Viruses and Virology (15-22) Flashcards

1
Q

What is a virus?

A

The smallest infectious agents
consisting of:
→ a genetic element (nucleus acid, DNA or RNA)
→ surrounded by a protein coat (caspid)

→ cannot replicated independently
→ don’t divide by binary fission

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2
Q

What does viral replication consist of?

A

→ assembly of pre-formed components into many new viral particles
→ viral components produced (eclipse phase)
→ components assemble to final viral particle

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3
Q

Why do we study viruses?

A

Technology → used in vaccination, used to deliver specific genes, CRISPR
Drugs → understanding life cycle helps development of antiviral drugs (how to target viruses without effecting our cells)
Protection → helps protect general population
Agriculturel importance

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4
Q

What reasons do you suggest for the delay in discovering viruses?

A

Very small → too small to see under a light microscope

→ developments made when electron microscope discovered

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5
Q

What are the main differences between bacteria and viruses?

A

Viruses
→ only invade living cells
→ replicate by inserting genome into host

Bacteria
→ single celled organism
→ can invade living and non-living things (soil, water)
→ divide by binary fission

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6
Q

What are bacteriophages?

A

Viruses that infect bacteria cells
→ structure: capsized head, neck, tail, tail fibres

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7
Q

How do viruses recognise host cells?

A

Specific interactions between viral attachment proteins and host cells

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8
Q

What is a virion?

A

A complete viral particle
containing:
nucleocaspid -
→ caspid (protein coating)
→ DNA or RNA

+ viral envelope

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9
Q

What is encoded for in a viral genome?

A

Structural proteins → cashed proteions, viral attachment proteins

Non-structural proteins → (viral replication) DNA/RNA polymerase, pathogenesis, transformation, modulation of host defences

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10
Q

What is not coded for in a viral genome?

A

→ the complete protein synthesis machinery
→ proteins involved in cell wall production or membrane biosynthesis
→ no centromeres or telomeres

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11
Q

What is the caspid?

A

The protein shell that surrounds a viral genome
→ composed of a number of protein molecules arranged in a precise repetitive pattern
→ made up of capsomeres - subunit of the capsid (smallest morphological unit visible on electron microscope)
→ protects from environmental conditions

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12
Q

How is metastability of viral particles achieved?

A

Stable structure:
→ symmetrical arrangement of many identical viral proteins subunits - provides maximal contact
→ each subunit has identical bonding contacts with its neighbours - repeated interaction provides symmetric arrangement

Unstable structure:
→ contact not covalent
→ can be dissociated or taken apart once the virus attaches to the host cell to release the genome

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13
Q

What are the 3 types of cashed arrangement?

A

Helical → e.g. TMV
Icosahedral → e.g. poliovirus
Complex → e.g. bacteriophage

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14
Q

Why are icosahedron caspids stable?

A

Permins the greatest number of cashmeres to be packed in a regular stable structure
→ easiest way of making a stable structure form the smallest number proteins (60 identical subunits)
→ no need for covalent bonds

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15
Q

What is a viral envelope?

A

A bilayer phospholipid membrane derived mainly from the host cell
→ viral genome does not encode
→ acquired by budding of the nucleocapsid through a cell membrane

→ enveloped viruses: influenza, coronaviruses

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16
Q

Are enveloped or non-enveloped viruses considered more stable?

A

Non-enveloped are more stable, only required their cashed to infect host cells
→ lack a lipid bilayer so are more resistant to stress

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17
Q

What are the disadvantages of classifying viruses based on diseases?

A

Not all viruses cause disease - many missed or ignored
→ a single viruses can cause more than one disease
→ viruses can infect more than one host

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18
Q

What is the main criteria for classifying viruses based on morphology?

A

Nucleus acid → DNA or RNA, ss or ds (polarity), linear, circular, single
Caspid symmetry → icosahedral, helical, complex
Presence of lipid envelope

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19
Q

What are the characteristics for the International Committee on Taxonomy of Viruses (ICTV)?

A

Host range → eukaryote, prokaryote, plant, animal
Morphological features
Nature of nucleic acid
Additional features → length of tail, specific genes
Phylogenetic trees

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20
Q

Wha are the seven major categories of virus proposed by Baltimore classification?

A

I → dsDNA (+&-)
II → ssDNA +ve
III → dsRNA (+&-)
IV → ssRNA +ve
V → ssRNA -ve
VI → ssDNA -ve
VII → incomplete dsDNA

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21
Q

What are viroids?

A

Single stranded circular RNA molecule
→ infectious pathogens to plants
→ unlike viruses, have no protein competent - no caspid
→ smallest self-replicating pathogen
→ appear as rod-shaped or dumb-bell-shaped

e.g. potato spindle tuber viroid (PSTVd) pathogen of potatoes

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22
Q

What must viruses do in order to replicate?

