Killing Viruses 101 Flashcards

1
Q

Survival: Non-enveloped vs. Enveloped

A

Non-enveloped viruses (e.g. parvovirus, rotavirus, circovirus) generally highly resistant - can survive in enviro or @ room temp. for periods

Enveloped viruses (e.g. retrovirus, coronaviruses) are fragile - survive only short periods

*Have spikes on lipoprotein - if it breaks, can’t attach to host

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2
Q

What we can attack

A
  1. Integrity of nucleic acid genome
  2. The integrity & bio activity of surface coat proteins (& envelope glycoproteins) involved in functions such as attachment & penetration

*Viral envelope pretty easy to destroy - once destroyed, attachment proteins lost & virus rendered non-infectious (inactivated)

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3
Q

Using Detergents & Surfactants

A

Detergents & Surfactants (& soaps) inactivate 2 ways;
-effect on the lipoprotein envelop
-protein denaturing activity
(Both take time)

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4
Q

Using Alcohols

A
  • Denatures proteins

* either Ethanol or isopropanol used (Best conc. is 70% - water helps the denaturing process)

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5
Q

Using Oxidants (3)

A

Sodium hypochlorite (Bleach)
-Derivatives of hypochlorous acid are strong oxidizing agents
-activity reduces in alkaline pH & w/ organic material
Potassium Peroxymonosulfate
-Principal ingredient in Virkon (disinfect. used in labs, human & vet hospitals)
Chloramines
-They don’t combine w/ organic material as readily as hypochlorites
-can be quite effective anti-viral agents

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6
Q

Using Iodophors

A
  • are organically bound iodine - active against enveloped viruses
  • Low toxicity for humans, but can stain skin, plastics, fabrics & corrosive to metals
  • Rapid activity (further increased by warm, acidic water - tho this is less stable) Needs contact time (10 mins)
  • Organic material inactivates iodophors (esp. if abundant protein present)
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7
Q

Using Alkylating Agents (2)

A
  • Not suitable for skin
  • Glutaraldehyde - v. effective, active at conc of 1-2%. Remains effective in moderate conc. of organic material, chemically stable & moderately corrosive.
  • Formaldehyde: disinfect. active against all viruses (& can be used for soil). Can be used as a gas, but is an irritant & toxic.
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8
Q

Using Heat

A

*Most viruses inactivated by moderate temp in liquid suspension (56-60 deg C)
Reaction varies;
-Circoviruses, parvoviruses and Newcastle disease Virus (NDV) all fairly resistant to heat.

  • Moderate temperatures denatures proteins
  • High Temperatures inactivate nucleic acids
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9
Q

Using Dessication

A

(Drying)

  • Many are quickly inactivate, but are some that can survive
    • i.e. poxviruses (still infectious in dried scabs for long periods)
  • Humidity also affects survival - enveloped generally more sensitive
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10
Q

Using Radiation

A
  • Ionising Radiation (X-rays, gamma radiation): Removes electrons from proteins & nucleic acids [can create dimers, induce breakages, cross-linking - basically inhibiting replication]
    • can also generate reactive oxygen species causing oxidative damage to lipid membranes
  • Larger the genome, the more sensitive the virus
  • Non-Ionising Radiation (UV Radiation): Short wavelength (Type C) more damaging - creates thymine-thymine dimers that inhibit DNA replication & increase risk of mutation.
    • used to sterilise open surfaces - needs to be directly exposed
    • most of sun’s shorter rays absorbed by ozone layer
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11
Q

Overview of the Immune System

A

*Is the defense against infection by micro-organisms;
Divided into 2 arms:
1. Innate immune System
2 Adaptive Immune system

*Micro-organisms have evolved ways to evade or overcome the immune systems of their hosts

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12
Q

Innate Immune System Components

A
  • Are all physical barriers*
  • Skin, scales, hair, horn
  • mucociliary escalator (in lungs), peristalsis (gut movement)
  • stomach acid
  • gastrointestinal proteases (breaks down proteins)
  • bile & other surfactants
  • sweat, sebum, mucus, tears, lysozyme (eye secretions)

Toll Like receptors: recognise pathogen-associated molecular patterns (are molecules on surface of cells to sample external enviro.
-can initiate inflammatory response (redness, swelling, heat)

