Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival

DeDiego, Marta L.; Nieto-Torres, José L.; Regla-Nava, José Ángel; Jiménez-Guardeño, Jose M.; Fernández‐Delgado, Raúl; Fett, Craig; Castaño-Rodríguez, Carlos; Perlman, Stanley; Enjuanes, Luis

doi:10.1128/jvi.02576-13

Cited by 388 publications

(426 citation statements)

References 75 publications

Supporting

Mentioning

400

Contrasting

Unclassified

Order By: Relevance

“…In the present study, we found that the expression of phospho-JNK in the cecum of model rats was significantly upregulated, and this was attenuated by treatment with berberine. Another TAK1 cascade, NF-kB, a protein responsible for cellular responses to stimuli such as cytokines, UV irradiation, free radicals, and viral or bacterial antigens and that plays a crucial role in regulating the immune response to infection (Brasier, 2006;Perkins, 2007;Yadav et al, 2013;Dediego et al, 2014), was also implicated in the anti-inflammation effect of berberine. Our results showed that the activation of NF-kB induced by abrasive surgery was significantly inhibited by berberine, as indicated by a decreased phospho-NF-kB expression.…”

Section: Discussionmentioning

confidence: 99%

Berberine Hydrochloride Prevents Postsurgery Intestinal Adhesion and Inflammation in Rats

Zhang

et al. 2014

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Intestinal adhesion, characterized by connection of the loops of the intestine with other abdominal organs by fibrous tissue bands, remains an inevitable event of abdominal operations and can cause a number of complications. Berberine hydrochloride (berberine), a natural plant alkaloid derived from Chinese herbal medicine, is characterized by diverse pharmacological effects, such as anticancer and lower elevated blood glucose. This study is designed to investigate the effects of berberine on adhesion and inflammation after abdominal surgeries and the underlying molecular mechanisms. Adhesion severity grades and collagen deposition were assessed 14 days after surgery. We evaluated the levels of intercellular adhesion molecule-1 (ICAM-1) and inflammatory cytokines interleukin-1b (IL-1b), IL-6, transforming growth factor b (TGF-b), tumor necrosis factor-a (TNF-a), and examined transforming growth factor-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor kB (NF-kB) signaling. The surgery group experienced the most severe adhesions, and berberine strikingly reduced the density and severity of adhesion. Results showed significant lower expression of IL-1b, IL-6, TGF-b, TNF-a, and ICAM-1, in berberine groups compared with the operation group. Activities of phosphorylated JNK and phosphorylated NF-kB were inhibited in the berberine groups compared with the surgery group. Our novel findings identified berberine hydrochloride as a promising strategy to prevent adhesion by downregulating ICAM-1 and reduce inflammation by inhibiting the TAK1/JNK and TAK1/NF-kB signaling after abdominal surgery, which brought out a good therapeutic approach for the development of clinical application for postoperative abdominal adhesion and inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Berberine Hydrochloride Prevents Postsurgery Intestinal Adhesion and Inflammation in Rats

Zhang

et al. 2014

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…This strategy was directly applied in the case of SARS-CoV using conventional mouse strains without the need for Tg mice expressing the human ACE2 receptor (Day et al, 2009;Frieman et al, 2012;Roberts et al, 2007). Mouse-adapted SARS-CoV obtained by passing the virus 15 times in mice (SARS-CoV-MA15) has been an excellent model as it reproduces very well the pathology caused by SARS-CoV in humans, including mortality (DeDiego et al, 2011(DeDiego et al, , 2014b. In contrast, in the case of MERS-CoV, the virus was grown in Tg or knockin humanized mice susceptible to MERS-CoV (K. Li, P. McCray, and S. Perlman, 2016, personal communication).…”

Section: Animal Models For Cov Vaccine and Antivirals Studiesmentioning

confidence: 99%

“…Some CoV proteins act as IFN antagonists by inhibiting its production or signaling (Fig. 2) (DeDiego et al, 2014b;Totura and Baric, 2012;Zhong et al, 2012). Potent cytokines involved in controlling viral infections and priming adaptive immune responses are generated in response to CoV infection (Totura and Baric, 2012;Zhou et al, 2015).…”