A
  1. get into the cell
  2. make more virus (produce viral proteins)
  3. get out of the cell (to infect others)
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23
Q

What are the steps of viral replication?

A
  1. attachment to target cell
  2. penetration into cell
  3. uncoating (removal of caspid)
  4. biosynthesis
  5. assembly (complete viral particle)
  6. release
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24
Q

How can viruses recognise cellular receptors on the host cell?

A

Through their VAPs - viral attachment proteins
→ interaction between VAPs and host cellular receptors is very specific and determines the host cell and species range

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25
Q

What is viral tropism?

A

The specificity of a virus to a specific host

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26
Q

How do enveloped viruses enter a host cell?

A

Fusion with plasma membrane (e.g. Herpes, HIV)
Via endosomes at low pH (e.g. influenza) - destabilises membrane

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27
Q

How do non-enveloped viruses enter a host cell?

A

Endocytosis
Entry directly across plasma membrane (e.g/ poliovirus)

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28
Q

What is uncoating?

A

Removal of the protein caspid
→ digestion of caspid by cellar enzymes releases viral genome

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29
Q

Where is viral nucleic acid delivered to?

A

DNA → into the nucleus (except poxvirus)
RNA → into the cytoplasm (except HIV, influenza)

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30
Q

What happens during biosynthesis of viral life cycle?

A

Protein and NA synthesis → mRNA is translated into proteins, nucleic acid is replicated
→ NA + proteins packaged into viral caspid

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31
Q

How do dsDNA viruses produce their mRNA?

A

Transcription with host RNA polymerase

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32
Q

What is required for replication of RNA viruses?

A

RNA-dependant RNA polymerase (RdRp) replicase
→ cells have to RdRp
→ RNA virus genome has to encode it

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33
Q

What is the difference between in vivo and in vitro culture systems?

A

In vivo → grows virus in host
e.g. animal, plant, bacteria, chicken eggs

In vitro → grows virus in isolated tissues/cells obtained from host - cell culture

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34
Q

How can viruses be cultivated in chicken eggs?

A

Different compartments can culture different viruses
Chorioallontoic membrane inoculation → herpes, poxvirus
Amniotic inoculation → influenza, mumps
Yolk sac inoculation → herpes
Allantoic inoculation → influenza, mumps, again adenovirus

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35
Q

How are viruses cultivated in cell cultures?

A
  1. individual cells isolated from tissue
  2. suspended in liquid culture medium in a petri dish
  3. cells stop dividing due to contact inhibition
  4. cells transferred to new medium - secondary cell culture
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36
Q

How are continuous cell cultures obtained?

A

Usually originate from naturally occurring tumours
→ heteroploid cells that will divide for ever
→ can be passaged or sub-cultured many time
→ have lost their contact inhibition

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37
Q

What is the HeLa cell line?

A

HeLa cells were the first continuous tissue-culture cell line
→ from Henrietta Lacks (31) diagnosed with cervical carcinoma
→ used to establish tissue culture important for research
→ discoveries related to polio, cancer and AIDS

38
Q

What are cyto pathic effects of viral infections?

A

Distinct observable cell abnormalities/changes in the cells due to viral infections
e.g. shrinking → poliovirus

39
Q

What is hemadsorption?

A

Cells infected with certain viruses acquire the ability to bind to and absorb red blood cells
→ some viruses produce no cytopathic effects so hemadsorption can be used to detect e.g. influenza, measles, mumps

40
Q

What is the purpose of virus titration?

A

Research for studying viruses and their effects
Therapeutic → effective at reducing viral load

41
Q

How can the number of viral particles be measured?

A

Electron micropscy
→ cons: time consuming, expensive, requires skilled personnel

42
Q

How can the amount of viral proteins be measures?

A

Enzyme-linked immunosorbent assay (ELIZA)
Immunofluorescence (IMF)

43
Q

How can the number of viral nucleic acids copies be measures?

A

PCR
→ determine how many viral nucleic acid copies in a sample

44
Q

How can cytopathic viruses be quantified?

A

Plaque assay
→ virus added to monolayer of cultured cells
→ agar added onto to prevent dilution
1 plaque = 1 plaque forming unit
→ serial dilution of sample

45
Q

What is pathogenicity assay?

A

Used to determine the infectious titre

46
Q

What is a haemagglutination assay?

A

Some viruses can bind to red blood cells (haemagglutinin)
→ they cross link the erythrocytes

→ serial dilution of sample + fixed number of red blood cells, wait 45 mins
→ titre - the highest dilution producing visible haemagglutination
simple, quick, economical

47
Q

What are the phases of bacterial cell growth curve?

