Structure-Function Investigation of Vsp Serotypes of Borrelia hermsii

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Structure-Function Investigation of Vsp Serotypes of the Spirochete
Borrelia hermsii

Rohit Mehra1, Diana Londoño1,2, Marie Sondey1, Catherine Lawson3, Diego
Cadavid1,2*

Abstract Top
Background

Relapsing fever (RF) spirochetes are notable for multiphasic antigenic
variation of polymorphic outer membrane lipoproteins, a phenomenon
responsible for immune evasion. An additional role in tissue
localization is suggested by the finding that isogenic serotypes 1 (Bt1)
and 2 (Bt2) of the RF spirochete Borrelia turicatae, which differ only
in the Vsp they express, exhibit marked differences in clinical disease
severity and tissue localization during infection.

Methodology/Principal Findings

Here we used known vsp DNA sequences encoding for B. turicatae and
Borrelia hermsii Vsp proteins with variable regions and then studied
whether there are differences in disease expression and tissue
localization of their corresponding serotypes during mouse infection.
For sequence and structural comparisons we focused exclusively on amino
acid residues predicted to project away from the spirochetes surface,
referred to as the Vsp dome. Disease severity and tissue localization
were studied during persistent infection with individual or mixed
serotypes in SCID mice. The results showed that all Vsp domes clustered
into 3 main trunks, with the domes for B. turicatae Vsp1 (BtVsp1) and
BtVsp2 clustering into separate ones. B. hermsii serotypes whose Vsp
domes clustered with the BtVsp1 dome were less virulent but localized to
the brain more. The BtVsp2 dome was the oddball among all and Bt2 was
the only serotype that caused severe arthritis.

Conclusion/Significance

These findings indicate that there is significant variability in Vsp
dome structure, disease severity, and tissue localization among
serotypes of B. hermsii.
Citation: Mehra R, Londoño D, Sondey M, Lawson C, Cadavid D (2009)
Structure-Function Investigation of Vsp Serotypes of the Spirochete
Borrelia hermsii. PLoS ONE 4(10): e7597. doi:10.1371/journal.pone.0007597

Editor: David M. Ojcius, University of California Merced, United States
of America

Received: April 17, 2009; Accepted: September 7, 2009; Published:
October 30, 2009

Copyright: © 2009 Mehra et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited.

Funding: These studies were supported by NIH grants 1R21NS053997-01 and
7R21NS057545-02 and UMDNJ Foundation Awards to Diego Cadavid. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.

Competing interests: Diego Cadavid is a full time employee of Biogen
Idec, Cambridge, MA. The present work is not related to his employment
with Biogen Idec. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This does not
alter the authors adherence to all the PLoS ONE policies on sharing data
and materials, as detailed online in the guide for authors
http://www.plosone.org/static/policies.action#sharing ].

* E-mail: dcadavid@partners.org