Therapeutic efficacy of Hypericum perforatum L. extract for mice infected with an influenza A virus

2012 ◽  
Vol 90 (2) ◽  
pp. 123-130 ◽  
Author(s):  
Pu Xiuying ◽  
Liang Jianping ◽  
Shang Ruofeng ◽  
Zhou Liye ◽  
Wang Xuehong ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Lung Tissue ◽  
Post Infection ◽  
Therapeutic Efficacy ◽  
Influenza A ◽  
Hypericum Perforatum ◽  
Viral Titer ◽  
Tnf Α ◽  
Hypericum Perforatum L ◽  
Ifn Γ

Hypericum perforatum L., a plant used in Chinese herbal medicine, has been proven effective against many viral diseases. In the present study, the therapeutic efficacy of an extract of H. perforatum (HPE) against influenza A virus (IAV) was investigated in mice. Whether HPE would be a promising agent for influenza treatment was evaluated by measuring the protection rate, mean survival days, lung index, and viral titer, as well as the secretion of IL-6, interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), and interferon-gamma (IFN-γ) in lung tissue and serum on days 3 and 5 post-infection. The results showed that HPE could reduce the lung index and viral titer of mice infected with IAV, decrease mortality, and prolong the mean survival time. HPE decreased the concentration of IL-6 and TNF-α in lung tissue and serum on day 5 post-infection. In contrast, HPE enhanced the lung and serum levels of IL-10 and IFN-γ on the days 3 and 5 post-infection. Our study indicates that HPE has significant therapeutic efficacy for mice infected with IAV. The possible reasons for these results were concluded to be pertaining to up-regulating the expression of IL-10 and IFN-γ, and down-regulating the secretion of IL-6 and TNF-α in lung and serum.

scholarly journals Pudilan xiaoyan oral liquid (PDL) inhibit the replication of influenza A virus through regulating TLR3/MyD88 signaling pathway

2022 ◽  
Author(s):  
Zheng Zhihui ◽  
Yuqian Zhang ◽  
Gang Tian ◽  
Zehua Wang ◽  
Ronghua Wang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Tnf Α ◽  
Oral Liquid ◽  
Ifn Γ

Abstract Background Pudilan Xiaoyan Oral Liquid (PDL) as a famous Chinese patent medicine has been widely used for treating upper respiratory tract infection. However, the antiviral effect of PDL remain unclear. Here, the antiviral effect of in vitro and in vivo of PDL against influenza A virus were for the first time investigated. Methods The in vitro inhibitory effect of PDL on influenza A virus was investigated using MDCK cell model. The in vivo inhibitory effect on influenza virus pneumonia was evaluated with the ICR female mice (14-16 g) model infected by influenza A virus (A/FM/1/47, H1N1, mouse-adapted). Moreover, expression levels of inflammatory cytokines including TNF-α, IP10, IL-10, IL-1β, IL-6 and IFN-γ in lung tissue were measured by qRT-PCR. The potential mechanism of PDL against acute lung injury caused by influenza A virus was investigated by RT-PCR and Western blot. Results Our results indicated that in vitro PDL has a broad-spectrum inhibitory effect on different subtypes of influenza A viruses and in vivo PDL could dose-dependently prevent weight loss of mice, increase food intake and reduce mortality caused by influenza A H1N1 virus. Furthermore, PDL could markedly improve the acute lung injury caused by influenza A virus and significantly reduce the mRNA levels of inflammatory factors such as TNF-α, IP10, IL-10, IL-1β, IL-6, and IFN-γ. Mechanistic research indicated that the protective effect of PDL on viral pneumonia might be achieved by inhibiting TLR3/MyD88/IRAK4/TRAF3 signaling pathway. Conclusion PDL not only showed a good inhibitory effect on influenza A virus in vitro, but also exhibited a significant protective effect against lethal influenza virus infection in vivo. These findings provide evidence for the clinical treatment of influenza A virus infection with PDL.

Anti-influenza A virus effect of Hypericum perforatum L. extract

2009 ◽  
Vol 24 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Xiu-ying Pu ◽  
Jian-ping Liang ◽  
Xue-hong Wang ◽  
Tao Xu ◽  
Lan-ying Hua ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Hypericum Perforatum ◽  
Hypericum Perforatum L

scholarly journals Expression of Cytokine and Chemokine Genes by Human Middle Ear Epithelial Cells Induced by Influenza A Virus and Streptococcus pneumoniae Opacity Variants

2003 ◽  
Vol 71 (8) ◽  
pp. 4289-4296 ◽  
Author(s):  
H. H. Tong ◽  
J. P. Long ◽  
P. A. Shannon ◽  
T. F. DeMaria
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mrna Expression ◽  
Influenza A Virus ◽  
Middle Ear ◽  
Influenza A ◽  
Primary Cultures ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Tnf Α ◽  
Human Middle Ear