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13
Q

Innate Immune system Components

A
  • Cells (neutrophils, macrophages, monocytes, dendrtic cells, eosinophils, basophils, natural killer cells, mast cells)
  • Cytokines (interferons, interleukins)
  • Complement
  • Defensins
  • Collectins
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14
Q

Adaptive Immune System (2 cells)

A
  1. T-Lymphocytes: turn into either cytotoxic T-cells or Helper T-Cells
    • Is the cell mediated immune response
  2. B-lymphocytes & plama cells - arise from activated B-cells which have been costimulated by helper T-cell. Each plasma cell dedicated to production & secretion of specific antibody
    • Afterwards, come T- & B- lymphocytes become long-lived memory cells
      - is the humoral immune response
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15
Q

Antiviral Chemotherapy - Can they be Clinically useful?

-Aim of successful antiviral drugs

A

2 major probs. in antiviral chemotherapy:

  1. Viruses depend on host cell - most subs. that inhibit virus replication interfere w/ cellular metabolism
  2. Viral production well advanced when clinical signs present
  • Aim of any successful antiviral drug = target unique events in replication of virus, e.g.:
  • Viral attachment to host cell
  • Block unique virus enzymes (e.g. reverse transcriptase)
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16
Q

Interferons - definition & what they enhance

A
Interferons: Glycoprotein cytokines that can interfere w/ viral infections by causing cells to become more resistant to viruses via several mechanisms (i.e. upregulation of p53 and class 1 & 2 MHC expression)
   -also enhance antiviral immune response by directly stimulating the activity of macrophages & natural killer cells

-They work instantly

17
Q

3 Types of Interferons

A
  1. Type 1: alpha, beta, epsilon interferons
  2. Type 2: Gamma interferons
  3. Type 3: Lambda Interferons
    - Distinguishable by seq., stimulus & cell type of productions
    - are mostly specific for animal cell type in which they are induced.
18
Q

3 Principal Biological Effects of Interferons

A
  1. Antiviral: Earliest apprearing of known host defenses; operates from few hours before to approx. 3 wks post infection
    • most effective before effective immune response dev.
    • Interferon secreted depresses virus replication in other cells that are subsequently infected
  2. Inhibition of Cell Growth (Anti-cellular): Inhibit proliferation of both norm. and malignant cells
  3. Immunoregulatory: Have complex effect on immune function. IFNs known to activate specific genes (called IFN-stimulated genes) - are responsible for definitive antiviral effects.
    • laymen’s: regulate T or B cells
19
Q

Anti-HIV Drugs;

  • NRTIs
  • NNRTIs
A

Nucleoside/Nucleotide reverse transcriptase inhibitors (NRTIs):
-analogues of native nucleotides - most lacking 3’ - OH group on ribose ring (stops nucleotides elongating DNA strands)
-All inhibit activity of normal cellular DNA polymerases to much lesser extent than reverse transcriptase
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs):
-Bind to reverse transcriptase in pocket distant from active site
-HIV-1 specific (Don’t work against HIV-2)

20
Q

Anti-HIV Drugs:

  • HAART
  • DRACO
A

Highly Active Anti-retroviral therapy (HAART):
-combo theropy of >1 anti-retroviral drug
-combos are subject to positive & negative synergies
-clinically implemented combos usu. comprise of 2 nucleoside analogues & 1 NNRTI or a protease inhibitor
Double-Stranded RNA Activated Capase Oligomerizer (DRACO):
-Is an experimental broad spectrum drug - dsRNA produced in virally infected cells are longer than dsRNA in uninfected cells
-Multiple DRACOs binding to samd dsRNA = apoptosis signalling = cell death
-Txd domain allows DRACO to enter cell cytoplasm

21
Q

Protease Inhibitors (PI) and Inhibitors of HIV entry

A

Protease Inhibitors:
-HIV relies on aspartyl protease to cleave Gag & Gag-Pol polyproteins into essential structures
-inhibition may be effective treatment - side effects can be problematic
Inhibitors of HIV entry
-Target conformational rearrangement of gp41 & fp120 - ccr5 interaction
-Need 2 injections daily & has adverse effects = limited clinical use
-Maravivoc first approved CCR5 treatment but has seen limited clinical use

22
Q

Using Acids & Bases

A
  • High & low pH solutions commonly used for disinfectant
  • Viruses vary in susceptibility
  • Can cause protein denaturation & therefore the inactivation of enzymes