scholarly journals Antiviral Effect of Resveratrol in Piglets Infected with Virulent Pseudorabies Virus

Viruses ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 457 ◽  
Author(s):  
Xinghong Zhao ◽  
Wenzhi Tong ◽  
Xu Song ◽  
Renyong Jia ◽  
Lixia Li ◽  
...  
Keyword(s):  
Pseudorabies Virus ◽  
Control Measure ◽  
Antiviral Effect ◽  
Economic Losses ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Viral Loads ◽  
Factor Alpha ◽  
Potent Inhibitory Activity

Pseudorabies virus (PRV) is one of the most important pathogens of swine, resulting in devastating disease and economic losses worldwide. Nevertheless, there are currently no antiviral drugs available for PRV infection. Resveratrol (Res) was identified to exert its antiviral activity by inhibiting the PRV replication in preliminary investigations. In our previous study, we found that Res has anti-PRV activity in vitro. Here, we show that Res can effectively reduce the mortality and increase the growth performance of PRV-infected piglets. After Res treatment, the viral loads significantly (p < 0.001) decreased. Pathological symptoms, particularly inflammation in the brain caused by PRV infection, were significantly (p < 0.001) relieved by the effects of Res. In Res-treated groups, higher levels of cytokines in serum, including interferon gama, interleukin 12, tumor necrosis factor-alpha and interferon alpha were observed at 7 days post infection. These results indicated that Res possesses potent inhibitory activity against PRV-infection through inhibiting viral reproduction, alleviating PRV-induced inflammation and enhancing animal immunity, suggesting that Res is expected to be a new alternative control measure for PRV infection.

scholarly journals Meclizine Inhibits Pseudorabies Virus Replication by Interfering With Virus Entry and Release

2021 ◽  
Vol 12 ◽  
Author(s):  
Panrao Liu ◽  
Danhe Hu ◽  
Lili Yuan ◽  
Zhengmin Lian ◽  
Xiaohui Yao ◽  
...  
Keyword(s):  
Viral Entry ◽  
Pseudorabies Virus ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Economic Losses ◽  
Swine Industry ◽  
Viral Attachment ◽  
Viral Loads

Pseudorabies virus (PRV) is a pathogen that causes substantial economic losses to the swine industry. With the emergence and widespread of PRV variants since 2011 in China, current commercial vaccines cannot provide complete protection against PRV infection. Therefore, antiviral drugs may work as an alternative way to control and prevent PRV. In this study, the inhibitory effects and underlying molecular mechanisms of meclizine against PRV were studied. Meclizine displayed a significant inhibitory effect against PRV when it was added before, simultaneously with, or after virus infection. The inhibitory effect of meclizine occurred during viral entry and cell-to-cell spreading but not at viral attachment into PK-15 cells. Meclizine also inhibited viral particle release at the late stage of infection. The antiviral effect of meclizine was tested in mice, and the results showed that meclizine reduced the severity of clinical symptoms and the viral loads in tissues, and delayed the death, after PRV challenge. The above results indicated that meclizine had an inhibitory effect on PRV. Our findings will contribute to the development of potential therapeutic drugs against PRV infection.

Kaempferol inhibits pseudorabies virus replication in vitro through regulation of MAPKs and NF-κB signaling pathways

2020 ◽  
Author(s):  
Xu Chen ◽  
Yaqin Chen ◽  
Zhongqiong Yin ◽  
Rui Wang ◽  
Huaiyue Hu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Virus Replication ◽  
Pseudorabies Virus ◽  
Target Genes ◽  
Control Measure ◽  
Control Measures ◽  
Economic Losses ◽  
Signal Pathways ◽  
Dependent Manner

