scholarly journals RNA Sequencing (RNA-Seq) Based Transcriptome Analysis in Immune Response of Holstein Cattle to Killed Vaccine against Bovine Viral Diarrhea Virus Type I

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 344 ◽  
Author(s):  
Bryan Irvine Lopez ◽  
Kier Gumangan Santiago ◽  
Donghui Lee ◽  
Seungmin Ha ◽  
Kangseok Seo

Immune response of 107 vaccinated Holstein cattle was initially obtained prior to the ELISA test. Five cattle with high and low bovine viral diarrhea virus (BVDV) type I antibody were identified as the final experimental animals. Blood samples from these animals were then utilized to determine significant differentially expressed genes (DEGs) using the RNA-seq transcriptome analysis and enrichment analysis. Our analysis identified 261 DEGs in cattle identified as experimental animals. Functional enrichment analysis in gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed the DEGs potentially induced by the inactivated BVDV type I vaccine, and might be responsible for the host immune responses. Our findings suggested that inactivated vaccine induced upregulation of genes involved in different GO annotations, including antigen processing and presentation of peptide antigen (via MHC class I), immune response, and positive regulation of interferon-gamma production. The observed downregulation of other genes involved in immune response might be due to inhibition of toll-like receptors (TLRs) by the upregulation of the Bcl-3 gene. Meanwhile, the result of KEGG pathways revealed that the majority of DEGs were upregulated and enriched to different pathways, including cytokine-cytokine receptor interaction, platelet activation, extracellular matrix (ECM) receptor interaction, hematopoietic cell lineage, and ATP-binding cassette (ABC) transporters. These significant pathways supported our initial findings and are known to play a vital role in shaping adaptive immunity against BVDV type 1. In addition, type 1 diabetes mellitus pathways tended to be significantly enriched. Thus, further studies are needed to investigate the prevalence of type 1 diabetes mellitus in cattle vaccinated with inactivated and live BVDV vaccine.

2020 ◽  
Author(s):  
Yanhua HE ◽  
Jinke HE ◽  
Yajun YANG ◽  
Xin HUANG ◽  
Yunfen ZHANG ◽  
...  

Abstract Background: Monocytes are significant players in the detection of invading pathogens, particularly in pathogen defense. Bovine Viral Diarrhea Virus (BVDV) can cause a persistent infection and immune suppression if animals are infected with an non-cytopathic (ncp) biotype. However, its exact role in ncp BVDV1-infected bovine monocytes remains poorly understood. Results: RNA sequencing (RNA-seq) was used to investigate the effect of ncp BVDV1 infection on the transcriptional profile of bovine monocytes. Compared with the non-infected cells, 9959 and 7977 differentially expressed gene (DEGs) were identified at 2 and 24 h hpi, respectively. These DEGs were associated with signal transduction, immune response, apoptotic process, cellular process , binding and cellular component. The differential expression profiles of select the type I interferon signaling pathway , interferon (IFN)-stimulated genes (ISGs), and genes involved in the innate immune response, including IRF7, DDX3X, TLR13, DDX58(RIG-I), MVAS, TLR9, TRAF6, IRF1, IFIT1, STAT1, ISG20, TRIM25, MX1,NLRX1, CYLD, SIKE1 and ZAP70 were confirmed by real-time quantitative PCR and consistent with the RNA-seq data. Conclusion: Our transciptome anslysis provides useful initial data towards better understanding of the infection mechanisms used by ncp BVDV1, while highlighting the potential molecular relationships occurring between the virus and the host’s immune response.


2009 ◽  
Vol 36 (3) ◽  
pp. 129-139 ◽  
Author(s):  
Natalia P. Smirnova ◽  
Andrey A. Ptitsyn ◽  
Kathleen J. Austin ◽  
Helle Bielefeldt-Ohmann ◽  
Hana Van Campen ◽  
...  

The consequences of viral infection during pregnancy include impact on fetal and maternal immune responses and on fetal development. Transplacental infection in cattle with noncytopathic bovine viral diarrhea virus (ncpBVDV) during early gestation results in persistently infected (PI) fetuses with life-long viremia and susceptibility to infections. Infection of the fetus during the third trimester or after birth leads to a transient infection cleared by a competent immune system. We hypothesized that ncpBVDV infection and presence of an infected fetus would alter immune response and lead to downregulation of proinflammatory processes in pregnant dams. Naïve pregnant heifers were challenged with ncpBVDV2 on day 75 (PI fetus) and day 175 [transiently infected (TI) fetus] or kept uninfected (healthy control fetus). Maternal blood samples were collected up to day 190 of gestation. Genome-wide microarray analysis of gene expression in maternal peripheral white blood cells, performed on days 160 and 190 of gestation, revealed multiple signal transduction pathways affected by ncpBVDV infection. Acute infection and presence of a TI fetus caused upregulation of the type I interferon (IFN) pathway genes, including dsRNA sensors and IFN-stimulated genes. The presence of a PI fetus caused prolonged downregulation of chemokine receptor 4 (CXCR4) and T cell receptor (TCR) signaling in maternal blood cells. We conclude that: 1) infection with ncpBVDV induces a vigorous type I IFN response, and 2) presence of a PI fetus causes downregulation of important signaling pathways in the blood of the dam, which could have deleterious consequences on fetal development and the immune response.


2019 ◽  
Author(s):  
Yanhua HE ◽  
Yajun YANG ◽  
Xin HUANG ◽  
Yunfen ZHANG ◽  
Chencheng XIAO ◽  
...  

