Virology Flashcards

1
Q

Why should we study viruses?

A

-Make up most of earths living matter
-We carry viral genomes ar part of our genetic material
-Can be harmful or helpful to hosts
-Can be used in studies to understand fundamental principles of molecular biology
-Can be engineered to deliver gene therapy and kill cancer/deliver vaccines

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2
Q

Define what a virus is?

A

Genetic element that can multiply only ina living cell
It is an obligate intracellular parasite (needs hsot cell for energy, metabolic intermediates and protein synthesis

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3
Q

What is a virion?

A

Virus particule: extracellular form of a virus
(exists outside of jost and facilitates transmission from one host cell to another

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4
Q

When does replication/reproduction of a virus occur?

A

Only when it is inside the cell - this is what causes infection

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5
Q

Describe the characteristics of a virion?

A

-Capsid (protein coat) surrounds nucleic acid (RNA or DNA)
-Nucleic acid + protein coat = nucleocapsid
-Some have a phospholipid envelope: phospholipid bilayer + glycoproteins (spike) that recognize and bind to the host cell

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6
Q

How were viruses discovered?

A

-Coinage of the term virus
-Tobacco mosaic disease transmissible
-Falls through filters designed for bacteria
-Isolation + characterization of TMD
-Viruses can lead to cancer

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7
Q

How did viral evolution occur?

A

No definitive explanation - viruses may have arisen prior to cells (free livingduring RNA world period) or from cells due to them needing a host

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8
Q

Why did viruses appear?

A

-Mechanism to quickly move genes (enrichment if genetic diversity)
-Cause of RNA to DNA transition (RNA viruses evolved DNA genomes)

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9
Q

Where can viruses be found?

A

Occupy nearly all organisms almost everywhere
94% of nucleic-acid containing particles
5% of biomass

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10
Q

How will climate change affect the spread of pathogenic disease?

A

Shift the geographic range of hosts
58% of disease have been aggravated already by climate change

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11
Q

Size of viruses?

A

Very small - cannot be seen by a light microscope (requries electron microscopy)
20-1000nm in length
Giant viruses have a diameter of 500nm

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12
Q

Name of first giant virus?
Alternate name for giant viruses?

A

Mimivirus (large capsid of 400nm) : large DNA genome
Nucleocytoplasmic large DNA viruses (NLDV)

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13
Q

What can giant viruses infect? +how they evolved

A

Eukaryotic unicellular hosts (amoebas, algae and other protists)
Large and diverse genomes - likely small viruses that were very good at stealing DNA material from their host via lateral gene transfer

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14
Q

What is a virophage? First one discovered? Relationship with giant viruses?

A

Small DNA viruses that replicate only in cells co-infected with a giant virus
Sputnik
Parasitic

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15
Q

Are all viruses bad?

A

No - most viruses are not pathogenic and just coexist with us

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16
Q

What is a bacteriophage?

A

Viruses that kill and infect bacteria

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17
Q

Function of the capsid?

A

Protects the genome
Delivery of the genome (capsid binds to host cell receptors) by direct penetration (just the genome enters the cell) or endocytosis (entire virus, then capsid is uncoated)

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18
Q

Three types of capsid morphology? + properties and type of nucleic acid

A

-helical (spiral or rod shaped - can only package ssRNA because they are less rigid than ds nucleic acids)
-isocahedral (spherical and rigid - ssRNa, dsRNA or DNA, creates triangular faces - most animal viruses)
-complex (neither helical or icosahedral - particularly bacterial viruses (polyhedral head, helical sheath) or poxviruses are described as brick shaped)

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19
Q

How do enveloped virions develop? What is the composition of the envelope? Role?

A

Budding of host cell
Cytoplasmic membrane + viral glycoproteins
Protection against immune system, but more sensitive to environmental changes

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20
Q

Describe the genome delivery process of enveloped virions

A

Step 1: attachemnt of the enveloped virion to the host cell membranes (glycoproteins bind to receptors)
Step 2: endocytosis (then uncoating) or membrane fusion(release of just capsid into cell)

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21
Q

Which virus types can be envelopped?

A

RNA or DNA - no correlation between genome structure and whether the virus can be envelopped or not

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22
Q

Main property of virions? How is it achieved

A

Metastable - stable enough to protect the genome, but unstable enough to come apart quickly to elease the viral genome in an infected cell
Stability = symmetrical arrangement of proteins
Instability = strucutre is not permanently bonded together

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23
Q

What was the proof that the viral nucleic acid genome is the genetic code?

A

-Hershey chase experiment (phages - radioactive protein then DNA))
-Fraenkels-Conrat + SInger (TMV RNA A + protein B = type A progeny)

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24
Q

4 options for viral genome composition + 2 subclasses

A

ss or ds RNA
or
ss or ds DNA
can be + sense or - sense
Positive sense = strand of DNA or RNA that can be directly translated into amino acids.

