CYTOMEGALOVIRUS

The cytomegalovirus has been known to science since the early years of the 20th century and has certainly coexisted with man for thousands of years previously. In so doing, it has developed some fascinating strategies to avoid attack within the human body, strategies which make it particularly difficult to combat.

In comparison to the human body which is a highly complex assemblage of individual cells - with very specialist functions -, a virus is a relatively simple organism. It consists of the genetic material (the DNA) wrapped in a protein outer coating and that's it. In order to reproduce itself, it needs to take over a cell within a living body. Once in the cell, the virus DNA replicates and the cell, when it divides, produces not two host cells but many thousands of virus particles, ccffplete with protein coating, which then go off to infect neighbouring host cells.

Humans, like all other complex animals, have defence mechanisms which keep virus attack under control - the immune system. When a virus enters the body, the protein coating is recognised as foreign and the body produces antibodies which lock onto the outer protein and render the virus harmless. Once attacked in this way the normal body cleaning mechanisms eventually throw out the intruder.

Vaccines utilise this mechanism to artificially stimulate the immune system to prevent disease.

The first technique which was used is often called the live vaccine method. This takes whole virus, grows it in the laboratory until a strain is found which stimulates the body's defences while not producing the illness. The altered virus is then used as a vaccine. Small pox was eradicated using a live attenuated virus.

One major problem-with!live vaccines is the danger that, once put back into the body, the attenuated,virus may mutate.back to a dangerous form and thereby give the person the illness. For this reason, live vaccines can only be licenced for use after extremely careful testing.

In the case of CMV, it.has such a long history of living and surviving within the human body that researchers have grave doubts about the safety of any live vaccine.

A second approach to a possible vaccine would involve using complex genetic engineering techniques on the CMV DNA. Within each cell of every living creature there is a long complex molecule called DNA, which is the set of instructions how to build that particular organism. The more cmplex the animal, the more complex the DNA. Unfortunately, although virus DNA is usually quite simple stuff, CMV DNA is a complicated molecule and researchers are only just beginning to understand its chemical make-up. How it may be manipulated to produce a safe CMV for use in a vaccine is a long way off.

The third approach involves growing virus in the laboratory and purifying the surface protein which the body's defences recognise as foreign and against which they make antibodies. This protein is then given as a vaccine, which, when injected, triggers the body to produce antibodies, These antibodies then lie in wait for the unsuspecting virus which is immediately attacked. Over time the antibody level usually drops, so follow up vaccinations are necessary.

This method has been successfully employed against Hepatitis B. This virus is made up of four proteins, one of which triggers the antibody reaction. The vaccine consists of this protein which triggers the body to produce antibody and thereby prevents the disease.

Unlike Hepatitis B, which contains only four proteins - so finding the right one was relatively easy, CW consists of over 200 proteins. It will take considerable effort to identify the right protein.

CMV has a fascinating second line of defence to this mechanism - it picks up host protein as an outer shell to its own protein coat - a bit like a hermit crab. The immune system is then unable to recognise it as foreign and leaves it alone. Present research is concentrating on how the virus sticks the host protein to its outer shell.

There is one possible loop-hole. It is thought that a newly-entered virus does not immediately coat itself in host protein and there may be a 'window of opportunity' where the virus is susceptible to a suitable vaccine.

Research of this kind is inevitably expensive, involving comlex techniques-and painstaking careful work, While a vaccine against CMV is not likely to be available for some time, there is no reason to suppose that a vaccine is not possible.

In the meantime, two things are important:

Firstly we can defend ourselves against CMV (if not entirely) by being aware of how it spreads, how it works, and by keeping ourselves and our body's defences in tip top shape.

Secondly we can ensure that within the competitive world of research and grants, CMV research is not neglected.