scholarly journals Defective presentation to class I-restricted cytotoxic T lymphocytes in vaccinia-infected cells is overcome by enhanced degradation of antigen.

1988 ◽  
Vol 168 (4) ◽  
pp. 1211-1224 ◽  
Author(s):  
A Townsend ◽  
J Bastin ◽  
K Gould ◽  
G Brownlee ◽  
M Andrew ◽  
...  
Keyword(s):  
Influenza A ◽  
Signal Sequence ◽  
Late Phase ◽  
Inhibitory Effect ◽  
Class I ◽  
Detectable Effect ◽  
Protein Fragments ◽  
Infected Target Cell ◽  
Infected Cells ◽  
The Relationship

Vaccinia infection interferes with the presentation of influenza Haemagglutinin (HA) and Nucleoprotein (NP) to class I-restricted CTL. The inhibitory effect is selective for certain epitopes, and is more profound during the late phase of infection. For influenza A/NT/60/68 NP, the block is present during both early and late phases of infection, and is selective for the COOH-terminal epitope defined by peptide 366-379, having no detectable effect on the presentation of the NH2-terminal epitope 50-63. The presentation of HA is inhibited only during the late phase of vaccinia infection. For both proteins, presentation is partially (NP) or completely (HA) restored by expression of rapidly degraded protein fragments in the vaccinia infected target cell. For HA, deletion of the NH2-terminal signal sequence completely overcomes the block. For NP, either a large NH2-terminal deletion or the construction of a rapidly degraded ubiquitin-NP fusion protein partially restores presentation. These results illustrate the relationship between degradation of viral proteins in the cytoplasm of an infected cell and recognition of epitopes at the cell surface by class I-restricted T cells.

scholarly journals Protective Role of Combined Polyphenols and Micronutrients against Influenza A Virus and SARS-CoV-2 Infection In Vitro

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1721
Author(s):  
Marta De Angelis ◽  
David Della-Morte ◽  
Gabriele Buttinelli ◽  
Angela Di Martino ◽  
Francesca Pacifici ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Viral Proteins ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Virus Infections ◽  
Infected Cells ◽  
Respiratory Virus Infections

Polyphenols have been widely studied for their antiviral effect against respiratory virus infections. Among these, resveratrol (RV) has been demonstrated to inhibit influenza virus replication and more recently, it has been tested together with pterostilbene against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present work, we evaluated the antiviral activity of polydatin, an RV precursor, and a mixture of polyphenols and other micronutrients, named A5+, against influenza virus and SARS-CoV-2 infections. To this end, we infected Vero E6 cells and analyzed the replication of both respiratory viruses in terms of viral proteins synthesis and viral titration. We demonstrated that A5+ showed a higher efficacy in inhibiting both influenza virus and SARS-CoV-2 infections compared to polydatin treatment alone. Indeed, post infection treatment significantly decreased viral proteins expression and viral release, probably by interfering with any step of virus replicative cycle. Intriguingly, A5+ treatment strongly reduced IL-6 cytokine production in influenza virus-infected cells, suggesting its potential anti-inflammatory properties during the infection. Overall, these results demonstrate the synergic and innovative antiviral efficacy of A5+ mixture, although further studies are needed to clarify the mechanisms underlying its inhibitory effect.

Macrophage-Mediated Inhibitory Effect ofZingiber officinaleRosc, A Traditional Oriental Herbal Medicine, on the Growth of Influenza A/Aichi/2/68 Virus

2006 ◽  
Vol 34 (01) ◽  
pp. 157-169 ◽  
Author(s):  
Nobuko Imanishi ◽  
Tsugunobu Andoh ◽  
Naoki Mantani ◽  
Shinya Sakai ◽  
Katsutoshi Terasawa ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Influenza A ◽  
Mdck Cells ◽  
Zingiber Officinale ◽  
Inhibitory Effect ◽  
Aichi Virus ◽  
Tnf Α ◽  
Infected Cells ◽  
Necrosis Factor ◽  
Darby Canine Kidney

