scholarly journals Cloning, Prokaryotic Soluble Expression, and Analysis of Antiviral Activity of Two Novel Feline IFN-ω Proteins

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 335 ◽  
Author(s):  
Xiaona Wang ◽  
Fengsai Li ◽  
Meijing Han ◽  
Shuo Jia ◽  
Li Wang ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Viral Diseases ◽  
Type I ◽  
Phylogenetic Tree Analysis ◽  
Diarrhea Virus ◽  
Genes Encoding ◽  
Cat Spleen ◽  
Spleen Lymphocytes

Cats are becoming more popular as household companions and pets, forming close relationships with humans. Although feline viral diseases can pose serious health hazards to pet cats, commercialized preventative vaccines are lacking. Interferons (IFNs), especially type I IFNs (IFN-α, IFN-β, and interferon omega (IFN-ω)), have been explored as effective therapeutic drugs against viral diseases in cats. Nevertheless, there is limited knowledge regarding feline IFN-ω (feIFN-ω), compared to IFN-α and IFN-β. In this study, we cloned the genes encoding feIFN-ωa and feIFN-ωb from cat spleen lymphocytes. Homology and phylogenetic tree analysis revealed that these two genes belonged to new subtypes of feIFN-ω. The recombinant feIFN-ωa and feIFN-ωb proteins were expressed in their soluble forms in Escherichia coli, followed by purification. Both proteins exhibited effective anti-vesicular stomatitis virus (VSV) activity in Vero, F81 (feline kidney cell), Madin–Darby bovine kidney (MDBK), Madin–Darby canine kidney (MDCK), and porcine kidney (PK-15) cells, showing broader cross-species antiviral activity than the INTERCAT IFN antiviral drug. Furthermore, the recombinant feIFN-ωa and feIFN-ωb proteins demonstrated antiviral activity against VSV, feline coronavirus (FCoV), canine parvovirus (CPV), bovine viral diarrhea virus (BVDV), and porcine epidemic diarrhea virus (PEDV), indicating better broad-spectrum antiviral activity than the INTERCAT IFN. The two novel feIFN-ω proteins (feIFN-ωa and feIFN-ωb) described in this study show promising potential to serve as effective therapeutic agents for treating viral infections in pet cats.

scholarly journals Identification of Feline Interferon Regulatory Factor 1 as an Efficient Antiviral Factor against the Replication of Feline Calicivirus and Other Feline Viruses

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yongxiang Liu ◽  
Xiaoxiao Liu ◽  
Hongtao Kang ◽  
Xiaoliang Hu ◽  
Jiasen Liu ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infections ◽  
Interferon Regulatory Factor ◽  
Feline Calicivirus ◽  
Type I ◽  
Norwalk Virus ◽  
Regulatory Factor ◽  
Feline Panleukopenia Virus ◽  
Protein Levels ◽  
Interferon Regulatory Factor 1

Interferons (IFNs) can inhibit most, if not all, viral infections by eliciting the transcription of hundreds of interferon-stimulated genes (ISGs). Feline calicivirus (FCV) is a highly contagious pathogen of cats and a surrogate for Norwalk virus. Interferon efficiently inhibits the replication of FCV, but the mechanism of the antiviral activity is poorly understood. Here, we evaluated the anti-FCV activity of ten ISGs, whose antiviral activities were previously reported. The results showed that interferon regulatory factor 1 (IRF1) can significantly inhibit the replication of FCV, whereas the other ISGs tested in this study failed. Further, we found that IRF1 was localized in the nucleus and efficiently activated IFN-β and the ISRE promoter. IRF1 can trigger the production of endogenous interferon and the expression of ISGs, suggesting that IRF1 can positively regulate IFN signalling. Importantly, the mRNA and protein levels of IRF1 were reduced upon FCV infection, which may be a new strategy for FCV to evade the innate immune system. Finally, the antiviral activity of IRF1 against feline panleukopenia virus, feline herpesvirus, and feline infectious peritonitis virus was demonstrated. These data indicate that feline IRF1 plays an important role in regulating the host type I IFN response and inhibiting feline viral infections.

scholarly journals Broadly Antiviral Activities of TAP1 through Activating the TBK1-IRF3-Mediated Type I Interferon Production