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25
Q

3 options for viral genome shape

A

linear, circular, segmented

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26
Q

What is the coding capacity of viral genomes?

A

4 to a few hundred genes

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27
Q

Differences between eukaryotic DNA viruses and eukaryotic RNA viruses?

A

DNA: mostly dsDNA - DNA replication mostly takes place in the nucleus
RNA: most ssRNA - RNA replication takes place in the cytoplasm

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28
Q

In what way do RNA viruses challenge the central dogma of molecular biology?

A

RNA viruses encode ro carry enzymes that:
-reverse transcribe RNA into DNA (reverse transcriptase
-synthesize RNA from and RNA template using RNA dependent RNA polymerase (RdRP)

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29
Q

How are polymerases named?

A

“using what’-dependent “making what” polymerase

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30
Q

What do RNA viruses require to replicate their genome? What do they synthesize? What’s the exception?

A

RdRP (carried by RNA virus genome)
Synthesis of viral mRNAs (as well as genome replication)
Retroviruses

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31
Q

How are viruses classified?

A

Using various viral attributes such as:
-Nature of nucleic acid in virion
-Symmetry of protein shell
-Presence or absence of envelope
-Host range

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32
Q

What is ICTV classification?
Linnaeus classification rules

A

Internation Committe on Taxonomy of Viruses
Classifies and provides nomenclautre of viruses
Order: virales
Family: viridae
Genus: virus
Species: descriptive common names used, with subspecies being assigned a number or letter

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33
Q

What is Baltimroe system of virus classification?

A

Classification of animal viruses based on three critera:
-nucleic acid composition
-way the virus is replicated
-way that virus makes mRNAs for viral protein expression

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34
Q

What are the 7 classes of viruses (based on the baltimore classification)

A

1: dsDNA
2: (+) ssDNA
3: dsRNA
4: (+) ssRNA
5: (-) ssRNA
6: ssRNA-RT
7: dsDNA-RT

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35
Q

(based on the baltimore classification) explain the transcription and replication mechanisms of class 1?

A

dsDNA
Transcription: dsDNA genome is directly transcribed to mRNA upon entry to host using host RNA pol (cytoplasm
Replication: uses hsot machinery (nucleus)

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36
Q

(based on the baltimore classification) explain the transcription and replication mechanisms of class 2?

A

(+) ssDNA
*rarely infects humans as the ssDNA is considered to be abnormal
Transcription: viral mRNAs are transcribed from dsDNA using host transcription machinery
Replication: Mostly circular genomes replicated using dsDNA intermediate, using host DNA pol (nucleus)

37
Q

(based on the baltimore classification) explain the transcription and replication mechanisms of class 3?

A

dsRNA
(everything in cytoplasm)
RdRP is needed for both trasncritpion and replication: carried in the viral particule

38
Q

(based on the baltimore classification) explain the transcription and replication mechanisms of class 4?

A

(+) ssRNA
(everything in the cytoplasm)
Trasncription: (+) ssRNA can be directly translated, but must EITHER carry or encode RdRP
Replication: synthesis of (-) strand by viral RdRP - serves as template for (+) stand synthesis

39
Q

(based on the baltimore classification) explain the transcription and replication mechanisms of class 5?

A

(-) ssRNA
(everything in cytoplasm)
*(-) ssRNA cannot be used by host ribosomes
Transcription: viruses must carry RdRP to make to make mRNA
Replication: (+) ssRNA (made in transcription) is used as a template

40
Q

(based on the baltimore classification) explain the transcription and replication mechanisms of class 6?

A

Retroviruses or ssRNA-RT
*uses reverse transcriptase (RT) to convert (+) ssRNA into dsDNA in cytoplasm - insetres into the host genome using integrase (RT and integrase carried) = provirus
Transcription: provirus is used as a template by host cell machinery
Replication: provirus used as a template to make (+) ssRNA by host machinery

41
Q

(based on the baltimore classification) explain the transcription and replication mechanisms of class 7?

A

Pararetroviruses or dsDNA-RT (partially gapped, not full ds)
gapped DNA is converted into dsDNA by cellular DNA repair mechanism or covalently closed cirucalr DNA (cccDNA)
Transcription: dsDNA is transcribed into mRNA (nucleus)
Replication: uses an ssRNA intermediate as a template for viral reversetranscriptase (encoded) (cytoplasm)

42
Q

What is the overall infectious cycle?

A

1) Attachment or adsorption of virion
2) Entry/penetration
3) Uncoating (for animal viruses)
4) Biosynthesis of new nucleic acids and viral proteins using host machinery
5) Assembly of new viral particles
6) Release of newly formed virions

43
Q

What are the two broad phases of the viral infectious cycle?

