{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:44:29Z","timestamp":1792028669269,"version":"4.4.0"},"reference-count":58,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,3,30]]},"abstract":"<jats:p>\n                    The risk of disease associated with persistent virus infections such as HIV-I, hepatitis B and C, and human T-lymphotropic virus-I (HTLV-I) is strongly determined by the virus load. However, it is not known whether a persistent class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response reduces viral load and is therefore beneficial or causes tissue damage and contributes to disease pathogenesis. HTLV-I-associated myelopathy (HAM\/TSP) patients have a high virus load compared with asymptomatic HTLV-I carriers. We hypothesized that HLA alleles control HTLV-I provirus load and thus influence susceptibility to HAM\/TSP. Here we show that, after infection with HTLV-I, the class I allele\n                    <jats:italic>HLA<\/jats:italic>\n                    -\n                    <jats:italic>A*02<\/jats:italic>\n                    halves the odds of HAM\/TSP (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001), preventing 28% of potential cases of HAM\/TSP. Furthermore,\n                    <jats:italic>HLA-A*02<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    healthy HTLV-I carriers have a proviral load one-third that (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.014) of\n                    <jats:italic>HLA<\/jats:italic>\n                    -\n                    <jats:italic>A*02<\/jats:italic>\n                    <jats:sup>\u2212<\/jats:sup>\n                    HTLV-I carriers. An association of\n                    <jats:italic>HLA<\/jats:italic>\n                    -\n                    <jats:italic>DRB1*0101<\/jats:italic>\n                    with disease susceptibility also was identified, which doubled the odds of HAM\/TSP in the absence of the protective effect of\n                    <jats:italic>HLA-A*02.<\/jats:italic>\n                    These data have implications for other persistent virus infections in which virus load is associated with prognosis and imply that an efficient antiviral CTL response can reduce virus load and so prevent disease in persistent virus infections.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.7.3848","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"3848-3853","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":336,"title":["HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy"],"prefix":"10.1073","volume":"96","author":[{"given":"Katie J. M.","family":"Jeffery","sequence":"first","affiliation":[{"name":"Departments of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St. Mary\u2019s, Norfolk Place, London W2 1PG, United Kingdom; Department of Medical Informatics, Third Department of Internal Medicine, and Division of Molecular Pathology, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan; Oxford Transplant Center, Nuffield Department of Surgery, Churchill Hospital, Oxford OX3 7LJ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Usuku","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St. Mary\u2019s, Norfolk Place, London W2 1PG, United Kingdom; Department of Medical Informatics, Third Department of Internal Medicine, and Division of Molecular Pathology, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan; Oxford Transplant Center, Nuffield Department of Surgery, Churchill Hospital, Oxford OX3 7LJ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Hall","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St. Mary\u2019s, Norfolk Place, London W2 1PG, United Kingdom; Department of Medical Informatics, Third Department of Internal Medicine, and Division of Molecular Pathology, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan; Oxford Transplant Center, Nuffield Department of Surgery, Churchill Hospital, Oxford OX3 7LJ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St. Mary\u2019s, Norfolk Place, London W2 1PG, United Kingdom; Department of Medical Informatics, Third Department of Internal Medicine, and Division of Molecular Pathology, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan; Oxford Transplant Center, Nuffield Department of Surgery, Churchill Hospital, Oxford OX3 7LJ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham P.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St. Mary\u2019s, Norfolk Place, London W2 1PG, United Kingdom; Department of Medical Informatics, Third Department of Internal Medicine, and Division of Molecular Pathology, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan; Oxford Transplant Center, Nuffield Department of Surgery, Churchill Hospital, Oxford OX3 7LJ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Procter","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St. Mary\u2019s, Norfolk Place, London W2 1PG, United Kingdom; Department of Medical Informatics, Third Department of Internal Medicine, and Division of Molecular Pathology, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan; Oxford Transplant Center, Nuffield Department of Surgery, Churchill Hospital, Oxford OX3 7LJ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Bunce","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St. Mary\u2019s, Norfolk Place, London W2 1PG, United Kingdom; Department of Medical Informatics, Third Department of Internal Medicine, and Division of Molecular Pathology, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan; Oxford Transplant Center, Nuffield Department of Surgery, Churchill Hospital, Oxford OX3 7LJ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham S.","family":"Ogg","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St. Mary\u2019s, Norfolk Place, London W2 1PG, United Kingdom; Department of Medical Informatics, Third Department of Internal Medicine, and Division of Molecular Pathology, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan; Oxford Transplant Center, Nuffield Department of Surgery, Churchill Hospital, Oxford OX3 7LJ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth I.","family":"Welsh","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St. Mary\u2019s, Norfolk Place, London W2 1PG, United Kingdom; Department of Medical Informatics, Third Department of Internal Medicine, and Division of Molecular Pathology, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan; Oxford Transplant Center, Nuffield Department of Surgery, Churchill Hospital, Oxford OX3 7LJ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan N.","family":"Weber","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St. Mary\u2019s, Norfolk Place, London W2 1PG, United Kingdom; 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