李锋，研究员、博士生导师、广州医科大学附属市八医院传染病研究所副所长，高等级生物安全实验室负责人，十三届广东省政协委员。专注病毒性传染病与病毒感染小鼠模型，包括HIV、肝炎病毒、流感病毒、虫媒病毒、新型冠状病毒等多种病毒。

主要学术贡献，1.首次在全球范围内精确描绘德尔塔变异株完整传播链，总结报道Delta的传播特征。2.证明了新冠病毒感染者复阳阶段可以安全出院，提出Ct＞35可作为判定住院后期感染风险的安全标准。3.构建了基于干扰素通路修饰的多种病毒感染的小鼠模型和人源化小鼠模型。以通讯作者发表SCI文章30余篇，主要研究发表在Nature Commutations (4篇), Cellular & Molecular Immunology (2篇), EClinicalMedicine (1篇)，National Science review (1篇), Molecular Biology and Evolution (1篇)，Emerging Microbes & Infections(2篇)等期刊上。相关研究获得十三五传染病重大专项和国家自然科学基金多项支持。转化发明专利2项。

电话：181-2279-3963 E-mail: fengli_unc@163.com,gz8h_lifeng@126.com

附：2020年以来以通讯作者发表与病毒学直接相关文章列表：

1 Yaping Wang, Liliangzi Guo, Jingrong Shi, Jingyun Li, Yanling Wen, Guoming Gu, Jianping Cui, Chengqian Feng, Mengling Jiang, Qinghong Fan, Jingyan Tang, Sisi Chen, Jun Zhang, Xiaowen Zheng, Meifang Pan, Xinnian Li, Yanxia Sun, Zheng Zhang, Xian Li, Fengyu Hu, Liguo Zhang, Xiaoping Tang*, Feng Li(李锋)*. Interferon stimulated immune profile changes in a humanized mouse model of HBV infection. Nature Communications. 2023.

2 Mei Hou#, Jingrong Shi#, Zanke Gong, Haijun Wen, Yun Lan, Xizi Deng, Qinghong Fan, Jiaojiao Li, Mengling Jiang, Xiaoping Tang*, Chung-I Wu*, Feng Li(李锋)* and Yongsen Ruan*. Intra- vs. inter-host evolution of SARS-CoV-2 driven by uncorrelated selection - The evolution thwarted. Molecular Biology and Evolution . 2023. 40(9):msad204,

3 Haisheng Yu# , Banghui Liu#, Yudi Zhang# , Xijie Gao#, Qian Wang#, Haitao Xiang#, Xiaofang Peng#, Caixia Xie#, Yaping Wang#, Peiyu Hu, Jingrong Shi, Quan Shi, Pingqian Zheng, Chengqian Feng, Guofang Tang，Xiaopan Liu, Liliangzi Guo, Xiumei Lin, Jiaojiao Li, Chuanyu Liu, Yaling Huang, Naibo Yang, Qiuluan Chen, Zimu Li, Mengzhen Su, Qihong Yan, Rongjuan Pei, Xinwen Chen, Longqi Liu, Fengyu Hu, Dan Liang, Bixia Ke, Changwen Ke*, Feng Li(李锋)*, Jun He*, Meiniang Wang*, Ling Chen*, Xiaoli Xiong*, Xiaoping Tang*. Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants. Nature Communications. 2023 Feb 24;14(1):1058.

4 Lu Li, Jianping Cui, Jingyan Tang, Jingrong Shi, Xilong Deng, Xiaowen Zheng, Qinghong Fan, Ying Liu, Haisheng Yu, Xiaoping Tang*, Fengyu Hu*, Feng Li(李锋)*. High titers of neutralizing antibodies in the blood fail to eliminate SARS-CoV-2 viral RNA in the upper respiratory tract. Journal of Medical Virology. 2023 Jan;95(1):e28219.

5 Xiaowen Zheng, Xiaoping Tang*, Feng Li(李锋)*. The compartmentalized upper respiratory mucosa needs time to rally sufficient immune force for SARS-CoV-2 clearance. Cellular & Molecular Immunology. 2022. Dec 19(12):1425-1428.

6 Lu Li, Jingyan Tang, Zhiwei Xie, Qingxin Gan, Guofang Tang, Zhongwei Hu, Huimin Zeng, Jingrong Shi, Jiaojiao Li, Yan Li, Changwen Ke, Min Kang, Dan Liang, Huan Lu, Yuwei Tong, Xilong Deng, Jinxin Liu, Hongzhou Lu, Fuxiang Wang, Fengyu Hu, Feng Li(李锋)*, Nanshan Zhong*, Xiaoping Tang*. Characteristics of SARS-CoV-2 Delta variant-infected individuals with intermittently positive retest viral RNA after discharge. National Science Review. 2022 Jul 26; 9(10):nwac141.

