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Infection and Immunity, January 2003, p. 327-334, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.327-334.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Antiviral Activity of Shiga Toxin Requires Enzymatic Activity and Is Associated with Increased Permeability of the Target Cells

Indira Basu,1,{dagger} Witold A. Ferens,1 Diana M. Stone,2 and Carolyn J. Hovde1*

Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844-3052,1 Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 991642

Received 10 July 2002/ Returned for modification 9 September 2002/ Accepted 15 October 2002

This study expanded our earlier finding that Shiga toxin type 1 (Stx1) has activity against bovine leukemia virus (BLV) (W. A. Ferens and C. J. Hovde, Infect. Immun. 68:4462-4469, 2000). The Stx molecular motifs required for antiviral activity were identified, and a mechanism of Stx action on virally infected cells is suggested. Using inhibition of BLV-dependent spontaneous lymphocyte proliferation as a measure of antiviral activity, we showed that Stx2 had antiviral activity similar to that of Stx1. Enzymatic and antiviral activities of three StxA1 chain mutants deficient in enzymatic activity or aspects of receptor-mediated cytotoxicity were compared. Using protein synthesis inhibition to measure enzymatic activity, the mutant E167D was 300-fold less catalytically active than wild-type StxA1, was minimally active in antiviral assays, and did not inhibit synthesis of viral proteins. Two StxA1 mutants, A231D-G234E and StxA11 (enzymatically active but unable to kill cells via the classical receptor-mediated route), had undiminished antiviral activity. Although binding of radiolabeled StxA1 to bovine blood cells or to free virus was not detected, flow cytometric analysis showed that the number of BLV-expressing cells were specifically reduced in cultures treated with Stx. These unique and rare lymphocytes were highly permeable to 40- and 70-kDa fluorescent dextrans, indicating that direct absorption of toxins by virus-expressing cells is a potential mechanism of target cell intoxication. These results support the hypothesis that Stx-producing Escherichia coli colonization of the gastrointestinal tract may benefit ruminant hosts by the ability of Stxs to exert antiviral activity.

* Corresponding author. Mailing address: Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, ID 83844-3052. Phone: (208) 885-5906. Fax: (208) 885-6518. E-mail: cbohach{at}uidaho.edu.

Editor: A. D. O'Brien

{dagger} Present address: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111.

Infection and Immunity, January 2003, p. 327-334, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.327-334.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hoffman, M. A., Menge, C., Casey, T. A., Laegreid, W., Bosworth, B. T., Dean-Nystrom, E. A. (2006). Bovine Immune Response to Shiga-Toxigenic Escherichia coli O157:H7. CVI 13: 1322-1327 [Abstract] [Full Text]  
  • Ferens, W. A., Cobbold, R., Hovde, C. J. (2006). Intestinal Shiga Toxin-Producing Escherichia coli Bacteria Mitigate Bovine Leukemia Virus Infection in Experimentally Infected Sheep.. Infect. Immun. 74: 2906-2916 [Abstract] [Full Text]  
  • Ferens, W. A., Grauke, L. J., Hovde, C. J. (2004). Shiga Toxin 1 Targets Bovine Leukemia Virus-Expressing Cells. Infect. Immun. 72: 1837-1840 [Abstract] [Full Text]  


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