Clinical response and immunomodulation following experimental challenge of calves with
type 2 noncytopathogenic bovine viral diarrhea virus

Archambault, Denis; Béliveau, Christian; Couture, Y.; Carman, Susy

doi:10.1051/vetres:2000117

Cited by 47 publications

(44 citation statements)

References 19 publications

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“…However, a marked lymphoid depletion of B-cell areas in the intestinal mucosa, together with the presence of pyknosis, cell fragmentation and TBMs, was observed. Although similar findings have been reported following infection by NCP strains of types 1 and 2 and in mucosal disease (Wilhelmsen et al, 1990;Archambault et al, 2000;Stoffregen et al, 2000;Teichmann et al, 2000; The difference compared with controls was statistically significant (*P,0.05; Mann-Whitney U-test for non-parametric distributions). et al, 2002, 2003a, b, 2004), the results obtained here demonstrate that GALT depletion was due to massive lymphocyte apoptosis, particularly in the B-cell compartments of Peyer's patches.…”

Section: Discussionsupporting

confidence: 78%

Apoptosis in lymphoid tissues of calves inoculated with non-cytopathic bovine viral diarrhea virus genotype 1: activation of effector caspase-3 and role of macrophages

Pedrera

Gómez-Villamandos

Romero-Trevejo

et al. 2009

Journal of General Virology

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The mechanisms responsible for lymphocyte apoptosis in bovine viral diarrhoea have not yet been clarified. Previous work suggests that bovine viral diarrhea virus (BVDV) is only directly responsible for the destruction of a small number of lymphocytes. The aim of this study was to clarify, in vivo, the role of macrophages in lymphocyte destruction through indirect mechanisms linked to the biosynthetic activation of these immunocompetent cells on ileal Peyer's patches, as well as the distribution and quantification of apoptosis. Eight colostrum-deprived calves were inoculated intranasally with a non-cytopathic strain of BVDV genotype 1 and killed in batches of two at 3, 6, 9 and 14 days post-inoculation (p.i.). The progressive depletion of Peyer's patches was found to be due to massive lymphocyte apoptosis, with an increase in cleaved caspase-3 and TUNEL-positive cells. Lymphoid depletion was accompanied, from 3 days p.i., by a significant rise in macrophage numbers both in lymphoid follicles and in interfollicular areas. Some macrophages showed signs of viral infection, together with subcellular changes indicative of phagocyte activation and, in some cases, of secretory activity. However, the number of macrophages that showed positive immunostaining for tumour necrosis factor-a and interleukin-1a, cytokines with a proven ability to induce apoptosis, remained low throughout the experiment in lymphoid follicles, where most apoptotic cells were found. These results thus appear to rule out a major involvement of macrophages and macrophage-secreted chemical mediators in the apoptosis of follicular B lymphocytes during BVDV infection. INTRODUCTIONApoptosis is a form of cell death recognized as an essential mechanism in morphogenesis and homeostasis of organs and tissues. The main morphological changes during apoptosis (cellular shrinkage, membrane blebbing, chromatin condensation at the nuclear periphery and nuclear fragmentation into apoptotic bodies) are the final result of a complex biochemical cascade of events (Huppertz et al., 1999;Rathmell & Thompson, 2002). The apoptosis cascade includes an initiation stage with induction of the cascade by external and internal stimuli, an execution stage with activation of effector proteases called caspases (cysteine-containing aspartic acid-specific proteases) and the apoptotic death stage including nuclear and cellular collapse (Huppertz et al., 1999;Hengartner, 2000). In vitro studies have elucidated two regulatory apoptosis pathways (intrinsic and extrinsic). Both pathways induce apoptosis via activation of the effector caspase-3, which, once activated, irreversibly executes cell death, so that activation of caspase-3 can be considered a hallmark of apoptosis (Stennicke et al., 1998;Huppertz et al., 1999).Apoptosis may also be involved in the immunopathogenesis of some viral diseases. There are several potential mechanisms by which viruses activate the apoptotic pathway. Some viruses may do so through the direct action of a specific viral protein (Noteborn et al., 1994;Zh...