7 Qinghong Fan, Jingrong Shi, Yanhong Yang, Guofang Tang, Mengling Jiang, Jiaojiao Li, Jingyan Tang, Lu Li, Xueliang Wen, Lieguang Zhang, Xizi Deng, Yaping Wang, Yun Lan, Liya Li, Ping Peng, Yuwei Tong, Huan Lu, Lili Yan, Ying Liu, Shuijiang Cai, Yueping Li, Xiaoneng Mo, Meiyu Li, Xilong Deng, Zhongwei Hu, Haisheng Yu, Fengyu Hu, Jinxin Liu * , Xiaoping Tang *, Feng Li(李锋)*. Clinical characteristics and immune profile alterations in vaccinated individuals with breakthrough Delta SARS-CoV-2 infections. Nature Communications. 2022 Jul 9;13(1):3979

8 Yaping Wang, Ruchong Chen, Fengyu Hu,, Yun Lan, Zhaowei Yang, Chen Zhan, Jingrong Shi, Xizi Deng, Mei Jiang, Shuxin Zhong, Baolin Liao, Kai Deng, Jingyan Tang, Liliangzi Guo, Mengling Jiang, Qinghong Fan, Meiyu Li, Jinxin Liu, Yaling Shi, Xilong Deng, Xincai Xiao, Min Kang, Yan Li, Weijie Guan, Yimin Li, Shiyue Li, Feng Li(李锋)*, Nanshan Zhong*, Xiaoping Tang*. Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou, China. EClinicalMedicine 2021 Oct;40:101129.

9 Chengqian Feng, Jingrong Shi, Qinghong Fan, Yaping Wang, Huang Huang, Fengjuan Chen, Guofang Tang, Youxia Li, Pingchao Li, Jiaojiao Li, Jianping Cui, Liliangzi Guo, Sisi Chen, Mengling Jiang, Liqiang Feng, Ling Chen, Chunliang Lei, Changwen Ke, Xilong Deng*, Fengyu Hu*, Xiaoping Tang*, Feng Li(李锋)*. Protective humoral and cellular responses against SARS-CoV-2 persist up to 1 year after recovery. Nature Communications. 2021 Aug 17. 12(1).

10 Rongsui Gao, Wenhong Zu, Yang Liu, Junhua Li, Zeyao Li, Yanling Wen, Haiyan Wang, Jing Yuan, Lin Cheng, Shengyuan Zhang, Yu Zhang, Shuye Zhang, Weilong Liu, Xun Lan, Lei Liu*, Feng Li(李锋)*, Zheng Zhang*. Quasispecies of SARS-CoV-2 revealed by single nucleotide polymorphisms (SNPs) analysis. Virulence. 2021 Dec;12(1):1209-1226.

11 Xianmiao Ye, Xinglong Liu, Tao Shu, Weiqi Deng, Min Liao, Yali Zheng, Xuehua Zheng, Xiaoyan Zhang, Ting Li, Wenxia Fan, Linbing Qu, Ling Chen, Feng Li(李锋)*, Liqiang Feng*. A Live-attenuated Zika Virus Vaccine with High Production Capacity Confers Effective Protection in Neonatal Mice. Journal of Virology. 2021. Jun 24;95(14):e0038321

12 Jinlin Wang, Tao Shu, Weiqi Deng, Yali Zheng, Min Liao, Xianmiao Ye, Lujie Han, Ping He, Xuehua Zheng, Ting Li, Ying Feng, Fengyu Hu, Pingchao Li, Caijun Sun, Ling Chen, Feng Li(李锋)*, Liqiang Feng*. Mucosal Priming with a Recombinant Influenza A Virus-Vectored Vaccine Elicits T-Cell and Antibody Responses to HIV-1 in Mice. Journal of Virology. 2021 May 24;95(12):e00059-21.

13 Fengyu Hu, Fengjuan Chen, Zhihua Ou, Qinghong Fan, Xinghua Tan, Yaping Wang, Yuejun Pan, Bixia Ke, Linghua Li, Yujuan Guan, Xiaoneng Mo, Jian Wang, Jinlin Wang, Chun Luo, Xueliang Wen, Min Li, Peidi Ren, Changwen Ke, Junhua Li, Chunliang Lei*, Xiaoping Tang*, Feng Li(李锋)* (2020) Compromised specific humoral immune response against SARS-CoV-2 receptor-binding domain is related to the viral persistence and periodic shedding in the gastrointestinal tract. Cellular & Molecular Immunology. 2020 Nov;17(11):1119-1125.