ABSTRACT Real-time PCR and enzyme-linked immunosorbent assay were used to evaluate the ability of influenza A virus and Streptococcus pneumoniae opacity variants, either alone or in combination, to induce cytokine and chemokine genes in primary cultures of human middle ear epithelial (HMEE) cells. Following treatment with influenza A virus, the induction of gene expression, which occurred in a dose- and time-dependent manner, was strong for macrophage inflammatory protein 1α (MIP-1α) and MIP-1β; moderate for tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8; and weak for IL-1β and monocyte chemotactic peptide 1 (MCP-1). Except for TNF-α, all the gene products were detected in the cell culture supernatants. In contrast, infection of HMEE cells with S. pneumoniae alone induced low levels of mRNA expression of MIP-1α and MIP-1β and did not significantly induce the transcription of the other cytokines and chemokines examined. However, both S. pneumoniae opacity variants increased mRNA expression of MIP-1α, MIP-1β, IL-6, and MCP-1 in HMEE cells activated by a prior influenza A virus infection compared to levels in cells treated with either agent alone. Up-regulation of IL-6, IL-8, and MCP-1 mRNA expression and production by the virus in combination with opaque S. pneumoniae was two- to threefold higher than that induced by the virus combined with the transparent S. pneumoniae variant. These data indicate that the activation of HMEE cells by influenza A virus enhances the induction of cytokine and chemokine gene transcripts by S. pneumoniae and that this effect appears to be most pronounced when S. pneumoniae is in the opaque phase.

scholarly journals TNF-α and IFN-α enhance influenza-A-virus-induced chemokine gene expression in human A549 lung epithelial cells

Virology ◽  
2006 ◽  
Vol 345 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Ville Veckman ◽  
Pamela Österlund ◽  
Riku Fagerlund ◽  
Krister Melén ◽  
Sampsa Matikainen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Influenza A Virus ◽  
Influenza A ◽  
Lung Epithelial Cells ◽  
Chemokine Gene ◽  
Tnf Α ◽  
Lung Epithelial ◽  
Human A549 ◽  
A549 Lung ◽  
Chemokine Gene Expression

scholarly journals Understanding the within-host dynamics of influenza A virus: from theory to clinical implications

2016 ◽  
Vol 13 (119) ◽  
pp. 20160289 ◽  
Author(s):  
Christoforos Hadjichrysanthou ◽  
Emilie Cauët ◽  
Emma Lawrence ◽  
Carolin Vegvari ◽  
Frank de Wolf ◽  
...  
Keyword(s):  
Viral Load ◽  
Influenza A Virus ◽  
Post Infection ◽  
Influenza A ◽  
Antiviral Drugs ◽  
Load Curve ◽  
Clinical Endpoints ◽  
Time To Peak ◽  
Infection Dynamics ◽  
Peak Viral Load

Mathematical models have provided important insights into acute viral dynamics within individual patients. In this paper, we study the simplest target cell-limited models to investigate the within-host dynamics of influenza A virus infection in humans. Despite the biological simplicity of the models, we show how these can be used to understand the severity of the infection and the key attributes of possible immunotherapy and antiviral drugs for the treatment of infection at different times post infection. Through an analytic approach, we derive and estimate simple summary biological quantities that can provide novel insights into the infection dynamics and the definition of clinical endpoints. We focus on nine quantities, including the area under the viral load curve, peak viral load, the time to peak viral load and the level of cell death due to infection. Using Markov chain Monte Carlo methods, we fitted the models to data collected from 12 untreated volunteers who participated in two clinical studies that tested the antiviral drugs oseltamivir and zanamivir. Based on the results, we also discuss various difficulties in deriving precise estimates of the parameters, even in the very simple models considered, when experimental data are limited to viral load measures and/or there is a limited number of viral load measurements post infection.

scholarly journals Factors affecting induction of peripheral IFN-γ recall response to influenza A virus vaccination in pigs

2017 ◽  
Vol 185 ◽  
pp. 57-65 ◽  
Author(s):  
Zahra F. Olson ◽  
Matthew R. Sandbulte ◽  
Carine Kunzler Souza ◽  
Daniel R. Perez ◽  
Amy L. Vincent ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Recall Response ◽  
Factors Affecting ◽  
Virus Vaccination ◽  
Ifn Γ

scholarly journals Diallel analysis reveals Mx1-dependent and Mx1-independent effects on response to influenza A virus in mice

2017 ◽  
Author(s):  
Paul L. Maurizio ◽  
Martin T. Ferris ◽  
Gregory R. Keele ◽  
Darla R. Miller ◽  
Ginger D. Shaw ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Post Infection ◽  
Influenza A ◽  
Diallel Analysis ◽  
Respiratory Pathogen ◽  
Phenotypic Variance ◽  
Additive Effects ◽  
Statistical Framework ◽  
Independent Effects ◽  
Heritable Effects

