scholarly journals Intestinal Shiga Toxin-Producing Escherichia coli Bacteria Mitigate Bovine Leukemia Virus Infection in Experimentally Infected Sheep

2006 ◽  
Vol 74 (5) ◽  
pp. 2906-2916 ◽  
Author(s):  
Witold A. Ferens ◽  
Rowland Cobbold ◽  
Carolyn J. Hovde
Keyword(s):  
Escherichia Coli ◽  
Antiviral Activity ◽  
Shiga Toxin ◽  
Bovine Leukemia Virus ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
Average Weight ◽  
E Coli ◽  
Infected Cells ◽  
The Impact

ABSTRACTRuminants often carry gastrointestinal Shiga toxin (Stx)-producingEscherichia coli(STEC). Stxs belong to a large family of ribosome-inactivating proteins (RIPs), found in many plants and some bacteria. Plant RIPs, secreted into extracellular spaces, limit the spread of viruses through plant tissues by penetrating and killing virally infected cells. Previously, we showed Stx activity against bovine leukemia virus (BLV)-infected cells in vitro and hypothesized that STEC bacteria have antiviral activity in ruminant hosts. Here, we investigated the impact of STEC on the initial phases of BLV infection in sheep. Sheep were treated with biweekly oral doses ofE. coliO157:H7 (an STEC) or an isogenicstxmutant strain. A different group of sheep were similarly treated with five naturally occurring ovine STEC isolates orstx-negativeE. coli. Intestinal STEC bacteria were enumerated and identified by standard fecal culture and DNA hybridization. Oral STEC treatment did not always result in carriage of STEC, although many animals consistently presented with >104CFU/g feces. BLV viremia was assessed by spontaneous lymphocyte proliferation (SLP) in cultures of blood mononuclear cells and by syncytium formation in cocultures of the same with F-81 indicator cells. SLP was lower (P< 0.05) and syncytia were fewer (P < 0.05) in STEC-treated sheep than in untreated sheep. Both lower SLP and fewer syncytia positively correlated with fecal STEC numbers. Average weight gain post-BLV challenge was higher in STEC-treated sheep than in untreated sheep (P< 0.05). These results support the hypothesis that in ruminants, intestinal STEC bacteria have antiviral activity and mitigate BLV-induced disease.

scholarly journals Antiviral Activity of Shiga Toxin 1: Suppression of Bovine Leukemia Virus-Related Spontaneous Lymphocyte Proliferation

2000 ◽  
Vol 68 (8) ◽  
pp. 4462-4469 ◽  
Author(s):  
Witold A. Ferens ◽  
Carolyn J. Hovde
Keyword(s):  
Antiviral Activity ◽  
Shiga Toxin ◽  
Bovine Leukemia Virus ◽  
Lymphocyte Proliferation ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
Interleukin 2 ◽  
Pokeweed Mitogen ◽  
Potent Antiviral Activity ◽  
The Impact

ABSTRACT Human infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) cause hemorrhagic colitis. The Stxs belong to a large family of ribosome-inactivating proteins (RIPs) that are found in a variety of higher plants and some bacteria. Many RIPs have potent antiviral activity for the plants that synthesize them. STEC strains, both virulent and nonvirulent to humans, are frequently isolated from healthy cattle. Interestingly, despite intensive investigations, it is not known why cattle carry STEC. We tested the hypothesis that Stx has antiviral properties for bovine viruses by assessing the impact of Stx type 1 (Stx1) on bovine peripheral blood mononuclear cells (PBMC) from cows infected with bovine leukemia virus (BLV). PBMC from BLV-positive animals invariably displayed spontaneous lymphocyte proliferation (SLP) in vitro. Stx1 or the toxin A subunit (Stx1A) strongly inhibited SLP. Toxin only weakly reduced the pokeweed mitogen- or interleukin-2-induced proliferation of PBMC from normal (BLV-negative) cows and had no effect on concanavalin A-induced proliferation. The toxin activity in PBMC from BLV-positive cattle was selective for viral SLP and did not abrogate cell response to pokeweed mitogen- or interleukin-2-induced proliferation. Antibody to virus or Stx1A was most effective at inhibiting SLP if administered at the start of cell culture, indicating that both reagents likely interfere with BLV-dependent initiation of SLP. Stx1A inhibited expression of BLV p24 protein by PBMC. A well-defined mutant Stx1A (E167D) that has decreased catalytic activity was not effective at inhibiting SLP, suggesting the inhibition of protein synthesis is likely the mechanism of toxin antiviral activity. Our data suggest that Stx has potent antiviral activity and may serve an important role in BLV-infected cattle by inhibiting BLV replication and thus slowing the progression of infection to its malignant end stage.

