• Title/Summary/Keyword: antiviral defense

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Development of a Platform for Natural Killer Cell Therapy with Antiviral Efficacy (항바이러스 효능을 가진 자연살해세포 치료제 플랫폼 개발)

  • Dongsoo Kim;Hyeongseok Yun;Jinhui Lee;Dayoung Yeon;Chi Ho Yu;Se Hum Gu;Young-Jo Song;Jung-Eun Kim;Seung-Ho Lee;Yong Han Lee;Gyeung Haeng Hur;Junghwa Kang
    • Journal of the Korea Institute of Military Science and Technology
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    • v.27 no.1
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    • pp.107-115
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    • 2024
  • Various vaccines were rapidly developed during the COVID-19 pandemic to prevent and treat infections but global infections continue, and concerns about new mutations and infectious diseases persist. Thus, active research focuses on developing, producing, and supplying vaccines and treatments for various infectious diseases and potential pandemics. Natural killer(NK) cells, as innate immune cells, can recognize and eliminate abnormal cells like virus-infected and cancer cells. Hence, their development as anticancer and antiviral treatments is rapidly advancing. In this study, optimal short-term culture conditions were identified for allogeneic NK cells by simplifying the culture process through the isolation of NK cells(referred to as NKi cells) and eliminating CD3+ cells(referred to as CD3- cells). NK cells demonstrated reduced viral titer in injection of NK cells into SARS-CoV-2 infected ACE-tg mice increased survival. The study's findings could form the basis for an antiviral treatment platform that swiftly responds to new viral disease pandemics.

Host Cell-Intrinsic Antiviral Defense Induced by Type I Interferons

  • Asano, Atsushi
    • Korean Journal of Agricultural Science
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    • v.35 no.2
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    • pp.177-182
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    • 2008
  • Type I Interferons (IFNs) are potent antiviral cytokines that modulate both innate immunity and adaptive immunity. Type I IFNs are immediately induced by viral infection, and stimulate production of a broad range of gene products such as double-stranded RNA-activated protein kinase (PKR), 2' 5'-oligoadenylate synthetase (OAS)/RNaseL and Mx GTPases. These proteins inhibit viral replication in host cells. Type I IFNs, in turn, lead to antiviral state at early phase of viral infection. We provide an overview of the knowledge of IFN-inducible antiviral proteins conserved in vertebrates.

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Structure and Function of the Influenza A Virus Non-Structural Protein 1

  • Han, Chang Woo;Jeong, Mi Suk;Jang, Se Bok
    • Journal of Microbiology and Biotechnology
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    • v.29 no.8
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    • pp.1184-1192
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    • 2019
  • The influenza A virus is a highly infectious respiratory pathogen that sickens many people with respiratory disease annually. To prevent outbreaks of this viral infection, an understanding of the characteristics of virus-host interaction and development of an anti-viral agent is urgently needed. The influenza A virus can infect mammalian species including humans, pigs, horses and seals. Furthermore, this virus can switch hosts and form a novel lineage. This so-called zoonotic infection provides an opportunity for virus adaptation to the new host and leads to pandemics. Most influenza A viruses express proteins that antagonize the antiviral defense of the host cell. The non-structural protein 1 (NS1) of the influenza A virus is the most important viral regulatory factor controlling cellular processes to modulate host cell gene expression and double-stranded RNA (dsRNA)-mediated antiviral response. This review focuses on the influenza A virus NS1 protein and outlines current issues including the life cycle of the influenza A virus, structural characterization of the influenza A virus NS1, interaction between NS1 and host immune response factor, and design of inhibitors resistant to the influenza A virus.

In vitro Antiviral Activities of Korean Marine Algae Extracts against Fish Pathogenic Infectious Hematopoietic Necrosis Virus and Infectious Pancreatic Necrosis Virus

  • Kang, So-Young;Kim, Seok-Ryel;Oh, Myung-Joo
    • Food Science and Biotechnology
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    • v.17 no.5
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    • pp.1074-1078
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    • 2008
  • To investigate the antiviral activity of marine algae against fish pathogenic viruses, which are often the causes of viral disease in aquaculture, the 80% methanolic extracts of 21 species collected from the coast of Korea were screened for their in vitro antiviral activities on infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV), using a flounder spleen (FSP) cell-line. Among them, Monostroma nitidum (10 ${\mu}g/mL$) exhibited the strongest inactivation on IHNV, showing a 2 log reduced virus titre as compared to the control in the determination of direct virucidal activity. In addition, Polysiphonia morrowii (100 ${\mu}g/mL$) remarkably reduced the virus titres of treated cells by 2-2.5 log, for both IHNV and IPNV, in the determination of cellular protective activity, implying the existence of substances that may modulate innate host defense mechanisms against viral infections. These results reveal that some marine algae could be promising candidates as sources of antiviral agents or as health-promoting feeds for aquaculture.

