hLife Pub Date : 2024-01-01 DOI: 10.1016/j.hlife.2023.08.001

Qun Yan , Yi Shi , George Fu Gao

引用次数: 0

Is the time right for systematically serotyping SARS-related coronaviruses? 对与 SARS 有关的冠状病毒进行系统血清分型的时机是否成熟？

hLife Pub Date : 2024-01-01 DOI: 10.1016/j.hlife.2023.12.007

Chee Wah Tan , Lin-Fa Wang

引用次数: 0

Crystal structures of RNA-dependent RNA polymerases from Jingmen tick virus and Alongshan virus 荆门蜱虫病毒和阿龙山病毒的 RNA 依赖性 RNA 聚合酶晶体结构

hLife Pub Date : 2024-01-01 DOI: 10.1016/j.hlife.2023.10.006

Zhenyang Liu , Qi Peng , Pu Han , Lu Kuai , Jianxun Qi , Yi Shi

{"title":"Crystal structures of RNA-dependent RNA polymerases from Jingmen tick virus and Alongshan virus","authors":"Zhenyang Liu , Qi Peng , Pu Han , Lu Kuai , Jianxun Qi , Yi Shi","doi":"10.1016/j.hlife.2023.10.006","DOIUrl":"10.1016/j.hlife.2023.10.006","url":null,"abstract":"<div><p>Jingmenviruses are a group of flavi-like viruses with segmented genome and have been found in various types of hosts, including humans, cattle, monkeys, bats, rodents, sheep, ticks, mosquitoes and nematodes. Jingmenviruses, including the Jingmen tick virus (JMTV) and Alongshan virus (ALSV), have been associated with febrile illness and flu-like symptoms in humans. Viral polymerase plays critical roles in genome replication and transcription and is an ideal target for antiviral drugs. Here, we determined the crystal structures of RNA-dependent RNA polymerase (RdRp) domains of JMTV and ALSV at 2.6 Å and 3.2 Å resolutions, respectively. The overall structures of JMTV and ALSV RdRp domains are similar to those from the typical unsegmented viruses in <em>Flaviviridae</em> family, especially the <em>Flavivirus</em> genus. JMTV and ALSV RdRps can be divided into three subdomains and the catalytical Motif A-G are conserved like the typical flaviviruses, whereas the zinc-binding pockets are absent from the JMTV and ALSV RdRps. The 5′-ends of jingmenvirus genomes are varied in length and sequence, and a highly conserved 8-nucleotide element located on the tip of stem loop A was identified and shown to be required for binding with RdRp and performing <em>de novo</em> replication activity. These findings provide important structural insights into RdRp of segmented flavivirus and reveal the key region of virus genome responsible for replication initiation, which would promote molecular understanding of segmented flavivirus replication and the structure-based design of antiviral drugs against flaviviruses.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 1","pages":"Pages 18-31"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928323000184/pdfft?md5=37ab197d096fad4e411d2c483b2dbbf9&pid=1-s2.0-S2949928323000184-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136169131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient inhibition of SARS-CoV-2 emerging EG.5, EG.5.1 and BA.2.86 variants by fusion inhibitor HY3000 peptide 融合抑制剂 HY3000 肽能有效抑制 SARS-CoV-2 新出现的 EG.5、EG.5.1 和 BA.2.86 变体

hLife Pub Date : 2024-01-01 DOI: 10.1016/j.hlife.2023.10.002

Lili Wu , Anqi Zheng , Yangming Tang , Xiaoyun Wang , Yue Gao , Wenwen Lei , Guizhen Wu , Qihui Wang , George Fu Gao

引用次数: 0

Assessing risk of Bombali virus spillover to humans by mutagenesis analysis of viral glycoprotein 通过病毒糖蛋白的诱变分析评估邦巴利病毒向人类扩散的风险