Bovine Leukemia Virus and Mycobacterium avium subsp. paratuberculosis Are Not Associated with Shiga Toxin–Producing Escherichia coli Shedding in Cattle

2016 ◽  
Vol 80 (1) ◽  
pp. 86-89
Author(s):  
CRISTINA VENEGAS-VARGAS ◽  
SHANNON D. MANNING ◽  
PAUL M. COUSSENS ◽  
JONATHAN A. ROUSSEY ◽  
PAUL BARTLETT ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mycobacterium Avium ◽  
Shiga Toxin ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Mycobacterium Avium Subsp ◽  
Antibody Detection ◽  
P Value ◽  
Beef Herds ◽  
Mycobacterium Avium Subsp Paratuberculosis

ABSTRACT Bovine leukemia virus (BLV) is a retrovirus that causes enzootic bovine leukosis in cattle, and Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne's disease in cattle. Both diseases are chronic in nature and can lead to the disruption of normal immunological or physiological processes. Cattle are the major reservoir of Shiga toxin–producing Escherichia coli (STEC), a cause of foodborne illness in humans. We tested the hypothesis that cattle infected with BLV or MAP are more likely to shed STEC. We conducted a cross-sectional study during the summers of 2011 and 2012 in 11 Michigan cattle herds. A fecal sample from each animal was collected for STEC culture, and multiplex PCR for stx1, stx2, and eaeA was used to screen suspect colonies for STEC confirmation. Antibody detection enzyme-linked immunosorbent assays for BLV and MAP were used to screen serum from each animal. Flow cytometry was used to quantify the percentage of lymphocytes, monocytes, and neutrophils in a subsample (n =497) of blood samples. Of the animals sampled, 34.9% were BLV positive, 2.7% were MAP positive, and 16% were shedding STEC. Cattle in the dairy herds had a higher frequency of BLV and MAP than did those in beef herds, but more cattle in beef herds were shedding STEC. Neither BLV nor MAP was associated with STEC shedding (P values of 0.6838 and 0.3341, respectively). We also observed no association between STEC status and the percentage of neutrophils (P value of 0.3565), lymphocytes (P value of 0.8422), or the lymphocyte-to-monocyte ratio (P value of 0.1800). Although controlling both BLV and MAP is important for overall herd health and productivity, we found no evidence that controlling BLV and MAP has an impact on STEC shedding in cattle.

scholarly journals Bovine Leukemia Virus Infection in Dairy Cattle: Effect on Serological Response to Immunization against J5Escherichia coliBacterin

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Ronald J. Erskine ◽  
Paul C. Bartlett ◽  
Kimberly M. Sabo ◽  
Lorraine M. Sordillo
Keyword(s):  
Escherichia Coli ◽  
Virus Infection ◽  
Dairy Cattle ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Geometric Mean ◽  
Serological Response ◽  
Antibody Isotype ◽  
E Coli ◽  
The Third

Thirteen bovine leukemia virus- (BLV-) negative and 22 BLV-positive Holstein cows were immunized with J5Escherichia colibacterin at dry off, three weeks before calving, during the second week after calving, and three weeks after the third immunization. Serum was collected before the initial immunization, immediately before the third and fourth immunizations, and 21 days after the fourth immunization. Anti-J5E. coliIgM, IgG1, and IgG2 titers were determined by ELISA. Anti-J5E. coliIgM titers did not differ significantly (P=.98) between groups. Increases in anti-J5E. coliIgG1 titers were higher in the BLV-negative cows (P=.057). Geometric mean anti-J5E. coliIgG2 titers increased fourfold in the BLV-negative cows, which was significantly higher (P=.007) than the twofold increase in the BLV-positive cows. Cattle infected with BLV may have impaired serologic responses following immunization with J5 bacterin, and response may differ according to antibody isotype.

scholarly journals Escherichia coli O157:H7 Strain Origin, Lineage, and Shiga Toxin 2 Expression Affect Colonization of Cattle

2009 ◽  
Vol 75 (15) ◽  
pp. 5074-5081 ◽  
Author(s):  
Ross M. S. Lowe ◽  
Danica Baines ◽  
L. Brent Selinger ◽  
James E. Thomas ◽  
Tim A. McAllister ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Shiga Toxin ◽  
Escherichia Coli O157 ◽  
Human Origin ◽  
E Coli ◽  
Unknown Factor ◽  
Shiga Toxin 2 ◽  
The Impact ◽  
Dose Dependent

