Viruses and Viral Disease Flashcards

Lecture 15 - 22

1
Q

Write 3 fun facts about viruses.

A

Viruses infect all living organisms.
We breath and eat billion of virus particles.
We carry viral genetic sequences as part of out own genetic materials.

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2
Q

Describe the history of viruses/virology.

A

Tobacco Mosaic Virus was identified in the 1930s.
Viral diseases like rabies have affected humans for many centuries.
The first written record of a virus infection is shown in hieroglyph from Memphis.
Pharaoh Ramses V (died 1196 BC) due to smallpox.
In the late 18th century, Edward Jenner observed a milkmaid who caught cowpox and was found to be immune to smallpox. In May (1796) Jenner used pus from that milkmaid to vaccinate the 8 year old boy. In July (1796) Jenner tried giving pus to the boy and he survived.

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3
Q

How did Dmitri Iwanowski (1892) help in the development of concepts of viruses.

A

He demonstrated that extracts from infected tobacco plants could transmit disease to other tobacco plants. He filtered the extract with the Chamberland filter (a porcelain filter developed to remove bacteria from drinking water). This didn’t prevent transmission.

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4
Q

How did Martinus Beijernick (1898) help in the development of the concept of viruses.

A

Showed that the filtrate contained a new form of infectious agents. He demonstrated that the agent multiplied in living cells. He called it a soluble living germ and used ‘filtrable agent’ to describe it.

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5
Q

How did Loeffler and Frosch (1898) aid in the discovery of the first animal and human viruses.

A

Repeated the TMV experiments and demonstrated Foot and Mouth Disease in cattle was caused by similarity small infectious agents.

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6
Q

How did Carlos Finlay (1901) discover the first human virus.

A

A Cuban physician, first conducted and published research that indicated that mosquitoes were carrying the cause of yellow fever. So the first human virus to be identified was the yellow fever virus.

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7
Q

5 properties of viruses.

A
  • Small
  • Contain DNA or RNA
  • Different replication strategy, they don’t divide by binary fission.
  • Obligate intracellular parasites
  • Simple structure.
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8
Q

3 reasons why we study viruses

A
  • To understand viral disease.
  • Develop therapeutics
  • Design measures to reduces viral transmission.
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9
Q

What is a virus definition?

A

Viruses are genetic elements surrounded with a capsid and can’t replicate independently of a living cell.

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10
Q

What isn’t encoded in viral genomes?

A

Genes that encode the complete protein synthesis machinery.
Genes encoding proteins involved in cell wall production or membrane biosynthesis.
Centromeres or telomeres found in standard host chromosomes.

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11
Q

Describe the CAPSID.

A

The protein shell that surrounds the viral genome.
It protects the nucleic acid.
Facilitates nucleic acid delivery into the host cells.
Composed of protein molecules arranged in a precise and highly repetitive pattern around the nucleic acid.
Viral genomes are small and encode a limited number of proteins.
Viral particle would be built with multiple copies of these few proteins.

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12
Q

What are the 3 types of CAPSID.

A

Helical, Icosahedral, Complex.

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13
Q

What is an Icosahedron in terms of its structure?

A

20 faces - each an equilateral triangle.
30 edges - each an interface between 2 faces.
12 vertices - each a point where 5 faces meet.
It permits the greatest number of capsomeres to be packed in a regular stable figure icosahedron. The easiest way of making regular stable structure from the smallest number of proteins. There is 2 fold, 3 fold and 5 fold symmetry.

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14
Q

Give an example of viruses with simple Icosahedral capsids.

A

Adeno-associated virus. Parvovirus B19. 25nm with 60 copies of a single viral capsid protein.

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15
Q

What is helical symmetry?

A

Rod - shaped viruses.
The length of virus determined by length of nucleic acid. Width of virus determined by size and packaging of protein subunits.

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16
Q

Describe how viral particles are metastable.

A

Protects viral genome (stable). Facilitates delivery of viral genome into the host cell, must dissociate on infection (unstable).

