Cytopathic and non-cytopathic bovine viral diarrhoea virus biotypes affect fluid phase uptake and mannose receptor-mediated endocytosis in bovine monocytes

Boyd, Bobbie; Lee, Tekla M.; Kruger, E.F; Pinchuk, Lesya M.

doi:10.1016/j.vetimm.2004.06.009

Cited by 15 publications

(20 citation statements)

References 58 publications

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“…In general, cp BVDV showed more profound effect on the protein expression levels in bovine monocytes with significantly increased number of down-regulated proteins and decreased number of up-regulated proteins compared to the ncp BVDV biotype. This observation is in accord with our previous reports that cp BVDV in general, had more profound effects on antigen uptake mechanisms, TLR, cytokine and co-stimulatory molecule gene and protein kinase protein expression levels in bovine monocytes [8,9,11]. The observed significant biotype-related differences might explain the mechanisms by which cp BVDV, in contrast to ncp biotypes that do not induce cell death, cause pathological changes in infected cells, in particular antigen presenting cells.…”

Section: Discussionsupporting

confidence: 93%

“…This observation strongly supports our hypothesis that low doses of BVDV infection can be crucial to understand the complex pathogenesis of BVDV [8,9,11]. …”

Section: Discussionsupporting

confidence: 88%

“…In our earlier work we assessed selective and non-selective antigen uptake mechanisms in BVDV-infected monocytes and outlined some similarities and differences between the two BVDV biotypes [8]. Following the differences in the antigen uptake function of monocytes and using the same infection protocols we determined the TLR, cytokine and costimulatory molecules gene expression in the infected cells [9].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of Bovine Viral Diarrhea Viruses-infected monocytes: identification of cytopathic and non-cytopathic biotype differences

et al. 2010

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BackgroundBovine Viral Diarrhea Virus (BVDV) infection is widespread in cattle worldwide, causing important economic losses. Pathogenesis of the disease caused by BVDV is complex, as each BVDV strain has two biotypes: non-cytopathic (ncp) and cytopathic (cp). BVDV can cause a persistent latent infection and immune suppression if animals are infected with an ncp biotype during early gestation, followed by a subsequent infection of the cp biotype. The molecular mechanisms that underscore the complex disease etiology leading to immune suppression in cattle caused by BVDV are not well understood.ResultsUsing proteomics, we evaluated the effect of cp and ncp BVDV infection of bovine monocytes to determine their role in viral immune suppression and uncontrolled inflammation. Proteins were isolated by differential detergent fractionation and identified by 2D-LC ESI MS/MS. We identified 137 and 228 significantly altered bovine proteins due to ncp and cp BVDV infection, respectively. Functional analysis of these proteins using the Gene Ontology (GO) showed multiple under- and over- represented GO functions in molecular function, biological process and cellular component between the two BVDV biotypes. Analysis of the top immunological pathways affected by BVDV infection revealed that pathways representing macropinocytosis signalling, virus entry via endocytic pathway, integrin signalling and primary immunodeficiency signalling were identified only in ncp BVDV-infected monocytes. In contrast, pathways like actin cytoskeleton signalling, RhoA signalling, clathrin-mediated endocytosis signalling and interferon signalling were identified only in cp BDVD-infected cells. Of the six common pathways involved in cp and ncp BVDV infection, acute phase response signalling was the most significant for both BVDV biotypes. Although, most shared altered host proteins between both BVDV biotypes showed the same type of change, integrin alpha 2b (ITGA2B) and integrin beta 3 (ITGB3) were down- regulated by ncp BVDV and up- regulated by cp BVDV infection.ConclusionsThis study shows that, as we expected, there are significant functional differences in the host proteins that respond to cp or ncp BVDV infection. The combined use of GO and systems biology network modelling facilitated a better understanding of host-pathogen interactions.

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Section: Discussionsupporting

confidence: 93%

“…This observation strongly supports our hypothesis that low doses of BVDV infection can be crucial to understand the complex pathogenesis of BVDV [8,9,11]. …”

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Analysis of Bovine Viral Diarrhea Viruses-infected monocytes: identification of cytopathic and non-cytopathic biotype differences

et al. 2010

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“…Phagocytosis and macropinocytosis antigen uptake mechanisms play a crucial role in the innate immune responses by clearing pathogens at sites of infection. The endothytic pathways are also important early steps in triggering the adaptive immune responses which require processing of bacterial and viral pathogens and presentation of their antigens to CD4+ and CD8+ T cells (Boyd et al 2004). Since BVDV viruses are able to affect virtually all organs and systems in the body, including the innate and the adaptive immune system, it is important to know the mechanistic framework for the viral-host interactions in the complex etiology of the disease.…”

