scholarly journals Melatonin as Immune Potentiator for Enhancing Subunit Vaccine Efficacy against Bovine Viral Diarrhea Virus

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1039
Author(s):  
Yi-Xuan Wang ◽  
Guang-Hui Yang ◽  
Lin-Lin Zhang ◽  
Jing Wang ◽  
Jiu-Feng Wang

Bovine viral diarrhea virus (BVDV) is a pathogen associated with substantial economic losses in the dairy cattle industry. Currently, there are no effective vaccines against BVDV. Melatonin (MT) has been shown to have anti-inflammatory and anti-viral properties, and the use of MF59 in vaccines significantly enhances vaccine efficiency. Here, MT and MF59 were added into the Erns-LTB vaccine. Subsequently, their inhibitory activity on the NF-κB signaling pathway in Mardin-Darby Bovine Kidney cells and the hippocampus was assessed using western blot and quantitative reverse transcription PCR. The findings revealed that MT in the Erns-LTB vaccine decreases the phosphorylation of p65 proteins caused by BVDV infection. In addition, MT decreased the mRNA levels of IL-1β and IL-6 in vitro, but increased the production of IFN-α, IFN-β, Mx1 in vitro, brain-derived neurotrophic factor, cyclic amp response element-binding protein, and the stem cell factor in vivo. Furthermore, treatment with Erns-LTB + MF59 + MT stimulated the production of T lymphocytes, alleviated pathological damage, decreased expressions of BVDV antigen, and tight junction proteins in mice. These findings imply that MT has potential for use in the Erns-LTB vaccine to inhibit BVDV infection and regulate the immune responses of T-cells by inhibiting the NF-κB signaling pathway.

2002 ◽  
Vol 76 (2) ◽  
pp. 923-927 ◽  
Author(s):  
B. Charleston ◽  
L. S. Brackenbury ◽  
B. V. Carr ◽  
M. D. Fray ◽  
J. C. Hope ◽  
...  

ABSTRACT In contrast to the results of previous in vitro studies, experimental infection of calves with noncytopathic bovine viral diarrhea virus (ncpBVDV) was found to induce strong alpha/beta and gamma interferon responses in gnotobiotic animals. These responses were associated with depressed levels of transforming growth factor β (TGF-β) in serum. The results of this study indicate that the immunosuppression caused by ncpBVDV is not associated with low interferon responses or elevated levels of TGF-β.


2008 ◽  
Vol 20 (1) ◽  
pp. 156 ◽  
Author(s):  
A. Bielanski ◽  
J. Algire ◽  
A. Lalonde

Bovine viral diarrhea virus (BVDV) infection affects cattle throughout the world. It causes significant economic losses in the cattle industry. The potential for transmission of a cytopathic biotype of BVDV by in vivo-derived embryos has been thought to be negligible. However, there is no study to prove non-transmission of the most common field isolate of noncytopathic biotype (NCPB) of BVDV by IVF embryos. Here we report on the preliminary outcome of embryo transfer (ET) of IVF embryos exposed in vitro to type-1 (NY-1) and type-2 (P-131) genotypes of NCPB of BVDV. For this experiment, IVF embryos were generated using standard methods which briefly involve: maturation of cumulus–oocyte complexes in TCM medium, fertilization of oocytes with BVDV-free semen, and culture of zygotes to the blastocyst stage in SOF medium without somatic cells. Day 7 blastocysts were exposed for 1 h to NY-1 or P-131 (103–107 TCID50 mL–1) BVDV strains before being washed (without trypsin) as recommended by IETS. Two embryos were transferred on each occasion. Embryo recipients were virus-free and anti-BVDV antibody-free prior to ET. The recipients remained individually in isolation premises after ET. In total, 126 ET procedures were performed resulting in 57 pregnancies and 34 calves born free of the infectious virus and BVDV antibodies (5 pregnancies are still pending). In total, 23 pregnancies were lost after 30 days. Exposure of embryos to type-2 BVDV resulted in a loss of 46% (17/37) of pregnancies after 30 days post-ET and 20 recipients seroconverted to BVDV. Within seroconverted and pregnant animals (n = 14), only 2 recipients maintained pregnancy and delivered uninfected calves at term. In contrast, exposure of embryos to type-1 caused 30% (6/20) of the pregnancy losses after 30 days and did not cause any seroconversion in ET recipients. After washing, 33% (3/9) and 38% (17/44) single embryos from the infected pool of IVF embryos tested positive for the BVDV. In conclusion, under these experimental conditions, a proportion of recipients was apparently infected after receipt of BVDV-exposed embryos. However, all of the calves that survived to term were BVDV-free and anti-BVDV antibody free.


