Objective Newly identified human rhinovirus C （HRV-C） and human bocavirus （HBoV） cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related va...Objective Newly identified human rhinovirus C （HRV-C） and human bocavirus （HBoV） cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses.Methods A platform for culturing human airway epithelia in a three-dimensional （3D） pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction {PCR）. Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA.Results Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-2, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial （HAE） cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system.Conclusion Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV.展开更多
Dear Editor,Cumulative evidence supports the role of early-life viral infections,especially respiratory syncytial virus(RSV)and human rhinovirus(HRV),as major antecedents of childhood asthma(Lemanske,2002;Jackson et a...Dear Editor,Cumulative evidence supports the role of early-life viral infections,especially respiratory syncytial virus(RSV)and human rhinovirus(HRV),as major antecedents of childhood asthma(Lemanske,2002;Jackson et al.,2008).In this study,the x TAG respiratory viral panel FAST(RVP FAST)assay,a multiplex polymerase chain reaction(PCR)-based method(Arens et al.,2010;BaladaLlasat et al.,2011;Gharabaghi et al.,2011;Selvaraju,2012),was used to investigate the association of infec-展开更多
Background： Human rhinoviruses （HRVs） are divided into three genetic species： HRV-A, HRV-B, and HRV-C. The association of different HRV species with asthma in children in China has not yet been evaluated. This pre...Background： Human rhinoviruses （HRVs） are divided into three genetic species： HRV-A, HRV-B, and HRV-C. The association of different HRV species with asthma in children in China has not yet been evaluated. This preliminary study aimed to assess the associations between different HRV species, particularly HRV-C, and asthma in young children in China. Methods： A total of 702 nasopharyngeal aspirates were obtained from 155 children with asthma （asthma group）, 461 children with acute respiratory infection （ARI） without asthma （nonasthma ARI group）, and 86 children from the control group. Semi-nested polymerase chain reaction （PCR） was used to detect HRVs, and PCR products were sequenced for species identification. Epidemiological characteristics of HRV-positive cases were analyzed. Results： HRVs were the most common pathogen （ 15.4%; 108/702） in the patients in this study. The prevalence of HRV was significantly different （F = 20.633, P = 0.000） between tile asthma （25.8%） and nonasthma ARI groups （11.1%）. Phylogenetic analysis indicated that in the 108 cases positive for HRVs, 41 were identified as HRV-A, 8 as HRV-B, and 56 as HRV-C, Comparing the asthma with the nonasthlna ARI group, Spearman＇s rank correlation analysis revealed an association between HRV-A （P 〈 0.05） and C （P 〈 0.01） and asthma, confirmed by regression analysis, with odds ratios of 2.2 （HRV-A） and 4.2 （HRV-C）. Conclusions： Our data revealed a high prevalence of HRVs in children in China, regardless of clinical status. HRV-C was the dominant species and may be one of the key factors in the association of HRVs with asthma.展开更多
Background Some research groups have hypothesized that human rhinoviruses （HRVs） delayed the circulation of the 2009 pandemic influenza A（H1N1） virus （A（H1N1）pdm09） at the beginning of Autumn 2009 in France.Th...Background Some research groups have hypothesized that human rhinoviruses （HRVs） delayed the circulation of the 2009 pandemic influenza A（H1N1） virus （A（H1N1）pdm09） at the beginning of Autumn 2009 in France.This study aimed to evaluate the relationship between HRV and A（H1N1）pdm09 in pediatric patients with influenza-like illness in Beijing,China.Methods A systematic analysis to detect A（H1N1）pdm09 and seasonal influenza A virus （FLU A） was performed on 4 349 clinical samples from pediatric patients with influenza-like illness during the period June 1,2009 to February 28,2010,while a one-step real-time RT-PCR （rRT-PCR） assay was used to detect HRV in 1 146 clinical specimens selected from those 4 349 specimens.Results During the survey period,only one wave of A（H1N1）pdm09 was observed.The percentage of positive cases for A（H1N1）pdm09 increased sharply in September with a peak in November 2009 and then declined in February 2010.Data on the monthly distribution of HRVs indicated that more HRV-positive samples were detected in September （2.2％） and October （3.3％）,revealing that the peak of HRV infection in 2009 was similar to that of other years.Among the 1 146 specimens examined for HRVs,21 （1.8％） were HRV-positive,which was significantly lower than that reported previously in Beijing （15.4％ to 19.2％） （P ＜0.01）.Overall,6 samples were positive for both A（H1N1）pdm09 and HRV,which represented a positive relative frequency of 1.60％ and 2.08％ HRV,considering the A（H1N1）pdm09-positive and-negative specimens,respectively.The odds ratio was 0.87 （95％ CI 0.32; 2.44,P=0.80）.Conclusions HRVs and A （H1N1）pdm09 co-circulated in this Chinese population during September and October 2009,and the HRV epidemic in 2009 did not affect A（H1N1）pdm09 infection rates in Beijing,China as suggested by other studies.However,the presence of A（H1N1）pdm09 might explain the unexpected reduction in the percentage of HRV positive cases during the period studied.展开更多