A
  1. lag phase → no increase
  2. log phase → exponential
  3. stationary phase → plateau
  4. death phase → decrease
48
Q

What are the phases of viral growth curve?

A
  1. inoculation → decline as virus binds to cells
  2. eclipse → virions penetrate cells
  3. burst → host cells release many viral particles
  4. burst size → (stationary) number of visions released per bacterium
49
Q

What is a susceptible cell?

A

A cell that expressed the specific receptors that are recognised by a specific virus through its VAPs
→ virus can bind + enter

50
Q

What is a permissive cell?

A

A cell that contains the proteins and molecules within it necessary for viral replication to occur
→ cells must be susceptible and permissive for viral infection

51
Q

What are the common portals on entry for viruses?

A

Conjunctiva
GI tract
Respiratory tract
Skin
Congenital infection
Genital tract

52
Q

How do viruses enter through the respiratory tract?

A

Middle-sized droplets are inhaled and transmit infection rapidly via Respiratory tract
→ viruses contained in larger droplets are deposited in the upper Respiratory tract
→ smaller aerosolised particles or liquids are able to travel into the lower Respiratory tract

53
Q

What conditions of the GI tract prevents infection?

A

Stomach acidity
Low pH
Digestive enzymes
Bile in intestines
→ inactivate most viruses

54
Q

What are the local barrier of the genital tract?

A

e.g. mucus and low pH of the vagina

55
Q

How can viruses enter through the skin?

A

Trauma or inoculation
Medical procedures → sharing needles
Insects or animals bites (rabies, yellow fever)

56
Q

What are the 3 types of vertical viral transmission?

A

In utero → during pregnancy (e.g. rubella, CMV)
Perinatal → during birth (e.g. neonatal HSV)
Postnatal → after birth (e.g. HIV)

57
Q

What is viermia?

A

The presence of virus in the blood e.g. HIV, hepatitis
→ transmitted through blood

58
Q

What is uraemia?

A

The presence of virus within the urine e.g. Hantavirus
→ transmitted to people through aerosolise or virions

59
Q

What are localised infections?

A

Replicate at the initial site of infection

60
Q

What is pathogenesis?

A

The ability/capacity of the virus to cause disease
→ measured quantitatively by virulence

61
Q

How can virulence be quantified?

A

Virus titre
Mean time to death
Mean time to appearance of disease
Measurement of fever, weight loss
Measurement of pathological lesions (poliovirus)
Reduction if CD4 T cell (HIV)
Case:fatality ratio / hospitalisation rate

62
Q

What are the mechanisms of viral injury and disease?

A

Direct cytotoxicity of the virus
Virus-induced immunopathogensis
Virus-induced immune suppression
Virus-induced transformation

63
Q

What is direct virus killing?

A

Damage to he host
→ may be a consequence of virus replication
e.g. poliovirus kills neurones
Ebola virus damages vascular endothelial cells causing haemorrhage

64
Q

What is virus-induced immunopathogenesis?

A

Tissue injury may reflect host defence mechanisms that include apoptosis or immune responses that target virus-infected cells

65
Q

What is virus-induced immune suppression?

A

Some viruses can specifically target and infect cells on the immune system causing immunodeficiency
→ HIV most prominent infection, causes AIDS

66
Q

What can virus-induced transformation cause?

A

Cancer → indirect effects from viral infection like immune suppression + HIV infection
Chronic inflammation → associated with HBV or HCV infection
Viral infection directly promotes tumour development

67
Q

What is HIV?

A

Human Immunodeficiency Virus
→ retrovirus
→ enveloped
→ two surface glycoproteins: gp120, gp41

68
Q

How does HIV replicate?

A

Recognised by interaction between VAP gp120 and host CD4 + entry
→ RNA genome released from caspid
→ synthesis of proteins + assembly

69
Q

What are the 3 stages of the pathogenesis of HIV?

A
  1. acute phase
  2. chronic phase
  3. AIDS phase
70
Q

What is the acute stage of HIV?

A

Characterised by infection of activated CD4+ T cells in mucosal lymphoid tissues and death of many infected cells

71
Q

What is the chronic stage of HIV?

A

Virus spreads throughout the body to helper T cells, macrophages, dendritic cells
→ may last for many years
→ virus contained without lymphoid tissues
→ patients are asymptomatic or suffer minor infections

72
Q

What is the AIDS stage of HIV?

