Research updates
HIV - a global challenge   page 3
Go back a page
Go forward a page
2. Infection by HIV Link to the Medical Research Council web site
Interactive diagram Interactive diagram
Interactive diagram Interactive diagram
Interactive diagram
Figure 4. Signal to act - the successful detection and destruction of a virus-infected cell depends on the killer T–cell’s (CTLs) receptor being able to recognise a peptide presented to it by the cell’s HLA molecule.
On page 2, we saw that the RNA from the retrovirus is translated into proviral DNA which is integrated into the DNA of the host cell (a CD4 T–cell). It remains dormant until the host cell is replicated or its DNA is translated into proteins.
The display system
Once produced, particular viral proteins will be cleaved by the cell’s enzymes into short peptides and transported into the endoplasmic reticulum. Here, the peptides fit and bind on to a cell protein called HLA. The combined viral peptide and HLA molecule then become inserted in the CD4 T-cell membrane, so exposing the foreign peptide to the cells of the immune system (Figure 4). Effectively, the HIV-infected CD4 T-cell is sacrificing itself to cytotoxic T-cells (CTLs), for the good of the whole organism.
Triggering immune response
The precise binding of the HLA molecule to a viral peptide is vital to stimulate a successful immune response. This process can be undermined by any alteration in the shape of viral peptides. Unfortunately, HIV is a highly variable virus with an enormous potential for mutation. Each time HIV reverse transcriptase makes a DNA copy of the viral RNA genome, it makes at least one error - one mutation.
So, on average, each one of the billion or so virus particles made every day by an HIV-infected individual will contain one mutation. Consequently, the virus may escape from both CTLs and activated (see Figure 5). If this is the case, HIV multiplying rapidly, destroying CD4 T–cells and progression to AIDS follows (see figure 4).
Interactive diagram
Figure 5. A good fit for a killer T-cell (CTL) to recognise a peptide as foreign, the peptide must fit both the HLA molecule and the T-cell receptor exactly. Otherwise either the immune system will not be activated or there will only be a partial response.
Self destruct
Even if the CTLs are successful in eliminating HIV-infected cells, not only is the virus destroyed but so too are the CD4 helper T-cells themselves. We know that CTLs require the help of CD4 T–cells to function. The destruction of the CD4 helper T-cells may be the reason why CTLs eventually fail to control HIV, and AIDS develops.
Go back a page Go to the top of the page Go forward a page