2021 ◽  
Vol 22 (9) ◽  
pp. 4668
Author(s):  
Jin Zhao ◽  
Ruiting Li ◽  
Yanjun Li ◽  
Jiaoshan Chen ◽  
Fengling Feng ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Antigen Presentation ◽  
Antigen Processing ◽  
Viral Infections ◽  
Emerging Infectious Diseases ◽  
Type I ◽  
Loss Of Function ◽  
Herpes Simplex Virus 1 ◽  
Host Interaction ◽  
Simplex Virus

Deeply understanding the virus-host interaction is a prerequisite for developing effective anti-viral strategies. Traditionally, the transporter associated with antigen processing type 1 (TAP1) is critical for antigen presentation to regulate adaptive immunity. However, its role in controlling viral infections through modulating innate immune signaling is not yet fully understood. In the present study, we reported that TAP1, as a product of interferon-stimulated genes (ISGs), had broadly antiviral activity against various viruses such as herpes simplex virus 1 (HSV-1), adenoviruses (AdV), vesicular stomatitis virus (VSV), dengue virus (DENV), Zika virus (ZIKV), and influenza virus (PR8) etc. This antiviral activity by TAP1 was further confirmed by series of loss-of-function and gain-of-function experiments. Our further investigation revealed that TAP1 significantly promoted the interferon (IFN)-β production through activating the TANK binding kinase-1 (TBK1) and the interferon regulatory factor 3 (IRF3) signaling transduction. Our work highlighted the broadly anti-viral function of TAP1 by modulating innate immunity, which is independent of its well-known function of antigen presentation. This study will provide insights into developing novel vaccination and immunotherapy strategies against emerging infectious diseases.

scholarly journals Direct antiviral activity of interferon stimulated genes is responsible for resistance to paramyxoviruses in ISG15-deficient cells

2019 ◽  
Author(s):  
David Holthaus ◽  
Andri Vasou ◽  
Connor G. G. Bamford ◽  
Jelena Andrejeva ◽  
Christina Paulus ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Antiviral Activity ◽  
Translational Control ◽  
Cellular Response ◽  
Viral Infections ◽  
Viral Disease ◽  
Significant Inhibition ◽  
Negative Regulator ◽  
Type I ◽  
Tetratricopeptide Repeats

AbstractInterferons (IFNs), produced during viral infections, induce the expression of hundreds of IFN- stimulated genes (ISGs). Some ISGs have specific antiviral activity while others regulate the cellular response. Besides functioning as an antiviral effector, IFN-stimulated gene 15 (ISG15) is a negative regulator of IFN signalling and inherited ISG15-deficiency leads to autoinflammatory interferonopathies where individuals exhibit elevated ISG expression in the absence of pathogenic infection. We have recapitulated these effects in cultured human A549-ISG15-/- cells and (using A549-UBA7-/- cells) confirmed that posttranslational modification by ISG15 (ISGylation) is not required for regulation of the type-I IFN response. ISG15-deficient cells pre-treated with IFN-α were resistant to paramyxovirus infection. We also showed that IFN-α treatment of ISG15-deficient cells led to significant inhibition of global protein synthesis leading us to ask whether resistance was due to the direct antiviral activity of ISGs or whether cells were non-permissive due to translation defects. We took advantage of the knowledge that IFN-induced protein with tetratricopeptide repeats 1 (IFIT1) is the principal antiviral ISG for parainfluenza virus 5 (PIV5). Knockdown of IFIT1 restored PIV5 infection in IFN-α-pre-treated ISG15-deficient cells, confirming that resistance was due to the direct antiviral activity of the IFN response. However, resistance could be induced if cells were pre-treated with IFN-α for longer times, presumably due to inhibition of protein synthesis. These data show that the cause of virus resistance is two-fold; ISG15-deficiency leads to the ‘early’ over-expression of specific antiviral ISGs, but the later response is dominated by an unanticipated, ISG15- dependent, loss of translational control.Key pointsCell culture model of ISG15-deficiency replicate findings in ISG15-/- patient cellsCause of resistance in ISG15-/- cells differs depending on duration of IFN treatmentISG15-/- patients without serious viral disease don’t prove ISGylation is unimportant

scholarly journals THE RESULTS OF THE USE OF BIOTECHNOLOGICAL DRUGS IN VETERINARY MEDICINE, PROMISING FOR MEDICINE (PART 1)