14 Weilie Chen, Yun Lan, Xiaozhen Yuan, Xilong Deng, Yueping Li, Xiaoli Cai, Liya Li, Ruiying He, Yizhou Tan, Xizi Deng, Ming Gao, Guofang Tang, Lingzhai Zhao, Jinlin Wang, Qinghong Fan, Chunyan Wen, Yuwei Tong, Yangbo Tang, Fengyu Hu*, Feng Li(李锋)* &Xiaoping Tang* (2020) Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity. Emerging Microbes & Infections. 2020 Feb 26;9(1):469-473.

15 Feng Li(李锋)*, Zhuo Wang, Fegnyu Hu, Lishan Su (2020) Cell Culture Models and Animal Models for HBV Study. Advances in Experimental Medicine and Biology. 2020;1179:109-135.

16 Ming Gao, Chengqian Feng, Ruosu Ying, Yuan Nie, Xizi Deng, Ying Zhu, Xiaoping Tang, Yujuan Guan, Fengyu Hu*, Feng Li(李锋)* . (2019) A novel one-step quantitative reverse transcriptional PCR assay for selective amplification of serum hepatitis B viral pregenomic RNA among the HBV DNA and RNA mixture. Archives of Virology. 2019 Nov;164(11):2683-2690.

报告题目：小鼠模型中III型干扰素通路的底层抗病毒和“保命”作用研究

主要内容：

干扰素（IFNs）可通过结合干扰素受体，诱导表达数百个干扰素诱导基因（ISGs），在抑制病毒侵入、复制和传播方面发挥重要作用（Schoggins, 2019）。人有I型、II型和III型干扰素三种，它们通过结合组织特异性分布的干扰素受体来发挥不同的抗病毒功能。因为IFNAR1/R2异二聚体受体在所有细胞类型中均有表达，I型干扰素通路可在所有细胞类型中发挥作用。而II型干扰素仅在免疫细胞内产生。III型干扰素受体由IFNLR1和IFNLR2（IL10RB）两个亚基构成，因为IFNLR1主要在上皮和黏膜表面表达，III型干扰素通常认为只在局部发挥作用（Lazear, 2015；Galani, 2017）。由于I型和III型IFN通路所激活的在下游信号激活（JAK/STAT2）和诱导的ISGs基因显著重叠，最初认为，I型和III型两种干扰素通路之间存在功能冗余。然而在进化上，III型干扰素通路出现早于I型干扰素通路，且比I型存在物种更广泛（Secombes，2017）。由于进化上功能获得的需要，I型干扰素是获得了一些新功能或加强了一些特殊功能（Wittling, 2020）。因此，关于I型和III型两种通路在功能上冗余的观点值得商榷。

越来越多的证据支持III型干扰素主要在宿主屏障和黏膜等局部感染中发挥主要作用，比如，呼吸道和胃肠道。人感染甲型流感病毒后，在呼吸道中立即产III型干扰素，但I型干扰素产生较为滞后，在病毒感染进展时才产生，起到加强抗病毒能力的作用，说明，I和III型干扰素通路发挥作用有明显时相特征。同样，Ifnlr1-/-小鼠粪便中诺如病毒浓度更高，说明III型干扰素在控制肠道病毒感染中有独特作用。在胃肠道中，III型干扰素可以保护肠上皮细胞免受轮状病毒（Doldan, 2022）和风疹病毒感染，而I型IFNs则主要负责防止病毒进一步感染脂肪组织和全身传播。因此，可看出，I型和III型干扰素在黏膜屏障中以互补方式发挥作用。

然而，III型干扰素的功能不仅限于黏膜组织。在与外界环境的直接联通的组织和器官（肝脏、脾脏、心脏、脑等）中，IFNLR也有较低水平表达。但是，由于I型干扰素在这些器官中的激活效应过于强大， III型干扰素的效应被掩盖。例如，与IFN-I相比，IFN-λ在抑制乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）以及丙型肝炎病毒（HDV）方面都比较有效（Bockmann, 2019; Etzion, 2023; Hamana, 2017; Lampertico, 2013; Novotny, 2021），并且诱导了差异化的ISG图谱（Jilg, 2014; Lampertico, 2013）。因此，III型干扰素在体内发挥功能的底层机制值得深入探索。

为研究在无I和II型干扰素干扰情况下的III型IFN作用，我们使用CRSPR/Cas9技术，通过敲除Ifnar2、Ifnlr2、Ifnar1和Ifngr2基因，得到了IFNAR-/-、IFNGR-/-和IFNLR-/-小鼠（简称AGL小鼠）。通过测试虫媒病毒的感染，我们观察到AGL小鼠对病毒感染更敏感，临床症状更明显。现有发现揭示了在I型干扰素的底层，III型干扰素在抗病毒、阻止病毒感染致病方面有着不可替代的作用。因此，探索III型干扰素通路的详细机制对其转化应用有重要价值。