Journal of Microbiology

Research Article

Korean Red ginseng enhances ZBP1-mediated cell death to suppress viral protein expression in host defense against Influenza A virus: Jueun Oh, Hayeon Kim, Jihye Lee, Suhyun Kim, Seyun Shin, Young-Eui Kim, Sehee Park, SangJoon Lee; J. Microbiol. 2025;63(1):e.2409007. Published online January 24, 2025; DOI: https://doi.org/10.71150/jm.2409007

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Abstract PDF Supplementary Material: Korean Red ginseng has emerged as a potent candidate in the fight against various viral infections, demonstrating significant efficacy both in vitro and in vivo, particularly against influenza A viruses. Despite substantial evidence of its antiviral properties, the detailed molecular mechanisms through which it reduces viral lethality remain insufficiently understood. Our investigations have highlighted the superior effectiveness of Korean Red ginseng against influenza viruses, outperforming its effects on numerous other viral strains. We aim to uncover the specific mechanisms by which Korean Red ginseng exerts its antiviral effects, focusing on influenza A viruses. Our prior studies have identified the role of Z-DNA-binding protein 1 (ZBP1), a signaling complex involved in inducing programmed cell death in response to influenza virus infection. Given the critical role of ZBP1 as a sensor for viral nucleic acid, we hypothesize that Korean Red ginseng may modulate the ZBP1-derived cell death pathway. This interaction is anticipated to enhance cell death while concurrently suppressing viral protein expression, offering novel insights into the antiviral mechanism of Korean Red ginseng against influenza A viruses.

Journal Articles

NEDD4 Regulated Pyroptosis Occurred from Co‑infection between Influenza A Virus and Streptococcus pneumoniae: Jiangzhou You , Linlin Zhou , Xudong San , Hailing Li , Mingyuan Li , Baoning Wang; J. Microbiol. 2023;61(8):777-789. Published online October 4, 2023; DOI: https://doi.org/10.1007/s12275-023-00076-y

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Co-infection of respiratory tract viruses and bacteria often result in excess mortality, especially pneumonia caused by influenza viruses and Streptococcus pneumoniae. However, the synergistic mechanisms remain poorly understood. Therefore, it is necessary to develop a clearer understanding of the molecular basis of the interaction between influenza virus and Streptococcus pneumonia. Here, we developed the BALB/c mouse model and the A549 cell model to investigate inflammation and pyroptotic cell death during co-infection. Co-infection significantly activated the NLRP3 inflammasome and induced pyroptotic cell death, correlated with excess mortality. The E3 ubiquitin ligase NEDD4 interacted with both NLRP3 and GSDMD, the executor of pyroptosis. NEDD4 negatively regulated NLRP3 while positively regulating GSDMD, thereby modulating inflammation and pyroptotic cell death. Our findings suggest that NEDD4 may play a crucial role in regulating the GSDMD-mediated pyroptosis signaling pathway. Targeting NEDD4 represents a promising approach to mitigate excess mortality during influenza pandemics by suppressing synergistic inflammation during co-infection of influenza A virus and Streptococcus pneumoniae.

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Yinqin Qingfei granules alleviate Mycoplasma pneumoniae pneumonia via inhibiting NLRP3 inflammasome-mediated macrophage pyroptosis
Zhe Song, Chengen Han, Guangzhi Luo, Guangyuan Jia, Xiao Wang, Baoqing Zhang
Frontiers in Pharmacology.2024;[Epub] CrossRef
Overexpression of DTX1 inhibits D-GalN/TNF-α-induced pyroptosis and inflammation in hepatocytes by regulating NLRP3 ubiquitination
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Toxicology Research.2024;[Epub] CrossRef
NLRP3 Inflammasomes: Dual Function in Infectious Diseases
Yanbo Li, Rui Qiang, Zhengmin Cao, Qingjuan Wu, Jiuchong Wang, Wenliang Lyu
The Journal of Immunology.2024; 213(4): 407. CrossRef

NF-κB/ROS and ERK pathways regulate NLRP3 inflammasome activation in Listeria monocytogenes infected BV2 microglia cells: Lin Yuan , Yurong Zhu , Shuang Huang , Lin Lin , Xugan Jiang , Shengxia Chen; J. Microbiol. 2021;59(8):771-781. Published online June 1, 2021; DOI: https://doi.org/10.1007/s12275-021-0692-9

