In recent years,various serious diseases caused by Zika virus(ZIKV)have made it impossible to be ignored.Confirmed existence of ZIKV in semen and sexually transmission of ZIKV suggested that it can break the blood–te...In recent years,various serious diseases caused by Zika virus(ZIKV)have made it impossible to be ignored.Confirmed existence of ZIKV in semen and sexually transmission of ZIKV suggested that it can break the blood–testis barrier(BTB),or Sertoli cell barrier(SCB).However,little is known about the underlying mechanism.In this study,interaction between actin,an important component of the SCB,and ZIKV envelope(E)protein domainⅢ(EDⅢ)was inferred from coimmunoprecipitation(Co-IP)liquid chromatography–tandem mass spectrometry(LC–MS/MS)analysis.Confocal microscopy confirmed the role of actin filaments(F-actin)in ZIKV infection,during which part of the stress fibers,the bundles that constituted by paralleled actin filaments,were disrupted and presented in the cell periphery.Colocalization of E and reorganized actin filaments in the cell periphery of transfected Sertoli cells suggests a participation of ZIKV E protein in ZIKV-induced F-actin rearrangement.Perturbation of F-actin by cytochalasin D(CytoD)or Jasplakinolide(Jas)enhanced the infection of ZIKV.More importantly,the transepithelial electrical resistance(TEER)of an in vitro mouse SCB(mSCB)model declined with the progression of ZIKV infection or overexpression of E protein.Co-IP and confocal microscopy analyses revealed that the interaction between F-actin and tight junction protein ZO-1 was reduced after ZIKV infection or E protein overexpression,highlighting the role of E protein in ZIKV-induced disruption of the BTB.We conclude that the interaction between ZIKV E and F-actin leads to the reorganization of F-actin network,thereby compromising BTB integrity.展开更多
Coronavirus disease 2019(COVID-19), reminiscent of the severe acute respiratory syndrome(SARS) outbreak in 2003,has been a tragic disaster to people all over the world. As there is no specific drug for COVID-19, neutr...Coronavirus disease 2019(COVID-19), reminiscent of the severe acute respiratory syndrome(SARS) outbreak in 2003,has been a tragic disaster to people all over the world. As there is no specific drug for COVID-19, neutralizing antibodies are attracting more and more attention as one of the most effective means to combat the pandemic. Here, we introduced the etiological and serological characteristics of COVID-19, discussed the current stage of development of human monoclonal antibodies against SARS-CoV-2 and summarized the antigenic epitopes in the S glycoprotein, which may deepen the understanding of the profile of immune recognition and response against SARS-CoV-2 and provide insight for the design of effective vaccines and antibody-based therapies.展开更多
Foxes are susceptible to SARS-CoV-2 in laboratory settings,and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes.In this study,we assessed the binding capacities of fox ACE2 t...Foxes are susceptible to SARS-CoV-2 in laboratory settings,and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes.In this study,we assessed the binding capacities of fox ACE2 to important sarbecoviruses,including SARS-CoV,SARS-CoV-2,and animal-origin SARS-CoV-2 related viruses.Our findings demonstrated that fox ACE2 exhibits broad binding capabilities to receptor-binding domains(RBDs)of sarbecoviruses.We further determined the cryo-EM structures of fox ACE2 complexed with RBDs of SARS-CoV,SARS-CoV-2 prototype(PT),and Omicron BF.7.Through structural analysis,we identified that the K417 mutation can weaken the ability of SARS-CoV-2 sub-variants to bind to fox ACE2,thereby reducing the susceptibility of foxes to SARS-CoV-2 sub-variants.In addition,the Y498 residue in the SARS-CoV RBD plays a crucial role in forming a vital cation-πinteraction with K353 in the fox ACE2 receptor.This interaction is the primary determinant for the higher affinity of the SARS-CoV RBD compared to that of the SARS-CoV-2 PT RBD.These results indicate that foxes serve as potential hosts for numerous sarbecoviruses,highlighting the critical importance of surveillance efforts.展开更多
Dear Editor,Alternative splicing of eukaryotic transcripts refers to the posttranscriptional process in which the coding regions(exons)of a precursor transcript are joined in different combinations through the removal...Dear Editor,Alternative splicing of eukaryotic transcripts refers to the posttranscriptional process in which the coding regions(exons)of a precursor transcript are joined in different combinations through the removal or retention of non-coding intervening sequences(introns)to produce distinct mature messenger RNA(mRNA)transcripts and further generate one or more mature mRNAs(Lee and Rio,2015).Alternative splicing is revealed dysregulation in infectious diseases.Many pathogens hijack the splicing mechanism of host cells to complete their replications,accompanied by dysregulated innate immune response or cell damage,leading to the changes of alternative splicing landscape in host cells(Ashraf et al.,2019;Tomezsko et al.,2020;Kremsdorf et al.,2021).The regulation mechanism of alternative splicing by viral pathogens,such as hepatitis B virus(Duriez et al.,2017),human immunodeficiency virus 1(Tomezsko et al.,2020),Zika virus(Bonenfant et al.,2020)and enterovirus 71(Li et al.,2020),have been explored.展开更多
