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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.
Hybrid FPMS: A New Fairness Protocol Management Scheme for Community Wireless Mesh Networks
( Chathuranga H. Widanapathirana ),( Y. Ahmet Sekercioglu ),( Bok-min Goi ) 한국인터넷정보학회 2011 KSII Transactions on Internet and Information Syst Vol.5 No.11
Node cooperation during packet forwarding operations is critically important for fair resource utilization in Community Wireless Mesh Networks (CoWMNs). In a CoWMN, node cooperation is achieved by using fairness protocols specifically designed to detect and isolate malicious nodes, discourage unfair behavior, and encourage node participation in forwarding packets. In general, these protocols can be split into two groups: Incentive-based ones, which are managed centrally, and use credit allocation schemes. In contrast, reputation-based protocols that are decentralized, and rely on information exchange among neighboring nodes. Centrally managed protocols inevitably suffer from scalability problems. The decentralized, reputation-based protocols lacks in detection capability, suffer from false detections and error propagation compared to the centralized, incentive-based protocols. In this study, we present a new fairness protocol management scheme, called Hybrid FPMS that captures the superior detection capability of incentive-based fairness protocols without the scalability problems inherently expected from a centralized management scheme as a network`s size and density grows. Simulation results show that Hybrid FPMS is more efficient than the current centralized approach and significantly reduces the network delays and overhead.
W.G.D. Chathuranga,S.H.P.P. Karunaratne,W.A. Priyanka P. De Silva 한국응용곤충학회 2020 Journal of Asia-Pacific Entomology Vol.23 No.1
Predation and cannibalism can affect the co-existence of mosquito species or the assemblage of mosquito species (i.e., community structure). In this study, predatory feeding patterns and cannibalism of larvae of Armigeres subalbatus mosquitoes were quantified under laboratory conditions using Aedes albopictus and Culex uniformis Co-existence larvae as prey organisms. Rate of consumption of prey larvae and the rate of cannibalism of 1st to 4th instar larvae of Armigeres subalbatus were reported at 24 h intervals with and without alternative food supplement. Both the 3rd and 4th instar larvae of Ar. subalbatus showed a substantial predation on the larvae of Ae. albopictus (33.6 ± 4.4) and Cx uniformis (47.3 ± 7.6). The cannibalism of the predatory larvae was strongly correlated to the larval density (r = 0.9). The predator and the prey density and the given food type were significant factors that determined the rate of pupation, death and the emergence as adults. A significant relationship was shown for the co-occurrence of predatory larvae and the prey larvae at the 85 natural breeding habitats observed at the field (χ 2 = 74.4, p < 0.001). Nine breeding sites (10.6%) were positive for both prey and predatory larvae. Our study showed robust information about the predatory and cannibalistic behavior of Ar. subalbatus larvae emphasizing their role in managing the population structure of mosquito communities.
( Dung T. Huynh ),( W. A. Gayan Chathuranga ),( Kiramage Chathuranga ),( Jong-soo Lee ),( Chul-joong Kim ) 한국미생물생명공학회 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 10LD<sub>50</sub> 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.
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>
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.
Dense Granule Protein-7 (GRA-7) of Toxoplasma gondii inhibits viral replication in vitro and in vivo
Weeratunga, Prasanna,Herath, Thilina U. B.,Kim, Tae-Hwan,Lee, Hyun-Cheol,Kim, Jae-Hoon,Lee, Byeong-Hoon,Lee, Eun-Seo,Chathuranga, Kiramage,Chathuranga, W. A. Gayan,Yang, Chul-Su,Ma, Jin Yeul,Lee, Jong MICROBIOLOGICAL SOCIETY OF KOREA 2017 JOURNAL OF MICROBIOLOGY -SEOUL- Vol. No.
<P>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 (VSV-GFP), 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.</P>
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.