| 1 | A protective human antibody against respiratory syncytial virus by targeting a prefusion epitope across sites IV and V of the viral fusion glycoprotein显示文摘Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation. | Lianpan Dai Jian Song Lili Xu Zhao Gao Senyu Xu Yan Chai Liang Wang Mi Yang Tong Ma Qihui Wang Sushan Cao Junming Yie Gang Zou Zhengde Xie Jim Zhen Wu George Fu Gao | 2023 | hLife2023，1，1： | 0 |
| 2 | STING strengthens host anti-hantaviral immunity through an interferon-independent pathway显示文摘Hantaan virus(HTNV),the prototype virus of hantavirus,could escape innate immunity by restraining type I interferon(IFN)responses.It is largely unknown whether there existed other efficient anti-hantaviral tactics in host cells.Here,we demonstrate that the stimulator of interferon genes(STING)strengthens the host IFNindependent anti-hantaviral immunity.HTNV infection activates RIG-I through IRE1-XBP 1-mediated ER stress,which further facilitates the subcellular translocation and activation of STING.During this process,STING triggers cellular autophagy by interacting with Rab7A,thus restricting viral replication.To note,the anti-hantaviral effects of STING are independent of canonical IFN signaling.Additionally,neither application of the pharmacological antagonist nor the agonist targeting STING could improve the outcomes of nude mice post HTNV challenge in vivo.However,the administration of plasmids exogenously expressing the mutant C-terminal tail(ΔCTT)STING,which would not trigger the type I IFN responses,protected the nude mice from lethal HTNV infection.In summary,our research revealed a novel antiviral pathway through the RIG-I-STING-autophagy pathway,which offered novel therapeutic strategies against hantavirus infection. | Kerong Wang Jian Zhang Yongheng Yang Yue Si Ziqing Zhou Xudong Zhu Sushan Wu He Liu Hui Zhang Liang Zhang Linfeng Cheng Wei Ye Xin Lv Yingfeng Lei Xijing Zhang Shilin Cheng Lixin Shen Fanglin Zhang Hongwei Ma | 2023 | Virologica Sinica2023，38，4： | 0 |
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