A

Lymph nodes and the spleen are sites of continuous HIV replication
→ cell destruction and the number of blood CD4+ T cells declines
→ eventually continuous cycle of virus infection and T cell death and new infection meds to loss od CD4+ T cells

73
Q

What are the cytopathic effects of HIV?

A

Production of viral proteins including gb41 and gp120 in the plasma membrane increase plasma membrane permeability
→ influx of lethal amounts of calcium, induces apoptosis
→ osmotic lysis of the cell caused by influx of water
→ viral production can interfere with cellular protein synthesis leading to cell death

74
Q

What are some viral virulence genes?

A

Gene/s that:
→ affect viral replication
→ encode toxins
→ encode modulators of the immune system
→ enable virus to spread in the host

75
Q

What is the concept of vaccination underpinned by?

A

Infection often leads to life-long immunity
The virulence of different strains of a pathogen may vary → infection with a low-virulence strain (causing mild or no disease) may lead to resistance to a high-virulence strain which would cause severe disease

76
Q

What is the smallpox vaccine?

A

Late 18th century by Edward Jenner
→ milkmaid cowpox - immune to smallpox
→ deliberately inoculated 8yo boy with cowpox-infected material

77
Q

What is a vaccine?

A

A biological product that can be used to safely induce an immune response that confers protection against infection and/or disease on subsequent exposure to a pathogen

78
Q

What is a live attenuated vaccine?

A

Contains the whole virus that has been weakened or attenuated - replicating but doesn’t cause disease
→ produces an immune response similar to that seen during natural infection

e.g. MMR, rotavirus, oral polio, infuenza

features: tend to create a strong lasting immune response, may not be suitable for immunocompromised individuals

79
Q

What is a killed/inactivated vaccine?

A

Contain whole virus which has been killed or have been altered so that they cannot replicate

e.g. inactivated polio vaccine or IPV, inactivated flu, Hep A, rabies

features: don’t create a string and lasting immune response, may be suitable for immunocompromised individuals

80
Q

What is a subunit vaccine?

A

Do not contain the whole virus at all
→ they contain one or more specific component/unit/antigens usually from the surface of the virus

e.g. Hep B, human papilloma virus

features: don’t create a strong and lasting immune response, may be suitable for immunocompromised individuals

81
Q

What is a nucleus acid/genetic vaccine?

A

Do not provide the viral protein/antigen. Instead they provide the genetic instructions/genes that encode for that specific viral antigen to host cells
→ these genes are the expressed by the host cells to produce the viral antigen, which stimulated an immune response

e.g. RNA: Pfizer, moderna / DNA

features: quick and easy to develop, provide significant promise for the development of vaccines in the future

82
Q

Why are vaccination programmes required?

A

In order to control a disease
→ must be effective vaccine + program must be effective

UK doctors paid bonus if they have high vaccination

effective vaccination programmes must be: cheap, safe and acceptable

83
Q

What are antiviral drugs?

A

Antivirals can stop infection once it has started
→ vaccines can prevent viral disease - they have limited or no therapeutic effect if someone is already infected
→ about 100 antiviral drugs are available - against HIV, HCV, Herpes

84
Q

What do antiviral drugs target?

A

Most target enzymes
→ polymerases, protease, integrase, NS5A, other virus, host

75% target virus, 25% target host

85
Q

Why do we have a limited number of antiviral drugs?

A

Many compounds that interfere with virus growth cause effects in the host
→ side effects common (unacceptable)
→ every step in viral replication cycle engage host functions

Some medically important viruses can’t be propagated, have no animal models or are dangerous
→ HPV, HBV, smallpox, Ebola virus, lassa virus

Must be potent-completely inhibit viral replication

Many acute viral infections are short-lived

86
Q

What are antiviral-binding inhibitors?

A

Maraviroc - anti-HIV
→ mode of action: blocks the chemokine receptor CCR5 - blocks binding

87
Q

What are antiviral-entry inhibitors?

A

Amantadine & rimantadine - anti-influenza
→ mode of action: inhibits entry and NA release - blockage of the M2 ion channel

88
Q

Why did hydroxychloroquine failed for SARS Cov-2?

A

Licensed drug (for Malaria)
→ known to inhibit replication of multiple viruses by inhibiting acidification of endomsomal acidification
→ found to inhibit SARS Cov-2 replication in cell culture
→ given emergency approval by FDA - but then failed

doesn’t inhibit SARS Cov-2 - doesn’t enter through pH dependant

89
Q

What are inhibitors of viral polymerases?

A

Oral and genenital herpes-HSV-1/2

90
Q

What are neuraminidase inhibitors influenza?

A

Neuraminidase - allows new viruses produced to escape
→ inhibits release of viruses prevents infecting other cells

Neuraminidase (NA) Tamiflu