ABSTRACT Enterohemorrhagic Escherichia coli O157:H7 has evolved into an important human pathogen with cattle as the main reservoir. The recent discovery of E. coli O157:H7-induced pathologies in challenged cattle has suggested that previously discounted bacterial virulence factors may contribute to the colonization of cattle. The objective of the present study was to examine the impact of lineage type, cytotoxin activity, and cytotoxin expression on the amount of E. coli O157:H7 colonization of cattle tissue and cells in vitro. Using selected bovine- and human-origin strains, we determined that lineage type predicted the amount of E. coli O157:H7 strain colonization: lineage I > intermediate lineages > lineage II. All E. coli O157:H7 strain colonization was dose dependent, with threshold colonization at 103 to 105 CFU and maximum colonization at 107 CFU. We also determined that an as-yet-unknown factor of strain origin was the most dominant predictor of the amount of strain colonization in vitro. The amount of E. coli O157:H7 colonization was also influenced by strain cytotoxin activity and the inclusion of cytotoxins from lineage I or intermediate lineage strains increased colonization of a lineage II strain. There was a higher level of expression of the Shiga toxin 1 gene (stx 1) in human-origin strains than in bovine-origin strains. In addition, lineage I strains expressed higher levels of the Shiga toxin 2 gene (stx 2). The present study supports a role for strain origin, lineage type, cytotoxin activity, and stx 2 expression in modulating the amount of E. coli O157:H7 colonization of cattle.

scholarly journals Shiga Toxin 1 Targets Bovine Leukemia Virus-Expressing Cells

2004 ◽  
Vol 72 (3) ◽  
pp. 1837-1840 ◽  
Author(s):  
Witold A. Ferens ◽  
Luke J. Grauke ◽  
Carolyn J. Hovde
Keyword(s):  
Shiga Toxin ◽  
Bovine Leukemia Virus ◽  
Direct Evidence ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
Peripheral Blood Mononuclear ◽  
Electron Microscopy Analysis ◽  
A Subunit ◽  
Microscopy Analysis

ABSTRACT Direct evidence that Escherichia coli Shiga toxin (Stx) acts against bovine leukemia virus (BLV)-expressing cells was obtained. The active A subunit of Stx type 1 (StxA1) targeted a selected population of permeable cells expressing BLV and inhibited BLV replication in a culture of bovine peripheral blood mononuclear cells. Cells were cultured with and without StxA1, and at various times cells expressing BLV were identified by being stained with MW1 monoclonal antibody specific for the BLV protein gp51. Before culture, permeable cells were tagged by uptake of one of the following: acetoxymethyl of 2′,7′-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein (BCECF), BCECF conjugated to 70-kDa dextran, or 70-kDa dextran conjugated to fluorescein. The tagged cells costaining with anti-gp51 were selectively eliminated in StxA1-treated cultures. Electron microscopy analysis of purified B lymphocytes showed sharply reduced numbers of BLV particles in StxA1-treated cultures.

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

2003 ◽  
Vol 71 (1) ◽  
pp. 327-334 ◽  
Author(s):  
Indira Basu ◽  
Witold A. Ferens ◽  
Diana M. Stone ◽  
Carolyn J. Hovde
Keyword(s):  
Antiviral Activity ◽  
Enzymatic Activity ◽  
Shiga Toxin ◽  
Leukemia Virus ◽  
Flow Cytometric Analysis ◽  
Target Cells ◽  
Flow Cytometric ◽  
Catalytically Active ◽  
Antiviral Activities ◽  
Infected Cells

ABSTRACT 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.

scholarly journals Dissemination of Bovine Leukemia Virus-Infected Cells from a Newly Infected Sheep Lymph Node

2006 ◽  
Vol 80 (16) ◽  
pp. 7873-7884 ◽  
Author(s):  
B. E. Fulton ◽  
M. Portella ◽  
K. Radke
Keyword(s):  
Lymph Node ◽  
B Cells ◽  
Blood Cells ◽  
Bovine Leukemia Virus ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
Immunoglobulin M ◽  
Surface Glycoprotein ◽  
Specific Antibodies ◽  
Infected Cells

