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Infect Immun, August 1998, p. 3689-3697, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Kinetics and In Vivo Induction of Genetic Variation of vlsE in Borrelia burgdorferi

Jing-Ren Zhangdagger and Steven J. Norris*

Department of Pathology and Laboratory Medicine and Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas 77030

Received 22 December 1997/Returned for modification 30 March 1998/Accepted 18 May 1998

The Lyme disease agent, Borrelia burgdorferi, is able to persistently infect humans and animals for months or years in the presence of an active immune response. It is not known how the organisms survive immune attack in the mammalian host. vlsE, a gene localized near one end of linear plasmid lp28-1 and encoding a surface-exposed lipoprotein in B. burgdorferi B31, was shown recently to undergo extensive genetic and antigenic variation within 28 days of initial infection in C3H/HeN mice. In this study, we examined the kinetics of vlsE sequence variation in C3H/HeN mice at 4, 7, 14, 21, and 28 days and at 7 and 12 months postinfection. Sequence changes were detected by PCR amplification and sequence analysis as early as 4 days postinfection and accumulated progressively in both C3H/HeN and CB-17 severe combined immunodeficient (SCID) mice throughout the course of infection. The sequence changes were consistent with sequential recombination of segments from multiple silent vls cassette sites into the vlsE expression site. No vlsE sequence changes were detected in organisms cultured in vitro for up to 84 days. These results indicate that vlsE recombination is induced by a factor(s) present in the mammalian host, independent of adaptive immune responses. The possible inducing conditions appear to be present in various tissue sites because isolates from multiple tissues showed similar degrees of sequence variation. The rate of accumulation of predicted amino acid changes was higher in the immunologically intact C3H/HeN mice than in SCID mice, a finding consistent with immune selection of VlsE variants.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Texas Medical School, 6431 Fannin, Houston, TX 77030. Phone: (713) 500-5338. Fax: (713) 500-0730. E-mail: norr{at}casper.med.uth.tmc.edu.

dagger Present address: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105.

Infect Immun, August 1998, p. 3689-3697, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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