The COVID-19 pandemic,which was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a worldwide health crisis due to its transmissibility.SARS-CoV-2 infection results in severe respiratory...The COVID-19 pandemic,which was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a worldwide health crisis due to its transmissibility.SARS-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected individuals.These complications encompass symptoms such as coughing,respiratory distress,fever,infectious shock,acute respiratory distress syndrome(ARDS),and even multiple-organ failure.Animal models serve as crucial tools for investigating pathogenic mechanisms,immune responses,immune escape mechanisms,antiviral drug development,and vaccines against SARS-CoV-2.Currently,various animal models for SARS-CoV-2 infection,such as nonhuman primates(NHPs),ferrets,hamsters,and many different mouse models,have been developed.Each model possesses distinctive features and applications.In this review,we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection,as well as the corresponding immune responses and applications of these models.A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 patients.Finally,we highlighted the current gaps in related research between animal model studies and clinical investigations,underscoring lingering scientific questions that demand further clarification.展开更多
The Streptococcus suis serotype 2（S. suis 2） isolates 05ZYH33 and 98HAH33 have caused severe human infections in China. Using a strand-specific RNA-seq analysis, we compared the in vitro transcriptomes of these two ...The Streptococcus suis serotype 2（S. suis 2） isolates 05ZYH33 and 98HAH33 have caused severe human infections in China. Using a strand-specific RNA-seq analysis, we compared the in vitro transcriptomes of these two Chinese isolates with that of a reference strain（P1/7）. In the89 K genomic island that is specific to these Chinese isolates, a toxin–antitoxin system showed relatively high levels of transcription among the S. suis. The known virulence factors with high transcriptional activity in these two highly-pathogenic strains are mainly involved in adhesion, biofilm formation, hemolysis and the synthesis and transport of the outer membrane protein. Furthermore,our analysis of novel transcripts identified over 50 protein-coding genes with one of them encoding a toxin protein. We also predicted over 30 small RNAs（s RNAs） in each strain, and most of them are involved in riboswitches. We found that six s RNA candidates that are related to bacterial virulence, including csp A and rli38, are specific to Chinese isolates. These results provide insight into the factors responsible for the difference in virulence among the different S. suis 2 isolates.展开更多
Persistent asymptomatic(PA)SARS-CoV-2 infections have been identified.The immune responses in these patients are unclear,and the development of effective treatments for these patients is needed.Here,we report a cohort...Persistent asymptomatic(PA)SARS-CoV-2 infections have been identified.The immune responses in these patients are unclear,and the development of effective treatments for these patients is needed.Here,we report a cohort of 23 PA cases carrying viral RNA for up to 191 days.PA cases displayed low levels of inflammatory and interferon response,weak antibody response,diminished circulating follicular helper T cells(cTfh),and inadequate specific CD4+and CD8+T-cell responses during infection,which is distinct from symptomatic infections and resembling impaired immune activation.Administration of a single dose of Ad5-nCoV vaccine to 10 of these PA cases elicited rapid and robust antibody responses as well as coordinated B-cell and cTfh responses,resulting in successful viral clearance.Vaccine-induced antibodies were able to neutralize various variants of concern and persisted for over 6 months,indicating long-term protection.Therefore,our study provides an insight into the immune status of PA infections and highlights vaccination as a potential treatment for prolonged SARS-CoV-2 infections.展开更多
The spatiotemporal regulation of threedimensional(3D)genome dynamics has been implicated in various genome functions including gene transcription,DNA recombination,DNA replication,and DNA repair(Bickmore,2013).
Postzygotic mutations are acquired in normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using...Postzygotic mutations are acquired in normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clocklike mutational processes,and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles.Notably,signature C,characterized by C>T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6%of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites;and individuals’genetic background may also influence their postzygotic mutation profiles.展开更多
基金supported by a grant from the National Key R&D Program of China(No.2021YFC2301700 JS,2022YFC2604102 JS)Major Project of Guangzhou National Laboratory(GZNL2023A01003)+3 种基金the National Natural Science Foundation of China(82025001 JCZ,81971500 JXZ,2022YFC2303700 ARZ)the Guangdong Basic and Applied Basic Research Foundation(2022B1515020059 JS,2021B15150005 JXZ)the State Key Laboratory of Respiratory Disease(SKLRD-Z-202304,QTH)the ZHONGNANSHAN MEDICAIFOUNDATION OF GUANGDONG PROVINCE(No.ZNSA2020013 JCZ).
文摘The COVID-19 pandemic,which was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a worldwide health crisis due to its transmissibility.SARS-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected individuals.These complications encompass symptoms such as coughing,respiratory distress,fever,infectious shock,acute respiratory distress syndrome(ARDS),and even multiple-organ failure.Animal models serve as crucial tools for investigating pathogenic mechanisms,immune responses,immune escape mechanisms,antiviral drug development,and vaccines against SARS-CoV-2.Currently,various animal models for SARS-CoV-2 infection,such as nonhuman primates(NHPs),ferrets,hamsters,and many different mouse models,have been developed.Each model possesses distinctive features and applications.In this review,we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection,as well as the corresponding immune responses and applications of these models.A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 patients.Finally,we highlighted the current gaps in related research between animal model studies and clinical investigations,underscoring lingering scientific questions that demand further clarification.