The common cold is most often a result of human rhinovirus （HRV） infection. Common cold symptoms including rhinorrhea and nasal obstruction frequently occur during HRV infection of the upper respiratory tract. Conve...The common cold is most often a result of human rhinovirus （HRV） infection. Common cold symptoms including rhinorrhea and nasal obstruction frequently occur during HRV infection of the upper respiratory tract. Conversely, HRV may also infect the epithelial cells of the lower respiratory tract. Symptom severity associated with HRV infection ranges from mild to potentially serious depending on a person＇s susceptibility and preexisting condition, such as chronic obstructive pulmonary disease. An over active host immune response is believed to be the primary contributor to HRV pathogenesis. Enhanced activity of various host cell cytokines and granulocytes mediate specific cellular pathways inducing many of the symptoms associated with HRV infection. There are over 100 serotypes of HRV which can be further categorized based on the specific characteristics of each type. The two main categories of HRV consist of the major and minor groups. The unique host cell receptor is the distinguishing factor between these two groups. Yet, these viruses may also differ in mechanism of infection and replication. Due to the high frequency of hospital and clinical visits and the corresponding economic burden, novel therapies are of interest. Several different treatment options varying from herbal remedies to anti-viral drugs have been studied. However, the vast number of HRV serotypes complicates the progress of developing a universal treatment for attenuating HRV infection.展开更多
Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world...Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world's public health and human life safety.Commonly used antiviral drugs have obvious side effects and a narrow scope of application.Respiratory viruses are susceptible to infection,mutation,and prevalence,which also pose challenges to traditional antiviral drugs and vaccine development.Traditional Chinese Medicine(TCM)has a long history of treating infectious diseases,with many herbs and compounds.Its multi-component,multi-target and multi-path characteristics have made it have great advantages and potential in the development of new anti-respiratory virus drugs.This review summarized TCM for the prevention and treatment of common respiratory viruses,and provided new strategies for the research and development of new TCM antiviral drugs and for responding to infectious respiratory virus diseases.展开更多
Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate ...Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.展开更多
Background A series of public health preventive measures has been widely implemented in Beijing to control the corona-virus disease-19(COVID-19)pandemic since January 2020.An evaluation of the effects of these prevent...Background A series of public health preventive measures has been widely implemented in Beijing to control the corona-virus disease-19(COVID-19)pandemic since January 2020.An evaluation of the effects of these preventive measures on the spread of other respiratory viruses is necessary.Methods Respiratory specimens collected from children with acute respiratory infections were tested by NxTAGTN,respiratory pathogen panel assays during January 2017 and December 2020.Specimens characterized as rhinoviruses(RVs)were sequenced to identify the RV species and types.Then,the epidemiology results of respiratory pathogens in 2020 were compared with those from 2017 to 2019 using SPSS statistics 22.0.Results The positive rates of adenovirus(ADV),influenza virus(flu),RVs,and respiratory syncytial virus(RSV)dropped abruptly by 86.31%,94.679c,94.59%,and 92.17%,respectively,from February to May 2020,compared with the average level in the same period during 2017-2019.Positive rates of RVs then steeply increased from June 2020(13.77%),to an apex(37.25%)in August 2020,significantly higher than the average rates(22.51%)in August 2017-2019(7^=0.005).The increase,especially in group>3 years,was accompanied by the reopening of schools and kindergartens after the 23rd and 24th week of 2020 in Beijing.Conclusions Whereas the abrupt drop in viral pathogen positive rates from February to May 2020 revealed the remarkable effects of the COVID-19 preventive measures,the sharp increase in positive rates of RVs from the 23rd week of 2020 might be explained by the reopening of schools and kindergartens in Beijing.展开更多
Human rhinoviruses(HRVs)are the predominant infectious agents for the common cold worldwide.The HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma.3C protease,a h...Human rhinoviruses(HRVs)are the predominant infectious agents for the common cold worldwide.The HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma.3C protease,a highly conserved enzyme,cleaves the viral polyprotein during replication and assists the virus in escaping the host immune system.These key roles make 3C protease an important drug target.A few structures of 3Cs complexed with an irreversible inhibitor rupintrivir have been determined.These structures shed light on the determinants of drug specificity.Here we describe the structures of HRV-C153C in free and inhibitor-bound forms.The volume-decreased S1'subsite and half-closed S2 subsite,which were thought to be unique features of enterovirus A 3C proteases,appear in the HRV-C 3C protease.Rupintrivir assumes an“intermediate”conformation in the complex,which might open up additional avenues for the design of potent antiviral inhibitors.Analysis of the features of the three-dimensional structures and the amino acid sequences of 3C proteases suggest new applications for existing drugs.展开更多
