The initial response of the human body to the HIV virus is the same as that to any other viral infection: the immune system activates its defense mechanisms to attack and destroy the infection. One of the most important of these defenses is the production of antibodies in vast quantities by the B cells of the immune system, under the direction of T cells. These sticky molecules are tailor-made to bind to specific shapes on the surface of invading pathogens, disabling them and marking them for destruction by immune cells, and in the majority of viral diseases, this is successful in clearing the infection from the body.
However in the case of HIV infection, even though antibodies are produced by the immune system, they are ineffective in disabling the virus, which continues to replicate rapidly within the body. HIV infects and destroys the very cells of the immune system that are responsible for directing the attack against it, leading to the eventual collapse of the immune response and the progressive disease known as AIDS.
There are a number of factors that account for this catastrophic failure of our immune defenses in the initial stages of HIV infection, during which the immune system is still intact and able to produce normal quantities of antibodies that nevertheless prove ineffective against the virus.
1. HIV replicates and mutates very rapidly
The main factor underlying the ability of HIV to evade the body’s immune response is its rapid rate of mutation, which results in constant changes to its structure. Antibodies, produced in great quantities by B cells following an encounter between the immune system and a pathogen,work by sticking to very specific shapes on the external surface of the infectious agent. If these shapes are no longer present, then the antibody cannot bind and the pathogen escapes destruction, as is the case with HIV.
The reason why HIV mutates so rapidly is that it makes a lot of errors when copying its genome. Just like in every human cell, each individual HIV virus particle contains a set of genetic instructions for creating more copies of itself, which must be passed down from generation to generation. However, whereas our DNA genomes are faithfully copied during every cell division with such precision that only around 1 mistake in every billion ‘bits’ of genetic data occurs, the HIV genome, made from a closely related molecule called RNA, is copied in a far less accurate manner – in fact, the HIV genome-copying machinery makes as many as 1 mistake in every 2000 ‘bits’: an error rate 500,000 times greater.
As a result, hundreds of new variants of the virus are produced in each generation, many of which are unrecognised by the current antibody repertoire. In addition, the production rate of new viruses is very high – around 10 billion per day in an infected person .What this means is that within a few months, the typical HIV patient will be infected with not just a single strain of HIV but multiple, related strains with different surface characteristics. The immune system, which takes a few days to produce specific antibodies to a novel pathogen, simply cannot respond quickly enough to keep up.
2. Parts of the virus that do not rapidly mutate are hidden from antibodies
Some parts of HIV are highly conserved, which means that they do not undergo such rapid mutation, usually because they are have a critical function and could not be altered without risking the survival of the virus. Such stable elements are much more likely to be recognised by the immune system – but, unfortunately, natural selection has ensured these are the very parts that remain hidden within the structure of the virus, where they are inaccessible to antibodies which can only bind to the components exposed on the surface.
3. Antibodies do not bind efficiently to the surface of HIV
Antibodies are Y-shaped molecules, consisting of a stalk and two arms, each of which has an identical binding site at the tip which attaches to the specific three-dimensional structure that it is shaped to fit. An antibody is most effective when bound by both of its arms, enabling it to remain firmly attached, with its stalk pointing outwards, where it can then be recognised by the immune cells that act to destroy its target. In order to do this, the structural elements that it recognises must be sufficiently numerous and close together for the each arm to be able to attach.
Unfortunately, this is not the case with the HIV virus, which has evolved so that its recognisable surface structures are few and far apart. Because of this, anti-HIV antibodies are usually only able to bind by one of their arms, meaning their attachment to the surface is much weaker, and they are more liable to lose their grip and float away before attracting the attention of immune cells.
4. HIV hides itself within cells
HIV is a retrovirus, which means that is has the ability to convert its RNA genome into a DNA copy, which it is then able to paste into the genome of the host cell, where it remains dormant, being copied along with the rest of the genome every time the cell divides. Even if antibodies were completely effective in ridding the body of circulating viruses, the instructions for making new viruses still remain within infected cells, ready to be reactivated and start a new infection at any time. This latent infection is the main reason why, despite the success of drug therapy in combating the virus by interfering with its life cycle, HIV cannot be completely eradicated from the body.
HIV is among the most formidable of pathogens that currently pose a threat to humankind, precisely because of its ability to persist within the body in spite of the immune system’s counter-attack.
The steady generation of new variants of the virus as a result of rapid mutation, and the survival and propagation of those best able to evade the defences of the host immune system, as well as the drugs that we deploy against them, is a perfect example of evolution and natural selection in action. It is these characteristics, more than any other, that underlie the failure of our in-built antibody defences to eliminate HIV infection and explain why AIDS remains an incurable disease.