hLife Pub Date : 2024-01-01 DOI: 10.1016/j.hlife.2023.11.003

Lincan Li , Tianyu Gan , Ziyue Ma , Yi Huang , Jin Zhong

{"title":"Assessing risk of Bombali virus spillover to humans by mutagenesis analysis of viral glycoprotein","authors":"Lincan Li , Tianyu Gan , Ziyue Ma , Yi Huang , Jin Zhong","doi":"10.1016/j.hlife.2023.11.003","DOIUrl":"10.1016/j.hlife.2023.11.003","url":null,"abstract":"<div><p>Ebolaviruses, such as the highly pathogenic Ebola virus (EBOV), belong to the family <em>Filoviridae</em> and have caused outbreaks of severe and fatal hemorrhagic fever over the past years. Bombali virus (BOMV) is a newly discovered ebolavirus from bats with unknown potential to infect humans. For most ebolaviruses, the interaction between viral glycoprotein (GP) and host receptor Niemann-Pick C1 (NPC1) is crucial for viral entry and determines host tropism. Here, we analyzed the BOMV GP-mediated virus entry into human cells using our recently developed EBOV transcription- and replication-competent virus-like particle (trVLP) system. We demonstrated that while BOMV GP can be efficiently incorporated into trVLPs, it is inefficient in mediating trVLP entry into human cells. However, BOMV GP-mediated virus entry into human cells can be significantly enhanced by a few mutations in the NPC1-binding domain of GP. Furthermore, we showed that these mutations increase the binding of BOMV-GP to human NPC1. In summary, our results suggested that although wild-type BOMV does not efficiently infect human cells, the emergence of mutations in viral GP may boost its ability to spill over to humans, highlighting the importance of monitoring BOMV GP evolution in preventing potential BOMV spillover events.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 1","pages":"Pages 32-42"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928323000287/pdfft?md5=9dec1ead677be227218b4d1290ead01c&pid=1-s2.0-S2949928323000287-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139292581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural plasticity of human leptin binding to its receptor LepR 人类瘦素与其受体 LepR 结合的结构可塑性

hLife Pub Date : 2023-12-01 DOI: 10.1016/j.hlife.2023.10.010

Yufeng Xie , Xiaoxiong Li , Jianxun Qi , Guijun Shang , Defen Lu , George Fu Gao

{"title":"Structural plasticity of human leptin binding to its receptor LepR","authors":"Yufeng Xie , Xiaoxiong Li , Jianxun Qi , Guijun Shang , Defen Lu , George Fu Gao","doi":"10.1016/j.hlife.2023.10.010","DOIUrl":"10.1016/j.hlife.2023.10.010","url":null,"abstract":"<div><p>Leptin receptor (LepR) signaling plays an essential role in balancing food intake and energy expenditure. The architecture of LepR signaling assembly is critical for its function. In this study, we determined the structures of three distinct conformations of human leptin–LepR using cryo-electron microscopy at resolutions of 3.88, 3.77, and 3.58 Å. Both 2:2 and 3:3 stoichiometric assemblies were observed, and the complexes exhibited asymmetric open conformations. Leptin undergoes substantial rearrangement of its flexible regions to accommodate binding to LepR. The assembled leptin–LepR complexes connect through a “hand-in-hand” geometry. The open, interlocked 3:3 trimeric assembly results from the engagement of a third leptin–LepR heterodimer with a 2:2 dimer. The asymmetric geometry of LepR is substantially distinct from that of other gp130 cytokine homologs, and that may be due to the twisted and rigid interface between the D3 and D4 domains. These results highlight the distinct engagement of leptin with LepR and provide important insights into the structural plasticity of LepR-signaling assemblies.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"1 2","pages":"Pages 115-123"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928323000226/pdfft?md5=7703ded16572c7d9a5a2589ecb7c4531&pid=1-s2.0-S2949928323000226-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135221139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A roadmap for exploring the untouched protein space for biology and medicine 探索生物学和医学未触及的蛋白质空间的路线图

hLife Pub Date : 2023-12-01 DOI: 10.1016/j.hlife.2023.06.001

Jun Wang

引用次数: 0

Structural basis of Semliki Forest virus entry using the very-low-density lipoprotein receptor 塞姆利基森林病毒利用极低密度脂蛋白受体进入人体的结构基础

hLife Pub Date : 2023-12-01 DOI: 10.1016/j.hlife.2023.11.001

Ying Li , Zhennan Zhao , Sheng Liu , Haichen Wang , Junqing Sun , Yan Chai , Jingya Zhou , Yinuo Wang , Yi Shi , Hao Song , George Fu Gao