ABSTRACT To investigate the early establishment of bovine leukemia virus (BLV) infection, we injected BLV-infected or mock-infected allogeneic cells into the shoulder of sheep in which an efferent lymphatic duct of the draining prescapular lymph node had been cannulated. Rare mononuclear cells acting as centers of BLV infection in culture were present within 4 to 6 days in efferent lymph and within 6 to 10 days in blood. Soon after BLV injection, immunoglobulin M+ (IgM+) and CD8+ cells increased in efferent lymph and oscillated reciprocally in frequency. CD8+ blasts increased on days 4 to 6, when infectious centers increased 100-fold in lymph. On days 6 and 7, both lymph and blood were enriched with CD8+ cells that were labeled late on day 5 with an intravenous pulse of 5-bromo-2′-deoxyuridine (BrdU). Lymph, but not blood, was enriched with BrdU+ B cells on day 7. Capsid-specific antibodies became detectable in efferent lymph on days 6 to 8 and surface glycoprotein-specific antibodies on day 9, preceding their detection in serum by 9 to 14 days. Systemic dissemination of BLV-infected cells was thus accompanied by an increase in proliferating CD8+ cells and the onset of BLV-specific antibodies in lymph. Infectious centers reached maximum frequencies of 0.2% in lymph by days 11 to 13, and then their frequencies increased by 5- to 40-fold in blood cells, suggesting that many infected blood cells do not recirculate back into lymph. Beginning on days 10 to 13, a subpopulation of B cells having high levels of surface IgM increased sharply in peripheral blood. Such cells were not present in lymph. After a day 16 pulse of BrdU, recently proliferated cells that stained intensely for surface IgM appeared in blood within 15 h. Predominantly B lymphocytes contained the viral capsid protein when lymph and blood cells were cultured briefly to allow BLV expression. However, both early in lymph and later in blood, BrdU+ B cells greatly exceeded productively infected cells, indicating that new BLV infections stimulate proliferation of two different populations of B cells.

scholarly journals Mouse Models ofEscherichia coliO157:H7 Infection and Shiga Toxin Injection

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Krystle L. Mohawk ◽  
Alison D. O'Brien
Keyword(s):  
Escherichia Coli ◽  
Mouse Models ◽  
Shiga Toxin ◽  
Therapeutic Strategies ◽  
Hemorrhagic Colitis ◽  
E Coli ◽  
Major Virulence Factor ◽  
Life Threatening ◽  
Uremic Syndrome ◽  
The Impact

Escherichia coliO157:H7 has been responsible for multiple food- and waterborne outbreaks of diarrhea and/or hemorrhagic colitis (HC) worldwide. More importantly, a portion ofE. coliO157:H7-infected individuals, particularly young children, develop a life-threatening sequela of infection called hemolytic uremic syndrome (HUS). Shiga toxin (Stx), a potent cytotoxin, is the major virulence factor linked to the presentation of both HC and HUS. Currently, treatment ofE. coliO157:H7 and other Stx-producingE. coli(STEC) infections is limited to supportive care. To facilitate development of therapeutic strategies and vaccines for humans against these agents, animal models that mimic one or more aspect of STEC infection and disease are needed. In this paper, we focus on the characteristics of various mouse models that have been developed and that can be used to monitor STEC colonization, disease, pathology, or combinations of these features as well as the impact of Stx alone.

scholarly journals Natural Infection of Dairy Cows with Bovine Leukemia Virus Affects Immunoglobulin Levels in Saliva and Serum but Not Milk

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 907
Author(s):  
Monika Dziuba ◽  
Vickie J. Ruggiero ◽  
Catherine Wilson ◽  
Paul C. Bartlett ◽  
Paul M. Coussens
Keyword(s):  
Pilot Study ◽  
Dairy Cows ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Natural Infection ◽  
Total Serum ◽  
Serum Samples ◽  
Retroviral Infection ◽  
Serum Iga ◽  
The Impact

Bovine leukemia virus (BLV) is a retroviral infection that disrupts the immune function of infected animals. It is widespread among U.S. dairy cattle. In this pilot study, the average total IgA and IgM concentrations in milk, saliva, and serum samples from BLV ELISA-positive (ELISA+) dairy cows were compared against samples from BLV ELISA-negative (ELISA−) cows using the Kruskal–Wallis test (with ties). The results from ELISA+ cows were also stratified by lymphocyte count (LC) and proviral load (PVL). In milk and saliva from ELISA+ cows, the average total IgA and IgM concentrations were decreased compared to ELISA− cows, although this was only statistically significant for saliva IgM in cows with low PVL (p = 0.0424). Numerically, the average total IgA concentrations were 33.6% lower in milk and 23.7% lower in saliva, and the average total IgM concentrations were 42.4% lower in milk and 15.5% lower in saliva. No significant differences were observed in the total serum IgA concentrations, regardless of PVL and LC. The total serum IgM from ELISA+ cows was significantly decreased (p = 0.0223), with the largest decreases occurring in the highest PVL and LC subgroups. This pilot study is a first step in investigating the impact of BLV on mucosal immunity and will require further exploration in each of the various stages of disease progression.

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