林宜玲 Yi-Ling Lin

研究病毒與宿主間交互作用 發展抗病毒策略

Covid-19 改變了世界，也改變了從事病毒研究數十年的我。這些年來，我們實驗室的研究重點從黃質病毒，例如日本腦炎病毒（JEV）和登革病毒（DENV），逐漸擴展到新興病毒，例如茲卡病毒（ZIKV）和新冠病毒（SARS-CoV-2）等。我們不僅關注病毒學基礎研究，也致力於如何快速反應新興病毒的威脅。因此，我們持續培育病毒專業研究人員，聚焦於病毒的分子生物學、病毒學、以及致病機轉等，希望瞭解病毒和宿主在感染過程中的多面向相互作用，以期發展出各種的抗病毒策略。

我們主要的研究發現和貢獻：

1) Flavivirus molecular signaling: We investigated how flaviviruses complete their life cycles and how host cells respond to infection. We made significant progress in understanding multiple signaling pathways in flavivirus infection, such as the discovery that ER stress and UPR are triggered by flavivirus to reduce its cytotoxicity.

2) Type I interferon（IFN）and flavivirus interplay: There is a continual 'arms race' between viruses and their hosts, especially in regards to the first line of defense, IFN. We found that cells can detect flavivirus infection to induce IFN production. Despite this, JEV has evolved to block IFN-stimulated Jak-Stat signaling, with JEV NS5 identified as a potent IFN antagonist. In contrast, DENV reduces IFN production through various strategies such as cleavage of MAVS and MITA by cellular caspase activation and viral protease.

3) Emerging ZIKV infection: ZIKV typically causes mild symptoms in humans, but the recent outbreak in Brazil linked ZIKV to congenital microcephaly. We established cell system and animal model to study its sexual and vertical transmission, as well as antiviral development. For example, we found the preventive effects of folic acid supplementation in ZIKV-associated poor pregnancy outcomes.

4) SARS-CoV-2 collaboration and service works: In response to the Covid-19 outbreak, we quickly established reagents and assay systems to aid in virus-related research in P3 facility. We performed anti-SARS-CoV-2 assays for researchers around Taiwan for their developed antiviral compounds and materials. We also provided contract services for biotech and vaccine companies to test their products' antiviral effects.

得獎感言

非常高興獲得傑出特約研究員的殊榮。衷心感謝多年來國科會、中央研究院以及各方單位的協助以及經費支持；也特別感謝實驗室同仁們努力不懈，尤其在Covid-19 疫情期間，不管是在中研院生醫所或是在生技研究園區的夥伴們，大家同心協力共同合作，化不可能為可能，如期完成各項任務。

希望在我退休前的這幾年，我們一起努力，記取在這些慘痛疫情中學到的經驗，建置日後所需的各項研究設施與體制，並培育特殊致病原的專業人才，以期未來在面對未知新興傳染病挑戰時，能做得更快、做得更好。