基金We graciously acknowledge Dr.George F.Gao of Institute of Microbiology,Chinese Academy of Sciences,Beijing,China for the gifts of ZIKV(ZIKA-SMGC-1,GenBank accession number:KX266255)ZIKV antibody FITC-Z6.This work was supported by grants from the National Science and Technology Major Project(Grant No.2018ZX10733403)。
文摘In recent years,various serious diseases caused by Zika virus(ZIKV)have made it impossible to be ignored.Confirmed existence of ZIKV in semen and sexually transmission of ZIKV suggested that it can break the blood–testis barrier(BTB),or Sertoli cell barrier(SCB).However,little is known about the underlying mechanism.In this study,interaction between actin,an important component of the SCB,and ZIKV envelope(E)protein domainⅢ(EDⅢ)was inferred from coimmunoprecipitation(Co-IP)liquid chromatography–tandem mass spectrometry(LC–MS/MS)analysis.Confocal microscopy confirmed the role of actin filaments(F-actin)in ZIKV infection,during which part of the stress fibers,the bundles that constituted by paralleled actin filaments,were disrupted and presented in the cell periphery.Colocalization of E and reorganized actin filaments in the cell periphery of transfected Sertoli cells suggests a participation of ZIKV E protein in ZIKV-induced F-actin rearrangement.Perturbation of F-actin by cytochalasin D(CytoD)or Jasplakinolide(Jas)enhanced the infection of ZIKV.More importantly,the transepithelial electrical resistance(TEER)of an in vitro mouse SCB(mSCB)model declined with the progression of ZIKV infection or overexpression of E protein.Co-IP and confocal microscopy analyses revealed that the interaction between F-actin and tight junction protein ZO-1 was reduced after ZIKV infection or E protein overexpression,highlighting the role of E protein in ZIKV-induced disruption of the BTB.We conclude that the interaction between ZIKV E and F-actin leads to the reorganization of F-actin network,thereby compromising BTB integrity.
基金supported by Grants from the National Science and Technology Major Project (Grant No.2018ZX10733403)。
文摘Coronavirus disease 2019(COVID-19), reminiscent of the severe acute respiratory syndrome(SARS) outbreak in 2003,has been a tragic disaster to people all over the world. As there is no specific drug for COVID-19, neutralizing antibodies are attracting more and more attention as one of the most effective means to combat the pandemic. Here, we introduced the etiological and serological characteristics of COVID-19, discussed the current stage of development of human monoclonal antibodies against SARS-CoV-2 and summarized the antigenic epitopes in the S glycoprotein, which may deepen the understanding of the profile of immune recognition and response against SARS-CoV-2 and provide insight for the design of effective vaccines and antibody-based therapies.
基金supported by the National Key R&D Program of China(2022YFC2303401,2021YFA1300803)National Natural Science Foundation of China(32122008)+2 种基金supported by Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)fellowships from the China Postdoctoral Science Foundation(2022T150688)the Postdoctoral Science Foundation of China(2021M700161).
文摘Foxes are susceptible to SARS-CoV-2 in laboratory settings,and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes.In this study,we assessed the binding capacities of fox ACE2 to important sarbecoviruses,including SARS-CoV,SARS-CoV-2,and animal-origin SARS-CoV-2 related viruses.Our findings demonstrated that fox ACE2 exhibits broad binding capabilities to receptor-binding domains(RBDs)of sarbecoviruses.We further determined the cryo-EM structures of fox ACE2 complexed with RBDs of SARS-CoV,SARS-CoV-2 prototype(PT),and Omicron BF.7.Through structural analysis,we identified that the K417 mutation can weaken the ability of SARS-CoV-2 sub-variants to bind to fox ACE2,thereby reducing the susceptibility of foxes to SARS-CoV-2 sub-variants.In addition,the Y498 residue in the SARS-CoV RBD plays a crucial role in forming a vital cation-πinteraction with K353 in the fox ACE2 receptor.This interaction is the primary determinant for the higher affinity of the SARS-CoV RBD compared to that of the SARS-CoV-2 PT RBD.These results indicate that foxes serve as potential hosts for numerous sarbecoviruses,highlighting the critical importance of surveillance efforts.
基金supported by the National Key Research and Development Plan of China(Grant No.2021YFC2300700).
文摘Dear Editor,Alternative splicing of eukaryotic transcripts refers to the posttranscriptional process in which the coding regions(exons)of a precursor transcript are joined in different combinations through the removal or retention of non-coding intervening sequences(introns)to produce distinct mature messenger RNA(mRNA)transcripts and further generate one or more mature mRNAs(Lee and Rio,2015).Alternative splicing is revealed dysregulation in infectious diseases.Many pathogens hijack the splicing mechanism of host cells to complete their replications,accompanied by dysregulated innate immune response or cell damage,leading to the changes of alternative splicing landscape in host cells(Ashraf et al.,2019;Tomezsko et al.,2020;Kremsdorf et al.,2021).The regulation mechanism of alternative splicing by viral pathogens,such as hepatitis B virus(Duriez et al.,2017),human immunodeficiency virus 1(Tomezsko et al.,2020),Zika virus(Bonenfant et al.,2020)and enterovirus 71(Li et al.,2020),have been explored.
