scholarly journals Effect of the preparation Ingavirin® (imidazolyl ethanamide pentandioic acid) on the interferon status of cells under conditions of viral infection

2016 ◽  
Vol 21 (4) ◽  
pp. 196-205
Author(s):  
Thomas Aschacher ◽  
Artem Krokhin ◽  
Irina Kuznetsova ◽  
Johannes Langle ◽  
Vladimir Nebolsin ◽  
...  

Ingavirin® (imidazolyl ethanamide pentandioic acid) is an original antiviral drug, which is used in Russia for treatment and profilaxis of influenza and other acute viral infections. We confirmed that imidazolyl ethanamide pentandioic acid (IEPA), not being interferon inducer itself, enhances synthesis of both interferon-a/fi receptors (IFNAR) to interferone and cell sensitivity to interferone signalling, which was suppressed by NS1 protein - pathogen factor of influenza virus. IEPA is able to promote antiviral effector proteins PKR and MxA in infected cells, in opposition to interferon system suppression by influenza virus. Theoretical ground of clinical efficacy of Ingavirine® could be confirmed by obtained data of influence to innate immune system during viral infection.

2009 ◽  
Vol 83 (13) ◽  
pp. 6566-6577 ◽  
Author(s):  
Katherine A. Richards ◽  
Francisco A. Chaves ◽  
Andrea J. Sant

ABSTRACT The specificity of the CD4 T-cell immune response to influenza virus is influenced by the genetic complexity of the virus and periodic encounters with variant subtypes and strains. In order to understand what controls CD4 T-cell reactivity to influenza virus proteins and how the influenza virus-specific memory compartment is shaped over time, it is first necessary to understand the diversity of the primary CD4 T-cell response. In the study reported here, we have used an unbiased approach to evaluate the peptide specificity of CD4 T cells elicited after live influenza virus infection. We have focused on four viral proteins that have distinct intracellular distributions in infected cells, hemagglutinin (HA), neuraminidase (NA), nucleoprotein, and the NS1 protein, which is expressed in infected cells but excluded from virion particles. Our studies revealed an extensive diversity of influenza virus-specific CD4 T cells that includes T cells for each viral protein and for the unexpected immunogenicity of the NS1 protein. Due to the recent concern about pandemic avian influenza virus and because CD4 T cells specific for HA and NA may be particularly useful for promoting the production of neutralizing antibody to influenza virus, we have also evaluated the ability of HA- and NA-specific CD4 T cells elicited by a circulating H1N1 strain to cross-react with related sequences found in an avian H5N1 virus and find substantial cross-reactivity, suggesting that seasonal vaccines may help promote protection against avian influenza virus.


2021 ◽  
Vol 10 (36) ◽  
pp. 167-169
Author(s):  
Camila Siqueira ◽  
Diogo Kuczera ◽  
Eneida Da Lozzo ◽  
Dorly Buchi ◽  
José Nelson Couceiro ◽  
...  

Introduction: Strains of macrophages, such as murine J774.G8 macrophages, are susceptible to influenza A infection [1]. One of the responses to viral infection involves the production of various types of immunostimulatory cytokines by infected cells [2]. Methods: In the present study, the macrophage strain J774.G8, maintained in RPMI medium, was submitted to treatment with 10% V/V of two different biotherapics prepared from influenza H3N2, both at 30x. Additionally, two control groups were analyzed: macrophages stimulated with water 30x and macrophages without any treatment. Biotherapics were prepared from intact H3N2 influenza virus and H3N2 inactivated by alcohol 70%. The compounding of both biotherapics followed this procedure: one part of viral particles was diluted in 9 parts of sterile distilled water. The 1:10 sample was submitted to 100 mechanical succussions using Autic® Brazilian machine, originating the first dilution, named decimal (1x). 1 ml of this solution was diluted in 9 ml of solvent and was submitted to 100 succussions, generating biotherapic 2x. This procedure was successively repeated, according to Brazilian Homeopathic Pharmacopoeia, to obtain the biotherapic 30x. By the same technique, water vehicle was prepared in the potency of 30x to be used as control. All samples were prepared under sterile and aseptic conditions, using laminar flow cabinet, class II, and were stored in the refrigerator (8ºC), to avoid microbiological contamination. J774.G8 macrophages were stimulated for 2 days, in a total of six stimuli. Immediately before infection with 25 µl of H3N2 influenza virus, the supernatants were collected and frozen at -20 ºC for later analysis. Next, 24 hours after the virus infection, the supernatants were aliquoted and frozen under the same conditions. Three independent experiments were done in triplicate. Analysis of supernatants was performed by flow cytometry using the Mouse Inflammation Kit. The cytokines detected in this experiment were IL-10, IL 12, TNF-α and MCP1. Results: In all cases, there were no significant differences compared to control groups. However, the production of TNF-α detected in macrophages treated by intact and inactivated biotherapics presented a tendency to increase after infection. In fact, similar results were previously detected in other experiments conducted only with the intact biotherapic [3]. The release of the cytokine MCP1 in all experimental situations presented a tendency to decrease after the viral infection when compared to untreated macrophages. No statistically significant difference was detected in the production of IL 12 and IL 10. These experiments will be repeated to confirm the data obtained.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Tomohiko Urushisaki ◽  
Tomoaki Takemura ◽  
Shigemi Tazawa ◽  
Mayuko Fukuoka ◽  
Junji Hosokawa-Muto ◽  
...  