The inhibitory effect of Zingiber officinale Rosc (ZOR), an Oriental traditional herbal medicine, on the growth of influenza A/Aichi/2/68 (Aichi) virus was investigated in Madin-Darby canine kidney (MDCK) cells. Direct addition of ZOR (0.1 ~ 100 μ g/ml ) to the infected cells did not have any inhibitory effect. However, the ZOR-induced conditioned medium (ZOR-CM) of RAW cells, a murine macrophage (Mφ) cell line, exhibited an apparent inhibitory effect on MDCK cells without cytotoxicity. In accordance with the time-dependent inhibitory effect of ZOR-CM, it has been demonstrated that tumor necrosis factor (TNF)-α was gradually accumulated in ZOR-CM by the induction of TNF-α mRNA expression in ZOR-stimulated RAW cells. Conversely, the inhibitory effect of ZOR-CM was reduced significantly by the removal of TNF-α after the formation of an immune complex with anti-TNF-α monoclonal antibody. These data suggested that ZOR itself has no inhibitory effect on the growth of influenza virus, but could exert its effect via macrophage activation leading to production of TNF-α.

scholarly journals An endogenous processing pathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class II-restricted T cells.

1990 ◽  
Vol 172 (3) ◽  
pp. 947-954 ◽  
Author(s):  
D Jaraquemada ◽  
M Marti ◽  
E O Long
Keyword(s):  
T Cells ◽  
Vaccinia Virus ◽  
Influenza A ◽  
Matrix Protein ◽  
De Novo ◽  
Class Ii ◽  
Class I ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Infected Cells

The recognition of virus-infected cells by class I MHC-restricted cytotoxic T cells requires endogenous processing of antigen for presentation. It is still unclear whether endogenous processing of antigen can be utilized by class II MHC molecules for presentation. To test this possibility, a human B cell line expressing HLA-A2 and HLA-DR1 was infected with a recombinant vaccinia virus expressing the Influenza A virus M1 matrix protein (VAC-M1) and was assayed for lysis by different M1-specific cytolytic T cell lines, restricted by either HLA-A2 or by HLA-DR1. Class II-restricted lysis of VAC-M1-infected cells did occur. This lysis required de novo M1 synthesis and was not due to exogenous antigen. Several properties of the endogenous processing pathway for class II-restricted presentation were different from those of the pathway utilized by class I molecules. First, class II-mediated recognition of VAC-M1 infected cells was less efficient, requiring higher doses of virus and longer infection times, than the class I-mediated recognition. Second, chloroquine completely blocked presentation of endogenous M1 to class II-restricted T cells but had no effect on the class I-restricted presentation. Third, the class II-restricted presentation of M1 was only mildly affected by Brefeldin A, a drug that prevents transport from the endoplasmic reticulum to the Golgi, whereas the class I-restricted presentation of M1 was completely abrogated by this drug. These data demonstrate the existence of an endogenous processing pathway for the presentation of cytosolic antigen by class II molecules and show that this pathway is distinct from the one used for presentation by class I molecules.

scholarly journals Major Histocompatibility Complex Class I Allele-specific Cooperative and Competitive Interactions between Immune Evasion Proteins of Cytomegalovirus

2002 ◽  
Vol 196 (6) ◽  
pp. 805-816 ◽  
Author(s):  
Markus Wagner ◽  
Anja Gutermann ◽  
Jürgen Podlech ◽  
Matthias J. Reddehase ◽  
Ulrich H. Koszinowski
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Surface Expression ◽  
Inhibitory Effect ◽  
Class I ◽  
Major Influence ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Allele Specific ◽  
Infected Cells

Cytomegaloviruses (CMVs) deploy a set of genes for interference with antigen presentation in the major histocompatibility complex (MHC) class I pathway. In murine CMV (MCMV), three genes were identified so far: m04/gp34, m06/gp48, and m152/gp40. While their function as immunoevasins was originally defined after their selective expression, this may not necessarily reflect their biological role during infection. The three immunoevasins might act synergistically, but they might also compete for their common substrate, the MHC class I complexes. To approach this question in a systematic manner, we have generated a complete set of mutant viruses with deletions of the three genes in all seven possible combinations. Surface expression of a set of MHC class I molecules specified by haplotypes H-2d (Kd, Dd, and Ld) and H-2b (Kb and Db) was the parameter for evaluation of the interference with class I trafficking. The data show the following: first, there exists no additional MCMV gene of major influence on MHC class I surface expression; second, the strength of the inhibitory effect of immunoevasins shows an allele-specific hierarchy; and third, the immunoevasins act not only synergistically but can, in certain combinations, interact antagonistically. In essence, this work highlights the importance of studying the immunosubversive mechanisms of cytomegaloviruses in the context of gene expression during the viral replicative cycle in infected cells.