2021 ◽  
pp. 60-72
Author(s):  
Yu. S. Alikin ◽  
M. V. Alekseeva ◽  
V. V. Ermolaev ◽  
V. P. Klimenko ◽  
Yu. V. Telegina
Keyword(s):  
Veterinary Medicine ◽  
Antiviral Activity ◽  
Serratia Marcescens ◽  
Antiviral Drug ◽  
Medical Industry ◽  
Viral Diseases ◽  
Leningrad Region ◽  
Industrial Complex ◽  
Novosibirsk Region ◽  
Wide Range

Cell and serum nucleases are considered as a natural biological barrier, one of the first links in the body’s antiviral defense: nucleases act on viruses that the usual immunological barrier cannot resist. Inactivation of the enzymatic properties of nucleases also leads to the loss of their antiviral activity. It was found that the nucleases do not inactivate the native virus outside the cell and act mainly on the virus that multiplies in the cells. There is a direct dependence of the antiviral activity of endonuclease on the concentration of the enzyme in the medium. The first antiviral drug created on the basis of the Serratia marcescens endonuclease was called bacterial endonuclease. Its technology was developed by joint research of NIKTI BAS of the Ministry of Medical Industry (Berdsk, Novosibirsk region) and ICIG SB of the USSR Academy of Sciences in 1973–1984. Serratia marcescens endonuclease is capable of cleaving the nucleic acids of both RNA and DNA-containing viruses. The enzyme inhibits the reproduction of vesicular stomatitis and smallpox vaccine viruses in chicken fibroblast cell culture, respectively. It was the first antiviral drug in the history of beekeeping, designed to prevent acute and chronic paralysis and other viral diseases of bees. The drug was also intended as an antiviral agent for a wide range of diseases in various organisms. The effectiveness of bacterial endonuclease as a means of prevention and treatment of respiratory viral diseases in calves was studied. The research was carried out at the industrial complex for growing heifers of the Gosnensky state farm in the Leningrad region on calves of a black-and-white breed of 20–60 days old. For the experiments, we used bacterial endonuclease produced by the Vyshnevolotsky Plant of Enzyme Preparations or NICTI BAS of the Ministry of Medical Industry. In the future, NIKTI BAV together with Diafarm LLC developed a second – generation antiviral drug, endoglucin, based on bacterial endonucleosis. Production experiments to study its effect as a therapeutic and prophylactic agent for respiratory diseases of calves were conducted during 2007– 2011. in the agricultural complex «Prichulymsky» of the Achinsky district of the Krasnoyarsk Territory with the participation of the Department of Epizootology and Parasitology of the Faculty of Veterinary Medicine of KrasGAU and in CJSC «Suzdalskoye» of the Dovolensky district of the Novosibirsk region. Prophylactic use of endoglucin in calves with bronchopneumonia can reduce the incidence from 2.2 to 3.1 times. The drug endoglucin in combination with drugs indicated for the treatment of pulmonary pathology, has therapeutic effectiveness in bronchopneumonia of calves.

scholarly journals In Vitro Antiviral Activity of Heterophyllaea pustulata Extracts

2012 ◽  
Vol 7 (8) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Brenda S. Konigheim ◽  
Mauricio Beranek ◽  
Laura R. Comini ◽  
Javier J. Aguilar ◽  
Juliana Marioni ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Antiviral Drug ◽  
Neutral Red ◽  
Type I ◽  
Saint Louis ◽  
Aerial Parts ◽  
Uptake Assay ◽  
Simplex Virus ◽  
Hsv 1

