Virology introduction Flashcards

1
Q

Are humans more closely related to bacteria e.g. E.coli or viruses?

A

We are far more closely related to E.coli than some viruses are to one another because viruses are massively variable -by grouping them it helps us to understand them

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2
Q

What is the definition of a virus?

A

Obligate intracellular parasite - they can’t replicate on their own, they require replication machinery of their host cell

They are essentially a protein shell protecting nucleic acids

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3
Q

What are viroids?

A

very small rod-like RNA molecules, only plant pathogens - they have no protein outer shell = therefore they are not viruses

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4
Q

What are prions?

A

no nucleic acids, therefore they are also not viruses

  • resistant to heat inactivation
  • resistant to radiation damage
  • resistant to DNAse and RNAse treatment
  • Sensitive to urea, SDS, phenol and other protein-denaturing chemicals
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5
Q

What are the key facts to know about viruses?

A

1) can’t replicate themselves - do not contain cells of any sort (acellular)
2) Cannot make energy or utilise nutrients
3) cannot synthesise anything
4) depend entirely on the cell they infect for all of these functions

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6
Q

What is the Baltimore system?

A

System of grouping viruses

  • based on what is within the cell free particle
    1) dsDNA viruses e.g. Herpes virus
    2) ssDNA viruses e.g. parvovirus
    3) dsRNA viruses e.g. rotaviruses
    4) (+) sense RNA viruses e.g. HCV, polio
    5) (-) sense RNA viruses e.g. influenza, ebola
    6) RNA reverse transcribing viruses e.g. HIV
    7) DNA reverse transcribing viruses e.g. HBV - strange virus which means all the groups are divided up with 4 groups of RNA viruses and 2.5 groups are DNA
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7
Q

What is the key difference between all organisms compared to viruses?

A

All organisms contain DNA and RNA but viruses contain RNA or DNA - never contain both

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8
Q

In simple terms, what do viruses look like?

A

nucleic acids surrounded by a capsid of proteins to protect the nucleic acids from nucleases

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9
Q

What are the 2 basic structural types of viruses?

A

Simple and complex
Simple - round or helical, clear symmetry
Complex - no clear symmetry

Viruses cannot be classified by shape like bacteria are

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10
Q

Where do you find helical capsids and what do they look like?

A

> 90% of viruses but no human viruses with human capsids - only measles and rabies have slight helical structure but don’t form the straight rods

Wedged shaped proteins that are all exactly the same - create an angle of 22 degree
360/22 = 16.3 therefore the 17th protein can’t fit in properly therefore the wedges go up in a spiral

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11
Q

What structure do most human viral pathogens take ?

A

Icosahedral capsids >90% of human pathogens = 20 triangles arranged in a sphere - internal surface if these triangles are basic and attract acidic DNA or RNA
This structure is much more size constrained so they is a limit to the genome size unlike helical capsid structured viruses

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12
Q

What host proteins within the central dogma does the virus to advantage of?

A

DNA polymerase
RNA polymerase
Translation machinery

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13
Q

Which viruses plug in to use RNA polymerase?

A

dsDNA - plug straight into transcription machinery to create products

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14
Q

Which viruses plug in to use translation machinery?

A

+ssRNA - plug in straight away and start making RNA products

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15
Q

Which viruses plug in to use DNA polymerase?

A

ssDNA - only need to replicate first and then they use all host machinery

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16
Q

How do host cells replicate RNA viruses?

A

When the RNA virus infects a cell it also brings along their own RNA polymerase to make

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17
Q

What do antisense and double stranded RNA viruses have to do when they enter the host cell?

A

they have to make transcripts before they can start making proteins

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18
Q

What signalling do obligate intracellular parasites/viruses always trigger first ?

A

intracellular sensing = CD8 and CTL

Whereas their extracellular signalling occurs later = CD4 and antibodies

Virus/parasites are presented on MHC class I - these molecules are present on all nucleated cells, therefore all cells have the potential to be infected

19
Q

What is the consequence of cells infected by an extracellular signal being leaky?

A

It means that although an infections (eg virus) can be leaked across into MHC class 1 system to generate a cytotoxic T lymphocyte response after they have already induced a CD4 response

20
Q

What do endogenous and exogenous antigens prime?

A
Endogenous can prime CD4 (class 2)
Exogenous can prime CD8 (class 1)
21
Q

What are the key mechanisms of actions of directly neutralising antibodies?

A

Block virus/receptor interaction
Block endocytosis
Block release into cytoplasm
Aggregate virus

  • almost all neutralise at the cell surface = lots of vaccines take advantage of this method
22
Q

What is the link between vaccination and B memory cells?