Section: Introductionmentioning

confidence: 99%

Understanding the Pathogenesis of Cytopathic and Noncytopathic Bovine Viral Diarrhea Virus Infection Using Proteomics

Ammari¹,

McCarthy²,

Nanduri³

et al. 2012

Proteomic Applications in Biology

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“…Although in-depth studies regarding the route of pestivirus entry are still lacking, it is believed that pestiviruses enter host cells by receptor-mediated endocytosis (12)(13)(14). Heparan sulfate and CD46 have been suggested to be cellular receptors for tissue culture-adapted BVDV and CSFV (15)(16)(17).…”

mentioning

confidence: 99%

Entry of Classical Swine Fever Virus into PK-15 Cells via a pH-, Dynamin-, and Cholesterol-Dependent, Clathrin-Mediated Endocytic Pathway That Requires Rab5 and Rab7

Shi

Liu

Zhou

et al. 2016

J Virol

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Classical swine fever virus (CSFV), a member of the genus Pestivirus within the family Flaviviridae, is a small, enveloped, positive-strand RNA virus. Due to its economic importance to the pig industry, the biology and pathogenesis of CSFV have been investigated extensively. However, the mechanisms of CSFV entry into cells are not well characterized. In this study, we used systematic approaches to dissect CSFV cell entry. We first observed that CSFV infection was inhibited by chloroquine and NH 4 Cl, suggesting that viral entry required a low-pH environment. By using the specific inhibitor dynasore, or by expressing the dominant negative (DN) K44A mutant, we verified that dynamin is required for CSFV entry. CSFV particles were observed to colocalize with clathrin at 5 min postinternalization, and CSFV infection was significantly reduced by chlorpromazine treatment, overexpression of a dominant negative form of the EPS15 protein, or knockdown of the clathrin heavy chain by RNA interference. These results suggested that CSFV entry depends on clathrin. Additionally, we found that endocytosis of CSFV was dependent on membrane cholesterol, while neither the overexpression of a dominant negative caveolin mutant nor the knockdown of caveolin had an effect. These results further suggested that CSFV entry required cholesterol and not caveolae. Importantly, the effect of DN mutants of three Rab proteins that regulate endosomal traffic on CSFV infection was examined. Expression of DN Rab5 and Rab7 mutants, but not the DN Rab11 mutant, significantly inhibited CSFV replication. These results were confirmed by silencing of Rab5 and Rab7. Confocal microscopy showed that virus particles colocalized with Rab5 or Rab7 during the early phase of infection within 45 min after virus entry. These results indicated that after internalization, CSFV moved to early and late endosomes before releasing its RNA. Taken together, our findings demonstrate for the first time that CSFV enters cells through the endocytic pathway, providing new insights into the life cycle of pestiviruses. IMPORTANCEBovine viral diarrhea virus (BVDV), a single-stranded, positive-sense pestivirus within the family Flaviviridae, is internalized by clathrin-dependent receptor-mediated endocytosis. However, the detailed mechanism of cell entry is unknown for other pestiviruses, such as classical swine fever (CSF) virus (CSFV). CSFV is the etiological agent of CSF, a highly contagious disease of swine that causes numerous deaths in pigs and enormous economic losses in China. Understanding the entry pathway of CSFV will not only advance our knowledge of CSFV infection and pathogenesis but also provide novel drug targets for antiviral intervention. Based on this objective, we used systematic approaches to dissect the pathway of entry of CSFV into PK-15 cells. This is the first report to show that the entry of CSFV into PK-15 cells requires a low-pH environment and involves dynamin-and cholesteroldependent, clathrin-mediated endocytosis that requires Rab5 and Rab7....

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Cytopathic and non-cytopathic bovine viral diarrhoea virus biotypes affect fluid phase uptake and mannose receptor-mediated endocytosis in bovine monocytes

Cited by 15 publications

References 58 publications

Analysis of Bovine Viral Diarrhea Viruses-infected monocytes: identification of cytopathic and non-cytopathic biotype differences

Analysis of Bovine Viral Diarrhea Viruses-infected monocytes: identification of cytopathic and non-cytopathic biotype differences

Understanding the Pathogenesis of Cytopathic and Noncytopathic Bovine Viral Diarrhea Virus Infection Using Proteomics

Entry of Classical Swine Fever Virus into PK-15 Cells via a pH-, Dynamin-, and Cholesterol-Dependent, Clathrin-Mediated Endocytic Pathway That Requires Rab5 and Rab7

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