scholarly journals Subversion of the Heme Oxygenase-1 Antiviral Activity by Zika Virus

Viruses ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 2 ◽  
Author(s):  
Chaker El Kalamouni ◽  
Etienne Frumence ◽  
Sandra Bos ◽  
Jonathan Turpin ◽  
Brice Nativel ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Heme Oxygenase ◽  
Zika Virus ◽  
Fluorescent Protein ◽  
Human Cells ◽  
Heme Oxygenase 1 ◽  
Viral Inhibition ◽  
Reporter Protein ◽  
Wide Range ◽  
Rna Replicon

Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in the degradation of heme, is induced in response to a wide range of stress conditions. HO-1 exerts antiviral activity against a broad range of viruses, including the Hepatitis C virus, the human immunodeficiency virus, and the dengue virus by inhibiting viral growth. It has been reported that HO-1 displays antiviral activity against the Zika virus (ZIKV) but the mechanisms of viral inhibition remain largely unknown. Using a ZIKV RNA replicon with the Green Fluorescent Protein (GFP) as a reporter protein, we were able to show that HO-1 expression resulted in the inhibition of viral RNA replication. Conversely, we observed a decrease in HO-1 expression in cells replicating the ZIKV RNA replicon. The study of human cells infected with ZIKV showed that the HO-1 expression level was significantly lower once viral replication was established, thereby limiting the antiviral effect of HO-1. Our work highlights the capacity of ZIKV to thwart the anti-replicative activity of HO-1 in human cells. Therefore, the modulation of HO-1 as a novel therapeutic strategy against ZIKV infection may display limited effect.

scholarly journals Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 2009
Author(s):  
Anne Grunenwald ◽  
Lubka T. Roumenina ◽  
Marie Frimat
Keyword(s):  
Kidney Disease ◽  
Heme Oxygenase ◽  
Current Knowledge ◽  
Kidney Diseases ◽  
Heme Oxygenase 1 ◽  
Wide Range ◽  
Significant Burden ◽  
Stage Renal Disease ◽  
End Stage ◽  
Positive Effect

The incidence of kidney disease is rising, constituting a significant burden on the healthcare system and making identification of new therapeutic targets increasingly urgent. The heme oxygenase (HO) system performs an important function in the regulation of oxidative stress and inflammation and, via these mechanisms, is thought to play a role in the prevention of non-specific injuries following acute renal failure or resulting from chronic kidney disease. The expression of HO-1 is strongly inducible by a wide range of stimuli in the kidney, consequent to the kidney’s filtration role which means HO-1 is exposed to a wide range of endogenous and exogenous molecules, and it has been shown to be protective in a variety of nephropathological animal models. Interestingly, the positive effect of HO-1 occurs in both hemolysis- and rhabdomyolysis-dominated diseases, where the kidney is extensively exposed to heme (a major HO-1 inducer), as well as in non-heme-dependent diseases such as hypertension, diabetic nephropathy or progression to end-stage renal disease. This highlights the complexity of HO-1’s functions, which is also illustrated by the fact that, despite the abundance of preclinical data, no drug targeting HO-1 has so far been translated into clinical use. The objective of this review is to assess current knowledge relating HO-1’s role in the kidney and its potential interest as a nephroprotection agent. The potential therapeutic openings will be presented, in particular through the identification of clinical trials targeting this enzyme or its products.

scholarly journals Heme Oxygenase-1 Exerts Antiviral Activity against Hepatitis A Virus In Vitro

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1229
Author(s):  
Dong-Hwi Kim ◽  
Hee-Seop Ahn ◽  
Hyeon-Jeong Go ◽  
Da-Yoon Kim ◽  
Jae-Hyeong Kim ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Protein Expression ◽  
Heme Oxygenase ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Health Concern ◽  
Heme Oxygenase 1 ◽  
Infected Cells ◽  
In Cells

Hepatitis A virus (HAV), the causative pathogen of hepatitis A, induces severe acute liver injuries in humans and is a serious public health concern worldwide. However, appropriate therapeutics have not yet been developed. The enzyme heme oxygenase-1 (HO-1) exerts antiviral activities in cells infected with several viruses including hepatitis B and C viruses. In this study, we demonstrated for the first time the suppression of virus replication by HO-1 in cells infected with HAV. Hemin (HO-1 inducer) induced HO-1 mRNA and protein expression, as expected, and below 50 mM, dose-dependently reduced the viral RNA and proteins in the HAV-infected cells without cytotoxicity. Additionally, HO-1 protein overexpression using a protein expression vector suppressed HAV replication. Although ZnPP-9, an HO-1 inhibitor, did not affect HAV replication, it significantly inhibited hemin-induced antiviral activity in HAV-infected cells. Additionally, FeCl3, CORM-3, biliverdin, and the HO-1 inducers andrographolide and CoPP inhibited HAV replication in the HAV-infected cells; andrographolide and CoPP exhibited a dose-dependent effect. In conclusion, these results suggest that HO-1 effectively suppresses HAV infection in vitro, and its enzymatic products appear to exert antiviral activity. We expect that these results could contribute to the development of a new antiviral drug for HAV.

