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Mammalian adaptation risk in HPAI H5N8: a comprehensive model bridging experimental data with mathematical insights

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Title
Mammalian adaptation risk in HPAI H5N8: a comprehensive model bridging experimental data with mathematical insights
Author(s)
Chokkakula, Santosh; Oh, Sol; Choi, Won-Suk; Kim, Chang Il; Jeong, Ju Hwan; Kim, Beom Kyu; Park, Ji-Hyun; Min, Seong Cheol; Kim, Eung-Gook; Baek, Yun Hee; Young Ki Choi; Song, Min-Suk
Publication Date
2024-04
Journal
Emerging Microbes & Infections, v.13, no.1
Publisher
Nature Publishing Group
Abstract
Understanding the mammalian pathogenesis and interspecies transmission of HPAI H5N8 virus hinges on mapping its adaptive markers. We used deep sequencing to track these markers over five passages in murine lung tissue. Subsequently, we evaluated the growth, selection, and RNA load of eight recombinant viruses with mammalian adaptive markers. By leveraging an integrated non-linear regression model, we quantitatively determined the influence of these markers on growth, adaptation, and RNA expression in mammalian hosts. Furthermore, our findings revealed that the interplay of these markers can lead to synergistic, additive, or antagonistic effects when combined. The elucidation distance method then transformed these results into distinct values, facilitating the derivation of a risk score for each marker. In vivo tests affirmed the accuracy of scores. As more mutations were incorporated, the overall risk score of virus heightened, and the optimal interplay between markers became essential for risk augmentation. Our study provides a robust model to assess risk from adaptive markers of HPAI H5N8, guiding strategies against future influenza threats. © 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.
URI
https://pr.ibs.re.kr/handle/8788114/15114
DOI
10.1080/22221751.2024.2339949
ISSN
2222-1751
Appears in Collections:
Korea Virus Research Institute(한국바이러스기초연구소) > Center for Study of Emerging and Re-emerging Viruses(신변종 바이러스 연구센터) > 1. Journal Papers (저널논문)
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