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MICROBIOLOGY Y1 > week 9 - virus entry > Flashcards

week 9 - virus entry Flashcards

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Biology 101 flashcards
1
Q

all viruses are…

A

obligate intracellular parasites

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2
Q

viruses are obligate intracellular parasites:
they must…

A
  • enter host cells to replicate and spread
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3
Q

viruses are obligate intracellular parasites:
virus particles are…

A

too big to diffuse through the plasma membrane

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4
Q

viruses are obligate intracellular parasites:
viruses cannot

A

actively invade a host (like a parasite, e.g. malaria)

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5
Q

viruses are obligate intracellular parasites:
the viral capsid/core which protects in transit must be….

A

removed or broken down for the genome to be released
o Paradox
o Making something really stable that Is easy to disassemble

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6
Q

virus entry is a multistep process

A
  • Binding (receptor engagement)
  • Diffusion and signaling
    o Not stagnant
    o Grab and move
  • Uptake
    o Endosymic vacuole
  • Intracellular transport (dependent on microtubules)
  • Fusion (from endosome or at PM)
  • Uncoating (cytoplasm or nucleus)
    o Disassemble capsid to get the genome
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7
Q

virus receptors come in 2 flavours:

A
  • Binding
    o Mediate attachment (virus stuck on cells)
    o Serve to concentrate virus
  • Entry
    o Activate cellular endocytosis
    once bound two outcomes:
  • Conformational change in virus fusion machinery
  • Bring virus to or recruitment of entry receptors
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8
Q

viruses only adhere to cells that have the right binding receptors (attachment factors)

A
  • Classic binding proteins
    o Glycosaminoglycans (GAGs)
    o Heparin- and Chondroitin- Sulphate
    o Large linear polysaccharides
    o Negatively charged
     These proteins have normal cell functions
  • Often referred to as ‘non specific’ as almost all mammalian viruses use them
  • However many viruses have dedicated GAG-binding proteins
    o Different kinds of Glycosaminoglycans
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9
Q

why dont tomato viruses effect humans

A

the virus doesnt have he right receptors

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10
Q

virus lateral diffusion

A

Bringing virus to and concentrating the virus on the cell surface, move them to entry hotspots and into close contact with entry receptors

Utilise retrograde flow of actin inside to move towards cell body in order to effect (get to the cell surface)

Brings itself close to where other things are being taken in to the cell (by the cell)
- invades

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11
Q

virus entry receptors are essential

A
  • Dictate what cells and hosts are permissive for infection
    o E.g. tomato virus have nothing to bind to in humans therefore don’t infect
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12
Q

virus receptors can be:

A

proteins, lipids or glycans

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13
Q

virus receptors serve as..

A

as bono fide signalling molecules

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14
Q

virus receptors serve to induce..

A

changes in virus fusion machinery or induce endocytic uptake

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15
Q

virus receptors:
1 receptor?

A
  • Some viruses have 1 receptor (Polio)
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16
Q

virus receptors:
multiple receptors

A
  • Viruses usually have multiple receptors (broaden host range/cell type/redundancy)
    o i.e. not all required at once
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17
Q

virus receptors:
multiple receptors activate…

A

multiple cell signalling pathways

18
Q

virus receptors:
virus receptor usage can be…

A

very complicated

e.g. hepatitis C

o very complex virus entry
o huge subset of cellular receptor to get into cells
(see notes for this)

19
Q

VIRUS ENTRY:
2 ways viruses enter cells

A
  1. Direct fusion with the plasma membrane
  2. endocytosis
20
Q

VIRUS ENTRY:
fusion at plasma membrane
example: measles morbillvirus (MeV)

A
  • (-)ssRNA virus (1 step to make mRNA)
  • Enveloped
  • Humans are natural host (no animal reservoir)
    o Has no where to hide so in theory can wipe it out (everyone must be vaccinated)
  • Causative agent of measles
  • Highly contagious respiratory virus (spread by aerosols)
  • Fever, cough, Macropapular rash
  • Can cause blindness, secondary pneumonia
  • Cause 2.6 million deaths annually before 1963 (mostly children)
  • ~140,000 people die/year due to lack of vaccine uptake
    o 95% vaccination rate needed
21
Q

VIRUS ENTRY:
measles virus plasma membrane fusions

A

combines with SLAM
Confirmational change
Can get into cell

22
Q

cells possess many different…

A

endocytic pathways

23
Q

VIRUS ENTRY:
main reasons not to fuse with plasma membrane

A
  • Immune system
  • Viral proteins sitting outside of cells
  • Immune system activated
    Doesn’t make sense to do this
24
Q