1.ABSTRACTInfluenza A virus (IAV) is a respiratory pathogen that causes substantial morbidity and mortality during both seasonal and pandemic outbreaks. Infection outcomes in unexposed populations are affected by host genetics, but this host genetic architecture is not well understood. Here we obtain a broad view of how heritable factors affect a mouse model of response to IAV infection using an 8×8 diallel of the eight inbred founder strains of the Collaborative Cross (CC). Expanding on a prior statistical framework for modeling treatment response in diallels, we explore how a range of heritable effects modify acute host response to IAV through 4 days post-infection. Heritable effects in aggregate explained about 57% of the variance in IAV-induced weight loss. Much of this was attributable to a pattern of additive effects that became more prominent through day 4 post-infection and was consistent with previous reports of anti-influenza myxovirus resistance 1 (Mx1) polymorphisms segregating between these strains; the additive effects largely recapitulated haplotype effects observed at the Mx1 locus in a previous study of the incipient CC (pre-CC), and are also replicated here in a CC recombinant intercross (CC-RIX) population. Genetic dominance of protective Mx1 haplotypes was observed to differ by subspecies origin: relative to the domesticus null Mx1 allele, musculus acts dominantly whereas castaneus acts additively. After controlling for Mx1, heritable effects, though less distinct, accounted for about 34% of the phenotypic variance. Implications for future mapping studies are discussed.

scholarly journals Beneficial Effect of Indigo Naturalis on Acute Lung Injury Induced by Influenza a Virus

2020 ◽  
Author(s):  
Peng Tu ◽  
Rong Tian ◽  
Yan Lu ◽  
Yunyi Zhang ◽  
Haiyan Zhu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Influenza A Virus ◽  
Lung Tissue ◽  
Influenza A ◽  
Influenza Viruses ◽  
Virus Growth ◽  
Indigo Naturalis ◽  
Anti Inflammatory

Abstract Background: Infections induced by influenza viruses, as well as COVID-19 pandemic induced by SARS-CoV-2 led to Acute lung injury (ALI) and multiorgan failure, during which traditional Chinese medicine played an important role in treatment of the pandemic. The study aimed to investigate the effect of indigo naturalis on ALI induced by influenza A virus (IAV) in mice.Method: The anti-influenza and anti-inflammatory properties of aqueous extracts of indigo naturalis (INAE) were evaluated in vitro. BALB/c mice inoculated intranasally with IAV (H1N1) were treated intragastrically with INAE (40, 80 and 160 mg kg-1/d) 2 h later for 4 or 7 days. Animal mortality and lifespan were recorded. Expression of high mobility group box-1 protein (HMGB-1) and toll-like receptor-4 (TLR4) were evaluated through immunohistological staining. Inflammatory cytokines were also monitored by ELISA.Result: INAE inhibited virus growth on Madin-Darby canine kidney (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated peritoneal macrophage in vitro. The results showed that oral administration of 160 mg/kg of INAE significantly improved the lifespan (P < 0.01) and survival rate of IAV infected mice, improved lung injury and lowered viral replication in lung tissue (P < 0.01). Treatment with INAE (40, 80 and 160 mg/kg) also significantly increased liver weight and liver index (P < 0.05), as well as spleen and thymus weight and organ index at 160 mg/kg (P < 0.05). The expression of HMGB-1 and TLR4 in lung tissue were also suppressed. Treatment with INAE reduced the high levels of interferon α (IFN-α), interferon β (IFN-β), interferon γ (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted factor (RANTES), interferon induced protein-10 (IP-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) (P < 0.05), with increased production of interleukin-10 (IL-10) (P < 0.05). The increased myeloperoxidase (MPO) activity and methylene dioxyamphetamine (MDA) level in lung tissues were inhibited by INAE treatment (P < 0.05).Conclusion: The results showed that INae alleviated IAV induced ALI in mice. The effect of INAE might be related with its anti-virus, anti-inflammatory and anti-oxidation properties, which give a hint that indigo naturalis might be effective on respiratory viruses infected acute lung injury or SAR-CoV-2 caused COVID-19.

scholarly journals Casein Kinase 1α Mediates the Degradation of Receptors for Type I and Type II Interferons Caused by Hemagglutinin of Influenza A Virus

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Chuan Xia ◽  
Jennifer J. Wolf ◽  
Madhuvanthi Vijayan ◽  
Caleb J. Studstill ◽  
Wenjun Ma ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
P38 Map Kinase ◽  
Casein Kinase ◽  
Type I ◽  
Type Ii ◽  
Ifn Γ ◽  
Cellular Responsiveness ◽  
Novel Strategy

