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Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus, South Korea
Yi, Hwajung,Lee, Joo-Yeon,Hong, Eun-Hye,Kim, Mi-Seon,Kwon, Donghyok,Choi, Jang-Hoon,Choi, Woo-Young,Kim, Ki-Soon,Lee, Jong-Koo,Oh, Hee-Bok,Kang, Chun Centers for Disease Control and Prevention 2010 Emerging infectious diseases Vol.16 No.12
<P>To identify oseltamivir resistance, we analyzed neuraminidase H275Y mutations in samples from 10 patients infected with pandemic (H1N1) 2009 virus in South Korea who had influenza that was refractory to antiviral treatment with this drug. A neuraminidase I117M mutation that might influence oseltamivir susceptibility was detected in sequential specimens from 1 patient.</P>
Yi, Hwajung,Lee, Mi-Seon,Lee, Joo-Yeon,Lee, Hae Kyung,Kang, Chun Springer-Verlag 2015 The journal of microbiology Vol.53 No.2
<P>Since the 2009 pandemic, monoclonal antibodies (mAbs) for rapid influenza diagnostic tests (RIDT) have been developed for specific diagnostics of pandemic viral infection. Most of the mAbs were poorly characterized because of urgency during the pandemic. Further characterization of the mAbs for RIDTs would be beneficial for understanding the immunological properties of the pandemic virus and utilizing the mAbs for other research purposes. In this study, it was confirmed that two mAbs (138 and D383) in an RIDT for H1N1pdm09 diagnostics were able to detect H1N1pdm09 virus through enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). Also, the two mAbs exhibited reactivity to hemagglutinins (HAs) of both the H1N1pdm09 and 1918 H1N1 viruses; therefore, the RIDT using the mAbs could detect HAs of H1N1pdm09 and also HAs of 1918 H1N1-like strains. In an extension to our previous study, the epitopes (Sa antigenic site and the interface area of F' and vestigial esterase subdomahis on the HA1 domain of HA of H1N1pdm09) recognized by the mAbs were corroborated in depth by IFA with escape-mutants from the mAbs and mapping of the epitopes on the crystal structure of human H1N1 viral HAs. Collectively, these results imply that the mAbs for the RIDT may be suitable for use in studying the immunological properties of H1N1pdm09 viruses and that the Sa antigenic site and the interface area between F' and vestigial esterase subdomains on influenza viral HA recognized by the mAbs are immunologically conserved regions between H1N1pdm09 and 1918 H1N1.</P>
Cho, Junhyung,Yi, Hwajung,Jang, Eun Young,Lee, Mi-Seon,Lee, Joo-Yeon,Kang, Chun,Lee, Chan Hee,Kim, Kisoon Elsevier 2017 Biochemical and biophysical research communication Vol.494 No.1
<P><B>Abstract</B></P> <P>Infection with the highly pathogenic avian influenza H5N1 virus results in a high incidence of mortality in humans. Severe complications from infection are often associated with hypercytokinemia. However, current neuraminidase inhibitors (NAIs) have several limitations including the appearance of oseltamivir-resistant H5N1 virus and the inability to completely ameliorate hyper-immune responses. To overcome these limitations, we evaluated the anti-viral activity of mycophenolic mofetil (MMF) against A/Vietnam/1194/2004 (H5N1) virus infection using MDCK cells and mice. The IC<SUB>50</SUB> of MMF (0.94 μM) was comparable to that of zanamivir (0.87 μM) in H5N1 virus-infected MDCK cells based on ELISA. Time-course assays demonstrated that MMF completely inhibited H5N1 viral mRNA replication and protein expression for approximately 8 h after the initiation of treatment. In addition, MMF treatment protected 100% of mice, and lung viral titers were substantially reduced. The anti-viral mechanism of MMF against H5N1 virus infection was further confirmed to depend on the inhibition of cellular inosine monophosphate dehydrogenase (IMPDH) by exogenous guanosine, which inhibits viral mRNA and protein expression. Moreover, IL-1β, IFN-β, IL-6, and IP-10 mRNA expression levels were significantly downregulated in MDCK cells with MMF treatment. These results indicated that MMF could represent a novel inhibitor of viral replication and a potent immunomodulator for the treatment of H5N1 virus infection.</P> <P><B>Highlights</B></P> <P> <UL> <LI> MMF inhibits H5N1 replication <I>in vitro</I> and <I>in vivo</I>. </LI> <LI> Inhibition of H5N1 replication by MMF mediated through guanosine depletion. </LI> <LI> MMF has immunomodulatory activity during H5N1 infection. </LI> </UL> </P>
STAT3 silencing enhances the efficacy of the HSV.tk suicide gene in gastrointestinal cancer therapy.
