Apoptosis and immuno-suppression in sheep infected with bluetongue virus serotype-23

Umeshappa, Channakeshava Sokke; Nanjundappa, Roopa Hebbandi; Pandey, Awadh Bihari

doi:10.1016/j.vetmic.2010.02.033

Cited by 32 publications

(65 citation statements)

References 45 publications

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“…The reduction in CD3 and CD79 reactivity in lymphoid tissues of BTV infected mice indicates lymphopenia, as it has been described commonly in sheep during infections with several BTV serotypes. One of the mechanisms proposed for lymphoid depletion includes apoptosis 34. Alternatively, BTV replication in lymphocytes, monocytes/macrophages and/or dendritic cells could result in cellular injury 35.…”

Section: Discussionmentioning

confidence: 99%

Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4

Marín-López¹,

Bermúdez²,

Calvo-Pinilla³

et al. 2016

Int. J. Biol. Sci.

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Bluetongue virus (BTV) replicates in lymphoid tissues where infected mononuclear leukocytes secrete proinflammatory and vasoactive mediators that can contribute to bluetongue (BT) pathogenesis. Using the well-characterized IFNAR(-/-) mice animal model, we have now studied the histopathology and dynamics of leukocyte populations in different target tissues (spleen, thymus, and lung) during BTV-4 infection by histological and immunohistochemical techniques. The spleen and thymus of BTV-4 infected mice showed severe lymphoid depletion on H&E stained sections. This finding was confirmed by IHC, showing moderate decreased immunopositivity against CD3 in the thymus, and scarce immunoreactivity against CD3 and CD79 in the rest of the white pulp in the spleen, together with an increase in MAC387 immunostaining. BTV-4 infection also induced the expression of active caspase-3 in the spleen, where apoptotic debris was observed by H&E. A dramatic increase in iNOS immunoreactivity associated to necrotic areas of the white pulp was observed, being less noticeable in the thymus and the lung. The induction of pro-inflammatory cytokines in tissues where BTV replicates was evaluated by measuring transcript levels by RT-qPCR. BTV-4 infection led to enhance transcription of IFN-γ, TNF, IL-6, IL-12-p40, and IL-1β mRNA in the thymus, spleen and lung, correlating with the level of virus replication in these tissues. Disease progression and pathogenesis in IFNAR(-/-) mice closely mimics hallmarks of bluetongue disease in ruminants. IFNAR(-/-) mice are a good choice to facilitate a faster advance in the field of orbiviruses.

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Section: Discussionmentioning

confidence: 99%

Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4

Marín-López¹,

Bermúdez²,

Calvo-Pinilla³

et al. 2016

Int. J. Biol. Sci.

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“…Various reports have indicated that infection of mammalian cells by viruses induces apoptosis (Roulston et al, 1999) and in some virus-induced diseases, apoptosis is a pathogenic mechanism that contributes in vivo to cell death, tissue injury and disease severity Samuel et al, 2007). Indeed, the induction of apoptosis has recently been implicated in the pathogenesis of bluetongue virus (BTV), the prototype orbivirus, in sheep (Umeshappa et al, 2010). In the present study, AHSV-infected insect and mammalian cells were analyzed for morphological and biochemical hallmarks of apoptosis.…”

