1' NAKED VIRUS TRANSLOCATION: particle crosses cell membrane intact cf Principles of Molecular Virol

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1. NAKED VIRUS - TRANSLOCATION particle crosses
cell membrane intact (cf Principles of Molecular
Virolgy, 3rd Edition, Alan J. Cann, Academic
Press p 117) 2. NAKED VIRUS - GENOME INJECTION
virus attaches to cell surface and releases its
genome which penetrates the cytoplasm via a pore
that has been created in the plasma membrane.
(Bacteriophages, which attack bacterial cells,
also inject their genomes and may use molecular
"syringes" to do so, please see our diagram of T4
phages injecting). 3. NAKED VIRUS - ENDOCYTOSIS
virus attaches to cell surface receptor molecules
and sinks into a clathrin coated pit. The pit
invaginates and finally closes off creating a
clathrin coated vesicle (drawn as a cage like
sphere) and so the contained virus particle is
drawn into the cytoplasm. The clathrin molecular
cage soon dissociates into component triskelions
(the propeller like objects) which leave a
vesicle. The resulting uncoated vesicle
transports the contained virion to an endosome.
At some stage thereafter, the viral components
are released. The virus shown in this example is
an Adenovirus
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4. ENVELOPED VIRUS - ENDOCYTOSIS MEMBRANE
FUSION virus enters cell by receptor mediated
endocytosis. The cell membrane merges (fuses)
with the endosome membrane and so the virus
components are released. The virus shown here is
an influenza virus, please see our Influenza
virus life cycle illustration. 5. ENVELOPED VIRUS
- MEMBRANE FUSION virus enters the cell when its
outer membrane fuses with the plasma membrane at
the cell surface. The viral contents are then
spilled into the cytoplasm of the cell. This
example is HIV, which is unusual in having a
conical core (most viral cores tend to be more
spherical). Please see our HIV illustrations.
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Figure 5.8 Cell receptors for Picornaviruses.
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Figure 5.9 ICAM,Pvr and Rhinovirus.
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Figure 5.11 HIV CD4
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Figure 5.12 Picornavirus interactions
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Figure 5.14 Influenza receptor
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Figure 5.15 Mechanisms of uptake of
macromolecules
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Figure5.16 Receptor mediated endocytosis
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Figure 5.18 Uncoating stragegies
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Figure 5.19 Penetration and uncoating at the PM
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Figure 5.20 Flu entry
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Figure 5.27 Polio entry model
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The process begins with interactions between the
trimeric envelope complex--a cluster of proteins
on HIV's outercoat, sometimes referred to as the
gp160 spike--and both CD4 and a chemokine
receptor (either CCR5 or CCR4) on the cell
surface. This complex is made up of three
transmembrane glycoproteins (gp41), which anchor
the cluster to the virus, and three extracellular
glycoproteins (gp120), which contain the binding
domains for both CD4 and the chemokine receptors.
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The first step in fusion involves the
high-affinity attachment of the CD4 binding
domains of gp120 to the N-terminal
membrane-distal domains of CD4. CD4 attachment
inhibitors (e.g., PRO 542) act here
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Once gp120 is bound with the CD4 protein, the
envelope complex undergoes a structural change,
bringing the chemokine binding domains of gp120
into proximity with the chemokine receptor,
allowing for a more stable two-pronged
attachment. Antagonists of CCR5 (e.g., SCH-C) and
CXCR4 act here. If the virus latches on to both
CD4 and the chemokine receptor, additional
conformational changes allow for the N-terminal
fusion peptide of gp141 to enter the CD4 cell
membrane.
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Two heptad repeat sequences--HR1 (blue) and HR2
(orange)--of gp41 interact, resulting in collapse
of the extracellular portion of gp41 to form a
hairpin, which is sometimes referred to as a
coiled-coil bundle. The fusion inhibitors T-20
and T-1249 act here by mimicking HR2, resulting
in a botched formation of the hairpin. In the
absence of an inhibitor, the hairpin structure
brings the virus and cell membrane close
together, allowing fusion of the membranes and
subsequent entry of viral RNA.
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Figure 5.29 HIV uncoating and cyclophilin A
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Figure 5.30 Location of Cyclophilin A and the
HIV capsid
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Figure 5.31 Nuclear localization signals
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Figure 5.32 Nuclear pore complex
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Figure 5.33 Protein Import Pathway
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