ABSTRACTAlthough influenza A virus (IAV) evades cellular defense systems to effectively propagate in the host, the viral immune-evasive mechanisms are incompletely understood. Our recent data showed that hemagglutinin (HA) of IAV induces degradation of type I IFN receptor 1 (IFNAR1). Here, we demonstrate that IAV HA induces degradation of type II IFN (IFN-γ) receptor 1 (IFNGR1), as well as IFNAR1, via casein kinase 1α (CK1α), resulting in the impairment of cellular responsiveness to both type I and II IFNs. IAV infection or transient HA expression induced degradation of both IFNGR1 and IFNAR1, whereas HA gene-deficient IAV failed to downregulate the receptors. IAV HA caused the phosphorylation and ubiquitination of IFNGR1, leading to the lysosome-dependent degradation of IFNGR1. Influenza viral HA strongly decreased cellular sensitivity to type II IFNs, as it suppressed the activation of STAT1 and the induction of IFN-γ-stimulated genes in response to exogenously supplied recombinant IFN-γ. Importantly, CK1α, but not p38 MAP kinase or protein kinase D2, was proven to be critical for HA-induced degradation of both IFNGR1 and IFNAR1. Pharmacologic inhibition of CK1α or small interfering RNA (siRNA)-based knockdown of CK1α repressed the degradation processes of both IFNGR1 and IFNAR1 triggered by IAV infection. Further, CK1α was shown to be pivotal for proficient replication of IAV. Collectively, the results suggest that IAV HA induces degradation of IFN receptors via CK1α, creating conditions favorable for viral propagation. Therefore, the study uncovers a new immune-evasive pathway of influenza virus.IMPORTANCEInfluenza A virus (IAV) remains a grave threat to humans, causing seasonal and pandemic influenza. Upon infection, innate and adaptive immunity, such as the interferon (IFN) response, is induced to protect hosts against IAV infection. However, IAV seems to be equipped with tactics to evade the IFN-mediated antiviral responses, although the detailed mechanisms need to be elucidated. In the present study, we show that IAV HA induces the degradation of the type II IFN receptor IFNGR1 and thereby substantially attenuates cellular responses to IFN-γ. Of note, a cellular kinase, casein kinase 1α (CK1α), is crucial for IAV HA-induced degradation of both IFNGR1 and IFNAR1. Accordingly, CK1α is proven to positively regulate IAV propagation. Thus, this study unveils a novel strategy employed by IAV to evade IFN-mediated antiviral activities. These findings may provide new insights into the interplay between IAV and host immunity to impact influenza virus pathogenicity.

scholarly journals Recombinant Measles AIK-C Vaccine Strain Expressing Influenza HA Protein

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 149
Author(s):  
Takashi Ito ◽  
Takuji Kumagai ◽  
Yoshiaki Yamaji ◽  
Akihito Sawada ◽  
Tetsuo Nakayama
Keyword(s):  
Influenza A ◽  
Inflammatory Cells ◽  
Alveolar Wall ◽  
Viral Loads ◽  
Empty Vector ◽  
Influenza Hemagglutinin ◽  
Tnf Α ◽  
Cotton Rats ◽  
Ifn Γ ◽  
Ha Protein

Recombinant measles AIK-C vaccine expressing the hemagglutinin (HA) protein of influenza A/Sapporo/107/2013(H1N1pdm) (MVAIK/PdmHA) was constructed. Measles particle agglutination (PA) and influenza hemagglutinin inhibition (HI) antibodies were induced in cotton rats immunized with MVAIK/PdmHA. Cotton rats immunized with two doses of the HA split vaccine were used as positive controls, and higher HI antibodies were detected 3 weeks after the first dose. Following the challenge of A/California/07/2009(H1N1pdm), higher viral loads (107 TCID50/g) were detected in the lung homogenates of cotton rats immunized with the empty vector (MVAIK) or control groups than those immunized with MVAIK/Pdm HA (103 TCID50/g) or the group immunized with HA split vaccine (105 TCID50/g). Histopathologically, destruction of the alveolar structure, swelling of broncho-epithelial cells, and thickening of the alveolar wall with infiltration of inflammatory cells and HA antigens were detected in lung tissues obtained from non-immunized rats and those immunized with the empty vector after the challenge, but not in those immunized with the HA spilt or MVAIK/PdmHA vaccine. Lower levels of IFN-α, IL-1β, and TNF-α mRNA, and higher levels of IFN-γ mRNA were found in the lung homogenates of the MVAIK/PdmHA group. Higher levels of IFN-γ mRNA were detected in spleen cell culture from the MVAIK/PdmHA group stimulated with UV-inactivated A/California/07/2009(H1N1pdm). In conclusion, the recombinant MVAIK vaccine expressing influenza HA protein induced protective immune responses in cotton rats.

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