Ahn, Ye-Hyeon,Yi, Hwajung,Shin, Ji-Young,Lee, Kang-Duck,Shin, Seung-Pil,Lee, Sang-Jin,Song, Jaewhan,Chun, Kyung-Hee Taylor Francis ; Rapid Science Publishers 2012 Clinical & experimental metastasis Vol.29 No.4
<P>Aberrant activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling has been shown to be associated with uncontrolled cell proliferation and suppression of host-immune surveillance. Conversely, silencing STAT3 can have the dual effects of inhibiting cancer cell proliferation and inducing anti-tumor immune responses. Here, we report on the effects of STAT3 silencing on suicide gene therapy with thymidine kinase (tk). STAT3 silencing by siRNA inhibited the proliferation of AGS human gastric cancer cells through G1 cell cycle arrest, decreased levels of immune-suppressive cytokines, and increased levels of immune-activating cytokines. CT26 mouse colon adenocarcinoma cells, in which STAT3 expression was knocked-down by a STAT3 shRNA-containing lentivirus, grew more slowly in syngenic model Balb/c mice than control CT26 cells. Moreover, we found that STAT3 silencing augmented the efficacy of suicide gene therapy in CT26 cell xenografted mice. When we administrated adenoviruses harboring the herpes simplex virus thymidine kinase gene (Ad5.CMV.HSV.tk) into STAT3-silenced CT26 cell tumors, extensive apoptosis was observed and there was a significant reduction in the size of CT26 cell tumors. STAT3 silencing also enhanced the recruitment and cytotoxic activity of CD3(+)CD8(+) T-cells, and changed the cytokine expression pattern of CT26 cell tumors, reflecting augmentation of anti-cancer immune responses. We conclude that combining suicide gene therapy with STAT3 silencing can result in enhanced anti-cancer effects.</P>
김진원,이민지,Shin Hwachul,최치환,Choi Myung-min,Jee Woong Kim,Hwajung Yi,유천권,이기은 질병관리본부 2022 Osong Public Health and Research Persptectives Vol.13 No.4
Objectives: Monkeypox outbreaks in nonendemic countries have been reported since early May 2022. The first case of monkeypox in the Republic of Korea was confirmed in a patient who traveled to Europe in June 2022, and an attempt was made to isolate and identify the monkeypox virus (MPXV) from the patient’s specimens.Methods: Clinical specimens from the patient were inoculated in Vero E6 cells. The isolated virus was identified as MPXV by the observation of cytopathic effects on Vero E6 cells, transmission electron microscopy, conventional polymerase chain reaction(PCR), and sequencing of PCR products.Results: Cytopathic effects were observed in Vero E6 cells that were inoculated with skin lesion swab eluates. After multiple passages from the primary culture, orthopoxvirus morphology was observed using transmission electron microscopy. In addition, both MPXV-specific (F3L and ATI) and orthopoxvirus-specific genes (A39R, B2R, and HA) were confirmed by conventional PCR and Sanger sequencing.Conclusion: These results indicate the successful isolation and identification of MPXV from the first patient in the Republic of Korea. The isolated virus was named MPXV-ROK-P1-2022.
Genomic Analysis of Monkeypox Virus During the 2023 Epidemic in Korea
Choi Chi-Hwan,Lee Minji,Lee Sang Eun,Kim Jin-Won,Shin Hwachul,Choi Myung-Min,Yi Hwajung,Kim Min-Kyung,Jeon Jaehyun,Park Jun-Sun,Kim Yeonjae,Lim So Yun,Chin BumSik,Chung Yoon-Seok 대한의학회 2024 Journal of Korean medical science Vol.39 No.18
We aimed to characterize the genomes of monkeypox virus isolates from the Far East, providing insights into viral transmission and evolution. Genomic analysis was conducted on 8 isolates obtained from patients with monkeypox virus disease in the Republic of Korea between May 2022 and early 2023. These isolates were classified into Clade IIb. Distinct lineages, including B.1.1, A.2.1, and B.1.3, were observed in 2022 and 2023 isolates, with only the B.1.3 lineage detected in six isolates of 2023. These genetic features were specific to Far East isolates (the Republic of Korea, Japan, and Taiwan), distinguishing them from the diverse lineages found in the Americas, Europe, Africa, and Oceania. In early 2023, the prevalence of the B.1.3 lineage of monkeypox virus identified in six patients with no overseas travel history is considered as an indicator of the potential initiation of local transmission in the Republic of Korea.