Abstract Pseudorabies virus (PRV), belonging to the family Herpesviridae, is a pathogen of Aujeszky’s disease leading great economic losses to pig industry. Re-outburst of pseudorabies implies that new control measures are urgent needed. The present study provides a candidate drug for PRV infection that kaempferol possesses the ability to inhibit PRV replication in a dose-dependent manner in vitro. Kaempferol at a concentration of 52.40 μM could decrease PRV-induced cell death by 90%. Kaempferol with a IC50 of 25.57μM is more effective than acyclovir (Positive control) with a IC 50 of 54.97 μM. Mode of action study indicated that kaempferol inhibited viral penetration and replication stages and virus load was decreased by 4-fold and 30-fold, respectively. Addition of kaempferol within 16 hours post infection (hpi) could significantly inhibit virus replication, and the DNA copies were decreased by almost 15-fold when kaempferol was added at 2 hpi. Kaempferol could regulate NF-κB and MAPKs signal pathways involved in PRV infection and change the levels of the target genes of MAPKs (ATF-2 and c-Jun) and NF-κB (IL-1α, IL-1β and IL-2) signaling pathways. All the results indicated that kaempferol has the ability to be an alternative control measure for PRV infection.¶ These authors contribute equally to this work and should be considered as the first author.

scholarly journals Miltefosine Efficiently Eliminates Leishmania major Amastigotes from Infected Murine Dendritic Cells without Altering Their Immune Functions

2009 ◽  
Vol 54 (2) ◽  
pp. 652-659 ◽  
Author(s):  
Klaus Griewank ◽  
Caroline Gazeau ◽  
Andreas Eichhorn ◽  
Esther von Stebut
Keyword(s):  
Dendritic Cells ◽  
Leishmania Major ◽  
Interleukin 12 ◽  
Immune Functions ◽  
Necrosis Factor Alpha ◽  
Mhc Ii ◽  
Intracellular Parasites ◽  
Factor Alpha

ABSTRACT As a treatment for leishmaniasis, miltefosine exerts direct toxic effects on the parasites. Miltefosine also modulates immune cells such as macrophages, leading to parasite elimination via oxidative radicals. Dendritic cells (DC) are critical for initiation of protective immunity against Leishmania through induction of Th1 immunity via interleukin 12 (IL-12). Here, we investigated the effects of miltefosine on DC in Leishmania major infections. When cocultured with miltefosine for 4 days, the majority of in vitro-infected DC were free of parasites. Miltefosine treatment did not influence DC maturation (upregulation of major histocompatibility complex II [MHC II] or costimulatory molecules, e.g., CD40, CD54, and CD86) or significantly alter cytokine release (IL-12, tumor necrosis factor alpha [TNF-α], or IL-10). Further, miltefosine DC treatment did not alter antigen presentation, since unrestricted antigen-specific proliferation of CD4+ and CD8+ T cells was observed upon stimulation with miltefosine-treated, infected DC. In addition, miltefosine application in vivo did not lead to maturation/emigration of skin DC. DC NO− production, a mechanism used by phagocytes to rid themselves of intracellular parasites, was also unaltered upon miltefosine treatment. Our data confirm prior studies indicating that in contrast to, e.g., pentavalent antimonials, miltefosine functions independently of the immune system, mostly through direct toxicity against the Leishmania parasite.

scholarly journals Interleukin 12 in Part Regulates Gamma Interferon Release in Human Whole Blood Stimulated with Leptospira interrogans

2003 ◽  
Vol 10 (2) ◽  
pp. 332-335 ◽  
Author(s):  
Maaike de Fost ◽  
Rudy A. Hartskeerl ◽  
Martijn R. Groenendijk ◽  
Tom van der Poll
Keyword(s):  
Whole Blood ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
Leptospira Interrogans ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Human Whole Blood ◽  
Factor Alpha ◽  
Ifn Γ

ABSTRACT Heat-killed pathogenic Leptospira interrogans serovar rachmati induced the production of gamma interferon (IFN-γ) and the IFN-γ-inducing cytokines interleukin-12p40 (IL-12p40) and tumor necrosis factor alpha in human whole blood in vitro. The production of IFN-γ was largely dependent on IL-12. These data establish that pathogenic leptospires can stimulate the production of type I cytokines involved in cellular immunity.

scholarly journals Mycobacterium tuberculosis 19-Kilodalton Lipoprotein Inhibits Mycobacterium smegmatis-Induced Cytokine Production by Human Macrophages In Vitro