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Section: Discussionsupporting

confidence: 78%

Apoptosis in lymphoid tissues of calves inoculated with non-cytopathic bovine viral diarrhea virus genotype 1: activation of effector caspase-3 and role of macrophages

Pedrera

Gómez-Villamandos

Romero-Trevejo

et al. 2009

Journal of General Virology

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“…The cp NADL reference strain of BVDV (ATCC # VR-534) was propagated in BVDVfree MDBK cells [4]. BMAdE1 220-8, 293A, and 293rtTA [15,25,26] were propagated in antibiotic-free Dulbecco minimal essential medium (DMEM) with high glucose concentration supplemented with 10% tetracycline-free fetal bovine serum (FBS) (Clontech Laboratories Inc., Palo Alto, BVDV NS3-induced apoptosis 215 USA).…”

Section: Cells and Virusesmentioning

confidence: 99%

The bovine viral diarrhea virus (BVDV) NS3 protein, when expressed alone in mammalian cells, induces apoptosis which correlates with caspase-8 and caspase-9 activation

2005

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-The bovine viral diarrhea virus (BVDV) strains exist as two biotypes, cytopathic (cp) and noncytopathic (ncp), according to their effects on tissue culture cells. It has been previously reported that cell death associated to cp BVDV in vitro is mediated by apoptosis. Here, experiments were conducted to determine the involvement of the NS3 protein in the induction of apoptosis. The NS3-and NS3∆50 (deleted from the NH2-terminal 50 amino acids)-cDNA encoding sequences of BVDV NADL cp reference strain were cloned into adenoviral vectors (AdV) from which the BVDV gene of interest could be expressed from a tetracycline-responsive promoter. A549tTA cells infected in vitro with NS3 or NS3∆50-expressing AdV showed cytopathic changes characterized by cell rounding and detachment, and nucleus chromatin condensation. DNA fragmentation assays, cytochrome c release, and activation of cellular caspases performed on these infected cells clearly correlated with the observed cytopathic changes with apoptosis. The BVDV NS3∆50-induced apoptotic process was inhibited by caspase-8-and -9-specific peptide inhibitors (Z-IETD-FMK and Z-LEHD-FMK). Furthermore, apoptosis was inhibited in cells expressing the R1 subunit of herpes simplex virus type 2 ribonucleotide reductase (HSV2-R1) or hsp70, two proteins which are known to inhibit apoptosis associated with caspase-8 activation and cytochrome c release-dependent caspase-9 activation, respectively. Given that HSV2-R1, a specific inhibitor of the caspase-8 activation pathway, efficiently suppressed apoptosis and also prevented caspase-9 activation, the overall results indicate that the BVDV NS3/NS3∆50 induces apoptosis initiated by caspase-8 activation and subsequent cytochrome c release-dependent caspase-9 activation. bovine viral diarrhea virus / NS3 protein / apoptosis / caspases

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“…Highly virulent isolates from field cases of severe acute BVD have been used to investigate the pathogenesis and pathology of acute BVD, 1,5,9,12,16,25,28,37 but there exists only 1 study using a BVDV 2 strain of low virulence. 27 It is still unclear how virus-host interactions differ between strains of high and low virulence.…”

Section: Bovine Viral Diarrhea Virus (Bvdv) Is a Pestivirusmentioning

confidence: 99%

“…8 Besides the highly virulent strains of BVDV 2, there also exist strains causing subclinical infections only. 35 These strains might be even more important for the spread of BVDV because they may circulate undetected in a herd for an extended time period and may predispose to secondary infections or disease.Highly virulent isolates from field cases of severe acute BVD have been used to investigate the pathogenesis and pathology of acute BVD, 1,5,9,12,16,25,28,37 but there exists only 1 study using a BVDV 2 strain of low virulence. 27 It is still unclear how virus-host interactions differ between strains of high and low virulence.…”

