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The D253N Mutation in the Polymerase Basic 2 Gene in Avian Influenza(H9N2) Virus Contributes to the Pathogenesis of the Virus in Mammalian Hosts

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Virologica Sinica 2018年第6期33卷 531-537页

作者： Jinfeng Zhang Rong Su Xiaoyun Jian Hongliang An Ronbing Jiang chris ka pun mok Laboratory Medicine Center Foshan Hospital of Traditional Chinese Medicine Guangzhou University of Chinese Medicine Department of Respiratory Medicine Foshan Hospital of Traditional Chinese Medicine Guangzhou University of Chinese Medicine State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University HKU-Pasteur Research Pole School of Public Health HKU Li Ka Shing Faculty of Medicine The University of Hong Kong

Mutations in the polymerase basic 2(PB2) gene of avian influenza viruses are important signatures for their adaptation to mammalian hosts. Various adaptive mutations have been identified around the 627 and nuclear localization sequence(NLS) domains of PB2 protein, and these mutations contribute to the replicative ability of avian influenza viruses.However, few studies have focused on adaptive mutations in other regions of PB2. In this study, we investigated the functional roles of the D253N mutation in PB2 in an H9N2 virus. This mutation was found to affect an amino acid residue in the middle domain of the PB2 protein. The virus with the D253N mutation showed higher polymerase activity and transiently increased viral replication in human cells. However, the mutant did not show significant differences in viral replication in the respiratory tract of mice upon infection. Our results supported that the D253N mutation in the middle domain of PB2, similar to mutations at the 627 and NLS domains, specifically contributed to the replication of avian influenza viruses in human cells.

关键词： Avian influenza virus Mammalian adaptation D253N Polymerase basic 2(PB2) H9N2

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Sheng Jiang San, traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidaseinhibition and immune regulation

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中国药理学与毒理学杂志 2019年第9期33卷 738-739页

作者： ZHANG Tian-bo XIAO Meng-jie Chun-Kwok WONG Ka-Pun CHRIS MOK ZHAO Xin TI Hui-hui Pang-Chui SHAW State Key Laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Molecular Target&Clinical PharmacologySchool of Pharmaceutical Sciences and The Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina The School of Life Sciences The Chinese University of Hong KongHong KongChina School of Public Health Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

OBJECTIVE Sheng Jiang San(SJS),a multi-herb formulation,is used in treating high fever,thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza in modern.However,there is no evidencebased investigation and mechanism research to support SJS′s anti-influenza efficacy.This study aims to investigate the anti-influenza effect of SJS and its possible mechanisms.METHODS In this study,we examined the inhibitory effect of SJS against different influenza viruses on Madin-Darby canine kidney cells.Influenza virus infected BALB/c mice were employed as in vivo model to evaluate the efficacy.Mice challenged with A/PR/8/34(H1N1)were orally administrated SJS 1 g·kg^-1 daily for seven days and monitored for 14 d.The survival rate,body mass changes,lung index,lung viral load,histopathologic changes and immune-regulation of the mice were measured.The underlying anti-influenza virus mechanisms were studied by a series of biological assays in vitro to determine if hemagglutinin,ribonucleoprotein complex or nerauminidase were targets of SJS.RESULTS SJS exerted a broad spectrum of inhibitory effects on multiple influenza strains in a dose-dependent manner.And IC50 of SJS against A/WSN/33(H1N1)was lower than 35 mg·L^-1.SJS also protected 50%of mice from influenza virus PR8 infection.The lung index and the lung viral load of SJS treated mice were signifi⁃cantly decrease compared with untreated mice.SJS 2 g·L^-1 inhibited 80%of neuraminidase enzymatic activity.SJS also up-regulated TNF-αand IFN-αand down-regulated IL-2 of influenza virus induced mice.CONCLUSION SJS is a useful formulation for treating influenza virus infection.

关键词： Sheng Jiang San anti-influenza activity neuraminidase inhibition immuno-regulation

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Baseline gut microbiota and metabolome predict durable immunogenicity to SARS-CoV-2 vaccines

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Signal Transduction and Targeted Therapy 2023年第10期8卷 5085-5095页

作者： Ye Peng Lin Zhang chris K.P.mok Jessica Y.L.Ching Shilin Zhao Matthew K.L.Wong Jie Zhu Chunke Chen Shilan Wang Shuai Yan Biyan Qin Yingzhi Liu Xi Zhang Chun pun Cheung Pui Kuan Cheong ka Long Ip Adrian C.H.Fung Kenneth K.Y.Wong David S.C.Hui Francis K.L.Chan Siew C.Ng Hein M.Tun Microbiota I-Center(MaglC) Hong KongChina Jockey Club School of Public Health and Primary Care The Chinese University of Hong KongHong KongChina Li ka Shing Institute of Health Sciences Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Department of Surgery LKS Faculty of MedicineThe University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina Centre for Gut Microbiota Research The Chinese University of Hong KongHong KongChina

The role of gut microbiota in modulating the durability of cOVID-19 vaccine immunity is yet to be characterised.In this cohort study,we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline,1 month,and 6 months post vaccination(p.v).Neutralisation antibody,plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition.

关键词： vaccine immunity vaccines

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