Science: Retroviruses turn up in more autoimmune diseases

日期:2019-03-04 05:13:09 作者:东乡骁呀 阅读:

By ROLF ZELL in WEST BERLIN EVIDENCE is mounting that previously unknown retroviruses may have a role in several diseases in which the immune system attacks the body’s own tissues. Results presented at the Seventh International Congress of Immunology, held last week in West Berlin, suggest that viruses related to HIV, the cause of AIDS, may play a part in the development of three different autoimmune diseases. The first firm indication that retroviruses might be associated with autoimmune disease came earlier this year. Franco Bottazzo and his colleagues at the Middlesex Hospital and the Institute of Cancer Research in London found DNA which was similar to that of HIV in the thyroids of five patients with Graves’ disease (New Scientist, Science, 27 May). People with this autoimmune condition produce antibodies to thyroid cells, causing the gland to enlarge and release too much thyroid hormone. In Berlin, Bottazzo’s group said that they had found evidence for DNA sequences of retroviral origin in all of eight patients suffering from Graves’ disease. A test for DNA resembling that from the gag region of HIV, which codes for the core protein p24, was positive in all the patients. However, in blood tests, none of the eight had antibodies to HIV-1 or HTLV-1, another retrovirus which causes a rare type of leukaemia. For their controls, Bottazzo and his colleagues tested thyroid tissue removed from people having surgery for cancer of the thyroid, but who did not have Graves’ disease. None of these four samples showed a positive result on the test for DNA of retroviral origin. This finding suggests that the retroviral DNA sequences are correlated with the disease. Further evidence comes from Norman Talal and his colleagues from the University of Texas Health Centre in San Antonio. They investigated patients with two other autoimmune diseases, called Sjogren’s syndrome and systemic lupus erythematosus (SLE). The symptoms of Sjogren’s syndrome are variable, but can include inflammation, arthritis and dry eyes and mouth. In SLE, sufferers have fever, skin rash and arthritis. Neither disease has a known cause. Talal’s group found antibodies against the p17 and p24 core proteins of HIV-1 in 14 out of 20 patients with Sjogren’s syndrome, as well as in 21 out of 60 patients with SLE. This is indirect evidence that these patients had proteins similar to those of HIV in their blood, although they were not infected with HIV itself. Some immunologists are sceptical about Talal’s findings, however. Friedel Krapf, from the Institute of Clinical Immunology at the University of Erlangen-Nurnberg in West Germany, pointed out that many people with these diseases must have had the highly sensitive Western blot test for diagnosis of HIV infection. He said: ‘It is astonishing that no other group found such proteins (during these tests). On the other hand, it is known that a fraction of AIDS patients develop autoimmune-like symptoms during the disease.’ Krapf and his collaborators provided the most direct evidence that retroviruses are associated with an autoimmune disease. They found sequences of DNA which closely matched retroviral genes, such as those from HIV-1 and HTLV-2 (also the cause of a rare leukaemia). The researchers also found messenger RNA copies of the fragments of retroviral DNA. This discovery indicates that patients with SLE are turning retroviral genetic messages into protein products. Krapf’s group began to investigate the possible connection with retroviruses when they found huge amounts of fragmented DNA in the plasma of cells from patients with SLE. Krapf said: ‘We found this phenomenon in only one other person who did not have SLE, and this was someone who was infected with herpes virus.’ The researchers isolated the DNA fragments from the cells of patients with SLE and put them into an immortalised line of B cells. After several weeks of incubation, 10 per cent of the B cells seemed to be damaged: they developed huge vacuoles and joined up to form syncytia, or clumps of fused cells. Scientists frequently observe this effect in cells infected with HIV that have been grown in the laboratory. The group carried out further tests to establish how closely related the viral material was to the genome of HIV. They identified four regions of the retroviral DNA that closely resembled fragments of the genome of HTLV-1, as well as the tat gene and other parts of the genome of HIV-1. (Without the protein product of the tat gene, HIV cannot reproduce itself.) According to Krapf, other experiments suggest that as many as 40 per cent of patients with SLE may have messenger RNA of retroviral origin. No one knows how retroviral DNA, messenger RNA of retroviral origin or the protein products of retroviral genes can account for the autoimmune characteristics of these diseases. Nor does anyone know the origin of the retroviral sequences found in some people with SLE. Krapf said: ‘We have only a slight hint’ that this material comes from a virus that people catch, rather than one which is passed on through the germ line. Other groups have found that patients with SLE have antibodies that bind to the DNA fragments in their cells. These researchers have found these antibodies in healthy sexual partners of patients with SLE, as well as in laboratory staff who handle material from people with SLE. Krapf said: