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Mutation protects from HIV - and increases risk of hepatitis C

July 17, 2002

More than 40 million people worldwide are infected with the human immunodeficiency virus HIV. In Africa alone this incurable immune deficiency caused more than two million deaths last year. Yet some people are resistant to infection: the reason for this is a mutation in their DNA which prevents the HIV virus from invading certain immune cells and destroying them. Bonn scientists have now discovered, however, that this resistance to HIV increases the probability of a persistent infection with hepatitis C, a disease which can also be fatal. The findings recently published in the journal Gastroenterology may have influence on possible therapeutic strategies for tackling HIV infections.

When a hepatitis C virus infects a liver cell, the cell secretes so-called chemokines into the blood. Chemokines are signal substances which normally attract inflammatory cells. These "T-lymphocytes" kill the infected cell and in doing so also kill the viruses which have caused the infection. T-lymphocytes have a sensor for chemokines on their surface. However, this sensor does not work in some humans: due to a mutation, their cells cannot express a functional sensor on the cell surface. Thus, a liver cell`s cry for help is not answered because the immune cells are blind and deaf to virus attacks. Therefore the body obviously finds it difficult to defend itself against other infections like hepatitis C.

However, the same mutation also prevents this person from contracting HIV infections: AIDS viruses, among other things, infect T-lymphocytes, put them out of action and in doing so cause the fatal immune deficiency which gave the disease its name. Most HIV strains enter the cells using the chemokine sensor as a 'gateway'. If it is altered, the virus cannot invade the immune cell.

Every cell has two copies of the sensor gene - one from the mother, one from the father. In people who have one mutated copy, HIV infection takes a less progressive course of disease. If both copies are mutated, the person affected is resistant to most HIV strains.

About one per cent of the German population has inherited two defective sensor genes. Among patients infected with the hepatitis C virus this percentage is markedly higher: 'Twelve people out of 153 with hepatitis C anti-bodies had two copies of the mutated gene,' Professor Ulrich Spengler from the Medical Clinic and Policlinic I explains. This is the equivalent to 7.8 per cent, which is much higher than would be statistically expected. 'The amount of viruses found in these patients` blood was up to four times as high as with hepatitis C patients without this mutation.'

The result indicates that the mutation facilitates to establish persistent infection by the viruses causing hepatitis. 'A powerful immune response is especially important in the early phase of a hepatitis C infection,' Professor Spengler explains: the more effective the immune system works in this 'acute phase', the more likely it is that the body will cope with the virus attack. Otherwise there is a risk of the hepatitis becoming chronic. The after-effects of this can involve scarring of this vital organ. The circulation of blood through a 'cirrhotic' liver is sometimes so difficult that, for example, the blood vessels inside the oesophagus may become pathologically distended and burst during food intake. Apart from that there is a substantially higher risk of liver cancer in cases of chronic hepatitis C.

There are around 150 million hepatitis C patients worldwide. One in 200 Germans are infected with the dangerous virus. In three quarters of those affected the disease becomes chronic - probably because their immune system was not sufficiently effective in the early phase. 'We do not know what exactly determines whether the body's defence is successful,' Professor Spengler admits, 'however, in some cases the mutation of the chemokine sensor gene seems to play an important part.' Possible defence strategies against AIDS which are based on interfering with the chemokine sensors could therefore have drastic side-effects - 'a risk which definitely needs to be considered as part of further research.'

Bonn, Universitaet