The antiviral activity was tested of different polarity extracts, with differing chemical composition, obtained from aerial parts of Heterophyllaea pustulata Hook f. (Rubiaceae) against Herpes Simplex Virus Type I (HSV-1) and Saint Louis Encephalitis Virus (SLEV). The Vero cell line was employed as a host cell for the antiviral assessment of benzene (Ben), ethyl acetate (EtOAc) and ethanol (EtOH) extracts by means of the Neutral Red uptake assay and plaque reduction test. None of the extracts showed antiviral activity against SLEV. Only the extracts (Ben and EtOAc) with a high content of anthraquinones (AQs) inhibited HSV-1 replication, exhibiting Selectivity Index (SI) values of 2.7 and 2.4, respectively. Therefore, these extracts could be good candidates as natural sources for antiviral drug development against HSV-1.

scholarly journals Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2235
Author(s):  
Anastasiya S. Sokolova ◽  
Valentina P. Putilova ◽  
Olga I. Yarovaya ◽  
Anastasiya V. Zybkina ◽  
Ekaterina D. Mordvinova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Rational Design ◽  
Ebola Virus ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Surface Proteins ◽  
Hantaan Virus

To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC50 = 45.3 µM), Ebola pseudotype viruses (IC50 = 0.12 µM), and authentic EBOV (IC50 = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC50 = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.

scholarly journals The Application of Porphyrins and Their Analogues for Inactivation of Viruses

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4368
Author(s):  
Natalya Sh. Lebedeva ◽  
Yury A. Gubarev ◽  
Mikhail O. Koifman ◽  
Oskar I. Koifman
Keyword(s):  
Antiviral Activity ◽  
Review Paper ◽  
Viral Infections ◽  
Inorganic Compounds ◽  
Viral Diseases ◽  
Photodynamic Inactivation

The problem of treating viral infections is extremely relevant due to both the emergence of new viral diseases and to the low effectiveness of existing approaches to the treatment of known viral infections. This review focuses on the application of porphyrin, chlorin, and phthalocyanine series for combating viral infections by chemical and photochemical inactivation methods. The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10–15 years in order to identify the most promising areas.

scholarly journals Immunological Activities of Isoprinosine Inhibition on Viral Infections Inhuman

2019 ◽  
Vol 16 (04) ◽  
pp. 773-778
Author(s):  
Hashim Ali Abdualmeer Al-Sherees ◽  
Sumaya NajimAbedali Al-khateeb ◽  
Fadhil Hussain Nasir Al-Muhannak
Keyword(s):  
Antiviral Activity ◽  
Cell Cultures ◽  
A549 Cell ◽  
Cytotoxic Effect ◽  
Viral Infections ◽  
Colorimetric Assay ◽  
Morphological Changes ◽  
Antiviral Drug ◽  
Virus Multiplication ◽  
Mtt Colorimetric Assay

Isoprinosine is a combination of inosine used as antiviral drug without effect on viral particle itself, but instead only and acts as on immunostimulant and also acts indirectly by activation of immune cells. Aim of this study was to determine level of interferon-alpha (INF-α) with parainfluenza viruses HPIV-2, and adenoviruses HAdV-2 replication. In the present study, cytotoxic effect of isoprinosine was assessed using A549 cell line exposed to different concentrations of compound (isoprinosine: 50-800μg/mL) for 48 hours. Cytotoxic effect was examined visually using light, inverted microscopy Olympus CK2 under 400x magnification and by the MTT colorimetric assay. The yield re­duction assay (YRA), which evaluates the ability of the isoprinosine (50-800 μg/mL) to inhibit virus multiplication in cell cultures, was applied. The cytopathic effect of the virus was evaluated 48 h after infection of A549 cell cultures with viruses by means of light, inverted microsco­py. The YRA method was used to determine the 50% end point (IC50) in the presence of Isoprinosine with the controlled one. MTT cytotoxicity assay confirmed microscopic observations. There were no morphological changes, as assessed visually, in cell cultures treated with isoprinosine. After conducting the experi­ments and analyzing the results we noticed that higher concentrations of isoprinosine strongly inhibited multiplication of all viruses. HPIV-2 and HAdV-2 showed the highest sensitivity to the antiviral activity of isoprinosine as compared with the control, however, increasing concentrations of isoprinosine up to 800 μg /ml slightly enhanced the antiviral activity of 400 μg/ml isoprinosine. Our study was conducted that HAdV-2 and HPIV-2 have the highest sensitivity to the antiviral activity of isoprinosine from all tested viral strains.

scholarly journals Antiviral and Cytotoxic Activity of Different Plant Parts of Banana (Musa spp.)

