Voortgezette Celbiologie Evelien Floor
Immune evasion by
Herpesviruses
Virology
A virus is a small infectious agent
that replicates only inside the living
cells of other organisms. A virus
consists of the genetic material
made from either DNA or RNA, a
protein coat, called the capsid,
which surrounds and protects the
genetic material; and in some cases
an envelope of lipids that surrounds
the protein coat.
There are a lot of different kinds of viruses; but herpesviruses have a very long history in their host
and they are adapted to their host.
There are nine different human herpesviruses:
1. Varicella zoster virus
2. Herpes simplex virus 1
Causes cold sores, they persist in neural ganglia and cause latent infection
3. Herpes simplex virus 2
Causes genital herpes, they persist in neural ganglia and cause latent infection
4. Human cytomegalovirus
Defects the unborn child, in adult’s infection will not lead to symptoms
5. Human herpesvirus 6A/B
Hardly cause disease
6. Human herpesvirus 7
1
, Voortgezette Celbiologie Evelien Floor
Hardly causes disease
7. Epstein-Barr virus
8. Human herpesvirus 8
Infection occurs when the immune system
doesn’t work properly, it leads to skin
tumors
the herpes simplex virus infects the skin via the neurons in
the face, it will remain in the neurons and will come back
whit a weakened immune system.
Inhibition of TAP
Viral proteins in the cell are degraded by the proteasome
and via the TAP protein the peptides are inserted into the ER. The peptides are presented at the cell
surface with the use of MHC class I. Cytotoxic T cells can recognize those presented peptides. Soon
after infection with a herpesvirus there is downregulation of MHC class I. This is mostly because of
the inhibition of TAP.
There is a method to measure if the
TAP protein is still functioning: first
the cell is permeabilized and the
peptide is fluorescently labeled.
Then ATP is added because it is
required for the function of TAP.
When peptides move to the ER via
TAP they will eventually be
glycosylated. If they are
glycosylated they can be trapped
with sepharose beads. After
trapping you can measure the
fluorescent signal.
TAP contains of a transmembrane
domain and a cytosolic domain.
First, the peptide binds to the
transmembrane domain and it will
close. When ATP binds to the
cytosolic domain TAP will open and
the peptide will be released to the
ER lumen.
Different types of herpesviruses all
encode for a similar kind of TAP-
inhibitor. They appear to be
acquired independently and
recently during evolution which is
proof for functional convergent
evolution. Convergent evolution is
the independent evolution of similar features in species of different lineages. They all acquired the
possibility to prevent peptide presentation by inhibition of TAP in a different way.
2
Immune evasion by
Herpesviruses
Virology
A virus is a small infectious agent
that replicates only inside the living
cells of other organisms. A virus
consists of the genetic material
made from either DNA or RNA, a
protein coat, called the capsid,
which surrounds and protects the
genetic material; and in some cases
an envelope of lipids that surrounds
the protein coat.
There are a lot of different kinds of viruses; but herpesviruses have a very long history in their host
and they are adapted to their host.
There are nine different human herpesviruses:
1. Varicella zoster virus
2. Herpes simplex virus 1
Causes cold sores, they persist in neural ganglia and cause latent infection
3. Herpes simplex virus 2
Causes genital herpes, they persist in neural ganglia and cause latent infection
4. Human cytomegalovirus
Defects the unborn child, in adult’s infection will not lead to symptoms
5. Human herpesvirus 6A/B
Hardly cause disease
6. Human herpesvirus 7
1
, Voortgezette Celbiologie Evelien Floor
Hardly causes disease
7. Epstein-Barr virus
8. Human herpesvirus 8
Infection occurs when the immune system
doesn’t work properly, it leads to skin
tumors
the herpes simplex virus infects the skin via the neurons in
the face, it will remain in the neurons and will come back
whit a weakened immune system.
Inhibition of TAP
Viral proteins in the cell are degraded by the proteasome
and via the TAP protein the peptides are inserted into the ER. The peptides are presented at the cell
surface with the use of MHC class I. Cytotoxic T cells can recognize those presented peptides. Soon
after infection with a herpesvirus there is downregulation of MHC class I. This is mostly because of
the inhibition of TAP.
There is a method to measure if the
TAP protein is still functioning: first
the cell is permeabilized and the
peptide is fluorescently labeled.
Then ATP is added because it is
required for the function of TAP.
When peptides move to the ER via
TAP they will eventually be
glycosylated. If they are
glycosylated they can be trapped
with sepharose beads. After
trapping you can measure the
fluorescent signal.
TAP contains of a transmembrane
domain and a cytosolic domain.
First, the peptide binds to the
transmembrane domain and it will
close. When ATP binds to the
cytosolic domain TAP will open and
the peptide will be released to the
ER lumen.
Different types of herpesviruses all
encode for a similar kind of TAP-
inhibitor. They appear to be
acquired independently and
recently during evolution which is
proof for functional convergent
evolution. Convergent evolution is
the independent evolution of similar features in species of different lineages. They all acquired the
possibility to prevent peptide presentation by inhibition of TAP in a different way.
2