Virology ◽  
2005 ◽  
Vol 331 (2) ◽  
pp. 349-356
Author(s):  
Christina L. Topliff ◽  
Seung K. Chon ◽  
Ruben O. Donis ◽  
Kent M. Eskridge ◽  
Clayton L. Kelling

2014 ◽  
Vol 60 (7) ◽  
pp. 455-460 ◽  
Author(s):  
Qiang Fu ◽  
Huijun Shi ◽  
Mengting Shi ◽  
Luping Meng ◽  
Hui Zhang ◽  
...  

MicroRNAs (miRNAs) are small, endogenous, noncoding RNA molecules that serve as powerful regulators of multiple cellular processes, including apoptosis, differentiation, growth, and proliferation. Bovine viral diarrhea virus (BVDV) contributes significantly to health-related economic losses in the beef and dairy industries. Although BVDV-induced apoptosis correlates with increased intracellular viral RNA accumulation and with bta-miR-29b (miR-29b) expression upregulation in Madin–Darby bovine kidney (MDBK) cells infected with BVDV strain NADL, the role of miR-29b in regulating BVDV-infection-related apoptosis remains unexplored. Here, we report that miR-29b serves as a new miRNA regulating apoptosis. We showed that miR-29b target sequences were present in the 3′ untranslated regions of 2 key apoptosis regulators mRNAs, cysteine aspartases-7 (caspase-7) and nuclear apoptosis-inducing factor 1 (NAIF1). Indeed, upon miRNA overexpression, both mRNA and protein levels of caspase-7 and NAIF1 were decreased. We further found that miR-29b attenuated apoptosis by directly regulating intracellular levels of caspase-7 and NAIF1. Moreover, apoptosis blockage by miR-29b was rescued upon co-infection of MDBK cells with lentiviruses expressing caspase-7 and NAIF1. Importantly, miR-29b decreased BVDV NADL envelope glycoprotein E1 mRNA levels and suppressed viral replication. These studies advance our understanding of the mechanisms of miRNAs in mediating the cells combating viral infections.


2021 ◽  
Vol 8 ◽  
Author(s):  
Kai Wang ◽  
Carole Thomas ◽  
Shujun Zhang ◽  
D. Claire Wathes ◽  
Zhangrui Cheng

Bovine Viral Diarrhea virus (BVDV) is a pestivirus with a single-stranded, positive sense RNA genome. It is endemic in many cattle populations, causing major economic losses in part due to reduced fertility. BVDV exhibits great genetic diversity and is classified as type 1 or 2 (BVDV-1, BVDV-2) with either non-cytopathogenic (ncp) or cytopathogenic (cp) biotypes. Differing strains of ncpBVDV differ in virulence, affecting clinical outcome. BVDV replicates in the reproductive tract, affecting host immunity and embryo survival. This study used an in vitro model of primary bovine endometrial cell cultures to compare the effects of two BVDV ncp type 1a strains of differing virulence (termed HO and KY) on endometrial transcription of candidate interferon stimulated genes (ISG) using qPCR. Half the cultures were stimulated with interferon tau (IFNT, the conceptus produced pregnancy recognition factor) in the presence or absence of viral infection. Cultures were replicated on cells from 10 BVDV-free cows. IFNT treatment stimulated transcription of 10 candidate ISGs, whereas both ncpBVDV-1 strains alone inhibited transcription of 8/10 ISGs. In combined BVDV-1+IFNT cultures, the stimulatory effect of IFNT on expression of GBP4, ISG15, HERC5, RSAD2, IFIH1, IFIT3, and MX1 was significantly inhibited by HO, but only ISG15, RSAD2, IFI27, and IFIT3 were decreased by KY. Inhibition by HO was generally greater. The IFNT-induced expression of TRIM56 was, however, increased by HO. These data show that HO, the more virulent ncpBVDV-1 strain, has a greater capacity to inhibit key antiviral pathways. These differences need confirmation at the protein level but may influence immune tolerance of the host. They could also reduce fertility by increasing uterine susceptibility to bacterial infection and disrupting IFNT-mediated pregnancy recognition.


2021 ◽  
Vol 8 ◽  
Author(s):  
Rui Yao ◽  
Yueren Xu ◽  
Lang Wang ◽  
Dawei Wang ◽  
Linchang Ren ◽  
...  

Bovine Viral Diarrhea Virus (BVDV) is the main pathogen of bovine viral diarrhea disease (BVD), which leads to enormous economic losses in the cattle industry. A sensitive and specific detection for BVDV is advantageous to the control of BVDV. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have been used for detecting virus RNA. In this study, the expression and purification of LwCas13a protein was optimized and the RNase activity of LwCas13a in vitro was verified. CRISPR-LwCas13a system could detect BVDV virus and BVDV RNA with high specificity and simplicity. The detection limit of the LwCas13a system was 103 pM, and there were no cross-reactions with HEK293T and MDBK. In summary, a sensitive, specific, and simple nucleic acid detection method based on CRISPR-Cas13a was developed for BVDV. This method provides a new detection strategy for early diagnosis of BVDV.


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