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17
Q

Describe how CAPSID proteins are related to Virus-Like Particles.

A

Some CAPSID proteins self-assemble into virus like particles.

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18
Q

Why are viruses classified?

A

To contrast viruses and to reveal information on newly discovered viruses by comparing them to similar viruses.
To study the origin of viruses and how they have evolved over time.

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19
Q

What is the disadvantages of classification based on diseases?

A

Focuses on some viruses and ignores the others.
A single virus may cause more than one disease.
Viruses infect more than one host and sometimes with different manifestations.

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20
Q

What are the disadvantages of classification based on host.

A

Some have restricted host range.
Others infect a small range of hosts.
Some infect very different species.
Some grouped based on the nature of the host cells.

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21
Q

What are the characteristics for the committee on taxonomy of viruses (ICTV).

A

Host range, morphological features of the virion, nature of the genome nucleic acid, additional features may allow subdivision allocation, phylogenetic trees may be established using nucleotide sequences.

22
Q

What is the baltimore classification of viruses.

A

Thousands of different viruses.
Cause different numbers of viral infections and diseases.
All viruses must make their mRNA.
mRNA will be read by the host ribosome to produce the viral proteins.
No exceptions to this.

23
Q

Describe viroids.

A

Novel agents of disease in plants. Contains a single circular ssRNA molecule as infectious materials. No protein components. Viroids genomes range in size from 220 to 400nt. The smallest self-replicating pathogens known. Up to 70% of the nucleotides in the genome RNAs are base-paired. They appear as rod-shaped or dumb-bell shaped molecules.

24
Q

Describe prions.

A

Originally thought to be viruses as they replicate slowly within their hosts. No nucleic acid has been found in association with infectious material. Agents of a number of diseases characterized by slow, progressive, neurological degeneration that are fatal. The diseases are associated with a spongy appearance of the brain. It induces changes in the shape of their normal homologoues with catastrophic consequences.