2001 ◽  
Vol 69 (3) ◽  
pp. 1433-1439 ◽  
Author(s):  
Frank A. Post ◽  
Claudia Manca ◽  
Olivier Neyrolles ◽  
Bernhard Ryffel ◽  
Douglas B. Young ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Cytokine Production ◽  
Human Monocyte ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Vaccination of mice with Mycobacterium vaccae orM. smegmatis induces some protection against M. tuberculosis challenge. The 19-kDa lipoprotein of M. tuberculosis, expressed in M. vaccae or M. smegmatis (M. smeg19kDa), abrogates this protective immunity. To investigate the mechanism of this suppression of immunity, human monocyte-derived macrophages (MDM) were infected with M. smeg19kDa. Infection resulted in reduced production of tumor necrosis factor alpha (TNF-α) (P < 0.01), interleukin-12 (IL-12) (P < 0.05), IL-6 (P < 0.05), and IL-10 (P < 0.05), compared to infection with M. smegmatis vector (M. smegV). Infection with M. smeg19kDa and with M. smegV had no differential effect on expression of costimulatory molecules on MDM, nor did it affect the proliferation of presensitized T cells cocultured with infected MDM. When MDM were infected withM. smegmatis expressing mutated forms of the 19-kDa lipoprotein, including non-O-glycosylated (M. smeg19NOG), nonsecreted (M. smeg19NS), and nonacylated (M. smeg19NA) variants, the reduced production of TNF-α or IL-12 was not observed. When the purified 19-kDa lipoprotein was added directly to cultures of infected monocytes, there was little effect on either induction of cytokine production or its inhibition. Thus, the immunosuppressive effect is dependent on glycosylated and acylated 19-kDa lipoprotein present in the phagosome containing the mycobacterium. These results suggest that the diminished protection against challenge with M. tuberculosis seen in mice vaccinated with M. smegmatis expressing the 19-kDa lipoprotein is the result of reduced TNF-α and IL-12 production, possibly leading to reduced induction of T-cell activation.

scholarly journals Early interleukin 12 production by macrophages in response to mycobacterial infection depends on interferon gamma and tumor necrosis factor alpha.

1995 ◽  
Vol 181 (5) ◽  
pp. 1615-1621 ◽  
Author(s):  
I E Flesch ◽  
J H Hess ◽  
S Huang ◽  
M Aguet ◽  
J Rothe ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Interferon Gamma ◽  
Tumor Necrosis ◽  
Mycobacterial Infection ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Factor Alpha ◽  
Necrosis Factor

Interleukin 12 (IL-12) produced by macrophages immediately after infection is considered essential for activation of a protective immune response against intracellular pathogens. In the murine Mycobacterium bovis Bacillus Calmette-Guérin (BCG) model we assessed whether early IL-12 production by macrophages depends on other cytokines. In vitro, murine bone marrow-derived macrophages produced IL-12 after infection with viable M. bovis BCG or stimulation with LPS, however, priming with recombinant interferon gamma (rIFN-gamma) was necessary. In addition, IL-12 production by these macrophages was blocked by specific anti-tumor necrosis factor alpha (TNF-alpha) antiserum. Macrophages from gene deletion mutant mice lacking either the IFN-gamma receptor or the TNF receptor 1 (p55) failed to produce IL-12 in vitro after stimulation with rIFN-gamma and mycobacterial infection. In vivo, IL-12 production was induced in spleens of immunocompetent mice early during M. bovis BCG infection but not in those of mutant mice lacking the receptors for IFN-gamma or TNF. Our results show that IL-12 production by macrophages in response to mycobacterial infection depends on IFN-gamma and TNF. Hence, IL-12 is not the first cytokine produced in mycobacterial infections.

scholarly journals Immunostimulating Properties of Intragastrically Administered Acetobacter-Derived Soluble Branched (1,4)-β-d-Glucans Decrease Murine Susceptibility to Listeria monocytogenes

2004 ◽  
Vol 72 (12) ◽  
pp. 7005-7011 ◽  
Author(s):  
Wei Li ◽  
Toshiki Yajima ◽  
Kimika Saito ◽  
Hitoshi Nishimura ◽  
Takashi Fushimi ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Protective Immunity ◽  
Extracellular Polysaccharide ◽  
Interleukin 12 ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Strong Activity ◽  
Factor Alpha ◽  
Phosphate Buffered Saline