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Abstract

Listeria monocytogenes is a food-borne pathogen responsible for neurolisteriosis, which is potentially lethal in immunocompromised individuals. Microglia are the main target cells for L. monocytogenes in central nervous system (CNS). However, the precise mechanisms by which they trigger neuroinflammatory processes remain unknown. The BV2 microglial cell line and a murine model of L. monocytogenes infection were used for experiments in this study. Listeria monocytogenes induced pyroptosis and nucleotide binding and oligomerization, leucine-rich repeat, pyrin domain-containing 3 (NLRP3) inflammasome activation in BV2. Pharmacological inhibition of the NLRP3 inflammasome attenuated L. monocytogenes- induced pyroptosis. Moreover, inhibition of nuclear factor kappa-B (NF-κB) and extracellular regulated protein kinases (ERK) pathways induced a decrease in caspase1 activation and mature IL-1β-17 secretion. Our collective findings support critical involvement of the NLRP3 inflammasome in L. monocytogenes-induced neuroinflammation and, to an extent, ROS production. In addition, ERK and NF-κB signaling play an important role in activation of the NLRP3 inflammasome, both in vitro and in vivo.

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Review

Recent advances in the development of β-lactamase inhibitors: Shivakumar S. Jalde , Hyun Kyung Choi; J. Microbiol. 2020;58(8):633-647. Published online July 27, 2020; DOI: https://doi.org/10.1007/s12275-020-0285-z

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Abstract

β-Lactam antibiotics are the most commonly prescribed antibiotics worldwide; however, antimicrobial resistance (AMR) is a global challenge. The β-lactam resistance in Gram-negative bacteria is due to the production of β-lactamases, including extended-spectrum β-lactamases, metallo-β-lactamases, and carbapenem-hydrolyzing class D β-lactamases. To restore the efficacy of BLAs, the most successful strategy is to use them in combination with β-lactamase inhibitors (BLI). Here we review the medically relevant β-lactamase families and penicillins, diazabicyclooctanes, boronic acids, and novel chemical scaffold-based BLIs, in particular approved and under clinical development.

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Research Support, Non-U.S. Gov'ts

Molecular characterization of mammalian-adapted Korean-type avian H9N2 virus and evaluation of its virulence in mice: Kuk Jin Park , Min-Suk Song , Eun-Ha Kim , Hyeok-il Kwon , Yun Hee Baek , Eun-hye Choi , Su-Jin Park , Se Mi Kim , Young-il Kim , Won-Suk Choi , Dae-Won Yoo , Chul-Joong Kim , Young Ki Choi; J. Microbiol. 2015;53(8):570-577. Published online July 31, 2015; DOI: https://doi.org/10.1007/s12275-015-5329-4

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Abstract

Avian influenza A virus (AIV) is commonly isolated from domestic poultry and wild migratory birds, and the H9N2 subtype is the most prevalent and the major cause of severe disease in poultry in Korea. In addition to the veterinary concerns regarding the H9N2 subtype, it is also considered to be the next potential human pandemic strain due to its rapid evolution and interspecies transmission. In this study, we utilize serial lung-to-lung passage of a low pathogenic avian influenza virus (LPAI) H9N2 (A/Ck/Korea/163/04, WT163) (Y439-lineage) in mice to increase pathogenicity and investigate the potential virulence marker. Mouse-adapted H9N2 virus obtained high virulence (100% mortality) in mice after 98 serial passages. Sequence results show that the mouse adaptation (ma163) possesses several mutations within seven gene segments (PB2, PA, HA, NP, NA, M, and NS) relative to the wild-type strain. The HA gene showed the most mutations (at least 11) with one resulting in the loss of an N-glycosylation site (at amino acid 166). Moreover, reverse genetic studies established that an E627K substitution in PB2 and the loss of the N-glycosylation site in the HA protein (aa166) are critical virulence markers in the mouse-adapted H9N2 virus. Thus, these results add to the increasing body of mutational analysis data defining the function of the viral polymerase and HA genes and their roles in mammalian host adaptation. To our knowledge, this is first report of the generation of a mammalian-adapted Korea H9N2 virus (Y493-lineages). Therefore, this study offers valuable insights into the molecular evolution of the LPAI Korean H9N2 in a new host and adds to the current knowledge of the molecular markers associated with increased virulence.