Biologically active compounds from natural and marine natural organisms with antituberculosis, antimalarial, leishmaniasis, trypanosomiasis, anthelmintic, antibacterial, antifungal, antiprotozoal, and antiviral activities

  • Asif, Mohammad
    • CELLMED
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    • v.6 no.4
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    • pp.22.1-22.19
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    • 2016
  • The biologically active compounds derived from different natural organisms such as animals, plants, and microorganisms like algae, fungi, bacteria and merine organisms. These natural compounds possess diverse biological activities like anthelmintic, antibacterial, antifungal, antimalarial, antiprotozoal, antituberculosis, and antiviral activities. These biological active compounds were acted by variety of molecular targets and thus may potentially contribute to several pharmacological classes. The synthesis of natural products and their analogues provides effect of structural modifications on the parent compounds which may be useful in the discovery of potential new drug molecules with different biological activities. Natural organisms have developed complex chemical defense systems by repelling or killing predators, such as insects, microorganisms, animals etc. These defense systems have the ability to produce large numbers of diverse compounds which can be used as new drugs. Thus, research on natural products for novel therapeutic agents with broad spectrum activities and will continue to provide important new drug molecules.

The Mechanism of Poly I:C-Induced Antiviral Activity in Peritoneal Macrophage

  • Pyo, Suh-Kenung
    • Archives of Pharmacal Research
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    • v.17 no.2
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    • pp.93-99
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    • 1994
  • Macrtophages play an important role in defense against virus infection by intrinsic resistance and by extrinsic resistance. Since interferon-induced enzymes which are 2'-5' oligoadenylate synthetase and p1/eIF-2 protein kinase have been shown to be involved in the inhibition of viral replication, I examined the mechanism by which poly I:C, an interferon inducer, exerts its antiviral effects in inflammatory macrophages infected with herpes simplex virus type 1 (HSV-1). The data presented here demonstrate that poly I:C-induced antiviral activity is partially due to the activation of 2'-5' pligoadenylate synthetase. The activation of 2'-5' oligoadenlate A synthetase by poly I:C is also at least mediated via the production of interferon-.betha.. Taken together, these data indicate that interferon-.betha. produced in response to poly I:C acts in an autocrine manner to activate the 2'-5' oligoadenylate synthetase and to induce resistance to HSV-1.

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Establishment of a Lethal Animal Model of Hantaan Virus 76-118 Infection (한탄바이러스 76-118을 이용한 치사 동물모델 확립)

  • Song, Young Jo;Yu, Chi Ho;Gu, Se Hun;Hur, Gyeung Haeng;Jeong, Seong Tae
    • Journal of the Korea Institute of Military Science and Technology
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    • v.24 no.3
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    • pp.348-355
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    • 2021
  • Hantaan virus(HTNV) causes hemorrhagic fever with renal syndrome(HFRS) with a case fatality rate ranging from <1 to 15 % in human. Hantavax is a vaccine against the Hantavirus, which has been conditionally approved by the Ministry of Food and Drug Safety(MFDS). However, only 50 % of volunteers had neutralizing antibodies 1 year following the boost. Effective antiviral treatments against HTNV infection are limited. Hantaviruses generally cause asymptomatic infection in adult mice. On the other hand, infection of suckling and newborn mice with hantaviruses causes lethal neurological diesease or persistant infection, which is different from the disease in humans. The development of vaccines and antiviral strategies for HTNV has been partly hampered by the lack of an efficient lethal mouse model to evaluate the efficacy of the candidate vaccines or antivirals. In this report, we established a lethal mouse model for HTNV, which may facilitate in vivo studies on the evaluation of candidate drugs against HTNV. The median lethal dose value of HTNV was calculated by probit analysis of deaths occurring within two weeks. Five groups of ten ICR mice were injected intracranially with serial 2-fold dilutions (from 50 to 3.125 PFU/head) of HTNV. Mice injected with HTNV began to die at 8 days post-infection. The lethal dose required to kill 50 % of the mice (LD50) was calculated to be 2.365 PFU/head.