Influenza A viral infections reached pandemic levels in 1918, 1957, 1968, and, most recently, in 2009 with the emergence of the swine-origin H1N1 influenza virus. The development of novel therapeutics or prophylactics for influenza virus infection is urgently needed. We examined the evaluation of the anti-influenza virus (A/WSN/33 (H1N1)) activity of Brazilian green propolis water extract (PWE) and its constituents by cell viability and real-time PCR assays. Our findings showed strong evidence that PWE has an anti-influenza effect and demonstrate that caffeoylquinic acids are the active anti-influenza components of PWE. Furthermore, we have found that the amount of viral RNA per cell remained unchanged even in the presence of PWE, suggesting that PWE has no direct impact on the influenza virus but may have a cytoprotective activity by affecting internal cellular process. These findings indicate that caffeoylquinic acids are the active anti-influenza components of PWE. Above findings might facilitate the prophylactic application of natural products and the realization of novel anti-influenza drugs based on caffeoylquinic acids, as well as further the understanding of cytoprotective intracellular mechanisms in influenza virus-infected cells.


2012 ◽  
Vol 93 (1) ◽  
pp. 113-118 ◽  
Author(s):  
Nicole C. Robb ◽  
Ervin Fodor

The influenza A virus M1 mRNA is alternatively spliced to produce M2 mRNA, mRNA3, and in some cases, M4 mRNA. Splicing of influenza mRNAs is carried out by the cellular splicing machinery and is thought to be regulated, as both spliced and unspliced mRNAs encode proteins. In this study, we used radioactively labelled primers to investigate the accumulation of spliced and unspliced M segment mRNAs in viral infection and ribonucleoprotein (RNP) reconstitution assays in which only the minimal components required for transcription and replication to occur were expressed. We found that co-expression of the viral NS1 protein in an RNP reconstitution assay altered the accumulation of spliced mRNAs compared with when it was absent, and that this activity was dependent on the RNA-binding ability of NS1. These findings suggest that the NS1 protein plays a role in the regulation of splicing of influenza virus M1 mRNA.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Jin-Young Min ◽  
Yong Ju Jang

Background. Macrolides have received considerable attention for their anti-inflammatory and immunomodulatory actions beyond the antibacterial effect. These two properties may ensure some efficacy in a wide spectrum of respiratory viral infections. We aimed to summarize the properties of macrolides and their efficacy in a range of respiratory viral infection.Methods. A search of electronic journal articles through PubMed was performed using combinations of the following keywords including macrolides and respiratory viral infection.Results. Bothin vitroandin vivostudies have provided evidence of their efficacy in respiratory viral infections including rhinovirus (RV), respiratory syncytial virus (RSV), and influenza virus. Much data showed that macrolides reduced viral titers of RV ICAM-1, which is the receptor for RV, and RV infection-induced cytokines including IL-1β, IL-6, IL-8, and TNF-α. Macrolides also reduced the release of proinflammatory cytokines which were induced by RSV infection, viral titers, RNA of RSV replication, and the susceptibility to RSV infection partly through the reduced expression of activated RhoA which is an RSV receptor. Similar effects of macrolides on the influenza virus infection and augmentation of the IL-12 by macrolides which is essential in reducing virus yield were revealed.Conclusion. This paper provides an overview on the properties of macrolides and their efficacy in various respiratory diseases.


2021 ◽  
Vol 11 (6) ◽  
pp. 225-237
Author(s):  
Kajal Chaudhary ◽  
Shweta Parihar ◽  
Devender Sharma