scholarly journals Papaya Fruit Pulp and Resulting Lactic Fermented Pulp Exert Antiviral Activity against Zika Virus

2020 ◽  
Vol 8 (9) ◽  
pp. 1257
Author(s):  
Juliano G. Haddad ◽  
Victoria Carcauzon ◽  
Omar El Kalamouni ◽  
Philippe Desprès ◽  
Cyrielle Garcia ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Zika Virus ◽  
Human Cells ◽  
Host Cells ◽  
Dependent Manner ◽  
Bacterial Strains ◽  
Lactic Fermentation ◽  
Papaya Pulp ◽  
Leuconostoc Pseudomesenteroides

There are a several emerging and re-emerging RNA viruses that are prevalent around the world for which there are no licensed vaccines or antiviral drugs. Zika virus (ZIKV) is an example of an emerging virus that has become a significant concern worldwide because of its association with severe congenital malformations and neurological disorders in adults. Several polyphenol-rich extracts from plants were used as nutraceuticals which exhibit potent in vitro antiviral effects. Here, we demonstrated that the papaya pulp extracted from Carica papaya fruit inhibits the infection of ZIKV in human cells without loss of cell viability. At the non-cytotoxic concentrations, papaya pulp extract has the ability to reduce the virus progeny production in ZIKV-infected human cells by at least 4-log, regardless of viral strains tested. Time-of-drug-addition assays revealed that papaya pulp extract interfered with the attachment of viral particles to the host cells. With a view of preserving the properties of papaya pulp over time, lactic fermentation based on the use of bacterial strains Weissella cibaria 64, Lactobacillus plantarum 75 and Leuconostoc pseudomesenteroides 56 was performed and the resulting fermented papaya pulp samples were tested on ZIKV. We found that lactic fermentation of papaya pulp causes a moderate loss of antiviral activity against ZIKV in a bacterial strain-dependent manner. Whereas IC50 of the papaya pulp extract was 0.3 mg/mL, we found that fermentation resulted in IC50 up to 4 mg/mL. We can conclude that papaya pulp possesses antiviral activity against ZIKV and the fermentation process has a moderate effect on the antiviral effect.

scholarly journals Levulinic Acid-Inducible and Tunable Gene Expression System for Methylorubrum extorquens

2021 ◽  
Vol 9 ◽  
Author(s):  
Chandran Sathesh-Prabu ◽  
Young Shin Ryu ◽  
Sung Kuk Lee
Keyword(s):  
Gene Expression ◽  
Levulinic Acid ◽  
Fluorescent Protein ◽  
Expression System ◽  
Constitutive Expression ◽  
Value Added ◽  
Total Protein Content ◽  
Reporter Protein ◽  
Gene Expression System ◽  
Wide Range

Methylorubrum extorquens AM1 is an efficient platform strain possessing biotechnological potential in formate- and methanol-based single carbon (C1) bioeconomy. Constitutive expression or costly chemical-inducible expression systems are not always desirable. Here, several glucose-, xylose-, and levulinic acid (LA)-inducible promoter systems were assessed for the induction of green fluorescent protein (GFP) as a reporter protein. Among them, the LA-inducible gene expression system (HpdR/PhpdH) showed a strong expression of GFP (51-fold) compared to the control. The system was induced even at a low concentration of LA (0.1 mM). The fluorescence intensity increased with increasing concentrations of LA up to 20 mM. The system was tunable and tightly controlled with meager basal expression. The maximum GFP yield obtained using the system was 42 mg/g biomass, representing 10% of the total protein content. The efficiency of the proposed system was nearly equivalent (90%–100%) to that of the widely used strong promoters such as PmxaF and PL/O4. The HpdR/PhpdH system worked equally efficiently in five different strains of M. extorquens. LA is a low-cost, renewable, and sustainable platform chemical that can be used to generate a wide range of products. Hence, the reported system in potent strains of M. extorquens is highly beneficial in the C1-biorefinery industry to produce value-added products and bulk chemicals.

scholarly journals Inducible and tunable gene expression systems for Pseudomonas putida KT2440

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chandran Sathesh-Prabu ◽  
Rameshwar Tiwari ◽  
Doyun Kim ◽  
Sung Kuk Lee
Keyword(s):  
Pseudomonas Putida ◽  
Target Genes ◽  
Fluorescent Protein ◽  
Low Cost ◽  
Inducible Promoter ◽  
Expression Systems ◽  
Reporter Protein ◽  
Pseudomonas Putida Kt2440 ◽  
Wide Range ◽  
Green Fluorescent