Section: Coronavirus Virulencementioning

confidence: 99%

Molecular Basis of Coronavirus Virulence and Vaccine Development

Enjuanes

Zúñiga

Castaño-Rodríguez

et al. 2016

Advances in Virus Research

147

141

View full text Add to dashboard Cite

Virus vaccines have to be immunogenic, sufficiently stable, safe, and suitable to induce long-lasting immunity. To meet these requirements, vaccine studies need to provide a comprehensive understanding of (i) the protective roles of antiviral B and T-cell-mediated immune responses, (ii) the complexity and plasticity of major viral antigens, and (iii) virus molecular biology and pathogenesis. There are many types of vaccines including subunit vaccines, whole-inactivated virus, vectored, and live-attenuated virus vaccines, each of which featuring specific advantages and limitations. While nonliving virus vaccines have clear advantages in being safe and stable, they may cause side effects and be less efficacious compared to live-attenuated virus vaccines. In most cases, the latter induce long-lasting immunity but they may require special safety measures to prevent reversion to highly virulent viruses following vaccination. The chapter summarizes the recent progress in the development of coronavirus (CoV) vaccines, focusing on two zoonotic CoVs, the severe acute respiratory syndrome CoV (SARS-CoV), and the Middle East respiratory syndrome CoV, both of which cause deadly disease and epidemics in humans. The development of attenuated virus vaccines to combat infections caused by highly pathogenic CoVs was largely based on the identification and characterization of viral virulence proteins that, for example, interfere with the innate and adaptive immune response or are involved in interactions with specific cell types, such as macrophages, dendritic and epithelial cells, and T lymphocytes, thereby modulating antiviral host responses and viral pathogenesis and potentially resulting in deleterious side effects following vaccination.

show abstract

“…At the C-terminal end, the residue most affected was Ala39, and a group of nearby residues. Interestingly, most of these C-terminal juxtamembrane residues (residues 38-43) form a conserved motif in RSV SH protein "A 39 ILNKL 43 ," suggesting that binding of the drug may not only alter channel activity. This binding site is located at the luminal-facing narrowest region of the channel lumen ( Figure 3B).…”

Section: Channel Activity Inhibitors Of Sars-cov E and Rsv Sh Proteinsmentioning

confidence: 99%

“…41 Infected cells by SARS-CoV ∆E underwent apoptosis more rapidly and to greater extent, showed upregulation of stress response genes, downregulation of inflammation genes, 42 and decreased nuclear factor kappa-light-chainenhancer of activated B cells-mediated inflammation response in infected cells and mice. 43 …”

mentioning

confidence: 99%

Pentameric viral ion channels: from structure to function

Surya¹,

Li²,

Torres³

2014

JRLCR

View full text Add to dashboard Cite

A family of small polypeptides in many virus types associate to form oligomers and have channel activity. These proteins have been referred to as viroporins or virochannels and are increasingly recognized as important virulence factors and potential drug targets. In this review, we focus on two of the viroporins that have been studied in more detail from a structural and functional point of view. One is the 76-residue envelope (E) protein found in coronaviruses (CoVs) that causes the severe acute respiratory syndrome (SARS). The other is the 65-residue small hydrophobic (SH) protein found in a paramyxovirus, the respiratory syncytial virus (RSV). RSV SH and SARS-CoV E proteins are short polypeptides with a single transmembrane domain. In both cases, the presence of the viroporin has a protective effect on cells, preventing early apoptosis, but it leads to increased virulence in infected animal models. Both viroporins form homopentameric oligomers that show channel activity with no or low selectivity. The role of channel activity is still unclear, but associations have been made to facilitation of the egress of the virus by modification of the secretory pathway, and contributions to inflammation. SARS-CoV E protein has a cytoplasmically oriented C-terminus and a lumenal N-terminus, whereas the opposite orientation is found in RSV SH protein. Despite this opposite topology, nuclear magnetic resonance (NMR)-based structural models of these two channels show a similar champagne flute shape, with the wider opening facing the cytoplasmic side. Good channel inhibitors are lacking, but those found seem to have a preference for the narrow end of the channel. Availability of good inhibitors will help reveal the specific role of these channels in the life cycle of these viruses.

show abstract

Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival

Cited by 388 publications

References 75 publications

Berberine Hydrochloride Prevents Postsurgery Intestinal Adhesion and Inflammation in Rats

Berberine Hydrochloride Prevents Postsurgery Intestinal Adhesion and Inflammation in Rats

Molecular Basis of Coronavirus Virulence and Vaccine Development

Pentameric viral ion channels: from structure to function

Contact Info

Product

Resources

About