Inhibitory Effect of TNF-α Produced by Macrophages Stimulated withGrifola frondosaExtract (ME) on the Growth of Influenza A/Aichi/2/68 Virus in MDCK Cells

2008 ◽  
Vol 36 (06) ◽  
pp. 1171-1183 ◽  
Author(s):  
Nobuko Obi ◽  
Katsumi Hayashi ◽  
Tatsurou Miyahara ◽  
Yutaka Shimada ◽  
Katsutoshi Terasawa ◽  
...  
Keyword(s):  
Influenza A ◽  
Mdck Cells ◽  
Inhibitory Effect ◽  
Fixed Dose ◽  
Madin Darby Canine Kidney ◽  
Tnf Α ◽  
Ultra Filtration ◽  
Infected Cells ◽  
Darby Canine Kidney

We investigated the inhibitory effect of the conditioned medium (CM) from P338D1 (D1) cells, a murine macrophage cell line, stimulated for 10 hours with a fixed dose (100 μg/ml) of the extracts from the fruit bodies of Grifola frondosa (ME) or its ultra filtration-based fractions (MFs), on the growth of influenza A/Aichi/2/68 virus in Madin-Darby canine kidney cells. Direct addition of ME and 3 kinds of MFs (MF1, MF2 and MF3) to the infected cells had no obvious inhibitory effect. However, virus yields were reduced in the presence of CMs. Notably, the inhibitory effect of the CM prepared by using MF2 (molecular weight of 30 Kd to 100 Kd) was the strongest (28% reduction compared to the control). RT-PCR and ELISA assays showed that the CMs could induce the expression of TNF-α mRNA in D1 cells leading to production of TNF-α, known as an antiviral cytokine. These findings suggest that ME and MFs (especially MF-2) might induce the production of certain factors, including TNF-α, which are responsible for the inhibition of viral growth in vitro.

scholarly journals Soluble Expression and Efficient Purification of Recombinant Class I Hydrophobin DewA

2021 ◽  
Vol 22 (15) ◽  
pp. 7843
Author(s):  
Sang-Oh Ahn ◽  
Ho-Dong Lim ◽  
Sung-Hwan You ◽  
Dae-Eun Cheong ◽  
Geun-Joong Kim
Keyword(s):  
Tertiary Structure ◽  
Signal Sequence ◽  
Soluble Expression ◽  
Class I ◽  
Soluble Form ◽  
Two Phase ◽  
E Coli ◽  
Small Proteins ◽  
Industrial Use ◽  
Shed Light

Hydrophobins are small proteins (<20 kDa) with an amphipathic tertiary structure that are secreted by various filamentous fungi. Their amphipathic properties provide surfactant-like activity, leading to the formation of robust amphipathic layers at hydrophilic–hydrophobic interfaces, which make them useful for a wide variety of industrial fields spanning protein immobilization to surface functionalization. However, the industrial use of recombinant hydrophobins has been hampered due to low yield from inclusion bodies owing to the complicated process, including an auxiliary refolding step. Herein, we report the soluble expression of a recombinant class I hydrophobin DewA originating from Aspergillus nidulans, and its efficient purification from recombinant Escherichia coli. Soluble expression of the recombinant hydrophobin DewA was achieved by a tagging strategy using a systematically designed expression tag (ramp tag) that was fused to the N-terminus of DewA lacking the innate signal sequence. Highly expressed recombinant hydrophobin DewA in a soluble form was efficiently purified by a modified aqueous two-phase separation technique using isopropyl alcohol. Our approach for expression and purification of the recombinant hydrophobin DewA in E. coli shed light on the industrial production of hydrophobins from prokaryotic hosts.

scholarly journals The inhibitory effect of melatonin on human prostate cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dexin Shen ◽  
Lingao Ju ◽  
Fenfang Zhou ◽  
Mengxue Yu ◽  
Haoli Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Theoretical Basis ◽  
Inhibitory Effect ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Anti Oxidant ◽  
Androgen Depletion ◽  
The Relationship ◽  
Future Utilization

