scholarly journals Inhibitory Effect of IL-1β on HBV and HDV Replication and HB Antigen-Dependent Modulation of Its Secretion by Macrophages

Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 65
Author(s):  
Marion Delphin ◽  
Suzanne Faure-Dupuy ◽  
Nathalie Isorce ◽  
Michel Rivoire ◽  
Anna Salvetti ◽  
...  
Keyword(s):  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Infection Models ◽  
Immune Molecule ◽  
B Virus ◽  
Pathogen Control ◽  
Inflammatory Macrophages ◽  
First Time ◽  
Delta Virus

Co-infection with the hepatitis B virus and hepatitis delta virus (HDV) leads to the most aggressive form of viral hepatitis. Using in vitro infection models, we confirmed that IL-1β, a crucial innate immune molecule for pathogen control, was very potent against HBV from different genotypes. Additionally, we demonstrated for the first time a strong and rapid antiviral effect induced by very low doses of IL-1β against HDV. In parallel, using co-culture assays, we demonstrated that monocytes exposed to HBV, and in particular to HBsAg, during differentiation into pro-inflammatory macrophages secreted less IL-1β. Altogether, our data emphasize the importance of developing combined antiviral strategies that would, for instance, reduce the secretion of HBsAg and stimulate the immune system to produce endogenous IL-1β efficient against both HBV and HDV.

Farnesoid X receptor alpha ligands inhibit hepatitis delta virus replication in vitro independently of their effect on hepatitis B virus

2020 ◽  
Vol 73 ◽  
pp. S834-S835
Author(s):  
Benoît Lacombe ◽  
Julie Lucifora ◽  
Camille Ménard ◽  
Michelet Maud ◽  
Adrien Foca ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Replication ◽  
Hepatitis Delta Virus ◽  
Farnesoid X Receptor ◽  
Hepatitis Delta ◽  
Receptor Alpha ◽  
B Virus ◽  
Delta Virus

scholarly journals Enhanced efficacy of endonuclease inhibitor baloxavir acid against orthobunyaviruses when used in combination with ribavirin

2020 ◽  
Vol 75 (11) ◽  
pp. 3189-3193
Author(s):  
Sebastiaan ter Horst ◽  
Yaiza Fernandez-Garcia ◽  
Marcella Bassetto ◽  
Stephan Günther ◽  
Andrea Brancale ◽  
...  
Keyword(s):  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Docking Simulation ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Surface Model ◽  
La Crosse Virus ◽  
Endonuclease Domain ◽  
Substrate Cleavage

Abstract Objectives Baloxavir acid is an endonuclease inhibitor approved for use against influenza. We evaluated whether this compound also targets the endonuclease domain of orthobunyaviruses and therefore could potentially be used against orthobunyavirus infections. Methods We performed a thermal shift assay and a fluorescence resonance energy transfer (FRET)-based nuclease monitoring assay using the La Crosse virus (LACV) endonuclease and baloxavir acid to prove their interaction and identify an inhibitory effect. Their interaction was further studied in a docking simulation using Glide SP. We show that baloxavir acid inhibits the viral replication of Bunyamwera virus (BUNV)–mCherry in vitro using high-content imaging and virus yield assay. Lastly, we investigated the use of baloxavir acid in combination with ribavirin in vitro by implementing the Zero Interaction Potency response surface model. Results We show that baloxavir acid augments LACV enzyme’s melting temperature with ΔTm 9.5 ± 0.4°C and inhibited substrate cleavage with IC50 0.39 ± 0.03 μM. Moreover, our docking simulation suggests that baloxavir acid is able to establish an efficient binding with the LACV endonuclease. In the cell-based assay, we observed that baloxavir acid and ribavirin inhibited BUNV–mCherry with an EC50 of 0.7 ± 0.2 μM and 26.6 ± 8.9 μM, respectively. When used in combination, we found a maximum synergistic effect of 8.64. Conclusions The influenza endonuclease inhibitor baloxavir acid is able to bind to and interfere with the endonuclease domain of orthobunyaviruses and yields a more potent antiviral effect than ribavirin against BUNV–mCherry. The combination of both compounds results in a more potent antiviral effect, suggesting that these molecules could potentially be combined to treat orthobunyavirus-infected patients.