AbstractInducible and tunable expression systems are essential for the microbial production of biochemicals. Five different carbon source- and substrate-inducible promoter systems were developed and further evaluated in Pseudomonas putida KT2440 by analyzing the expression of green fluorescent protein (GFP) as a reporter protein. These systems can be induced by low-cost compounds such as glucose, 3-hydroxypropionic acid (3HP), levulinic acid (LA), and xylose. 3HP-inducible HpdR/PhpdH was also efficiently induced by LA. LvaR/PlvaA and XutR/PxutA systems were induced even at low concentrations of LA (0.1 mM) and xylose (0.5 mM), respectively. Glucose-inducible HexR/Pzwf1 showed weak GFP expression. These inducer agents can be used as potent starting materials for both cell growth and the production of a wide range of biochemicals. The efficiency of the reported systems was comparable to that of conventional chemical-inducible systems. Hence, the newly investigated promoter systems are highly useful for the expression of target genes in the widely used synthetic biology chassis P. putida KT2440 for industrial and medical applications.

scholarly journals Protein Therapy Using Heme-Oxygenase-1 Fused to a Polyarginine Transduction Domain Attenuates Cerebral Vasospasm after Experimental Subarachnoid Hemorrhage

2011 ◽  
Vol 31 (11) ◽  
pp. 2231-2242 ◽  
Author(s):  
Tomoyuki Ogawa ◽  
Daniel Hänggi ◽  
Yumei Wu ◽  
Hiroyuki Michiue ◽  
Kazuhito Tomizawa ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Therapeutic Effect ◽  
Cerebral Vasospasm ◽  
Heme Oxygenase ◽  
Fluorescent Protein ◽  
Male Rats ◽  
Heme Oxygenase 1 ◽  
Protein Transduction ◽  
Arginine Residues ◽  
Basilar Arteries

A sequence of 11 consecutive arginine residues (11R) is one of the best protein transduction domains for introducing proteins into cell membranes. Heme-oxygenase-1 (HO-1) is involved in heme catabolism and reduces the contractile effect of hemoglobin after subarachnoid hemorrhage (SAH). Therefore, we constructed 11R-fused HO-1 protein to achieve successful transduction of the protein into the cerebral arteries and examined the therapeutic effect of the 11R-HO-1 protein for cerebral vasospasm (CV) after SAH. We injected the 11R-HO-1 protein into the cisterna magna of male rats and, several hours after the injection, performed immunofluorescence staining and western blotting analysis of the rat basilar arteries (BAs) to determine transduction efficacy. We also assessed intraarterial HO-1 activity as cGMP (cyclic guanosine 3′, 5′-cyclic monophosphate) accumulation in SAH and determined whether protein transduction of 11R-HO-1 quantified the therapeutic effect in a rat double-hemorrhage model of SAH. The BAs expressed significantly more HO-1 in the group injected with 11R-HO-1 (3.56±0.54 (11R-HO-1) versus control (saline)), and transduction of 11R-HO-1 resulted in higher activity (>3.25-fold) in rat BAs with SAH. Moreover, the results of the rat double-hemorrhage model showed that the 11R-HO-1 protein significantly attenuated CV after SAH (317.59±23.48 μm (11R-HO-1) versus 270.08±14.66 μm (11R-fused enhanced green fluorescent protein), 252.05±13.95 μm (saline), P<0.01).

[419] ANTIVIRAL ACTIVITY AND HEPATOPROTECTION BY HEME OXYGENASE-1 IN MODELS OF HUMAN HEPATITIS B INFECTION

2007 ◽  
Vol 46 ◽  
pp. S161
Author(s):  
U. Protzer ◽  
S. Seyfried ◽  
M. Quasdorff ◽  
G. Sass ◽  
F. Bohne ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Antiviral Activity ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Hepatitis B Infection ◽  
Human Hepatitis

scholarly journals Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication

Virology ◽  
2017 ◽  
Vol 503 ◽  
pp. 1-5 ◽  
Author(s):  
Hanxia Huang ◽  
Barry Falgout ◽  
Kazuyo Takeda ◽  
Kenneth M. Yamada ◽  
Subhash Dhawan
Keyword(s):  
Virus Replication ◽  
Heme Oxygenase ◽  
Host Defense ◽  
Zika Virus ◽  
Heme Oxygenase 1

scholarly journals Bach1 Functions as a Hypoxia-inducible Repressor for the Heme Oxygenase-1 Gene in Human Cells

2003 ◽  
Vol 278 (11) ◽  
pp. 9125-9133 ◽  
Author(s):  
Tomomi Kitamuro ◽  
Kazuhiro Takahashi ◽  
Kazuhiro Ogawa ◽  
Reiko Udono-Fujimori ◽  
Kazuhisa Takeda ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Human Cells ◽  
Heme Oxygenase 1
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