

A
64
Q

Can crystallography be used to study whole virus particles?

A
65
Q

When studying viruses what is NMR normally used for?

A
66
Q

Outline the role of Cryo-EM in studying viruses?

A
67
Q

What is Cryo-electron tomography (cryo-ET) commonly used for when studying viruses?

A
68
Q

What Case study did Bossman Steph Curry present?

A

Real world project of crystallography project in Virology

Foot & Mouth Disease virus (FMDV) replication - looking specifically at the role of 3Cpro

Why do we care about FMDV?

Foot-and-mouth disease virus is an economically important disease of cattle, sheep, pigs, goats… –> important to understand to maintain healthy livestock

69
Q

What type of Virus is FMDV? What is the organisation of its genome? How many ORFs?

A
70
Q

Outline the importance of 3C protease in FMDV - in particular refrencing how it contributes to Capsid formation

A
71
Q

FMDV 3Cpro: why is it a good target for antivirals?

A
72
Q

Case Study 3CPro - Part 1 –> How did they manage to crystallize the protein?

A
73
Q

Case Study 3CPro - Part 2 –> What did the Crystal structure of FMDV 3Cpro show us?

A
74
Q

Case Study 3CPro - Part 3 –> How did their 3Cpro compare to other picornavirus 3Cpro structures?

A
75
Q

Case Study 3CPro - Part 4 –> From other structures what did the active site of 3Cpro resemble?

A
76
Q

Recap - How does the chymotrypsin catalytic triad work?

A
77
Q

Case Study 3CPro - Part 5 –> WHat was the proposed machanism of FMDV 3CPro? What did it look like?

A
78
Q

Case Study 3CPro - Part 6 –> Why was there confusion surrounding the mechanism of 3Cpro in viruses?

A
79
Q

Case Study 3CPro - Part 7 –> What was the final verdict - what new data got released to draw the final conclusion on 3Cpro mechanism?

A
80
Q

Case Study 3CPro - Part 8 –> What was wrong with the original structure obtained for FMDV 3Cpro? Why could it not be used for Drug studies? How was this problem solved?

A

Problems with the original crystals

Substrate binding site obscured by crystal packing – forming a crystal contact - would not be able to soak candidate drugs into crystal

Solution - Used existing crystal form, engineered crystal contact mutants:

K51Q, R68E, R97E, R126E, L134Q - mutations that were introduced deliberately to disrupt crystal contacts but had to ensure that the active site would not get disrupted in the process

Mutant 3C(K51Q) crystallised - Obtained a new crystal form

81
Q

Case Study 3CPro - Part 9 –> When measuring enzyme activity of 3Cpro what problem did they encounter? How was this overcome?

A
82
Q

Generally speaking, how does the protease recognise sequences to be cleaved?

A
83
Q

Case Study 3CPro - Part 10 –> What peptide did they decide to co-crystallize with the 3Cpro in order to examine binding at the active site?

A
84
Q

Case Study 3CPro - Part 11 -> What did they learn from the Co-crystallization with the peptide?

A
85
Q

In which Serotypes is FMDV 3Cpro conserved?

A
86
Q

Going back to the mutant containing C142 not presenting enzymatic activity in FMDV 3Cpro - Why did this problem arise?

A
87
Q

How can the C142 problem be exploited when trying to create a vaccine?

A
88
Q

FMDV 3Cpro Cleavage Specificity?

A
89
Q

Overview of coronaviruses - Discovered? Imaged? Structure? Genome?

A
90
Q

Outline the Coronavirus Taxonomy - Order? Genera? Hosts? Where are human Coronaviruses found ?

A
91
Q

Outline the structure of the SARS-CoV 1 Genome?

A
92
Q

How do CoV genomes generally vary?

A
93
Q

Outline the SARS-CoV Replication Cycle?

A
94
Q

Have the number of structures produced for SARS-Cov2 increased dramatically?

A

SARS CoV 2 genome sequenced in Jan 2020

28 Apr: 136 structures

6 May: 159 structures

3 Dec: >1,000 structures* - many are repeat structures

95
Q

What strucutre for SARS-CoV 2 – nucleoprotein (N) structures have been published?

A

SARS-CoV 2 – nucleoprotein (N) structures

28 Apr: 4 structures

3 of the N-terminal RNA binding domain

1 of the C-terminal dimerization domain

Function?

96
Q

What strucutres for the SARS-CoV 2 – Spike (S) structures have been solved?

A
97
Q

What did the Cryo-Em structure of the 6vxx - The Spike protein homotrimer reveal?

A
98
Q

Outline the functions of the Spike protein in Cell attachment and fusion - SARS-CoV2

A
99
Q

What strucutre for SARS-CoV 2 – nsp7-nsp8 structure has been released?

A
100
Q

What structure for SARS-CoV 2 – 3C-like protease (nsp5) has been released?

A
101
Q

What is a drug fragment screening project? What does it entail? How does it differ from normal drug searching?

A
102
Q

What structure for SARS-CoV 2 – for RNA-dependent RNA polymerase (nsp12) has been released?

A
103
Q

What does it mean that the active site is involved in crystal contacts? Does it interact with active site of another protein monomer or somewhere else? What type of interactions are involved?

A
104
Q

Why do we call RNA viruses - Quasi-species?

A

In general, we refer to RNA viruses having a quasi-species - as RNA viruses have a high mutation rate resulting in an ever changing genome

Imperial Y2 - Genes & Genomics (6 decks)

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