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An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization
Carol M. Sheppard, Daniel H. Goldhill, Olivia C. Swann, Ecco Staller, Rebecca Penn, Olivia K. Platt, Ksenia Sukhova, Laury Baillon, Rebecca Frise, Thomas P. Peacock, Ervin Fodor, Wendy S. Barclay
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Current situation and control strategies of H9N2 avian influenza in South Korea
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Antigenic Evolution Characteristics and Immunological Evaluation of H9N2 Avian Influenza Viruses from 1994–2019 in China
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Molecular epidemiology and pathogenicity of H5N1 and H9N2 avian influenza viruses in clinically affected chickens on farms in Bangladesh
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Anti-influenza Effect of Cordyceps militaris through Immunomodulation in a DBA/2 Mouse Model: Hwan Hee Lee , Heejin Park , Gi-Ho Sung , Kanghyo Lee , Taeho Lee , Ilseob Lee , Man-seong Park , Yong Woo Jung , Yu Su Shin , Hyojeung Kang , Hyosun Cho; J. Microbiol. 2014;52(8):696-701. Published online July 18, 2014; DOI: https://doi.org/10.1007/s12275-014-4300-0

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Abstract

The immune-modulatory as well as anti-influenza effects of Cordyceps extract were investigated using a DBA/2 mouse model. Three different concentrations of Cordyceps extract, red ginseng extract, or drinking water were orally administered to mice for seven days, and then the mice were intranasally infected with 2009 pandemic influenza H1N1 virus. Body weight changes and survival rate were measured daily post-infection. Plasma IL-12, TNF-α, and the frequency of natural killer (NK) cells were measured on day 4 post-infection. The DBA/2 strain was highly susceptible to H1N1 virus infection. We also found that Cordyceps extract had an antiinfluenza effect that was associated with stable body weight and reduced mortality. The anti-viral effect of Cordyceps extract on influenza infection was mediated presumably by increased IL-12 expression and greater number of NK cells. However, high TNF-α expression after infection of H1N1 virus in mice not receiving treatment with Cordyceps extract suggested a two-sided effect of the extract on host immune regulation.

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Cyclic Dipeptides from Lactic Acid Bacteria Inhibit Proliferation of the Influenza A Virus: Min-Kyu Kwak , Rui Liu , Jun-Oh Kwon , Min-Kyu Kim , Andrew HyoungJin Kim , Sa-Ouk Kang; J. Microbiol. 2013;51(6):836-843. Published online December 19, 2013; DOI: https://doi.org/10.1007/s12275-013-3521-y

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Abstract

We isolated Lactobacillus plantarum LBP-K10 from the traditional Korean fermented food kimchi. When organic acids were removed, the culture filtrate of this isolate showed high antiviral activity (measured using a plaque-forming assay) against the influenza A (H3N2) virus. Two fractions that were active against influenza A virus were purified from the culture filtrate using a C18 column with high-performance liquid chromatography. These active fractions were crystallized and identified to be the cyclic dipeptides cis-cyclo (L-Leu-L-Pro) and cis-cyclo(L-Phe-L-Pro) using gas chromatography-mass spectrometry; this identification was confirmed by X-ray crystallography. These cyclic dipeptides were identified in the culture filtrate of other lactic acid bacteria, including Lactobacillus spp., Leuconostoc spp., Weissella spp., and Lactococcus lactis.

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Adjuvant Efficacy of mOMV against Avian Influenza Virus Infection in Mice: Byeong-Jae Lee , Sang-Ho Lee , Min-Suk Song , Philippe Noriel Q. Pascua , Hyeok-il Kwon , Su-Jin Park , Eun-Ha Kim , Arun Decano , Se Mi Kim , Gyo Jin Lim , Doo-Jin Kim , Kyu-Tae Chang , Sang-Hyun Kim , Young Ki Choi; J. Microbiol. 2013;51(5):682-688. Published online October 31, 2013; DOI: https://doi.org/10.1007/s12275-013-3411-3