基金supported by the CAS Key Laboratory of Pathogenic Microbiology and Immunology of China (Grant No. 2009CASPMI-007) to DZthe National Natural Science Foundation of China (Grant No. 81201700) to DZ
文摘The Streptococcus suis serotype 2（S. suis 2） isolates 05ZYH33 and 98HAH33 have caused severe human infections in China. Using a strand-specific RNA-seq analysis, we compared the in vitro transcriptomes of these two Chinese isolates with that of a reference strain（P1/7）. In the89 K genomic island that is specific to these Chinese isolates, a toxin–antitoxin system showed relatively high levels of transcription among the S. suis. The known virulence factors with high transcriptional activity in these two highly-pathogenic strains are mainly involved in adhesion, biofilm formation, hemolysis and the synthesis and transport of the outer membrane protein. Furthermore,our analysis of novel transcripts identified over 50 protein-coding genes with one of them encoding a toxin protein. We also predicted over 30 small RNAs（s RNAs） in each strain, and most of them are involved in riboswitches. We found that six s RNA candidates that are related to bacterial virulence, including csp A and rli38, are specific to Chinese isolates. These results provide insight into the factors responsible for the difference in virulence among the different S. suis 2 isolates.
基金the National Key R&D Program of China(2021YFC2302004 and 2021YFC2301102)National Natural Science Foundation of China(82172240,82101836,81901623 and 82201933)+6 种基金China National Postdoctoral Program for Innovative Talents(BX2021087),China Postdoctoral Science Foundation(2021M690787 and 2022M710892)Guangdong Basic and Applied Basic Research Foundation(2021B1515130005 and 2022B1515020059)Guangdong Medical Technology Research Foundation(B2022233)Guangzhou Science and Technology Planning Program Municipal School/Institute-Joint Funded Program(202102010143)PhD Startup Foundation from Guangzhou Women and Children’s Medical Center(2018-2020)State Key Laboratory of Respiratory Diseases Funded Program(SKLRD-Z-202330)Zhong Nanshan Medical Foundation of Guangdong Province(ZNSA-202001,ZNSXS-2020012,ZNSA-2020013 and ZNSXS-20220015).
文摘Persistent asymptomatic(PA)SARS-CoV-2 infections have been identified.The immune responses in these patients are unclear,and the development of effective treatments for these patients is needed.Here,we report a cohort of 23 PA cases carrying viral RNA for up to 191 days.PA cases displayed low levels of inflammatory and interferon response,weak antibody response,diminished circulating follicular helper T cells(cTfh),and inadequate specific CD4+and CD8+T-cell responses during infection,which is distinct from symptomatic infections and resembling impaired immune activation.Administration of a single dose of Ad5-nCoV vaccine to 10 of these PA cases elicited rapid and robust antibody responses as well as coordinated B-cell and cTfh responses,resulting in successful viral clearance.Vaccine-induced antibodies were able to neutralize various variants of concern and persisted for over 6 months,indicating long-term protection.Therefore,our study provides an insight into the immune status of PA infections and highlights vaccination as a potential treatment for prolonged SARS-CoV-2 infections.
基金the National Natural Science Foundation of China(81572795 and 81773304)the‘Hundred,Thousand and Ten Thousand Talent Project’by Beijing Municipal Government(2017A02)the National Natural Science Foundation of China(31701135).We thank Beijing Municipal Government and the Ministry of Science and Technology of China for funds allocated to NIBS.D.H.and Y.Z.conceived the study.D.H.,X.M.t G.L.J.D.,Y.H.y Q.H.f J.X.f and X.S.performed experiments and analyzed data.Y.Z.analyzed data and wrote the manuscript with support from all authors.
文摘The spatiotemporal regulation of threedimensional(3D)genome dynamics has been implicated in various genome functions including gene transcription,DNA recombination,DNA replication,and DNA repair(Bickmore,2013).
基金supported by the grants from the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB13020500)the National Natural Science Foundation of China(NSFC)(Grant Nos.91131905,31471199,and 91631304)+3 种基金the Key Research Program of Chinese Academy of Sciences(Grant No.KJZD-EW-L14 to CZ)the NSFC(Grant Nos.31440057 and 31701081 to WC)the 111 Project(Grant No.B13003 to WC and DZ)the Innovation Promotion Association of Chinese Academy of Sciences(Grant Nos.2016098 to DZ and 2019103 to AC)。
文摘Postzygotic mutations are acquired in normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clocklike mutational processes,and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles.Notably,signature C,characterized by C>T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6%of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites;and individuals’genetic background may also influence their postzygotic mutation profiles.