A

Immunological memory e.g. B memory cells normally develop during/after an infection
Vaccines are artificial ways of introducing memory against a pathogen - therefore vaccines are mimics of the natural response

23
Q

What are the 2 major traditional types of vaccines and what are the 2 major new types?

A

Traditional

1) Live attenuated (BCG, OPV, MMR)
2) Inactivated (pertussis, IPV)

New

1) Recombinant protein (HBV)
2) DNA based (experimental, flu)

24
Q

What are the features of effective vaccines?

A

Safe- don’t cause the illness itself
Protective- effective against illness occurring upon exposure to live pathogen
Gives sustained protection - lasts several years
Induces neutralising antibody- stops pathogen infecting cells
Induces protective T cells- particularly intracellular pathogens are more effectively dealt with by T cells so their vaccines induce at cell mediated response
Practical considerations - low cost per dose, biological stability, ease of admin, minimal side effects

25
What is a live attenuated vaccine?
Vast majority of vaccines Pathogenic virus is isolated and grown in non-permissive cells to encourage mutations that attenuate growth in original host = push virus through incorrect cell types (e.g. monkey cells) to induce mutations
26
What is an issue of using live attenuated vaccines in an immunocompromised person?
It can cause serious infection
27
What is a severe worry with the polio type 3 vaccine?
It is only 2 mutations away from the wild type strain - if it was injected into immunocompromised child/adult it could back mutate and cause a vaccine associated disease
28
What are inactivated vaccines?
Virus is inactivated by UV, chemicals (formaldehyde, phenol, beta proplolactone) or heat e.g. inactivated polio vaccine IPV and then injected Following inactivation it becomes just a protein, so its no longer alive Chemicals and UV are more commonly used compared to heat, because heat can destroy surface antigens, reducing immunogenicity
29
What are the technical issues associated with attenuate vs inactivated vaccines?
- not all pathogens will grow in alternative hosts - yield of virus in culture may be low and therefore increase cost - vaccines have a limited shelf life and often require refrigeration
30
What are the safety issues associated with attenuate vs inactivated vaccines?
- Incomplete inactivation is a potential risk - reversion of attenuated virus to virulence - immunocompromise vaccinees
31
What are the duration of immunity issues associated with attenuate vs inactivated vaccines?
attenuated are more enduring that inactivated
32
What do live attenuated vaccines do to your immune response?
Induce a subclinical infection = responses much longer lived
33
How are antivirals developed?
1) Medical need- need to identify how disease happens, mechanism, target proteins in a dysfunctional system 2) Targets that do something = "HITS" -those that do something but do kill you = "lead compounds" - test this in tissue culture, then preclinical (animals) and then humans = drug candidate
34
What is the newest approach to developing antivirals?
"designer approach" this is a smarter method of developing drugs to fight infections = allows your to work out the active side of the protein using a crystal approach on a computer
35
What is the benefit of using the crystal approach to develop antivirals?
Doesn't take as long
36
What is sequinavir?
computer generated space filling molecule designed to occupy the active site of HIV protease, totally synthetic non-natural product = only effective against HIV-1 and was produced in 17.5 months
37
What are the advantages of "designer" drugs?
Highly specific- safe = do not recognise anything in nature, making them incredibly safe Defined specificity Relatively rapid to develop
38
What are the disadvantages of "designer" drugs?
Highly specific - limited utility for diverse viruses - not all viruses follow the rules Defined specificity = resistance mutations occur rapidly Relatively costly to manufacture - creating it into a real compound is costly, challenging and can produce low yields
39
What does it mean by cross resistance?
Mutations to resistance to one drug often leads to resistance to many members of the same drug family
40
What are acyclovir and gangcyclovir?
inhibitors of viral DNA polymerase e.g. inhibitors of herpes simplex virus and other ds DNA viruses Because viral replication machinery is much simpler than ours, they will incorporate these molecules and this will lead to the killing of the virus
41
What is zidovudine?
inhibitors of reverse transcriptase - it is a thymidine with an added azide group Fortunately HIV can't tell the difference therefore it incorporates it during viral replication and this kills the virus
42
Why is a parasite a chronic infection?
Parasite is in a constant arms race with its host, in order to maintain itself. this interplay of the host and parasite can persist in a meta-stable state for years
43
Why are viruses able to rapidly evolve?
Viral mutations are common- for ever 1 in 10,000 nucleotides an error occurs - their replication machinery is incredibly inaccurate