A

Early phase:
Attachement & delivery to the genome, early proteins synthesized soon after infection to take control of host cell and for viral genome replication
Late phase:
Synthesis of late proteins (structural proteins)
Assembly and release

44
Q

What are the two possible life cycles for bacteriophages?

A

Lytic cycle (lysis + death of host cell)
Lysogenic cycle (host cell stays alive, incorporation of phage DNA into the host DNA)

45
Q

For both bacteriophages and animal viruses, how does attachment/adsorption work?

A

bacteriophages:
chemical attraction between viral proteins and cell proteisns + sometime fibers
Animal viruses:
either glycoprotein spikes on envelope or some other attachment molecule that mediate attachement to plasma membrane proteins/receptors

46
Q

For both bacteriophages and animal viruses, how does entry/penetration work?

A

Bacteriophages:
-release of protein enzyme lysozyme weakens the bacterial cell well
-phage tail pierces through the cell wall: nucleic acid alone passes through tail into cell
Animal virus:
-direct penentration (creation of pore - just the nucleic acids)
-membrane fusion or,
-endocytosis

47
Q

For both bacteriophages and animal viruses, hwo does unccoating work?

A

Bacteriophages:
does not occur, no capsid
Animal viruses:
*separation of viral nucleic acid from its capsid
-action of the lysosomal enzymes of the host cell
-acidification of the content of the endosome causes disassembly of the capsid

48
Q

For both bacteriophages and animal viruses, how does biosynthesis work?

A

Bacteriophages:
Synthesis of many cophies of phage DNA using host cell machinery, then gene expression
Animal viruses:
Biosynthesis occurs based on Baltimore class

49
Q

For both bacteriophages and animal viruses, how does assembly work?

A

Bacteriophages:
Occurs spontaneously, but we don’t know how
Animal viruses:
Spontenous, DNA in nucleus, RNA in cytoplasm

50
Q

For both bacteriophages and animal viruses, how does release work?

A

Bacteriophages:
Lysis of cell or host cell death
Animal viruses:
Budding (enveloped virus)
Exotycosis or lysis for naked viruses

51
Q

Lytic vs lysogenic life cycle of bacteriophage? Describe + relationship between the two types of life cycles
in bacteriophages

A

Lysogenic: Cell will reproduce normally with phage DNA within its genome
Can be excised, allowing for cell to enter lytic life cycle
Lytic: Assembly into virions that are released post lysis.
Same start point (injection of phage DNA into cell)

52
Q

Name given to cells with dormant animal viruses?

A

Latent viruses or proviruses

53
Q

Three requirements of a successful infection?

A

-Enough virus
-Cell must be both suceptible and permissive
-Local antiviral defense absent or overcome

54
Q

What are the 5 possible patterns of viral infection?

A

-Abortive infection (cannot complete replication cycle)
-Acute infection (short term intense)
-Chronic infection (long lasting continuous production of low levels of virus particules)
-Persistent (long lasting, periodic reactivation and replication
-Latent infection (dormant)

55
Q

What is viral tropism (3 types)?

A

Specificity of a virus for a aprticular cell type
-Cellular (specific to a cell type)
-Tissue (specific to cells within a tissue)
-Host (specific to a host species)

56
Q

What is a localized infection?

A

Virus contained by tissue structure, cell susceptibility and immune system

57
Q

What is a systemic infection?

A

Spread beyond primary site of infection

58
Q

What is viral pathogenesis?

A

Describes the processes by which viral infections cause disease and involve virus-host interactions

59
Q

What are the two components of viral disease?

A

-Effects of viral replication on the host
-Effects if host response on both virus and host

60
Q

What are the three modes of virus transmission?

A

-DIrect transmission from person to person
-Transmission from animal to animal (humans are accidental hosts)
-Transmission from arthropod vectors

61
Q

What is horizontal transmission?

A

Between members of the same species

62
Q

What is vertical transmission?

A

Transfer of infection between parent and offspring

63
Q

What is germ line transmission

A

Agent is transmitted as a part of the genome

64
Q

What is nosocomial transmission?

A

When an individual is infected while in hospital or healthcare facility

65
Q

What are factors contributing to viral disease emergence?

A

-Environmental changes
-Human behvaiour
-Social, political and economic factors
-Travel and commerce
-Health care (transfusion, immunosupressive drugs)
-Microbial adaptation
-Public health measures

66
Q

Why can viruses not grow in standard biological media? What is standard biological media? Where are they culture instead (3)

A

Culture media (broth) or agar plates - they cannot replicate by themselves
In living hosts
-Mature organism
-Fertilized eggs
-Cell cultures

67
Q

What is phage assay technique? What does it tell us?