Abstract Background: Monocytes are significant players in the detection of invading pathogens, particularly in pathogen defense. Bovine Viral Diarrhea Virus (BVDV) can cause a persistent infection and immune suppression if animals are infected with an non-cytopathic (ncp) biotype. However, its exact role in ncp BVDV-infected bovine monocytes remains poorly understood. To explore the immune suppression mechanisms of ncp BVDV, we used a transcriptomics approach to find genes with differential expression patterns in monocytes during infection with ncp BVDV over time. Results: Bovine monocytes were sampled at 2 and 24 h post-infection (hpi) to represent the early and late stages of an ncp biotype strain of bovine viral diarrhea virus infection. Compared with the non-infected cells, 9959 and 7977 differentially expressed gene (DEGs) were identified at 2 and 24 h hpi, respectively. These DEGs were associated with signal transduction, immune response, apoptotic process, cellular process , binding and cellular component. The differential expression profiles of select the type I interferon signaling pathway , interferon (IFN)-stimulated genes (ISGs), and genes involved in the innate immune response, including IRF7, DDX3X, TLR13, DDX58(RIG-I), MVAS, TLR9, TRAF6, IRF1, IFIT1, STAT1, ISG20, TRIM25, MX1,NLRX1, CYLD, SIKE1 and ZAP70 were confirmed by real-time quantitative PCR and consistent with the RNA-seq data. These results indicated that infection with ncp BVDV could activate type I interferon signaling pathway in bovine monocytes and induces weak ISGs responses, which extends our present understanding how the virus modulates the immune response and leads to better understanding behind the immunopathogenesis of ncp BVDV. Conclusion: Our transciptome anslysis provides useful initial data towards better understanding of the infection mechanisms used by ncp BVDV, while highlighting the potential molecular relationships occurring between the virus and the host’s immune response.


1998 ◽  
Vol 10 (2) ◽  
pp. 135-139 ◽  
Author(s):  
Steven R. Bolin ◽  
Julia F. Ridpath

One thousand lots of pooled fetal bovine serum (FBS) were tested for contamination with bovine viral diarrhea virus (BVDV) and/or for contamination with neutralizing antibody against BVDV. Noncytopathic or cytopathic BVDV was isolated from 203 lots of FBS. Analysis of the viral isolates identified 115 type 1 and 65 type 2 BVDV isolates. An additional 23 virus isolates were mixtures of >2 BVDV isolates and were not classified to viral genotype. Further characterization of the type 1 viruses identified 51 subgenotype 1a and 64 subgenotype 1b BVDV isolates. Viral neutralizing antibody was detected in 113 lots of FBS. Differential viral neutralization indicated that type 1 BVDV induced the antibody detected in 48 lots of FBS and type 2 BVDV induced the antibody detected in 16 lots of FBS.


2007 ◽  
Vol 88 (3) ◽  
pp. 748-757 ◽  
Author(s):  
Cristina T. Rosas ◽  
Patricia König ◽  
Martin Beer ◽  
Edward J. Dubovi ◽  
B. Karsten Tischer ◽  
...  

Bovine viral diarrhea virus (BVDV) is an economically important pathogen of cattle that is maintained in the population by persistently infected animals. Virus infection may result in reproductive failure, respiratory disease and diarrhoea in naïve, susceptible bovines. Here, the construction and characterization of a novel vectored vaccine, which is based on the incorporation of genes encoding BVDV structural proteins (C, Erns, E1, E2) into a bacterial artificial chromosome of the equine herpesvirus type 1 (EHV-1) vaccine strain RacH, are reported. The reconstituted vectored virus, rH_BVDV, expressed BVDV structural proteins efficiently and was indistinguishable from parental vector virus with respect to growth properties in cultured cells. Intramuscular immunization of seronegative cattle with rH_BVDV resulted in induction of BVDV-specific serum neutralizing and ELISA antibodies. Upon experimental challenge infection of immunized calves with the heterologous BVDV strain Ib SE5508, a strong anamnestic boost of the neutralizing-antibody response was observed in all vaccinated animals. Immunized animals presented with reduced viraemia levels and decreased nasal virus shedding, and maintained higher leukocyte counts than mock-vaccinated controls.


2020 ◽  
Vol 103 (3) ◽  
pp. 560-571 ◽  
Author(s):  
Hanah M Georges ◽  
Katie J Knapek ◽  
Helle Bielefeldt-Ohmann ◽  
Hana Van Campen ◽  
Thomas R Hansen

Abstract Bovine viral diarrhea virus continues to cost the cattle industry millions of dollars each year despite control measures. The primary reservoirs for bovine viral diarrhea virus are persistently infected animals, which are infected in utero and shed the virus throughout their lifetime. The difficulty in controlling the virus stems from a limited understanding of transplacental transmission and fetal development of immunotolerance. In this study, pregnant bovine viral diarrhea virus naïve heifers were inoculated with bovine viral diarrhea virus on day 75 of gestation and fetal spleens were collected on gestational days 82, 97, 190, and 245. Microarray analysis on splenic RNA from days 82 and 97 revealed an increase in signaling for the innate immune system and antigen presentation to T cells in day 97 persistently infected fetuses compared to controls. Reverse transcription quantitative polymerase chain reaction on select targets validated the microarray revealing a downregulation of type I interferons and lymphocyte markers in day 190 persistently infected fetuses compared to controls. Protein was visualized using western blot and tissue sections were analyzed with hematoxylin and eosin staining and immunohistochemistry. Data collected indicate that fetal immunotolerance to bovine viral diarrhea virus developed between days 97 and 190, with mass attenuation of the immune system on day 190 of gestation. Furthermore, lymphocyte transcripts were initially unchanged then downregulated, suggesting that immunotolerance to the virus stems from a blockage in lymphocyte activation and hence an inability to clear the virus. The identification of lymphocyte derived immunotolerance will aid in the development of preventative and viral control measures to implement before or during pregnancy.


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