25
Describe the steps in finding the 'right' cellular receptor.
1. Adhering to the cellular surface. 2. Attaching to the specific receptor on the cell surface. 3. Release of the viral genome into the cytoplasm
26
Describe the 3 ways in which viruses can enter into a host cell.
Fusion of viral envelope with cell membrane at the cell surface. Fusion of viral envelope with cell membrane within the cytoplasm. Endocytosis.
27
Describe how the uncoating of the protein capsid.
1. DNA must be delivered into the nucleus except poxviruses, RNA must be delivered into the cytoplasm, except HIV, Influenza virus.
28
Describe how virions exit cells.
They exit via budding or lysing of cells. Not every released virion is infectious.
29
Describe the cultivation of viruses and their culture systems.
In vivo: - Animal, Plant, Bacteria, Chicken Eggs. In vitro: - Cell Culture.
30
Describe the replication of RNA viruses.
Replication of RNA viruses is via RNA-dependent RNA polymerase. Cells have no RNA-dependent RNA polymerase. RNA virus genomes encode. RdRp produces RNA genomes and mRNA from RNA templates.
31
Describe in vivo culture systems.
Mice are most frequently used for isolation of viruses in addition to monkey, rabbits and hamsters. After innoculation, animals are observed for symptoms of disease and death. The virus can also then be isolated by sacrificing the animals and purifying the viruses from their tissue.
32
Describe the cultivation of viruses in eggs.
Fertilised eggs must be 8-11 days old. The virus is innoculated into any of the compartments. Viral growth is indicated by the death of the embryo, by embryo cell damage, changes in fluids or by the formation of typical pocks or lesions on membranes.
33
Describe the cultivation of viruses in cell cultures.
A culture of normal cells obtained freshly from animal organs or tissues. Have a short life span so must be transferred to another fresh growth medium. Capable of a limited number of divisions, so cannot be passaged for many times. Eg. monkey kidney cells.
34
Describe the HeLa cell line.
Henrietta Lacks was diagnosed with cervical carcinoma (1951). HeLa cells were first continuous tissue-culture cell line. They were used to establish tissue culture as an important technology for research in cell biology, virology and medicine. Henrietta lacks cells are still alive and are actively being used for commercial and research purposes, this includes research discoveries related to polio, cancer and AIDS.
35
What is the CytoPatheic Effect?
The CPE is any observable, distinct change in shape, appearance, morphological features in infected cells due to growth and replication of viruses. CPE produced by different types of viruses are characteristic and help in the initial identification of virus isolated.
36
Describe the Cytopathic Effect-Syncytia.
Fusion of the plasma membranes of multiple infected cells to produce giant cell with multiple nuclei. Fused cells are short lived and subsequently lyse. Eg. mumps, measles, herpesviruses.
37
What are non-infectivity assays?
Physical measurements of viruses. - Electron microscopes - ELISA - Immunofluorescence - Haemagglutinin assay
38
What are infectivity assays?
Measure the number of infectious viral particles. - Plaque assay - TCID50 assay - AID50 assay
39
Describe the discovery of the first bacterial viruses.
Phages were first mentioned in 1915 by an English doctor called Frederick Twort. He described how a phage infection of Staph gave rise to clear zones of lysis as phages appeared to destroy the bacteria.
40
How do you calculate PFU?
1. Select the dilution that produced countable number of plaques (20-80) 2. Work out the number of plaques in the undiluted sample by multiplying the number by the dilution factor or by dividing it by the dilution. 3. Work out the number of plagues in 1ml by dividing the number of plaques, in the undiluted sample, by the inoculum volume (in ml)
41
Describe viral pathogenesis.
Pathogenesis: The ability/capacity of the virus to cause disease. Virulence: Quantitative or relative measure of the pathogenesis of the infecting virus. - Virus A is more virulent than Virus B - Virulent vs avirulent.
42
Describe virus-induced immunopathogenesis.
Tissue injury may reflect host defence mechanisms that include apoptosis or immune response that target virus-infected cells. Eg. Ebola virus damages vascular endothelial cells causing haemorrhage due to the release of cytokines and other tissue factors that attack and damage the vascular endothelial cells.
43
Describe the viral virulence genes.
Gene products that affect viral replication. Genes encoding toxins. Genes encoding modulators of the immune response. Oncogenes. Gene products that enable the virus to spread in the host.
44
Describe virulence genes and their relation to encoding genes.
They are not always encoding genes.
45
Describe other determinants of virulence.
- Age: very young: immature immune responses - Old: less elastic alveoli, weaker respiratory muscles, diminished cough reflex.
46
What are some requirements of an effective vaccine?
- Safe & acceptable. - Protection must be long-lasting. - Genetically stable. - Storage consideration. - Deliver (oral vs needle) - Cheap (polio a few pence, HBV about £100)
47
What are live attenuated vaccines?
It contains the whole virus that has been weakened or attenuated to produce an immune response similar to that seen during natural infection. Eg. measles, rotavirus, flu vaccine. It contains the weakened virus which is recognised by the immune system to trigger a response without causing illness.
48
Describe killed/inactivated vaccine.
Contains whole virus which has been killed or have been altered, so that they can't replicate. Eg. Polio vaccine, Hep A vaccine, Rabies vaccine. It contains the killed virus which can trigger the immune response without causing illness.
49
Describe subunit vaccines.
They don't contain the whole virus, they contain one or more specific component/antigens usually from the surface of the virus. They contain proteins from the virus, which are recognised by the immune system to trigger a response without causing illness. Features: - Don't create a strong and lasting immune response. - May be suitable for immunocompromised individuals. Eg. Influenza subunit vaccine.
50
Give 2 advantages and disadvantages of subunit vaccines.
Advantages: - Recombinant DNA technology fast. - No viral genomes are infectious. Disadvantages: - Expensive - Injected.
51
How do anti-HIV drugs.
Control viral replication prolonging survival. Anti-HIV drugs inhibit viral replication at many different phases of the HIV replicative cycle.