AbstractProstate cancer (PCa) is one of the most commonly diagnosed human cancers in males. Nearly 191,930 new cases and 33,330 new deaths of PCa are estimated in 2020. Androgen and androgen receptor pathways played essential roles in the pathogenesis of PCa. Androgen depletion therapy is the most used therapies for primary PCa patients. However, due to the high relapse and mortality of PCa, developing novel noninvasive therapies have become the focus of research. Melatonin is an indole-like neurohormone mainly produced in the human pineal gland with a prominent anti-oxidant property. The anti-tumor ability of melatonin has been substantially confirmed and several related articles have also reported the inhibitory effect of melatonin on PCa, while reviews of this inhibitory effect of melatonin on PCa in recent 10 years are absent. Therefore, we systematically discuss the relationship between melatonin disruption and the risk of PCa, the mechanism of how melatonin inhibited PCa, and the synergistic benefits of melatonin and other drugs to summarize current understandings about the function of melatonin in suppressing human prostate cancer. We also raise several unsolved issues that need to be resolved to translate currently non-clinical trials of melatonin for clinic use. We hope this literature review could provide a solid theoretical basis for the future utilization of melatonin in preventing, diagnosing and treating human prostate cancer.

scholarly journals Volatile scents of influenza A and S. pyogenes (co-)infected cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Selina Traxler ◽  
Gina Barkowsky ◽  
Radost Saß ◽  
Ann-Christin Klemenz ◽  
Nadja Patenge ◽  
...  
Keyword(s):  
Influenza A ◽  
Early Recognition ◽  
Bacterial Species ◽  
Bacterial Load ◽  
Gas Chromatography Mass Spectrometry ◽  
Sampling System ◽  
Infected Cells ◽  
Infection Processes ◽  
Non Destructive

AbstractInfluenza A is a serious pathogen itself, but often leads to dangerous co-infections in combination with bacterial species such as Streptococcus pyogenes. In comparison to classical biochemical methods, analysis of volatile organic compounds (VOCs) in headspace above cultures can enable destruction free monitoring of metabolic processes in vitro. Thus, volatile biomarkers emitted from biological cell cultures and pathogens could serve for monitoring of infection processes in vitro. In this study we analysed VOCs from headspace above (co)-infected human cells by using a customized sampling system. For investigating the influenza A mono-infection and the viral-bacterial co-infection in vitro, we analysed VOCs from Detroit cells inoculated with influenza A virus and S. pyogenes by means of needle-trap micro-extraction (NTME) and gas chromatography mass spectrometry (GC-MS). Besides the determination of microbiological data such as cell count, cytokines, virus load and bacterial load, emissions from cell medium, uninfected cells and bacteria mono-infected cells were analysed. Significant differences in emitted VOC concentrations were identified between non-infected and infected cells. After inoculation with S. pyogenes, bacterial infection was mirrored by increased emissions of acetaldehyde and propanal. N-propyl acetate was linked to viral infection. Non-destructive monitoring of infections by means of VOC analysis may open a new window for infection research and clinical applications. VOC analysis could enable early recognition of pathogen presence and in-depth understanding of their etiopathology.

scholarly journals Dicer is involved in protection against influenza A virus infection

2007 ◽  
Vol 88 (10) ◽  
pp. 2627-2635 ◽  
Author(s):  
Alexey A. Matskevich ◽  
Karin Moelling
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Mammalian Cells ◽  
Influenza A ◽  
Virus Production ◽  
Vero Cells ◽  
Antiviral Response ◽  
Protein Levels ◽  
Infected Cells ◽  
Influenza A Virus Infection

In mammals the interferon (IFN) system is a central innate antiviral defence mechanism, while the involvement of RNA interference (RNAi) in antiviral response against RNA viruses is uncertain. Here, we tested whether RNAi is involved in the antiviral response in mammalian cells. To investigate the role of RNAi in influenza A virus-infected cells in the absence of IFN, we used Vero cells that lack IFN-α and IFN-β genes. Our results demonstrate that knockdown of a key RNAi component, Dicer, led to a modest increase of virus production and accelerated apoptosis of influenza A virus-infected cells. These effects were much weaker in the presence of IFN. The results also show that in both Vero cells and the IFN-producing alveolar epithelial A549 cell line influenza A virus targets Dicer at mRNA and protein levels. Thus, RNAi is involved in antiviral response, and Dicer is important for protection against influenza A virus infection.

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