scholarly journals Matrine exhibits antiviral activity in a PRRSV/PCV2 co-infected mouse model

2020 ◽  
Author(s):  
Na Sun ◽  
Hua Zhang ◽  
Panpan Sun ◽  
Ajab Khan ◽  
Jianhua Guo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Interstitial Pneumonia ◽  
Normal Control ◽  
Virus Replication ◽  
Pcv2 Infection ◽  
Economic Losses ◽  
Treatment Groups ◽  
Qpcr Analysis ◽  
Antiviral Activities ◽  
Pcv2 Replication

Abstract BackgroundPRRSV and PCV2 co-infection is very common in swine industry which results in huge economic losses worldwide. Although vaccination is used to prevent viral diseases, immunosuppression induced by PRRSV and PCV2 leads to vaccine failure. Our previous results have demonstrated that Matrine possessed antiviral activities against PRRSV/PCV2 co-infection in vitro. To establish a PRRSV/PCV2 co-infected KM mouse model and evaluate the antiviral activities of Matrine against PRRSV/PCV2 co-infection. A total of 144 KM mice were randomly divided into six groups with 24 mice in each group, named as: normal control, PRRSV/PCV2 co-infected group (PRRSV/PCV2 group), Ribavirin treatment positive control (Ribavirin control) and Matrine treatment groups (Matrine 40 mg/kg, Matrine 20 mg/kg and Matrine 10 mg/kg). Except normal control group, all mice in other five groups were inoculated with PRRSV, followed by PCV2 at 2 h later. At 7 days post-infection (dpi), mice in the treatment groups were intraperitoneally administered with various doses of Matrine and Ribavirin, twice a day for 5 consecutive days. ResultsPRRSV N and PCV2 CAP genes were detected by PCR in multiple tissues including heart, liver, spleen, lungs, kidneys, thymus and inguinal lymph nodes. The viral load of PCV2 was the highest in liver followed by thymus and spleen. Although PRRSV were detected in most of the tissues, but the replication of PRRSV was not significantly increased, as shown by qPCR analysis. Comparing with PCV2 infection alone, PRRSV infection significantly elevated PCV2 replication and also exacerbated PCV2 induced interstitial pneumonia. qPCR analysis demonstrated that 40 mg/ml Matrine significantly attenuated PCV2 replication in liver and alleviated virus induced interstitial pneumonia, suggesting that Matrine could directly inhibit virus replication. In addition, Matrine treatment enhanced peritoneal macrophages phagocytosis at 13 and 16 dpi, and 40 mg/kg of Matrine increased the proliferation activity of lymphocytes. Body weight gain was continuously promoted by administrating Matrine at 10 mg/kg.ConclusionMatrine possessed antiviral activities via inhibiting virus replication and regulating immune functions in mice co-infected by PRRSV/PCV2. These data provide new insight into controlling PRRSV and PCV2 infection and support further the research for developing Matrine as a new possible veterinary medicine.

scholarly journals Immunogenicity and protective efficacy of enterotoxigenic Escherichia coli (ETEC) total RNA against ETEC challenge in a mouse model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mandi Liu ◽  
Yue Zhang ◽  
Di Zhang ◽  
Yun Bai ◽  
Guomei Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mouse Model ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Enterotoxigenic Escherichia Coli ◽  
Economic Losses ◽  
Th2 Response ◽  
Total Rna ◽  
Etec Infection

AbstractEnterotoxigenic Escherichia coli (ETEC), an essential cause of post-weaning diarrhea (PWD) in piglets, leads to significant economic losses to the pig industry. The present study aims to identify the role of ETEC total RNA in eliciting immune responses to protect animals against ETEC infection. The results showed that the total RNA isolated from pig-derived ETEC K88ac strain effectively stimulated the IL-1β secretion of porcine intestinal epithelial cells (IPEC-J2). The mouse model immunized with ETEC total RNA via intramuscular injection (IM) or oral route (OR) was used to evaluate the protective efficiency of the ETEC total RNA. The results suggested that 70 μg ETEC total RNA administered by either route significantly promoted the production of the serum IL-1β and K88ac specific immunoglobulins (IgG, IgM, and IgA). Besides, the ETEC RNA administration augmented strong mucosal immunity by elevating K88ac specific IgA level in the intestinal fluid. Intramuscularly administered RNA induced a Th1/Th2 shift toward a Th2 response, while the orally administered RNA did not. The ETEC total RNA efficiently protected the animals against the ETEC challenge either by itself or as an adjuvant. The histology characterization of the small intestines also suggested the ETEC RNA administration protected the small intestinal structure against the ETEC infection. Particularly of note was that the immunity level and protective efficacy caused by ETEC RNA were dose-dependent. These findings will help understand the role of bacterial RNA in eliciting immune responses, and benefit the development of RNA-based vaccines or adjuvants.

