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Regulation of antiviral innate immune signaling and viral evasion following viral genome sensing
Chathuranga Kiramage,Weerawardhana Asela,Dodantenna Niranjan,이종수 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-
A harmonized balance between positive and negative regulation of pattern recognition receptor (PRR)-initiated immune responses is required to achieve the most favorable outcome for the host. This balance is crucial because it must not only ensure activation of the first line of defense against viral infection but also prevent inappropriate immune activation, which results in autoimmune diseases. Recent studies have shown how signal transduction pathways initiated by PRRs are positively and negatively regulated by diverse modulators to maintain host immune homeostasis. However, viruses have developed strategies to subvert the host antiviral response and establish infection. Viruses have evolved numerous genes encoding immunomodulatory proteins that antagonize the host immune system. This review focuses on the current state of knowledge regarding key host factors that regulate innate immune signaling molecules upon viral infection and discusses evidence showing how specific viral proteins counteract antiviral responses via immunomodulatory strategies.
이병훈,Kiramage Chathuranga,Md Bashir Uddin,Prasanna Weeratunga,김면수,조원경,김홍익,마진열,이종수 한국미생물학회 2017 The journal of microbiology Vol.55 No.6
Coptidis Rhizoma is derived from the dried rhizome of Ranunculaceous plants and is a commonly used traditional Chinese medicine. Although Coptidis Rhizoma is commonly used for its many therapeutic effects, antiviral activity against respiratory syncytial virus (RSV) has not been reported in detail. In this study, we evaluated the antiviral activities of Coptidis Rhizoma extract (CRE) against RSV in human respiratory tract cell line (HEp2) and BALB/c mice. An effective dose of CRE significantly reduces the replication of RSV in HEp2 cells and reduces the RSV-induced cell death. This antiviral activity against RSV was through the induction of type I interferon- related signaling and the antiviral state in HEp2 cells. More importantly, oral administration of CRE exhibited prophylactic effects in BALB/c mice against RSV. In HPLC analysis, we found the presence of several compounds in the aqueous fraction and among them; we confirmed that palmatine was related to the antiviral properties and immunemodulation effect. Taken together, an extract of Coptidis Rhizoma and its components play roles as immunomodulators and could be a potential source as promising natural antivirals that can confer protection to RSV. These outcomes should encourage further allied studies in other natural products.
Intracellular sensing of viral genomes and viral evasion
Hyun-Cheol Lee,Kiramage Chathuranga,Jong-SooLee 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
During viral infection, virus-derived cytosolic nucleic acids are recognized by host intracellular specific sensors. The efficacy of this recognition system is crucial for triggering innate host defenses, which then stimulate more specific adaptive immune responses against the virus. Recent studies show that signal transduction pathways activated by sensing proteins are positively or negatively regulated by many modulators to maintain host immune homeostasis. However, viruses have evolved several strategies to counteract/evade host immune reactions. These systems involve viral proteins that interact with host sensor proteins and prevent them from detecting the viral genome or from initiating immune signaling. In this review, we discuss key regulators of cytosolic sensor proteins and viral proteins based on experimental evidence.
Dung T. Huynh,W.A. Gayan Chathuranga,Kiramage Chathuranga,Jong-Soo Lee,Chul-Joong Kim The Korean Society for Microbiology and Biotechnol 2024 Journal of microbiology and biotechnology Vol.34 No.3
Avian influenza is a serious threat to both public health and the poultry industry worldwide. This respiratory virus can be combated by eliciting robust immune responses at the site of infection through mucosal immunization. Recombinant probiotics, specifically lactic acid bacteria, are safe and effective carriers for mucosal vaccines. In this study, we engineered recombinant fusion protein by fusing the hemagglutinin 1 (HA1) subunit of the A/Aquatic bird/Korea/W81/2005 (H5N2) with the Bacillus subtilis poly γ-glutamic acid synthetase A (pgsA) at the surface of Lactobacillus casei (pgsA-HA1/L. casei). Using subcellular fractionation and flow cytometry we confirmed the surface localization of this fusion protein. Mucosal administration of pgsA-HA1/L. casei in mice resulted in significant levels of HA1-specific serum IgG, mucosal IgA and neutralizing antibodies against the H5N2 virus. Additionally, pgsA-HA1/L. casei-induced systemic and local cell-mediated immune responses specific to HA1, as evidenced by an increased number of IFN-γ and IL-4 secreting cells in the spleens and higher levels of IL-4 in the local lymphocyte supernatants. Finally, mice inoculated with pgsA-HA1/L. casei were protected against a 10LD50 dose of the homologous mouse-adapted H5N2 virus. These results suggest that mucosal immunization with L. casei displaying HA1 on its surface could be a potential strategy for developing a mucosal vaccine against other H5 subtype viruses.
