J Vet Sci.  2008 Dec;9(4):375-379. 10.4142/jvs.2008.9.4.375.

Low numbers of intestinal Shiga toxin-producing E. coli correlate with a poor prognosis in sheep infected with bovine leukemia virus

  • 1Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, ID 83844-3052, USA. cbohach@uidaho.edu
  • 2Department of Veterinary Microbiology and Pathology, Washington Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, Washington State University, Pullman WA, 99164, USA.
  • 3Field Disease Investigation Unit, Washington State University, Pullman WA, 99164-6610, USA.


Healthy ruminants carry intestinal Shiga toxin (Stx)-producing Escherichia coli (STEC). Stx has antiviral activities in vitro and STEC numbers correlate with reduced early viremia in sheep experimentally infected with bovine leukemia virus (BLV). This study assessed the impact of intestinal STEC on BLV-induced disease for one year post-BLV-challenge. High STEC scores (CFU/g feces x frequency of STEC-positive samples) correlated with good health, whereas poor weight gain, distress, and tumor development occurred only among animals with low STEC scores. STEC carriage was associated with increased percentages of B cells in peripheral blood.


bovine leukemia virus; sheep; Shiga toxin-producing; Escherichia coli

MeSH Terms

Deltaretrovirus Infections/microbiology/*veterinary
Leukemia Virus, Bovine/*physiology
Sheep Diseases/*microbiology
Shiga-Toxigenic Escherichia coli/*physiology


  • Fig. 1 Low Shiga toxin-producing Escherichia coli (STEC) score correlated with poor health at the advanced stage of bovine leukemia virus (BLV) infection. STEC scores were calculated form 6 samples (average logarithm of CFU/g feces, multiplied by proportion of STEC- positive samples). The horizontal broken line separates low (STEC score ≤ 1.5) from high (STEC score ≥ 2.3) rank. Animals presenting with symptoms of poor health are indicated by letter "P", and letter "T" indicates an animal with tumors.

  • Fig. 2 Weight gain in sheep challenged with bovine leukemia virus (BLV) correlated with Shiga toxin-producing Escherichia coli (STEC) scores. Weight at 6 months post BLV challenge is plotted against STEC scores. (A) BLV-challenged sheep, (B) control sheep. Points in panel A were fitted with a second-power polynomial curve.

  • Fig. 3 Shiga toxin-producing Escherichia coli (STEC) treatment correlated with percentages of B cells in blood. Data are group averages + SEM of B cell percentages. A bracket indicates group 1 significantly different from control (ANOVA, p < 0.05).

  • Fig. 4 Peak B-cell percentages differentially correlated with Shiga toxin-producing Escherichia coli (STEC) scores. (A) % B-cells in bovine leukemia virus (BLV)-challenged sheep were negatively correlated with STEC scores. (B) % B-cells from BLV-free control sheep were positively correlated with STEC scores.


1. Asakura H, Makino S, Shirahata T, Tsukamoto T, Kurazono H, Ikeda T, Takeshi K. Detection and genetical characterization of Shiga toxin-producing Escherichia coli from wild deer. Microbiol Immunol. 1998. 42:815–822.
2. Bettelheim KA, Bensink JC, Tambunan HS. Serotypes of verotoxin-producing (Shiga toxin-producing) Escherichia coli isolated from healthy sheep. Comp Immunol Microbiol Infect Dis. 2000. 23:1–7.
3. Beutin L, Geier D, Steinrück H, Zimmermann S, Scheutz F. Prevalence and some properties of verotoxin (Shiga-like toxin)-producing Escherichia coli in seven different species of healthy domestic animals. J Clin Microbiol. 1993. 31:2483–2488.
4. Butler T, Islam MR, Azad MA, Jones PK. Risk factors for development of hemolytic uremic syndrome during shigellosis. J Pediatr. 1987. 110:894–897.
5. Davis WC, Davis JE, Hamilton MJ. Use of monoclonal antibodies and flow cytometry to cluster and analyze leukocyte differentiation molecules. Methods Mol Biol. 1995. 45:149–167.
6. Djilali S, Parodi AL, Levy D, Cockerell GL. Development of leukemia and lymphosarcoma induced by bovine leukemia virus in sheep: a hematopathological study. Leukemia. 1987. 1:777–781.
7. Endo Y, Mitsui K, Motizuki M, Tsurugi K. The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28 S ribosomal RNA caused by the toxins. J Biol Chem. 1987. 262:5908–5912.
8. Ferens WA, Hovde CJ. Antiviral activity of shiga toxin 1: suppression of bovine leukemia virus-related spontaneous lymphocyte proliferation. Infect Immun. 2000. 68:4462–4469.
9. Ferens WA, Cobbold R, Hovde CJ. Intestinal Shiga toxin-producing Escherichia coli bacteria mitigate bovine leukemia virus infection in experimentally infected sheep. Infect Immun. 2006. 74:2906–2916.
10. Ferens WA, Hovde CJ. The non-toxic A subunit of Shiga toxin type 1 prevents replication of bovine immunodeficiency virus in infected cells. Virus Res. 2007. 125:29–41.
11. Griffin PM, Tauxe RV. The epidemiology of infections caused by Escherichia coli O157:H7, other enterohemorrhagic E. coli, and the associated hemolytic uremic syndrome. Epidemiol Rev. 1991. 13:60–98.
12. Kabeya H, Ohashi K, Onuma M. Host immune responses in the course of bovine leukemia virus infection. J Vet Med Sci. 2001. 63:703–708.
13. Karch H, Meyer T. Single primer pair for amplifying segments of distinct Shiga-like-toxin genes by polymerase chain reaction. J Clin Microbiol. 1989. 27:2751–2757.
14. Kenyon SJ, Ferrer JF, McFeely RA, Graves DC. Induction of lymphosarcoma in sheep by bovine leukemia virus. J Natl Cancer Inst. 1981. 67:1157–1163.
15. Mirsky ML, Olmstead CA, Da Y, Lewin HA. The prevalence of proviral bovine leukemia virus in peripheral blood mononuclear cells at two subclinical stages of infection. J Virol. 1996. 70:2178–2183.
16. Nizetic D, Drmanac R, Lehrach H. An improved bacterial colony lysis procedure enables direct DNA hybridisation using short (10, 11 bases) oligonucleotides to cosmids. Nucleic Acids Res. 1991. 19:182.
17. Olson MC, Ramakrishnan S, Anand R. Ribosomal inhibitory proteins from plants inhibit HIV-1 replication in acutely infected peripheral blood mononuclear cells. AIDS Res Hum Retroviruses. 1991. 7:1025–1030.
18. Schwartz I, Bensaid A, Polack B, Perrin B, Berthelemy M, Levy D. In vivo leukocyte tropism of bovine leukemia virus in sheep and cattle. J Virol. 1994. 68:4589–4596.
19. Wang P, Tumer NE. Virus resistance mediated by ribosome inactivating proteins. Adv Virus Res. 2000. 55:325–355.
20. Yan W, Malik MN, Peterkin PI, Sharpe AN. Comparison of the hydrophobic grid-membrane filter DNA probe method and the Health Protection Branch standard method for the detection of Listeria monocytogenes in foods. Int J Food Microbiol. 1996. 30:379–384.
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