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confidence: 99%

Distribution of Viral Antigen and Development of Lesions after Experimental Infection of Calves with a BVDV 2 Strain of Low Virulence

Liebler-Tenorio

Ridpath²,

Neill³

2003

J VET Diagn Invest

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Abstract. To examine the virus-host interaction in subclinical bovine viral diarrhea virus (BVDV) infections, the spread of a BVDV 2 strain of low virulence to different organs and the development of lesions were investigated. Eight colostrum-deprived, clinically healthy, 2-3-month-old calves were intranasally inoculated with 10 6 tissue culture infective dose of the naturally occurring BVDV 2 strain 28508-5 of low virulence, and 2 served as controls. Two calves each were euthanized at days 3, 6, 9, and 13 postinoculation (pi). Representative tissues were processed for histology and immunohistology. Signs of overt clinical disease were absent. However, a mild temperature elevation at days 7 or 8 pi and a moderate decrease of circulating lymphocytes occurred in all inoculated calves. The BVDV antigen was detected at day 3 pi in several lymphoid tissues. At day 6 pi, BVDV antigen was found widespread in lymphoid tissues and multifocally in intestinal epithelial cells but was associated with no or subtle lesions only. At day 9 pi, much less BVDV antigen was detectable, but there was severe depletion of lymphoid tissues. At day 13 pi, BVDV antigen had been cleared from most lymphoid tissues that were at variable phases of depletion and recovery. In conclusion, the BVDV strain of low virulence spread to lymphoid tissues and intestinal epithelial cells but was rapidly eliminated. Transient depletion of lymphoid tissues was followed by recovery. Bovine viral diarrhea virus (BVDV) is a Pestivirusin the family Flaviviridae. 17 Infections with BVDV are widespread in cattle herds and cause severe economical losses in North America and Europe despite intense efforts to control or eradicate them. 19 On the basis of genomic differences in the 5ЈNTR region of BVDV, 2 species, BVDV 1 and BVDV 2, are currently differentiated. 4,17,33 The BVDV strains can grow in epithelial cell cultures with or without inducing a cytopathic (cp) effect, thus allowing further grouping in cp and noncytopathic (ncp) biotypes. 13,32 Infections with BVDV of both genotypes have been associated with a wide variety of clinical conditions including subclinical infection, reproductive failure, severe acute disease with or without hemorrhagic diathesis, and mucosal disease. 3 During the last decade, an increased number of field cases of severe acute BVD in all age groups of cattle has been reported. 8,10,18,30 The BVDV isolates from these outbreaks in North America predominantly belong to BVDV 2. 8 Besides the highly virulent strains of BVDV 2, there also exist strains causing subclinical infections only. 35 These strains might be even more important for the spread of BVDV because they may circulate undetected in a herd for an extended time period and may predispose to secondary infections or disease.Highly virulent isolates from field cases of severe acute BVD have been used to investigate the pathogenesis and pathology of acute BVD, 1,5,9,12,16,25,28,37 but there exists only 1 study using a BVDV 2 strain of low virulence. 27 It is still unclear how virus...

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Clinical response and immunomodulation following experimental challenge of calves with type 2 noncytopathogenic bovine viral diarrhea virus

Cited by 47 publications

References 19 publications

Apoptosis in lymphoid tissues of calves inoculated with non-cytopathic bovine viral diarrhea virus genotype 1: activation of effector caspase-3 and role of macrophages

Apoptosis in lymphoid tissues of calves inoculated with non-cytopathic bovine viral diarrhea virus genotype 1: activation of effector caspase-3 and role of macrophages

The bovine viral diarrhea virus (BVDV) NS3 protein, when expressed alone in mammalian cells, induces apoptosis which correlates with caspase-8 and caspase-9 activation

Distribution of Viral Antigen and Development of Lesions after Experimental Infection of Calves with a BVDV 2 Strain of Low Virulence

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