Melia azedarach extract exhibits a broad spectrum of antiviral effect in vitro and in vivo
N. A. Nadeeka Nethmini,김면수,Kiramage Chathuranga,마진열,김홍익,이종수 충북대학교 동물의학연구소 2020 Journal of Biomedical and Translational Research Vol.21 No.3
Melia azedarach is commonly used in traditional and folk medicine in Korea and China to treat a variety of diseases including diarrheal, diabetic, rheumatic, and hypertensive disease. The aim of this study was to determine the potential prophylactic and therapeutic effects of Melia azedarach against a broad spectrum of viruses in in vitro cell culture model and the protective effect against different influenza A subtypes in BALB/c mice model. An effective dose of pre-treatment, co-treatment, and post-treatment of Melia azedarach significantly reduced the replication of coxsackievirus, herpes simplex virus, influenza A virus, enterovirus, and bovine rhinovirus in both epithelial and macrophage cell lines. Melia azedarach treatment remarkably promoted the phosphorylation of the key molecules associated with the type-1 interferon and NF-κB signaling pathways. Furthermore, it induced the secretion of type-1 interferon and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in both epithelial and macrophage cells. Interestingly, oral inoculation of an effective dose of herb extract significantly improved viral clearance in the lungs of BALB/c mice, thus exhibiting protection against several subtypes of influenza A virus. Together with our results indicate that an extracts of Melia azedarach and its components could exhibit a potential natural source of an antiviral drug candidate for a broad spectrum of viruses in animal and humans.
Lee Seung-Chul,Kim Yongkwan,Cha Ji-Won,Chathuranga Kiramage,Dodantenna Niranjan,Kwon Hyeok-Il,Kim Min Ho,Jheong Weonhwa,Yoon In-Joong,Lee Joo Young,Yoo Sung-Sik,Lee Jong-Soo 한국미생물학회 2024 The journal of microbiology Vol.62 No.2
African swine fever virus (ASFV) is the causative agent of the highly lethal African swine fever disease that affects domestic pigs and wild boars. In spite of the rapid spread of the virus worldwide, there is no licensed vaccine available. The lack of a suitable cell line for ASFV propagation hinders the development of a safe and effective vaccine. For ASFV propagation, primary swine macrophages and monocytes have been widely studied. However, obtaining these cells can be time-consuming and expensive, making them unsuitable for mass vaccine production. The goal of this study was to validate the suitability of novel CA-CAS-01-A (CAS-01) cells, which was identified as a highly permissive cell clone for ASFV replication in the MA-104 parental cell line for live attenuated vaccine development. Through a screening experiment, maximum ASFV replication was observed in the CAS-01 cell compared to other sub-clones of MA-104 with 14.89 and log10 7.5 ± 0.15 Ct value and TCID50/ ml value respectively. When CAS-01 cells are inoculated with ASFV, replication of ASFV was confirmed by Ct value for ASFV DNA, HAD50/ ml assay, TCID50/ ml assay, and cytopathic effects and hemadsoption were observed similar to those in primary porcine alveolar macrophages after 5th passage. Additionally, we demonstrated stable replication and adaptation of ASFV over the serial passage. These results suggest that CAS-01 cells will be a valuable and promising cell line for ASFV isolation, replication, and development of live attenuated vaccines.