VARIOUS TYPES OF ENDOCYTOSIS TAKE UP DIFFERENT THINGS:
phagcytosis

A

(cell-eating) ingestion of large objects (>1um) by cells, such as bacteria and dead cells
Not normally used by viruses
Really glued to the surface

25
Q

VARIOUS TYPES OF ENDOCYTOSIS TAKE UP DIFFERENT THINGS:
Pinocytosis

A

cell drinking) uptake of solutes and small molecules (<100nm)

26
Q

VARIOUS TYPES OF ENDOCYTOSIS TAKE UP DIFFERENT THINGS:
receptor-mediated

A

specific process triggered by ligand/receptor interaction (clathrin mediated endocytosis; <100nm

27
Q

VARIOUS TYPES OF ENDOCYTOSIS TAKE UP DIFFERENT THINGS:
macropinocytosis

A

cell drinking. Fluid phase uptake. Used for uptake of small and large particles (>100nm-10um)
- Can take up very big things

28
Q

VIRUS ENTRY:
plasma membrane

A
  • Many viruses that can fuse at the plasma membrane
    o Prefer to use endocytosis (VACV, HSV, HIV)
29
Q

VIRUS ENTRY:
many endocytic mechanisms are…

A

pre-exisiting, on-going

o Costs the virus nothing to use them

30
Q

VIRUS ENTRY:
endocytic mechanisms allow viruses a…

A

free ride through the cortical cytoskeleton
o Dissolve and pass through

31
Q

VIRUS ENTRY:
endosomes are transported to the…

A

nucleus on microtubules
o Free passage through cell
o No accessory protein required
 Takes virus where it wants to be

  • Endosomes provide ques for the virus to facilitate infection
    o Low pH, proteases
32
Q

VIRUS ENTRY:
immune detection?

A

delayed immune detected

hijacking endocytic pathways Leaves no evidence of virus entry on the cell surface

33
Q

VIRUS ENTRY:
entry by Clathrin mediated endocytosis

A
  • Form of receptor mediated endocytosis
  • Constitutive process (always on-going)
  • Used by multiple receptors (transferrin)
  • Important for receptor recycling, signalling synapse function, immune response
34
Q

VIRUS ENTRY:
Clathrin-mediated endocytosis
adapter proteins recruit…

A

clathrinn
Clathrinin produces a coat around the virus
Builds a uniform circular, vesicular structure

Recycled once virus goes into cell

Not for virus but virus utilises them

Basically virus stealing virus coat

35
Q

VIRUS ENTRY:
what is Clathrin?

A
  • Clathrin is a triskelion molecule
  • Forms a polyhedral lattice around vesicle
  • With 12 coordnating pentagons
  • Limits vesicle size to ~100nm
36
Q

VIRUS ENTRY:
Clathrin mediated endocytosis
Example: Semliki Forrest Virus (SFV

A
  • (+) ssRNA virus (2 steps to make mRNA)
  • Enveloped 70nm, icosahedral capsid T=4
  • Isolated from mosquitos
  • Can infect animals and cause disease
  • Encephalitis in rodents
  • Mild in humans:
    o 1 recorded death (immune-compromised)
  • Virus model system for ssRNA viruses (entry replication)
    o Everyone used it because it was small and simple]
  • Used as a vector for oncolytic therapy
37
Q

VIRUS ENTRY:
how does low pH-mediated fusion with endosomes work?

A

Sticks hydrophobic domains into the host
Folds in on itself
Drags membrane together –> to exclude the water
Once water gone lipids naturally undergo lipid mixing

38
Q

VIRUS ENTRY:
entry by macropinocytosis

A
  • Complex pathway
  • Can be trigger via a vast array of surface molecules
  • Only pathway that allows for entry of large viruses > 100nm in size
    o only two option phagocytosis and macropinocytosus –> phagocytosis destroys cell so opt. for macropincytosis
  • systemic in nature
    o trigger global uptake with localized receptor activation
39
Q

VIRUS ENTRY:
entry by macropinocytosis
Example: Vaccinia virus (Poxvirus)

A
  • dsDNA virus
  • enveloped 370nm x 250nm brick shaped,
  • complex structure (no symmetry implied)
  • unknown origin
  • first mammalian virus seen by EM
  • first virus isolated, purified and analysed
  • lab model poxvirus (96% identical to smallpox)
40
Q

Vaccinia virus (Poxvirus):
served as a…

A

vaccine for the eradication of smallpox
- Varoila virus
- Killed 300,000,000 people between 1914-1977
- Spread by contact, aerosol R0=5-7 30% mortality
- Only eradicated human virus

41
Q
A

MICROBIOLOGY Y1 (28 decks)

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