Human rhinovirus(HRV)is one of the most important cold-causing pathogens in humans.Piwi-interacting RNAs(piRNAs)are a recently discovered class of small non-coding RNAs whose best-understood function is to repress mob...Human rhinovirus(HRV)is one of the most important cold-causing pathogens in humans.Piwi-interacting RNAs(piRNAs)are a recently discovered class of small non-coding RNAs whose best-understood function is to repress mobile element(ME)activity in animal germline.However,the profile of human/host piRNA during HRV infection is largely unknown.Here we performed high-throughput sequencing of piRNAs from H1-HeLa cells infected with HRV16 at 12 h,24 h,and 36 h.The results showed that 22,151,664,24,362,486 and 22,726,546 piRNAs displayed differential expression after HRV16 infection for three time points.A significant differential expression of 21 piRNAs was found in all time points and further verified by RT-qPCR,including 7 known piRNAs and 14 newly found piRNAs.In addition,piRNA prediction was performed on Piano using the SVM algorithm and transposon information.It found that novel_pir78110,novel_pir78107,novel_pir78097,novel_pir78094 and novel_pir76584 are associated with the DNA/hobo of Drosophila,Ac of maize and Tam3 of snapdragon(hAT)-Charlie transposon.The novel_pir97924,novel_pir105705 and novel_pir105700 recognize long interspersed nuclear elements 1(LINE-1).The novel_pir33182 and novel_pir46604 are related to the long terminal repeat(LTR)/(Endogenous Retrovirus1)ERV1 repetitive element.The novel_pir73855 is related to the LTR/ERVK repetitive element.Both novel_pir70108 and novel_pir70106 are associated with the LTR/ERVL-MaLR repetitive element.The novel_pir15900 is associated with the DNA/hAT-Tip100 repetitive element.Overall,our results indicated that rhinovirus infection could reduce the expression of some piRNAs to facilitate upregulation of LINE-1 transcription or retrotransposons'expression,which is helpful to further explore the mechanism of rhinovirus infection.展开更多
基金supported by grants from the Major Project Specialized for Infectious Diseases of the Chinese Health and Family Planning Commission[2014ZX10004002-004-002,2014ZX10004002-004-001]Young Talent Scholar Plan of Higher School in Hebei Province[BJ2017008]
文摘Objective Newly identified human rhinovirus C （HRV-C） and human bocavirus （HBoV） cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses.Methods A platform for culturing human airway epithelia in a three-dimensional （3D） pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction {PCR）. Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA.Results Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-2, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial （HAE） cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system.Conclusion Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV.
基金supported by Special Funds for Public WelfareProjects (2015SQ00160)the Beijing Municipal Health Bureau "Advanced Personnel Training Program" (No. 2011-3-068)the Beijing Municipal Science and Technology Commission (No. Z111107056811041)
文摘Dear Editor,Cumulative evidence supports the role of early-life viral infections,especially respiratory syncytial virus(RSV)and human rhinovirus(HRV),as major antecedents of childhood asthma(Lemanske,2002;Jackson et al.,2008).In this study,the x TAG respiratory viral panel FAST(RVP FAST)assay,a multiplex polymerase chain reaction(PCR)-based method(Arens et al.,2010;BaladaLlasat et al.,2011;Gharabaghi et al.,2011;Selvaraju,2012),was used to investigate the association of infec-
文摘Background： Human rhinoviruses （HRVs） are divided into three genetic species： HRV-A, HRV-B, and HRV-C. The association of different HRV species with asthma in children in China has not yet been evaluated. This preliminary study aimed to assess the associations between different HRV species, particularly HRV-C, and asthma in young children in China. Methods： A total of 702 nasopharyngeal aspirates were obtained from 155 children with asthma （asthma group）, 461 children with acute respiratory infection （ARI） without asthma （nonasthma ARI group）, and 86 children from the control group. Semi-nested polymerase chain reaction （PCR） was used to detect HRVs, and PCR products were sequenced for species identification. Epidemiological characteristics of HRV-positive cases were analyzed. Results： HRVs were the most common pathogen （ 15.4%; 108/702） in the patients in this study. The prevalence of HRV was significantly different （F = 20.633, P = 0.000） between tile asthma （25.8%） and nonasthma ARI groups （11.1%）. Phylogenetic analysis indicated that in the 108 cases positive for HRVs, 41 were identified as HRV-A, 8 as HRV-B, and 56 as HRV-C, Comparing the asthma with the nonasthlna ARI group, Spearman＇s rank correlation analysis revealed an association between HRV-A （P 〈 0.05） and C （P 〈 0.01） and asthma, confirmed by regression analysis, with odds ratios of 2.2 （HRV-A） and 4.2 （HRV-C）. Conclusions： Our data revealed a high prevalence of HRVs in children in China, regardless of clinical status. HRV-C was the dominant species and may be one of the key factors in the association of HRVs with asthma.