scholarly journals Cyclic Hypoxia Exposure Accelerates the Progression of Amoebic Gill Disease

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 597
Author(s):  
Tina Oldham ◽  
Tim Dempster ◽  
Philip Crosbie ◽  
Mark Adams ◽  
Barbara Nowak
Keyword(s):  
Atlantic Salmon ◽  
Economic Losses ◽  
Post Inoculation ◽  
Diel Pattern ◽  
Marine Aquaculture ◽  
Hypoxia Exposure ◽  
Qpcr Analysis ◽  
Serious Infections ◽  
Gill Disease ◽  
Hypoxic Treatment

Amoebic gill disease (AGD), caused by the amoeba Neoparamoeba perurans, has led to considerable economic losses in every major Atlantic salmon producing country, and is increasing in frequency. The most serious infections occur during summer and autumn, when temperatures are high and poor dissolved oxygen (DO) conditions are most common. Here, we tested if exposure to cyclic hypoxia at DO saturations of 40–60% altered the course of infection with N. perurans compared to normoxic controls maintained at ≥90% DO saturation. Although hypoxia exposure did not increase initial susceptibility to N. perurans, it accelerated progression of the disease. By 7 days post-inoculation, amoeba counts estimated from qPCR analysis were 1.7 times higher in the hypoxic treatment than in normoxic controls, and cumulative mortalities were twice as high (16 ± 4% and 8 ± 2%), respectively. At 10 days post-inoculation, however, there were no differences between amoeba counts in the hypoxic and normoxic treatments, nor in the percentage of filaments with AGD lesions (control = 74 ± 2.8%, hypoxic = 69 ± 3.3%), or number of lamellae per lesion (control = 30 ± 0.9%, hypoxic = 27.9 ± 0.9%) as determined by histological examination. Cumulative mortalities at the termination of the experiment were similarly high in both treatments (hypoxic = 60 ± 2%, normoxic = 53 ± 11%). These results reveal that exposure to cyclic hypoxia in a diel pattern, equivalent to what salmon are exposed to in marine aquaculture cages, accelerated the progression of AGD in post-smolts.

scholarly journals Acute lung injury inhibition by juglone in LPS induced sepsis mouse model involves Sirt1 activation

2020 ◽  
Vol 19 (5) ◽  
pp. 1001-1007
Author(s):  
Qiong Hu ◽  
Chunai Yang ◽  
Fenshuang Zheng ◽  
Hongdan Duan ◽  
Yangshan Fu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Inflammatory Cytokines ◽  
Alveolar Epithelial Cells ◽  
Control Group ◽  
Western Blot Assay ◽  
Edema Formation ◽  
Sirt1 Expression ◽  
Treatment Groups

Purpose: To investigate the effect of juglone on LPS induced lung injury in a mouse model and in TC 1cell line.Methods: Edema formation in lungs were measured by determination of lung wet/dry weight. Expressions of various proteins were assessed by western blot assay, while Sirt1 level was assessed using immunohistochemistry. Mice were randomly assigned to nine groups of 10 mice each: normal control, untreated and seven juglone treatment groups. Acute lung injury was induced in mice by injecting LPS (10 mg/kg) via intraperitoneal route (ip). The treatment groups were given 10, 20, 30, 40, 50, 60 and 100 μM of juglone, ip, respectively.Results: The levels of MMP-9, IL-6, IL-1β and iNOS were significantly higher in acute lung injury induced mice compared than the control group (p < 0.05). Treatment of the mice with juglone significantly decreased LPS-induced up-regulation of inflammatory cytokines in a dose-dependentmanner. The production of inflammatory cytokines was almost completely inhibited in the mice treated with 100 mg/kg dose of juglone, while treatment of the LPS-stimulated TC 1 cells with juglone upregulated the expression of Sirt1 mRNA. Down-regulation of Sirt1 expression by siRNA inhibited the effect of juglone on LPS-induced increase in inflammatory cytokine production.Conclusion: Juglone prevents lung injury in mice via up-regulation of Sirt1 expression. Therefore, juglone might be useful for the development of a treatment strategy for lung injury. Keywords: Inflammatory, Sirtuin, Edema, Cytokines, Lung injury, TC 1 lung alveolar epithelial cells, Sirt1

The small molecule AZD6244 inhibits dengue virus replication in vitro and protects against lethal challenge in a mouse model

2020 ◽  
Vol 165 (3) ◽  
pp. 671-681 ◽  
Author(s):  
Leonardo C. de Oliveira ◽  
Aryádina M. Ribeiro ◽  
Jonas D. Albarnaz ◽  
Alice A. Torres ◽  
Luís F. Z. Guimarães ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dengue Virus ◽  
Virus Replication ◽  
Small Molecule ◽  
Lethal Challenge

scholarly journals Inhibition of Vaccinia Virus Replication by Two Small Interfering RNAs Targeting B1R and G7L Genes and Their Synergistic Combination with Cidofovir

