Osong Public Health and Research Perspectives

Joo-Yeon Lee

4 Articles

Generation and Characterization of Recombinant Influenza A(H1N1) Viruses Resistant to Neuraminidase Inhibitors: WooYoung Choi, Jin-Young Shin, Hwan-Eui Jeong, Mi-Jin Jeong, Su-Jin Kim, Joo-Yeon Lee, Chun Kang; Osong Public Health Res Perspect. 2013;4(6):323-328. Published online December 31, 2013; DOI: https://doi.org/10.1016/j.phrp.2013.10.005

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Abstract PDF: Objectives
To examine the effect of neuraminidase (NA) mutations on the NA inhibitor (NAI) resistance phenotype, the recombinant influenza A/Chungbuk/4448/2008(H1N1) virus isolated in South Korea during the 2008–2009 season was generated by reverse genetics.
Methods
Site-directed mutagenesis was introduced on the NA gene of A/Chungbuk/4448/2008(H1N1) virus, and a total of 23 single, double, and triple mutants were generated. Resistance phenotype of these recombinant viruses was determined by NA-inhibition (NAI) assays based on a fluorometric method using two NAIs (oseltamivir and zanamivir).
Results
NA-inhibition assays showed that all the single and double mutants containing the Y275 except the single Y275-E119V mutant conferred important levels of resistance to oseltamivir, whereas all the single, double, and triple mutants containing the E119V mutation were associated with the resistance to zanamivir.
Conclusion
Considering the effect of mutations in NA gene on the resistance to NAIs, it is important to monitor the possible emergence and dissemination of multidrug-resistant variants in the human population due to amino acid changes at NA gene as well as to develop novel NAIs.

Development of a Specific and Rapid Diagnostic Method for Detecting Influenza A (H1N1) pdm09 Virus Infection Using Immunochromatographic Assay: Mi Jung Ji, Byung Ki Cho, Young Shik Cho, Young Jin Choi, Donghyok Kwon, Kyeongcheol Shin, Joo-Yeon Lee, Chun Kang, Byoung Su Yoon; Osong Public Health Res Perspect. 2013;4(6):342-346. Published online December 31, 2013; DOI: https://doi.org/10.1016/j.phrp.2013.10.006

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Abstract PDF: Objectives
The aim of this study was to develop an immunochromatographic assay (ICA) for the detection of influenza A (H1N1) pdm09 virus infection. Materials and methods Several monoclonal antibodies against influenza A (H1N1) pdm09 virus were generated and an ICA (pdm09-ICA) was developed for the rapid and specific detection of influenza A (H1N1) pdm09 virus infection. The specificity and sensitivity of the developed assay were compared with that of hemagglutination assay and real-time reverse-transcription polymerase chain reaction (rRT-PCR).
Results
The detection limit was estimated to be 1/2 (8) hemagglutinating unit; the sensitivity and specificity rates of pdm09-ICA were 75.86% (110/145) and 100% (43/43), respectively, compared with rRT-PCR. The cross-reactivity for 20 influenza viruses, including seasonal H1N1 viruses, was found to be negative except for the H1N1 virus (A/Swine/Korea/GC0503/2005).
Conclusion
These results indicate that the proposed method can be easily used for rapid and specific detection of the pdm09 infection. The assay developed in this study would be a useful tool for distinguishing the pdm09 infection from seasonal influenza A and B infections.

The Emergence of Oseltamivir-Resistant Seasonal Influenza A (H1N1) Virus in Korea During the 2008-2009 Season: Woo-Young Choi, Inseok Yang, Sujin Kim, Namjoo Lee, Meehwa Kwon, Joo-Yeon Lee, Chun Kang; Osong Public Health Res Perspect. 2011;2(3):178-185. Published online December 31, 2011; DOI: https://doi.org/10.1016/j.phrp.2011.11.042

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Abstract PDF: Objectives
To monitor antiviral drug resistance among seasonal influenza viruses isolated in Korea during the 2008-2009 influenza season, we examined influenza isolates collected through Korea Influenza Surveillance Scheme for antiviral drug susceptibility.
Methods
For genetic analysis of antiviral drug resistance, the matrix (M2) and neuraminidase (NA) genes of each isolate were amplified by reverse transcription-polymerase chain reaction and followed by nucleotide sequencing. For phylogenetic analyses, the sequences of hemagglutinin (HA) and NA genes of each isolate were aligned using multiple alignment program. For phenotypic analysis of antiviral drug resistance, drug susceptibilities against M2 inhibitor (amantadine) and NA inhibitors (oseltavimir and zanamivir) were determined by virus yield reduction assay and fluorometric NA inhibition assay, respectively.
Results
In Korea, the resistant influenza viruses against oseltamivir were first detected in sealsonal influenza A(H1N1) viruses on Week 48 of 2008. Since then, the number of oseltamivir-resistant A(H1N1) viruses was continuously increased and had reached the highest peak on Week 52 of 2008. 533 (99.8%) of 534 A(H1N1) viruses were resistant to oseltamivir and all of them harbored the H275Y mutation in the NA gene during the 2008-2009 season. The oseltamivir resistance identified by sequencing was confirmed by NA inhibition assay. Genetic analysis based on HA gene of the resistant A(H1N1) viruses revealed that the viruses were identified as A/Brisbane/10/2007-like strain which was vaccine strain for the 2008-2009 season.
Conclusions
The oseltamivir-resistant A(H1N1) viruses were first emerged in Europe in November 2007 and then circulated globally. One year later, the oseltamivir-resistant A(H1N1) viruses were first detected in Korea in November 2008 and continued circulating until the Week 7 of 2009 during the 2008-2009 season. Considering the pandemic preparedness, it should be continued to monitor the emergence and the characterization of antiviral drug resistant influenza viruses.

Pathogenesis and Chronologic Localization of the Human Influenza A (H1N1) Virus in Cotton Rats: Donghyok Kwon, Kyeongcheol Shin, Jin-Young Shin, Joo-Yeon Lee, Yooncheol Ha, Nam-Joo Lee, Hee-Bok Oh, Chanhee Chae, Chun Kang; Osong Public Health Res Perspect. 2011;2(1):15-22. Published online June 30, 2011; DOI: https://doi.org/10.1016/j.phrp.2011.04.005

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Abstract PDF: Objectives
We aimed to evaluate the pathogenesis and chronologic localization of human influenza A (H1N1) virus in experimentally infected cotton rats.
Methods
The animals were intranasally inoculated with 10⁷ plaque-forming units of A/Solomon Islands/3/2006 (H1N1) influenza virus and evaluated for pathogenicity for a period of 28 days. Virus replication kinetics and pathological properties were assessed chronologically. Acute antiviral responses were evaluated by mean of real-time polymerase chain reaction.
Results
Cotton rats infected with A/Solomon Islands/3/2006 virus lost weight until 6 days post-inoculation (DPI) and showed decreased activity until 3 DPI. At necropsy, focal areas of redness and consolidation of lungs were evident at 1, 2, and 3 DPI. Lung histopathology showed moderate to severe interstitial pneumonia, alveolitis and bronchiolitis. Influenza A specific viral protein was detected in bronchiolar epithelial cells, alveolar septa and pneumocytes. Influenza viruses were recovered from the lungs during the early period of infection and the titer peaked at 1 DPI. Viral proteins were detected from 4 hours to 6 hours DPI. These trends correlate with the up-regulation of mRNA expression of the IFN-α, Mx1, and Mx2 genes that play critical roles in the anti-influenza response at the early stage of infection.
Conclusion
Our results provide evidence that supports the use of cotton rats for the study of influenza virus pathogenesis and the immune response.

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