Antiviral activity of interferon-like cytokine (ILC) produced by head kidney leucocytes of common carp, Cyprinus carpio L (잉어 두신 백혈구에서 생성된 Interferon-like cytokine (ILC)의 항바이러스 활성)

  • Jo, Mi-Yeong;Kim, Eun-Jeon;Im, Sang-Gu;Kim, Jun-U;Park, Su-Il
    • Journal of fish pathology
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    • v.17 no.2
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    • pp.75-82
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    • 2004
  • Interferons are kinds of cytokines that play an important role in antiviral defense mechanisms during viral infection by converting cells to synthesize proteins that inhibit viral replication. In the present study, an antiviral response against Spring viremia of carp virus (SVCV) was developed in common carp, Cyprinus carpio following stimulation with the potent interferon inducer, poly inosinic : cytidylic acid (poly I:C). Poly I:C injected fish showed lower cumulative mortalities against SVCV than untreated fish did. Moreover, in vitro study showed that head kidney leucocytes (HKLs) produced an interferon-like cytokine (ILC) after stimulation with poly I:C. According cytopathic effect reduction (CPER) assay to examine antiviral activity of crude ILC, the capacity of HKLs for ILC production was highest at 1×$10^6$cells/ml and significantly enhanced when treated with 20~50$\mu{g}$/ml of poly I:C. The optimal temperature and concentration of FBS to induce the highest ILC production were $20^\circ{C}$ and 5%, respectively.

Host Innate Immunity against Hepatitis E Virus and Viral Evasion Mechanisms

  • Kang, Sangmin;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • v.27 no.10
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    • pp.1727-1735
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    • 2017
  • Hepatitis E virus (HEV) infections cause epidemic or sporadic acute hepatitis, which are mostly self-limiting. However, viral infection in immunocompromised patients and pregnant women may result in serious consequences, such as chronic hepatitis and liver damage, mortality of the latter of which reaches up to 20-30%. Type I interferon (IFN)-induced antiviral immunity is known to be the first-line defense against virus infection. Upon HEV infection in the cell, the virus genome is recognized by pathogen recognition receptors, leading to rapid activation of intracellular signaling cascades. Expression of type I IFN triggers induction of a barrage of IFN-stimulated genes, helping the cells cope with viral infection. Interestingly, some of the HEV-encoded genes seem to be involved in disrupting signaling cascades for antiviral immune responses, and thus crippling cytokine/chemokine production. Antagonistic mechanisms of type I IFN responses by HEV have only recently begun to emerge, and in this review, we summarize known HEV evasion strategies and compare them with those of other hepatitis viruses.

Human Cytomegalovirus Inhibition of Interferon Signal Transduction

  • Daniel M. Miller
    • Korean Journal of Microbiology
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    • v.38 no.4
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    • pp.203-203
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    • 2002
  • Cytomegalovirus (CMV), a beta-herpesvirus with worldwide distribution, exhibits host persistence, a distinguishing characteristic of all herpesviruses. This persistence is dependent upon restricted gene expression in infected cells as well as the ability of productively infected cells to escape from normal cell-mediated anti-viral immunosurveillance. Type I (IFN-α/β) and type II (IFN-γ) interferons are major components of the innate defense system against viral infection. They are potent inducers of MHC class I and II antigens and of antigen processing proteins. Additionally, IFNS mediate direct antiviral effects through induction effector molecules that block viral infection and replications such as 2′, 5-oligoadenylate synthetase (2, 5-OAS). IFNS function through activation of well-defined signal transduction pathways that involve phosphorylation of constituent proteins and ultimate formation of active transcription factors. Recent studies have shown that a number of diverse viruses, including CMV, EBV, HPV mumps and Ebola, are capable of inhibiting IFN-mediated signal transduction through a variety of mechanisms. As an example, CMV infection inhibits the ability of infected cells Is transcribe HLA class I and II antigens as well as the antiviral effector molecules 2, 5-OAS and MxA I. EMSA studies have shown that IFN-α and IFN-γ are unable to induce complete signal transduction in the presence of CMV infection, phenomena that are associated with specific decreases in JAKl and p48. Viral inhibition of IFN signal transduction represents a new mechanistic paradigm for increased viral survival, a paradigm predicting widespread consequences in the case of signal transduction factors common to multiple cytokine pathways.