Section: Intrinsic Pathwaymentioning

confidence: 99%

African horse sickness virus induces apoptosis in cultured mammalian cells

2012

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Infection of mammalian cell cultures with African horse sickness virus (AHSV) is known to result in dramatic cytopathic effects (CPE), but no CPE is observed in infected insect cell cultures despite productive virus replication. The basis for this phenomenon has not yet been investigated, but is suggestive of apoptosis being induced following virus infection of the mammalian cells. To investigate whether AHSV can induce apoptosis in infected mammalian cells, Culicoides variipennis (KC) insect cells and BHK-21 mammalian cells were infected with AHSV-9 and analyzed for morphological and biochemical hallmarks of apoptosis. In contrast to KC cells, infection of BHK-21 cells with AHSV-9 resulted in ultrastructural changes and nuclear DNA fragmentation, both of which are associated with the induction of apoptosis. Results also indicated that AHSV-9 infection of BHK-21 cells resulted in activation of caspase-3, a key agent in apoptosis, and in mitochondrial membrane depolarization. Cumulatively, the data indicate that the intrinsic pathway is activated in AHSVinduced apoptosis.Keywords: African horse sickness virus; Apoptosis; BHK-21 cells; Culicoides variipennis cells; Caspases; Intrinsic pathwayAfrican horse sickness virus (AHSV) is a species in the genus Orbivirus, family Reoviridae (Calisher and Mertens, 1998), and is the causative agent of African horse sickness (AHS), a highly infectious arthropod-borne (Culicoides spp.) disease of equids, of which the mortality rate in horses may exceed 90% (Coetzer and Erasmus, 1994;Guthrie, 2007). Although African horse sickness virus (AHSV) causes severe oedema and haemorrhages in horses, it is asymptomatic in the insect host (Mellor and Hamblin, 2004;Wilson et al., 2009). This is also reflected in tissue culture where AHSV causes rapid cell death in infected mammalian cells in culture, whereas infection of insect cells are unapparent and show no CPE (Mirchamsy et al., 1970;Osawa and Hazrati, 1965). The basis for this differential host response is not known, but may be due to the induction of apoptosis in infected mammalian cells. Indeed, analyses of endothelial cells of animals infected with AHSV indicated ultrastructural changes that could be suggestive of apoptosis (Gómez-Villamandos et al., 1999).Apoptosis is a selective process of physiological cell deletion in response to numerous developmental and environmental stimuli (Kerr et al., 1972). There are two common pathways for the induction of apoptosis, i.e. the extrinsic pathway, which is primarily initiated by virus attachment to receptors, and the intrinsic pathway, which is mediated by damage to the mitochondria (Duprez et al., 2009). Various reports have indicated that infection of mammalian cells by viruses induces apoptosis (Roulston et al., 1999) and in some virus-induced diseases, apoptosis is a pathogenic mechanism that contributes in vivo to cell death, tissue injury and disease severity Samuel et al., 2007). Indeed, the induction of apoptosis has recently been implicated in the pathogenesis of bluetong...

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“…Other viruses with immunosuppressive capacity have been reported to disrupt hematopoiesis (27,30,38). Various studies have shown that BTV induces a transient immunosuppression with a predisposition to secondary microbial infections (7,22,39). Therefore, our new findings in which BTV targets HSCs suggest that this phenomenon is likely to contribute to the transient immunosuppression observed in the pathogenesis of BTV at early time points of infection.…”

Section: Btv Infects Ovine Thymus and Spleen Cells But Not Hscsmentioning

confidence: 66%

“…In addition, several reports have pointed out that BTV can induce lymphopenia at the peak of infection, leading to immunosuppression, and can increase susceptibility to secondary microbial infection (22)(23)(24). One of the mechanisms proposed for BTV-induced immunosuppression and lymphoid depletion in lymph nodes includes lymphocyte apoptosis (22,25).…”

mentioning

confidence: 99%

Type I Interferon Limits the Capacity of Bluetongue Virus To Infect Hematopoietic Precursors and Dendritic Cells In Vitro and In Vivo

Rodríguez-Calvo

Rojas

Martı́n

et al. 2014

J Virol

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Apoptosis and immuno-suppression in sheep infected with bluetongue virus serotype-23

Cited by 32 publications

References 45 publications

Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4

Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4

African horse sickness virus induces apoptosis in cultured mammalian cells

Type I Interferon Limits the Capacity of Bluetongue Virus To Infect Hematopoietic Precursors and Dendritic Cells In Vitro and In Vivo

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