00:01
So let’s now focus on the HIV virus and
the Acquired Immune Deficiency Syndrome.
00:09
HIV is a retrovirus and it can infect CD4+
T-cells, macrophages and dendritic cells.
00:24
The HIV binds to CD4 and also
to a chemokine receptor.
00:31
We often use the term co-receptor for the
chemokine receptor, it needs to bind to both.
00:37
Here we can see on the surface of a helper T-cell, the
CD4 molecule and also the chemokine receptor, CXCR4.
00:47
And the HIV virus is binding
to both of those receptors.
00:53
The same applies to macrophages
that can become infected with HIV,
but here the chemokine receptor that is utilized is different.
01:01
Instead of using CXCR4, the chemokine receptor CCR5
is employed as the co-receptor in addition to CD4.
01:18
So in HIV infection, there
is depletion of CD4+ T-cells.
01:26
And this is due to a direct cytopathic effect
of the virus, due to HIV gp120-mediated
cytotoxicity, due to activation-induced
apoptotic cell death of the infected cells,
and also due to CD8+ T-cell killing of
infected CD4+ cells due to recognition of
peptide MHC Class I, with the peptides being
derived from proteins in the HIV virus.
02:00
Here we have the HIV virus bound
to the surface of a T-lymphocyte.
02:07
You really just need to focus on a couple of points
on this slide, and they are illustrated here.
02:15
The gp120 molecule on the surface of a virus; remember,
when you come across these kind of designations such as gp120,
it means that it’s a glycoprotein, that’s what the gp
stands for, and it has molecular weight of 120,000 Daltons.
02:31
That’s why it’s called gp120.
02:33
And gp120 is essential for the virus to bind to
the surface of the cell that it’s going to infect.
02:40
And as we’ve already heard, the molecule
CD4 plus a chemokine receptor are essential
because the gp120 needs to bind to both of
these receptors in order to infect the cell.
02:55
Virion binding to CD4 and the chemokine
receptor will lead to infection of the cell.
03:03
There is fusion of the HIV membrane
with the cell membrane, and entry of
the viral genome into the cytoplasm
of the cell that is being infected.
03:17
The enzyme reverse transcriptase
mediates synthesis of proviral DNA.
03:24
Remember the HIV virus is a retrovirus,
which is an RNA virus, so it
needs to turn its RNA into DNA in
order to replicate in the host cell.
03:35
There is integration of provirus into the cell
genome, followed by cytokine activation of the
cell, with transcription of HIV genome, transport
of spliced and unspliced RNAs to the cytoplasm.
03:52
Followed by synthesis of the HIV proteins
and assembly of virion core structure.
03:58
Expression of gp120 and gp41 on the cell surface
occurs, with budding of the mature virion.
04:07
The acute phase of HIV infection involves death
of memory CD4+ T-cells in mucosal tissues.
04:18
There is then dissemination of virus to lymph
nodes, and the virus then becomes latent.
04:25
And during latency, there is low level
replication of the virus in lymphoid tissues.
04:31
There is a slow progressive
T-cell depletion over time.
04:36
And in the chronic phase, the ongoing
activation of T-cells results in
extensive death of CD4+ T-cells,
resulting in profound immunodeficiency.
04:51
So here we can see the infection of mucosal tissues, the
death of mucosal memory CD4 T-cells occurs, the virus
is transported to the lymph nodes, and infection is
established in lymphoid tissues such as the lymph nodes.
05:12
There is a spread of infection
throughout the body with viremia.
05:16
There is a partial control of replication,
as the immune response kicks in.
05:24
A stage of clinical latency is established
with chronic infection, the virus
is concentrated in lymphoid tissues, there
is a low level of virus production.
05:36
But following other events such
as other microbial infections, the
production of cytokines and so forth,
virus replication becomes increased.
05:47
And ultimately there is destruction of lymphoid tissue, and
crucially a depletion of those all important CD4+ helper T-cells.
05:57
And once they are depleted below a certain level,
the patient will go on and develop full blown AIDS.