ABSTRACT We previously found that AC-1, an extracellular polysaccharide, produced by Acetobacter xylinum and composed of (1,4)-β-d-glucan with branches of glucosyl residues, showed a strong activity to induce production of interleukin-12 (IL-12) p40 and tumor necrosis factor alpha by macrophages in vitro via Toll-like receptor 4 (TLR-4) signaling. In the present study, we examined the effect of oral administration of AC-1 on protective immunity against Listeria monocytogenes. Mice were given AC-1 or phosphate-buffered saline (PBS) intragastrically 2 days before, on the day of, and 2 days after an intraperitoneal inoculation of L. monocytogenes. The survival rate of AC-1-treated mice was significantly improved and bacterial growth in AC-1-treated mice was severely retarded compared to those of PBS-treated mice after infection with L. monocytogenes. IL-12 p40 levels in serum and magnitudes of CD4+ Th1 and CD8+ Tc1 responses against Listeria antigen were significantly higher in AC-1-treated mice than in PBS-treated mice. The effect of AC-1 on antilisterial activity was diminished in C3H/HeJ mice carrying mutated TLR-4. Thus, AC-1, a potent IL-12 inducer through TLR-4, enhanced protective immunity against L. monocytogenes via augmentation of Th1 responses. These results suggest that infectious processes driven by intracellular microorganisms could be prevented to develop by the (1,4)-β-d-glucan.

scholarly journals CRISPR/Cas9-based generation of a recombinant double-reporter pseudorabies virus and its characterization in vitro and in vivo

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Peng-Fei Fu ◽  
Xuan Cheng ◽  
Bing-Qian Su ◽  
Li-Fang Duan ◽  
Cong-Rong Wang ◽  
...  
Keyword(s):  
Pseudorabies Virus ◽  
Fluorescent Protein ◽  
Antiviral Agents ◽  
Firefly Luciferase ◽  
Inhibitory Effect ◽  
Economic Losses ◽  
Green Fluorescent ◽  
Swine Herds

AbstractPseudorabies, caused by pseudorabies virus (PRV) variants, has broken out among commercial PRV vaccine-immunized swine herds and resulted in major economic losses to the pig industry in China since late 2011. However, the mechanism of virulence enhancement of variant PRV is currently unclear. Here, a recombinant PRV (rPRV HN1201-EGFP-Luc) with stable expression of enhanced green fluorescent protein (EGFP) and firefly luciferase as a double reporter virus was constructed on the basis of the PRV variant HN1201 through CRISPR/Cas9 gene-editing technology coupled with two sgRNAs. The biological characteristics of the recombinant virus and its lethality to mice were similar to those of the parental strain and displayed a stable viral titre and luciferase activity through 20 passages. Moreover, bioluminescence signals were detected in mice at 12 h after rPRV HN1201-EGFP-Luc infection. Using the double reporter PRV, we also found that 25-hydroxycholesterol had a significant inhibitory effect on PRV both in vivo and in vitro. These results suggested that the double reporter PRV based on PRV variant HN1201 should be an excellent tool for basic virology studies and evaluating antiviral agents.

scholarly journals Mannoproteins from Cryptococcus neoformans Promote Dendritic Cell Maturation and Activation

2005 ◽  
Vol 73 (2) ◽  
pp. 820-827 ◽  
Author(s):  
Donatella Pietrella ◽  
Cristina Corbucci ◽  
Stefano Perito ◽  
Giovanni Bistoni ◽  
Anna Vecchiarelli
Keyword(s):  
Cryptococcus Neoformans ◽  
Nuclear Factor Κb ◽  
Dendritic Cell Maturation ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Histocompatibility Complex ◽  
Factor Alpha ◽  
Human Dendritic Cells ◽  
Mannose Receptors

ABSTRACT Our previous data show that mannoproteins (MPs) from Cryptococcus neoformans are able to induce protective responses against both C. neoformans and Candida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to IκBα phosphorylation, which is necessary for nuclear factor κB transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi.

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