김면수,차투랑가 기라마게,김홍익,이종수,김철중,Kim, Myun Soo,Chathuranga, Kiramage,Kim, Hongik,Lee, Jong-Soo,Kim, Chul-Joong 대한수의학회 2018 大韓獸醫學會誌 Vol.58 No.3
Althaea rosea has been used in traditional Chinese medicine to treat numerous diseases, but no studies have investigated its anti-influenza properties to date. In this study, we investigated the anti-influenza effects of Althaea rosea. BALB/c mice orally pretreated with Althaea rosea ($200{\mu}L$, 0.1 mg/mL concentration in phosphate-buffered saline) and followed by infection of influenza A virus nasally showed higher survivability and lower lung virus titer against divergent subtypes of influenza A virus infection. We also found that oral administration of Althaea rosea elicited antiviral innate immune responses in serum, bronchoalveolar lavage fluid, small intestinal fluid, and the lungs. Taken together, these findings suggest that aqueous extracts of Althaea rosea are a potential candidate for use as an anti-influenza drug.
Dense Granule Protein-7 (GRA-7) of Toxoplasma gondii inhibits viral replication in vitro and in vivo
Prasanna Weeratunga,틸리나,김태환,이현철,김재훈,이병훈,이은서,Kiramage Chathuranga,W. A. Gayan Chathuranga,양철수,마진열,이종수 한국미생물학회 2017 The journal of microbiology Vol.55 No.11
Dense granule protein-7 (GRA-7) is an excretory protein of Toxoplasma gondii. It is a potential serodiagnostic marker and vaccine candidate for toxoplasmosis. Previous reports demonstrated that GRA-7 induces innate immune responses in macrophages by interacting with TRAF6 via the MyD88- dependent pathway. In the present study, we evaluated the antiviral activity and induction of an antiviral state by GRA-7 both in vitro and in vivo. It was observed that GRA-7 markedly reduced the replication of vesicular stomatitis virus (VSVGFP), influenza A virus (PR8-GFP), coxsackievirus (H3- GFP), herpes simplex virus (HSV-GFP), and adenovirus-GFP in epithelial (HEK293T/HeLa) and immune (RAW264.7) cells. These antiviral activities of GRA-7 were attributed to the induction of type I interferon (IFN) signaling, resulting in the secretion of IFNs and pro-inflammatory cytokines. Additionally, in BALB/c mice, intranasal administration of GRA-7 prevented lethal infection by influenza A virus (H1N1) and exhibited prophylactic effects against respiratory syncytial virus (RSV-GFP). Collectively, these results suggested that GRA-7 exhibits immunostimulatory and broad spectrum antiviral activities via type I IFN signaling. Thus, GRA-7 can be potentially used as a vaccine adjuvant or as a candidate drug with prophylactic potential against viruses.
Kim, Tae-Hwan,Lee, Hyun-Cheol,Kim, Jae-Hoon,Hewawaduge, C. Y.,Chathuranga, Kiramage,Chathuranga, W. A. Gayan,Ekanayaka, Pathum,Wijerathne, H. M. S. M.,Kim, Chul-Joong,Kim, Eunhee,Lee, Jong-Soo Public Library of Science 2019 PLoS pathogens Vol.15 No.8
<P> Fas-associated factor 1 is a death-promoting protein that induces apoptosis by interacting with the Fas receptor. Until now, FAF1 was reported to interact potentially with diverse proteins and to function as a negative and/or positive regulator of several cellular possesses. However, the role of FAF1 in defense against bacterial infection remains unclear. Here, we show that FAF1 plays a pivotal role in activating NADPH oxidase in macrophages during <I>Listeria monocytogenes</I> infection. Upon infection by <I>L. monocytogenes,</I> FAF1 interacts with p67phox (an activator of the NADPH oxidase complex), thereby facilitating its stabilization and increasing the activity of NADPH oxidase. Consequently, knockdown or ectopic expression of FAF1 had a marked effect on production of ROS, proinflammatory cytokines, and antibacterial activity, in macrophages upon stimulation of TLR2 or after infection with <I>L. monocytogenes.</I> Consistent with this, FAF1<SUP>gt/gt</SUP> mice, which are knocked down in FAF1, showed weaker inflammatory responses than wild-type mice; these weaker responses led to increased replication of <I>L. monocytogenes.</I> Collectively, these findings suggest that FAF1 positively regulates NADPH oxidase-mediated ROS production and antibacterial defenses. </P>