Structural similarities between Ig and TCR.

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Structural similarities between Ig and TCR.
charged aas which interact with CD3
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Affinity constants and Roles of Co-receptors in
TCR binding.
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Viruses
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• The Structure Complexity of Virus Genomes
• more varied than any of those seen in the entire
  bacterial, plant or animal kingdoms
• may be single-stranded or double-stranded,
  linear, circular or segmented
• Single-stranded virus genomes may be
• positive ()sense, i.e. of the same polarity
  (nucleotide sequence) as mRNA
• negative (-)sense
• ambisense - a mixture of the two.
• Virus genomes range in size from approximately
  3,200 nucleotides (nt) (e.g. Hepadnaviruses) to
  approximately 800 kilobase pairs (kbp,
  Mimivirus)

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• Virus genomes may contain in either DNA or RNA.
• Viruses are obligate intracellular parasites
• genome must contain information which can be
  recognized decoded its host cell
• The viral genetic code must match or at least be
  recognized by the host organism.
• Control signals which direct the expression of
  virus genes must be appropriate to the host.

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Types of Viral Genomes

• RNA viruses

ds
sense ss
- sense ss
retroviruses

• DNA viruses

ds
Gapped circle
ss
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HIV buds out of cells.
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Figure 5.11 HIV CD4
CD4 yellow contacts with HIV
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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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Uncoating
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Figure 5.29 HIV uncoating and cyclophilin A
A chaperone destabilizes capsid
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Figure 5.30 Location of Cyclophilin A and the
HIV capsid
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Negative-Strand RNA Viruses Viruses with
negative-sense RNA genomes are a little more
diverse than positive-stranded viruses. Possibly
because of the difficulties of expression, they
tend to have larger genomes encoding more genetic
information. Because of this, segmentation is a
common though not universal feature of such
viruses.
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Negative-sense RNA genomes are not infectious as
purified RNA. Virus particles all contain a
virus-specific polymerase. The first event when
the virus genome enters the cell is that the
(-)sense genome is copied by the polymerase,
forming either ()sense transcripts which are
used directly as mRNA, or a double-stranded
molecule known either as the replicative
intermediate (RI) or replicative form (RF), which
serves as a template for further rounds of mRNA
synthesis.
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Figure 5.10
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Figure 5.14 Influenza receptor--sialic
acid Different strains prefer different oligos
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Viral Uptake
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Figure 5.20 Flu entry
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Fig. A-8 Orthomyxoviruses (like Flu)
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Figure A-9 Flu Life Cycle
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Figure 5-21 HA changes
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Figure 5-22
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Figure 5-24
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Figure 6.9 Flu RNA replication
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Figure 6.11 Activation of Flu RdRp
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Figure 6.18