sequential broadening of ctl responses in early hiv-1 infection is associated with viral escape连续扩大ctl反应早期的hiv - 1感染病毒逃脱.pdfVIP

Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral Escape 1,2 3 1 4 5 3 6 Annika C. Karlsson *, Astrid K. N. Iversen , Joan M. Chapman , Tulio de Oliveira , Gerald Spotts , Andrew J. McMichael , Miles P. Davenport , Frederick M. Hecht5., Douglas F. Nixon1,5. 1 Gladstone Institute of Virology and Immunology, University of California, San Francisco, California, United States of America, 2 The Swedish Institute for Infectious Disease Control, and Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden, 3 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom, 4 Department of Zoology, University of Oxford, Oxford, United Kingdom, 5 Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America, 6 University of New South Wales, Sydney, Australia Background. Antigen-specific CTL responses are thought to play a central role in containment of HIV-1 infection, but no consistent correlation has been found between the magnitude and/or breadth of response and viral load changes during disease progression. Methods and Findings. We undertook a detailed investigation of longitudinal CTL responses and HIV-1 evolution beginning with primary infection in 11 untreated HLA-A2 positive individuals. A subset of patients developed broad responses, which selected for consensus B epitope variants in Gag, Pol, and Nef, suggesting CTL-induced adaptation of HIV-1 at the population level. The patients who developed viral escape mutations and broad autologous CTL responses over time had a significantly higher increase in viral load during the first year of inf