{"title":"Structural basis of Semliki Forest virus entry using the very-low-density lipoprotein receptor","authors":"Ying Li , Zhennan Zhao , Sheng Liu , Haichen Wang , Junqing Sun , Yan Chai , Jingya Zhou , Yinuo Wang , Yi Shi , Hao Song , George Fu Gao","doi":"10.1016/j.hlife.2023.11.001","DOIUrl":"https://doi.org/10.1016/j.hlife.2023.11.001","url":null,"abstract":"<div><p>Alphaviruses are a group of important viruses that cause significant diseases in humans. Among them, Semliki Forest virus (SFV) not only causes symptoms such as joint pain but also infects neuron cells and induces encephalitis in rodents. Recently, the very-low-density lipoprotein receptor (VLDLR) was identified as the cellular receptor for SFV entry. In this study, we present the cryo-electron microscopy structure of SFV bound to human VLDLR. VLDLR targets E1-DIII region of SFV using its membrane-distal LDLR class A (LA) repeats. Structural and functional analyses emphasize the synergistic role of multiple VLDLR repeats in the SFV entry. Remarkably, VLDLR's binding mode to SFV closely mirrors that of minor group human rhinoviruses but differs significantly from other alphaviruses' interactions with receptors in the canyon region of the E protein. We also assessed SFV binding to VLDLR or apolipoprotein E receptor 2 (ApoER2) proteins in horses and mosquitoes and revealed their use of multiple but different LA repeats for binding. Our findings illuminate SFV's cross-species infectivity, offering insights into potential antiviral strategies against alphavirus infections.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"1 2","pages":"Pages 124-136"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928323000263/pdfft?md5=fe67554da8e81dc625862928eb355ba4&pid=1-s2.0-S2949928323000263-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139108132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ppGpp is present in, and functions to regulate sleep of, Drosophila ppGpp存在于果蝇体内，并具有调节果蝇睡眠的功能

hLife Pub Date : 2023-12-01 DOI: 10.1016/j.hlife.2023.10.004

Xihuimin Dai , Wei Yang , Xiaohui Zhang , Enxing Zhou , Renbo Mao , Ying Liu , Tao Wang , Wenxia Zhang , Xinxiang Zhang , Yi Rao

{"title":"ppGpp is present in, and functions to regulate sleep of, Drosophila","authors":"Xihuimin Dai , Wei Yang , Xiaohui Zhang , Enxing Zhou , Renbo Mao , Ying Liu , Tao Wang , Wenxia Zhang , Xinxiang Zhang , Yi Rao","doi":"10.1016/j.hlife.2023.10.004","DOIUrl":"10.1016/j.hlife.2023.10.004","url":null,"abstract":"<div><p>Sleep is essential for animals, and receives inputs from circadian, homeostasis, and environment, yet the mechanisms of sleep regulation remain elusive. Discovery of molecules in living systems and demonstration of their functional roles are pivotal in furthering our understanding of the molecular basis of biology. Here, we report that guanosine-5′-diphosphate, 3′-diphosphate (ppGpp) is present in <em>Drosophila</em>, and plays an important role in regulation of sleep and starvation-induced sleep loss (SISL). ppGpp is detected in germ-free <em>Drosophila</em> and hydrolyzed by an enzyme encoded by the <em>mesh1</em> gene in <em>Drosophila</em>. Nighttime sleep and SISL were defected in <em>mesh1</em> mutant flies, and rescued by expression of wildtype Mesh1, but not the enzymatically defective mutant Mesh1E66A. Ectopic expression of RelA, the <em>Escherichia coli</em> synthetase for ppGpp, phenocopied <em>mesh1</em> knockout mutants, whereas overexpression of Mesh1 resulted in the opposite phenotypes, supporting that ppGpp is both necessary and sufficient in sleep regulation. A chemo connectomic screen followed by genetic intersection experiments implicates the Dilp2 neurons in the <em>pars intercerebralis</em> (PI) brain region as the site of ppGpp function. Our results have thus validated the presence of ppGpp in <em>Drosophila</em> and revealed a physiological role of ppGpp in sleep regulation for the first time.</p></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"1 2","pages":"Pages 98-114"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928323000160/pdfft?md5=c49fbcfe1d692440c4c9245b6238a22a&pid=1-s2.0-S2949928323000160-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135762812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Global public health crisis response: A roundtable discussion with Professor George Fu Gao, Professor Jules A Hoffmann, Professor Chris Walzer and Professor Jiahai Lu 全球公共卫生危机应对：与 George Fu Gao 教授、Jules A Hoffmann 教授、Chris Walzer 教授和 Lu Jiahai 教授的圆桌讨论

hLife Pub Date : 2023-12-01 DOI: 10.1016/j.hlife.2023.10.001

George Fu Gao , Jules A Hoffmann , Chris Walzer , Jiahai Lu

引用次数: 0

hLife最新文献