2009 ◽  
Vol 53 (6) ◽  
pp. 2579-2588 ◽  
Author(s):  
Solenne Vigne ◽  
Sophie Duraffour ◽  
Graciela Andrei ◽  
Robert Snoeck ◽  
Daniel Garin ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Virus Replication ◽  
Synergistic Effects ◽  
Terrorist Attack ◽  
Combined Therapy ◽  
Interferon Response ◽  
Small Interfering Rnas ◽  
Antiviral Activities ◽  
Inhibitory Agents

ABSTRACT In view of the threat of the potential use of variola virus in a terrorist attack, considerable efforts have been performed to develop new antiviral strategies against orthopoxviruses. Here we report on the use of RNA interference, either alone or in combination with cidofovir, as an approach to inhibit orthopoxvirus replication. Two selected small interfering RNAs (siRNAs), named siB1R-2 and siG7L-1, and a previously reported siRNA, i.e., siD5R-2 (which targets the viral D5R mRNA), were evaluated for antiviral activity against vaccinia virus (VACV) by plaque reduction and virus yield assays. siB1R-2 and siG7L-1, administered before or after viral infection, reduced VACV replication by more than 90%. Also, these two siRNAs decreased monkeypox virus replication by 95% at a concentration of 1 nM. siB1R-2 and siG7L-1 were demonstrated to specifically silence their corresponding transcripts, i.e., B1R and G7L mRNAs, without induction of a beta interferon response. Strong synergistic effects were observed when siB1R-2, siG7L-1, or siD5R-2 was combined with cidofovir. In addition, the antiviral activities of these three siRNAs were evaluated against VACV resistant to cidofovir and other acyclic nucleoside phosphonates. siG7L-1 and siD5R-2 remained active against four of five VACV mutants, while siB1R-2 showed activity against only one of the mutants. Our results showed that siRNAs are potent inhibitory agents in vitro, not only against wild-type VACV but also against several cidofovir-resistant VACV. Furthermore, we showed that a combined therapy using siRNA and cidofovir may be useful in the treatment of poxvirus infections.

scholarly journals The Viral Polymerase Inhibitor 2'-C-Methylcytidine Inhibits Norwalk Virus Replication and Protects against Norovirus-Induced Diarrhea and Mortality in a Mouse Model

2013 ◽  
Vol 87 (21) ◽  
pp. 11798-11805 ◽  
Author(s):  
J. Rocha-Pereira ◽  
D. Jochmans ◽  
Y. Debing ◽  
E. Verbeken ◽  
M. S. J. Nascimento ◽  
...  
Keyword(s):  
Mouse Model ◽  
Virus Replication ◽  
Norwalk Virus ◽  
Viral Polymerase ◽  
Polymerase Inhibitor

scholarly journals Generation of PCV2 in PK15 cells transfected with recombinant baculovirus containing a 1.1 copy of the PCV2 genome

2017 ◽  
Vol 65 (2) ◽  
pp. 278-290 ◽  
Author(s):  
Jie Cai ◽  
Xiaohong Xie ◽  
Yi Hu ◽  
Yang Zhan ◽  
Wanting Yu ◽  
...  
Keyword(s):  
Genomic Dna ◽  
Recombinant Baculovirus ◽  
Porcine Circovirus ◽  
Economic Losses ◽  
Loop Structure ◽  
Swine Industry ◽  
Stem Loop ◽  
Stem Loop Structure ◽  
Pcv2 Replication ◽  
Pcv2 Genome

Porcine circovirus associated diseases (PCVAD) caused by PCV2 are responsible for severe economic losses in the swine industry. The mechanism of PCV2 replication has not been fully elucidated yet. PCV2 may be successfully rescued by means of either an infectious DNA clone containing the full length of the viral genomic DNA, or from PCV2-infected clinical tissues in PK15 cell culture. However, viruses harvested by both methods have low titres. In this study, PCV2 was prepared with a higher titre from PK15 cells infected by recombinant baculoviruses containing 1PCV2 (one stem-loop structure) or 1.1PCV2 (two stem-loop structure) genomic DNA copy. In addition, infectious DNA clones containing two stem-loop structures in either plasmid or baculovirus backbones are capable of generating a higher virus titre than the DNA clones with only one copy of stem-loop structure.

Interleukin-15 suppresses hepatitis B virus replication via IFN-β production in a C57BL/6 mouse model

2012 ◽  
Vol 32 (8) ◽  
pp. 1306-1314 ◽  
Author(s):  
Wenwei Yin ◽  
Long Xu ◽  
Rui Sun ◽  
Haiming Wei ◽  
Zhigang Tian
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mouse Model ◽  
Virus Replication ◽  
B Virus ◽  
Interleukin 15
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