scholarly journals Role of N Glycosylation of Hepatitis B Virus Envelope Proteins in Morphogenesis and Infectivity of Hepatitis Delta Virus

2003 ◽  
Vol 77 (9) ◽  
pp. 5519-5523 ◽  
Author(s):  
Camille Sureau ◽  
Chantal Fournier-Wirth ◽  
Patrick Maurel
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis Delta Virus ◽  
Envelope Proteins ◽  
Virus Envelope ◽  
Hepatitis Delta ◽  
B Virus ◽  
L Proteins ◽  
Delta Virus

ABSTRACT Hepatitis delta virus (HDV) particles are coated with the large (L), middle (M), and small (S) hepatitis B virus envelope proteins. In the present study, we constructed glycosylation-defective envelope protein mutants and evaluated their capacity to assist in the maturation of infectious HDV in vitro. We observed that the removal of N-linked carbohydrates on the S, M, and L proteins was tolerated for the assembly of subviral hepatitis B virus (HBV) particles but was partially inhibitory for the formation of HDV virions. However, when assayed on primary cultures of human hepatocytes, virions coated with S, M, and L proteins lacking N-linked glycans were infectious. Furthermore, in the absence of M, HDV particles coated with nonglycosylated S and L proteins retained infectivity. These results indicate that carbohydrates on the HBV envelope proteins are not essential for the in vitro infectivity of HDV.

scholarly journals Characterization of the secretory profile and exosomes of limbal stem cells in the canine species

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244327
Author(s):  
Antonio J. Villatoro ◽  
Cristina Alcoholado ◽  
María del Carmen Martín-Astorga ◽  
Gustavo Rico ◽  
Viviana Fernández ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ocular Surface ◽  
Inhibitory Effect ◽  
Proteomic Profile ◽  
Limbal Stem Cells ◽  
High Concentrations ◽  
First Time

Limbal stem cells (LSCs) are a quiescent cell population responsible for the renewal of the corneal epithelium. Their deficiency is responsible for the conjunctivization of the cornea that is seen in different ocular pathologies, both in humans and in the canine species. The canine species represents an interesting preclinical animal model in ocular surface pathologies. However, the role of LSCs in physiological and pathological conditions in canine species is not well understood. Our objective was to characterize for the first time the soluble factors and the proteomic profile of the secretome and exosomes of canine LSCs (cLSCs). In addition, given the important role that fibroblasts play in the repair of the ocular surface, we evaluated the influence of the secretome and exosomes of cLSCs on their proliferation in vitro. Our results demonstrated a secretory profile of cLSCs with high concentrations of MCP-1, IL-8, VEGF-A, and IL-10, as well as significant production of exosomes. Regarding the proteomic profile, 646 total proteins in the secretome and 356 in exosomes were involved in different biological processes. Functionally, the cLSC secretome showed an inhibitory effect on the proliferation of fibroblasts in vitro, which the exosomes did not. These results open the door to new studies on the possible use of the cLSC secretome or some of its components to treat certain pathologies of the ocular surface in canine species.