Viral contaminations speak to a general medical issue and one of the main sources of worldwide mortality. A large portion of the antiviral medications have low permeability, low dissolvability and other related physical properties which make them less efficient for the antiviral treatment. To conquer these constraints, different nanomedicine stages have been planned. Nanomaterials offer special physico-chemical properties that have various advantages for medicate conveyance as perfect devices for viral treatment. This review focuses on the currently used medicines used in viral infection, presents a broad overview of the application of nanosized materials for the treatment of common viral infections and shed light on the potential of nanotechnology to provide more effective treatment for HIV, Herpes simplex virus, Influenza virus and Hepatitis C virus. The action of antiviral medications could be improved with nanomedicine formulations. As the physicochemical properties of nanocarriers can empower their capacity to target the specific sites. When it comes to structuring nanocarriers, size is the most important factor and the nanoparticles can permit the controlled delivery kinetics, enhanced bioavailability, altered pharmacokinetics, and less side effects. Nanocarriers that build them appealing candidates for antiviral drug such as Improves bioavailability of the encapsulated actives, controlled release, reduce the toxicity associated with the anti-viral drugs. One of the important physicochemical properties mainly size is the most important design factor for nanocarriers for anti-viral drug delivery to the specific sites. Nanobased drug delivery also leads to enhance the potential of currently approved antiviral drugs. Keywords: Nanotechnology, HIV, Hepatits virus, Influenza, HSV


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1260-1260 ◽  
Author(s):  
Yuki Asano-Mori ◽  
Hiroshi Shimazu ◽  
Kazuya Ishiwata ◽  
Nobuaki Nakano ◽  
Masanori Tsuji ◽  
...  

Abstract Abstract 1260 Although the efficacy of cord blood transplantation (CBT) from unrelated donors as viable alternative for patients in need of hemtopoietic stem cell transplantation (HSCT) is supported by growing evidences, viral infections related to delayed immune reconstitution remains important problems for further improvement of clinical outcomes. To evaluate incidences and outcomes of late viral infections after CBT by comparison with those after unrelated bone marrow transplantation (uBMT), we retrospectively analyzed the records of 281 Japanese adult patients who underwent allogeneic unrelated HSCT for the first time at the Toranomon Hospital between January, 2002 and March, 2010, and who survived more than 100 days after HSCT without the lost-to-follow-up or retransplantation before day 100. Between 50 days and 5 years after HSCT, 116 patients had at least one late infectious episode with a cumulative incidence of 52.2%, at a median of 157 (50-1597) days after HSCT. The 5-year cumulative incidence of any late viral infections was greater in CBT versus uBMT recipients (60.7% vs. 42.2%, respectively; P=0.039, Figure 1). Thirty-three patients (28.4%) had 2 or more episodes caused by different viruses, and a total of 152 late infectious episodes were documented. The median onset of the episodes was similar between the both groups (median onset 226 days vs 222 days, P=0.89). The most common late viral infection is varicella-zoster virus (VZV) reactivation, accounting for 28.8% (disseminated 10, localized 34), followed by hemorrhagic cystitis associated with adeno- and/or BK viruria (28.2%), cytomegalovirus (CMV) diseases (16.4%; gastrointestinal diseases 23, retinitis 1, pneumonia 1), and respiratory tract infections caused by influenza virus, parainfluenza virus or respiratory syncytial virus (15.8%; upper 26, lower 8), and Epstein-barr virus lymphoproliferative diseases (4.6%). The remaining 10 infectious episodes were caused by relatively rare type of viruses including herpes simplex virus, JC virus, measles virus, mumps virus, norovirus and parvovirus, all of which occurred only in CBT recipients. Of all these viral infections, only VZV reactivation developed significantly more frequent in CBT than in uBMT recipients (P=34.0% vs 17.0%, P=0.023). There was no difference of dissemination rate between the both groups, and all the patients responded well to treatment with antiviral agents. The late viral infection was a primary cause of death in 3 episodes, all of which were pneumonia caused by CMV, influenza virus and parainfluenza virus. The 5-year incidence of infection-related mortality did not differ between CBT and uBMT recipients (0.7% vs 3.1%, P=0.46). Non-relapse mortality occurred in 11.8 % and 16.4 % patients in the CBT and uBMT groups (P=0.71). These findings suggested that cord blood might be as an acceptable and useful stem-cell source as bone marrow from unrelated donors in terms of risks of viral infection in the late posttransplant period. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 90 (7) ◽  
pp. 3661-3675 ◽  
Author(s):  
Sathya N. Thulasi Raman ◽  
Guanqun Liu ◽  
Hyun Mi Pyo ◽  
Ya Cheng Cui ◽  
Fang Xu ◽  
...  

