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Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection.
- Source :
-
PLoS pathogens [PLoS Pathog] 2009 Feb; Vol. 5 (2), pp. e1000293. Date of Electronic Publication: 2009 Feb 13. - Publication Year :
- 2009
-
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. Analysis of clones with apparent single recombination events indicated that recombinations into vlsE are nonselective with regard to the silent cassette utilized, as well as the length and location of the recombination event. Sequence changes as small as one base pair were common. Fifteen percent of recovered vlsE variants contained "template-independent" sequence changes, which clustered in the variable regions of vlsE. We hypothesize that the increased frequency and complexity of vlsE sequence changes observed in clones recovered from immunocompetent mice (as compared with SCID mice) is due to rapid clearance of relatively invariant clones by variable region-specific anti-VlsE antibody responses.
- Subjects :
- Animals
Antigens, Bacterial chemistry
Antigens, Bacterial immunology
Bacterial Proteins chemistry
Bacterial Proteins immunology
Base Sequence
Data Interpretation, Statistical
Disease Models, Animal
Female
Gene Expression
Lipoproteins chemistry
Lipoproteins immunology
Mice
Mice, Inbred C3H
Mice, SCID
Molecular Sequence Data
Sequence Analysis, DNA
Sequence Analysis, Protein
Antigenic Variation genetics
Antigens, Bacterial genetics
Bacterial Proteins genetics
Borrelia burgdorferi genetics
Borrelia burgdorferi immunology
Lipoproteins genetics
Lyme Disease microbiology
Recombination, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 5
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 19214205
- Full Text :
- https://doi.org/10.1371/journal.ppat.1000293