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 549
Author(s):  
Sujogya Kumar Panda ◽  
Ana Hortência Fonsêca Castro ◽  
Ramin Saleh Jouneghani ◽  
Pieter Leyssen ◽  
Johan Neyts ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Cytotoxic Activity ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Antiviral Drug ◽  
Enterovirus 71 ◽  
Fever Virus ◽  
Therapeutic Window ◽  
Viral Diseases ◽  
Banana Plant

Chikungunya and yellow fever virus cause vector-borne viral diseases in humans. There is currently no specific antiviral drug for either of these diseases. Banana plants are used in traditional medicine for treating viral diseases such as measles and chickenpox. Therefore, we tested selected banana cultivars for their antiviral but also cytotoxic properties. Different parts such as leaf, pseudostem and corm, collected separately and extracted with four different solvents (hexane, acetone, ethanol, and water), were tested for in vitro antiviral activity against Chikungunya virus (CHIKV), enterovirus 71 (EV71), and yellow fever virus (YFV). Extracts prepared with acetone and ethanol from leaf parts of several cultivars exhibited strong (EC50 around 10 μg/mL) anti-CHIKV activity. Interestingly, none of the banana plant extracts (concentration 1–100 µg/mL) were active against EV71. Activity against YFV was restricted to two cultivars: Namwa Khom–Pseudostem–Ethanol (5.9 ± 5.4), Namwa Khom–Corm–Ethanol (0.79 ± 0.1) and Fougamou–Corm–Acetone (2.5 ± 1.5). In most cases, the cytotoxic activity of the extracts was generally 5- to 10-fold lower than the antiviral activity, suggesting a reasonable therapeutic window.

scholarly journals Porcine Epidemic Diarrhea Virus-Induced Epidermal Growth Factor Receptor Activation Impairs the Antiviral Activity of Type I Interferon

2018 ◽  
Vol 92 (8) ◽  
Author(s):  
Lijun Yang ◽  
Jiayu Xu ◽  
Longjun Guo ◽  
Taijie Guo ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Type I Interferon ◽  
Growth Factor Receptor ◽  
Type I ◽  
Specific Inhibition ◽  
Diarrhea Virus ◽  
Egfr Activation ◽  
Epidermal Growth ◽  
Porcine Epidemic Diarrhea

ABSTRACTPorcine epidemic diarrhea virus (PEDV) causes acute and devastating enteric disease in suckling piglets and results in huge economic losses in the pig industry worldwide. To establish productive infection, viruses must first circumvent the host innate immune response. In this study, we found that PEDV infection stimulated epidermal growth factor receptor (EGFR) activation, which has been linked to not only anticancer therapeutics, but also antiviral signaling. Therefore, we determined whether EGFR activation affected PEDV infection by using an activator or overexpression assay. The data showed that EGFR activation enhanced virus replication in both cases. We also found that specific inhibition of EGFR by either inhibitors or small interfering RNA (siRNA) led to a decrease in virus yields. Further analysis revealed that inhibition of EGFR produced augmentation of type I interferon genes. We next observed that the EGFR downstream cascade STAT3 was also activated upon PEDV infection. Similar to the case of EGFR, specific inhibition of STAT3 by either inhibitor or siRNA increased the antiviral activity of interferon and resulted in decreased PEDV RNA levels, and vice versa. The data on STAT3 depletion in combination with EGFR activation suggest that the attenuation of antiviral activity by EGFR activation requires activation of the STAT3 signaling pathway. Taken together, these data demonstrate that PEDV-induced EGFR activation serves as a negative regulator of the type I interferon response and provides a novel therapeutic target for virus infection.IMPORTANCEEGFR is a transmembrane tyrosine receptor that mediates various cellular events, as well as several types of human cancers. In this study, we investigated for the first time the role of EGFR in PEDV infection. We observed that PEDV infection induced EGFR activation. The role of EGFR activation is to impair the antiviral activity of type I interferon, which requires the involvement of the EGFR downstream signaling cascade STAT3. Our findings reveal a new mechanism evolved by PEDV to circumvent the host antiviral response, which might serve as a therapeutic target against virus infection.

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