A

Mix of bacteria and phages with liquid warm nutrient agar
Lysis of bacteria produces plaques (plaques are cuased by virulent phages - lytic cycle, but not lysogenic phages
Allows for an estimation of phage numbers

68
Q

What type of study can only be done using virus cultures in live animals?
Cons of using live animals

A

Study of an immune systems response to viral infection
Animal innoculation can also be used for diagnostic purposes
Expensive, difficult, ethically concerning

69
Q

Pros and cons of use of embryonated eggs

A

-Inexpensive
-Sterile
-Ideal site for virus growth
-Viral growth can be signalled by death of the egg

70
Q

How is a culture grown in embryonated eggs

A

A hole is drilled in shell and viral suspension is injected into the eggs fluid at the site best suited for their replication

71
Q

How do virus cell cultures work?
2 types of cells in a cell culture

A

*preferred growth medium
less expensive or ethically dubious
Isolated cells are grown on a medium or in a broth
Can test antibiotics and be treated with enzymes to separate cells
-Normal cells (reduce to form monolayer)
-Transformed cells (do not grow in a monolayer - cancerous)

72
Q

What is a cell line?
2 types?

A

Group of cells that can be grown indefinitely in a laboratory setting.
-Primary cell lines: derived from tissues or organs, tend to die out after only a few generations or passages due to contact inhibition (growth can only be sustained by a secondary culture)
-Continuous cell lines:transformed cells, can maintaine an indefinite number of generations

73
Q

What is CPE?

A

Cytopathic effect - changes in cell morphology caused by infecting virus
(ex: cell death, swelling, fusion with adjacent cell…)

74
Q

What notion is the plaque assay based on?

A

That a single virus is sufficient to produce a plaque assay
-serial dilutions allow you to determine the stock concentration : this is known as the plaque forming units

75
Q

What is MOI?

A

multiplicity of infection - average number of infectious particles added per cell (ratio of number of virus particles to the number of host cells)

76
Q

What distribution best describes the distribution of virus per cell?

A

Poisson distribution (% of cells infected vs MOI)

77
Q

What is FFA?

A

Focus forming assay
*used as not all viruses lyse cells
Immunostaining technique and variation of a plaque assay
host cells from clusters of infected cells (foci) that can be visualized with fluorescence or stain using antibodies against a viral antigen

78
Q

What is neoplasia?

A

Uncontrolled cell division in a multicellular animal
Mass of neoplastic cells = tumor
*cell division is (generally) under strict genetic control

79
Q

Difference between benign and maligant tumors?

A

Begnin tumors remain in one place and are not generally harmful
Maligant tumors are called cancers and can spread in a process known as metastasis

80
Q

What is the oncogene theory?

A

Describes the induction of cancer in humans
-Presence of proto-oncogenes promote cell growth and division
-Uncontrolled activation of proto-oncogenes (then called oncogenes) leads to the transformation of normal cells into cancerous cells
*environmental factors can contribute to the activation of oncogenes

81
Q

What is the relationship between viruses and cancers?

A

Viruses may cause 20-25% of human cancers
-carry copies of oncogenes as part of their genomes and promote oncogenes already present in the host
- interfere with tumor repression
-oncogenic viruses bevome integrated into the host cells DNA and induce tumors

82
Q

What transformations can occur to cells when they become tumor cells?

A

Irregular shapes
increased cell motility
loss of contact inhibition in cultures

83
Q

What is the name of viruses that can treat cancers? How?

A

-Oncolytic viruses - infection and lysis of cancer cells (genetically modified)
-Oncolytic viral therapy may provide treatment for some cancers (in clinical mice phases)

84
Q

WHat type of virus is SARS-CoV-2?
What do they cause, at what frequency

A

Enveloped (+)ssRNA virus, ACE-2 receptor on cells required for entry
coronaviruses cause mild upper respiratory infections (generally) - 10-30% of common cold cases

85
Q

What is the chain of transmission of SARS-CoV-2?

A

Bats (natural hosts)
Possible intermediate
Zoonotic transmission to humans
Human to human transmission (direct or nosocomial)

86
Q

Basic composition of an RNA vaccine? How do they work

A

mRNA encoding the antigen of choice, encapsulated in a lipid nanoparticule
protein production (peaking 24-48h after injection, lasting for a few days
(simple and quick to synthesize)

87
Q

What type is the influenza virus?

A

(-) ssRNA (segmented) genome in a helical capsid, enveloped

88
Q

What is the plasticity pf the influenza genome? Effect + 2 mechanisms

A

accommodate many mutations and changes
Antigenic drift: minor change due to gene mutation
Antigenic shift: major change due to gene reassortment