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.

scholarly journals Host poly(A) polymerases PAPD5 and PAPD7 provide two layers of protection that ensure the integrity and stability of hepatitis B virus RNA

2021 ◽  
Author(s):  
Fei Liu ◽  
Amy C.H Lee ◽  
Fang Guo ◽  
Andrew S. Kondratowicz ◽  
Holly M Micolochick Steuer ◽  
...  
Keyword(s):  
Dominant Role ◽  
Regulatory Element ◽  
Rna Stability ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Stem Loop ◽  
Knock Out ◽  
The Individual

Noncanonical poly(A) polymerases PAPD5 and PAPD7 (PAPD5/7) stabilize HBV RNA via the interaction with the viral post-transcriptional regulatory element (PRE), representing new antiviral targets to control HBV RNA metabolism, HBsAg production and viral replication. Inhibitors targeting these proteins are being developed as antiviral therapies, therefore it is important to understand how PAPD5/7 coordinate to stabilize HBV RNA. Here, we utilized a potent small-molecule AB-452 as a chemical probe, along with genetic analyses to dissect the individual roles of PAPD5/7 in HBV RNA stability. AB-452 inhibits PAPD5/7 enzymatic activities and reduces HBsAg both in vitro (EC50 ranged from 1.4 to 6.8 nM) and in vivo by 0.93 log10. Our genetic studies demonstrate that the stem-loop alpha sequence within PRE is essential for both maintaining HBV poly(A) tail integrity and determining sensitivity towards the inhibitory effect of AB-452. Although neither single knock-out (KO) of PAPD5 nor PAPD7 reduces HBsAg RNA and protein production, PAPD5 KO does impair poly(A) tail integrity and confers partial resistance to AB-452. In contrast, PAPD7 KO could not result in any measurable phenotypic changes, but displays a similar antiviral effect as AB-452 treatment when PAPD5 is depleted simultaneously. PAPD5/7 double KO confers complete resistance to AB-452 treatment. Our results thus indicate that PAPD5 plays a dominant role in stabilizing viral RNA by protecting the integrity of its poly(A) tail, while PAPD7 serves as a second line of protection. These findings inform PAPD5 targeted therapeutic strategies and open avenues for further investigating PAPD5/7 in HBV replication.

scholarly journals Ivermectin the Promising Drug to Stave off the COVID-19 Crisis: A Review

2021 ◽  
Vol 7 (2) ◽  
pp. 95-98
Author(s):  
Zakia Jahan ◽  
Masudul Hassan
Keyword(s):  
Infectious Diseases ◽  
Specific Treatment ◽  
In Vitro Study ◽  
Antiviral Effect ◽  
Viral Particles ◽  
The World ◽  
Infected Cells ◽  
Almost All ◽  
First Time

The Coronavirus disease 2019 (COVID-19) outbreak, forcing us to face unprecedented moments in the world. The huge devastating impact of the world due to the covid-19 attack causes the brink of no return. However, there is no proven and specific treatment for Covid -19. Very few medications have received Emergency Use of Authorization. A recent in vitro study was the first time to find out and to assess the antiviral effect of Ivermectin on COVID-19. The study showed that Ivermectin was active against COVID- 19-infected cells, was able to kill effectively almost all viral particles within 48 h. In these moments of crisis, FDA-approved ivermectin is a ray of hope. Bangladesh Journal of Infectious Diseases 2020;7(2):95-98

scholarly journals Author Correction: Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Peter Jianrui Liu ◽  
James M. Harris ◽  
Emanuele Marchi ◽  
Valentina D’Arienzo ◽  
Thomas Michler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
State Of The Art ◽  
Infection Models ◽  
Chronic Hepatitis B Virus ◽  
B Virus

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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.

scholarly journals Hepatitis delta virus facilitates the selection of hepatitis B virus mutants in vivo and functionally impacts on their replicative capacity in vitro

2016 ◽  
Vol 22 (1) ◽  
pp. 98.e1-98.e6 ◽  
Author(s):  
E. Shirvani-Dastgerdi ◽  
M.R. Pourkarim ◽  
U. Herbers ◽  
S. Amini-Bavil-Olyaee ◽  
E. Yagmur ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis Delta Virus ◽  
Replicative Capacity ◽  
Hepatitis Delta ◽  
B Virus ◽  
Selection Of ◽  
Delta Virus
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