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Abstract: Highly pathogenic avian influenza H5N1 viruses are found chiefly in birds and have caused severe disease and death in infected humans. Development of influenza vaccines capable of inducing heterosubtypic immunity against a broad range of influenza viruses is the best option for the preparedness, since vaccination remains the principal method in controlling influenza viral infections. Here, a mOMV-adjuvanted recombinant H5N2 (rH5N2) whole virus antigen vaccine with A/Environment/Korea/W149/06(H5N1)-derived H5 HA and A/Chicken/Korea/ma116/04(H9N2)-derived N2 NA in the backbone of A/Puerto Rico/8/34(H1N1) was prepared and generated by reverse genetics. Groups of mice were vaccinated by a prime-boost regime with the rH5N2 vaccine (1.75 μg of HA with/without 10 μg mOMV or aluminum hydroxide adjuvant for comparison). At two weeks post-immunizations, vaccinated mice were challenged with lethal doses of 103.5 EID50/ml of H5N1 or H9N2 avian influenza viruses, and were monitored for 15 days. Both mOMV- and alum-adjuvant vaccine groups had high survival rates after H5N1 infection and low levels of body weight changes compared to control groups. Interestingly, the mOMV-adjuvanted group induced better cross-reactive antibody responses serologically and promoted cross-protectivity against H5N1 and H9N2 virus challenges. Our results suggest that mOMV could be used as a vaccine adjuvant in the development of effective vaccines used to control influenza A virus transmission.

Journal Article

The Effect of Dietary Intake of the Acidic Protein Fraction of Bovine Colostrum on Influenza A (H1N1) Virus Infection: Mei Ling Xu , Hyoung Jin Kim , Don Yong Chang , Hong-Jin Kim; J. Microbiol. 2013;51(3):389-393. Published online April 26, 2013; DOI: https://doi.org/10.1007/s12275-013-2683-y

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Abstract: Acidic protein levels in the milk decrease markedly as lactation progresses, suggesting that it is an important part of the colostrum. However, little attention has been paid to their biological function. In this study, we isolated the acidic protein fraction of bovine colostrum (AFC, isoelectric point <5) by anion-exchange chromatography, and investigated the effect of its dietary intake on influenza A (H1N1) virus infection. 100% of mice infected with 1 LD50 of the virus survived when administered AFC for 14 days prior to infection, compared with 33% survival when administered phosphate buffered saline (PBS). Moreover, consumption of AFC reduced the weight loss associated with infection. We propose that dietary intake of AFC has a prophylactic effect on influenza A virus infection.

Research Support, Non-U.S. Gov't

Molecular Characterization and Phylogenetic Analysis of H3N2 Human Influenza A Viruses in Cheongju, South Korea: Yun Hee Baek , Jeung Hyun Park , Young Jun Song , Min-Suk Song , Philippe Noriel Q. Pascua , Yoon-Soo Hahn , Heon-Seok Han , Ok-Jun Lee , Ki-Soon Kim , Chun Kang , Young-Ki Choi; J. Microbiol. 2009;47(1):91-100. Published online February 20, 2009; DOI: https://doi.org/10.1007/s12275-008-0207-y

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Abstract: To investigate the genetic characteristics of human influenza viruses circulating in Chungbuk province, we tested 510 clinical samples of nasopharyngeal suction from pediatric patients diagnosed with respiratory illness between June 2007 and June 2008. Genetic characterization of the HA genes of H3N2 isolates indicated the relative higher similarity to A/Virginia/04/07 (99.6%) rather than that of A/Wisconsin/67/2005 (98.4%), a Northern Hemisphere 2007~2008 vaccine strain, based on amino acid sequences. We found several altered amino acids at the H3 HA1 antigenic sites compared with the vaccine strain; K140I at site A, K158R at site B, and K173N (H471) or K173Q, and S262N at site E, but there was no antigenic shift among the H3N2 viruses. Interestingly, A/Cheongju/H383/08 and A/Cheongju/H407/08 isolates had single amino acid substitution at D151G on the catalytic site of the N2 NA while A/Cheongju/H412/08 and A/Cheongju/H398/07 isolates had one amino acid deletion at residue 146. Furthermore, we found that 25% (3 out of 12 isolates) of the H3N2 subtype viruses had the amino acid substitution at position 31 on the M2 protein (Aspartic acid to Asparagine) and confirmed their drug-resistance by biological assays. Taken together, the results of this study demonstrated continuous evolutions of human H3N2 viruses by antigenic drift and also highlighted the need to closely monitor antigenic drug resistance in influenza A viruses to aid in the early detection of potentially pandemic strains, as well as underscore the need for new therapeutics.

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