ABSTRACTDDX3 belongs to the DEAD box RNA helicase family and is a multifunctional protein affecting the life cycle of a variety of viruses. However, its role in influenza virus infection is unknown. In this study, we explored the potential role of DDX3 in influenza virus life cycle and discovered that DDX3 is an antiviral protein. Since many host proteins affect virus life cycle by interacting with certain components of the viral machinery, we first verified whether DDX3 has any viral interaction partners. Immunoprecipitation studies revealed NS1 and NP as direct interaction partners of DDX3. Stress granules (SGs) are known to be antiviral and do form in influenza virus-infected cells expressing defective NS1 protein. Additionally, a recent study showed that DDX3 is an important SG-nucleating factor. We thus explored whether DDX3 plays a role in influenza virus infection through regulation of SGs. Our results showed that SGs were formed in infected cells upon infection with a mutant influenza virus lacking functional NS1 (del NS1) protein, and DDX3 colocalized with NP in SGs. We further determined that the DDX3 helicase domain did not interact with NS1 and NP; however, it was essential for DDX3 localization in virus-induced SGs. Knockdown of DDX3 resulted in impaired SG formation and led to increased virus titers. Taken together, our results identified DDX3 as an antiviral protein with a role in virus-induced SG formation.IMPORTANCEDDX3 is a multifunctional RNA helicase and has been reported to be involved in regulating various virus life cycles. However, its function during influenza A virus infection remains unknown. In this study, we demonstrated that DDX3 is capable of interacting with influenza virus NS1 and NP proteins; DDX3 and NP colocalize in the del NS1 virus-induced SGs. Furthermore, knockdown of DDX3 impaired SG formation and led to a decreased virus titer. Thus, we provided evidence that DDX3 is an antiviral protein during influenza virus infection and its antiviral activity is through regulation of SG formation. Our findings provide knowledge about the function of DDX3 in the influenza virus life cycle and information for future work on manipulating the SG pathway and its components to fight influenza virus infection.


2010 ◽  
Vol 84 (15) ◽  
pp. 7603-7612 ◽  
Author(s):  
Susana de Lucas ◽  
Joan Peredo ◽  
Rosa María Marión ◽  
Carmen Sánchez ◽  
Juan Ortín

ABSTRACT The influenza A virus genome consists of 8 negative-stranded RNA segments. NS1 is a nonstructural protein that participates in different steps of the virus infectious cycle, including transcription, replication, and morphogenesis, and acts as a virulence factor. Human Staufen1 (hStau1), a protein involved in the transport and regulated translation of cellular mRNAs, was previously identified as a NS1-interacting factor. To investigate the possible role of hStau1 in the influenza virus infection, we characterized the composition of hStau1-containing granules isolated from virus-infected cells. Viral NS1 protein and ribonucleoproteins (RNPs) were identified in these complexes by Western blotting, and viral mRNAs and viral RNAs (vRNAs) were detected by reverse transcription (RT)-PCR. Also, colocalization of hStau1 with NS1, nucleoprotein (NP), and PA in the cytosol of virus-infected cells was shown by immunofluorescence. To analyze the role of hStau1 in the infection, we downregulated its expression by gene silencing. Human HEK293T cells or A549 cells were silenced using either short hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) targeting four independent sites in the hStau1 mRNA. The yield of influenza virus was reduced 5 to 10 times in the various hStau1-silenced cells compared to that in control silenced cells. The expression levels of viral proteins and their nucleocytoplasmic localization were not affected upon hStau1 silencing, but virus particle production, as determined by purification of virions from supernatants, was reduced. These results indicate a role for hStau1 in late events of the influenza virus infection, possibly during virus morphogenesis.


2008 ◽  
Vol 83 (4) ◽  
pp. 1881-1891 ◽  
Author(s):  
Dipanwita Basu ◽  
Marcin P. Walkiewicz ◽  
Matthew Frieman ◽  
Ralph S. Baric ◽  
David T. Auble ◽  
...  

ABSTRACT The innate immune system guards against virus infection through a variety of mechanisms including mobilization of the host interferon system, which attacks viral products mainly at a posttranscriptional level. The influenza virus NS1 protein is a multifunctional facilitator of virus replication, one of whose actions is to antagonize the interferon response. Since NS1 is required for efficient virus replication, it was reasoned that chemical inhibitors of this protein could be used to further understand virus-host interactions and also serve as potential new antiviral agents. A yeast-based assay was developed to identify compounds that phenotypically suppress NS1 function. Several such compounds exhibited significant activity specifically against influenza A virus in cell culture but had no effect on the replication of another RNA virus, respiratory syncytial virus. Interestingly, cells lacking an interferon response were drug resistant, suggesting that the compounds block interactions between NS1 and the interferon system. Accordingly, the compounds reversed the inhibition of beta interferon mRNA induction during infection, which is known to be caused by NS1. In addition, the compounds blocked the ability of NS1 protein to inhibit double-stranded RNA-dependent activation of a transfected beta interferon promoter construct. The effects of the compounds were specific to NS1, because they had no effect on the ability of the severe acute respiratory syndrome coronavirus papainlike protease protein to block beta interferon promoter activation. These data demonstrate that the function of NS1 can be modulated by chemical inhibitors and that such inhibitors will be useful as probes of biological function and as starting points for clinical drug development.


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