detailed analysis of sequence changes occurring during vlse antigenic variation in the mouse model of borrelia burgdorferi infection详细分析序列的变化发生在vlse抗原变异感染伯氏疏螺旋体的小鼠模型.pdfVIP

Detailed Analysis of Sequence Changes Occurring during vlsE Antigenic Variation in the Mouse Model of Borrelia burgdorferi Infection ¨ 1¤ 1,2 1 1,2 Loıc Coutte , Douglas J. Botkin , Lihui Gao , Steven J. Norris * 1 Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, Texas, United States of America, 2 Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas, United States of America Abstract Lyme disease Borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. The vls antigenic variation system, which expresses the surface-exposed lipoprotein VlsE, plays a major role in B. burgdorferi immune evasion. Gene conversion between vls silent cassettes and the vlsE expression site occurs at high frequency during mammalian infection, resulting in sequence variation in the VlsE product. In this study, we examined vlsE sequence variation in B. burgdorferi B31 during mouse infection by analyzing 1,399 clones isolated from bladder, heart, joint, ear, and skin tissues of mice infected for 4 to 365 days. The median number of codon changes increased progressively in C3H/HeN mice from 4 to 28 days post infection, and no clones retained the parental vlsE sequence at 28 days. In contrast, the decrease in the number of clones with the parental vlsE sequence and the increase in the number of sequence changes occurred more gradually in severe combined immunodeficiency (SCID) mice. Clones containing a stop codon were isolated, indicating that continuous expression of full-length VlsE is not required for survival in vivo; also, these clones continued to undergo vlsE recombination. An