基金This study was supported by the grants from the National Natural Science Foundation of China （No. 30872153） and the Beijing Outstanding Personnel Training Grant from the Beijing Municipal Committee for Science and Technology （No. 2006A63）.Acknowledgements： We would like to thank all the doctors and nurses in the Department of Emergency and the Outpatient Department at the Affiliated Children＇s Hospital of the Capital Institute of Pediatrics for collecting specimens from patients and information from their parents.
文摘Background Some research groups have hypothesized that human rhinoviruses （HRVs） delayed the circulation of the 2009 pandemic influenza A（H1N1） virus （A（H1N1）pdm09） at the beginning of Autumn 2009 in France.This study aimed to evaluate the relationship between HRV and A（H1N1）pdm09 in pediatric patients with influenza-like illness in Beijing,China.Methods A systematic analysis to detect A（H1N1）pdm09 and seasonal influenza A virus （FLU A） was performed on 4 349 clinical samples from pediatric patients with influenza-like illness during the period June 1,2009 to February 28,2010,while a one-step real-time RT-PCR （rRT-PCR） assay was used to detect HRV in 1 146 clinical specimens selected from those 4 349 specimens.Results During the survey period,only one wave of A（H1N1）pdm09 was observed.The percentage of positive cases for A（H1N1）pdm09 increased sharply in September with a peak in November 2009 and then declined in February 2010.Data on the monthly distribution of HRVs indicated that more HRV-positive samples were detected in September （2.2％） and October （3.3％）,revealing that the peak of HRV infection in 2009 was similar to that of other years.Among the 1 146 specimens examined for HRVs,21 （1.8％） were HRV-positive,which was significantly lower than that reported previously in Beijing （15.4％ to 19.2％） （P ＜0.01）.Overall,6 samples were positive for both A（H1N1）pdm09 and HRV,which represented a positive relative frequency of 1.60％ and 2.08％ HRV,considering the A（H1N1）pdm09-positive and-negative specimens,respectively.The odds ratio was 0.87 （95％ CI 0.32; 2.44,P=0.80）.Conclusions HRVs and A （H1N1）pdm09 co-circulated in this Chinese population during September and October 2009,and the HRV epidemic in 2009 did not affect A（H1N1）pdm09 infection rates in Beijing,China as suggested by other studies.However,the presence of A（H1N1）pdm09 might explain the unexpected reduction in the percentage of HRV positive cases during the period studied.
文摘The common cold is most often a result of human rhinovirus （HRV） infection. Common cold symptoms including rhinorrhea and nasal obstruction frequently occur during HRV infection of the upper respiratory tract. Conversely, HRV may also infect the epithelial cells of the lower respiratory tract. Symptom severity associated with HRV infection ranges from mild to potentially serious depending on a person＇s susceptibility and preexisting condition, such as chronic obstructive pulmonary disease. An over active host immune response is believed to be the primary contributor to HRV pathogenesis. Enhanced activity of various host cell cytokines and granulocytes mediate specific cellular pathways inducing many of the symptoms associated with HRV infection. There are over 100 serotypes of HRV which can be further categorized based on the specific characteristics of each type. The two main categories of HRV consist of the major and minor groups. The unique host cell receptor is the distinguishing factor between these two groups. Yet, these viruses may also differ in mechanism of infection and replication. Due to the high frequency of hospital and clinical visits and the corresponding economic burden, novel therapies are of interest. Several different treatment options varying from herbal remedies to anti-viral drugs have been studied. However, the vast number of HRV serotypes complicates the progress of developing a universal treatment for attenuating HRV infection.
文摘Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world's public health and human life safety.Commonly used antiviral drugs have obvious side effects and a narrow scope of application.Respiratory viruses are susceptible to infection,mutation,and prevalence,which also pose challenges to traditional antiviral drugs and vaccine development.Traditional Chinese Medicine(TCM)has a long history of treating infectious diseases,with many herbs and compounds.Its multi-component,multi-target and multi-path characteristics have made it have great advantages and potential in the development of new anti-respiratory virus drugs.This review summarized TCM for the prevention and treatment of common respiratory viruses,and provided new strategies for the research and development of new TCM antiviral drugs and for responding to infectious respiratory virus diseases.
基金Supported by The Tonjes-Vagt-Stiftung,Bremen,Germany.
文摘Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.
基金This work was supported by grants from The Pediatric Medical Coordinated Development Center of the Beijing Hospitals Authority(No.XTZD20180505)Beijing Municipal Commission of Health and Family(No.2060399 PXM2017_026268_00005_00254486).
文摘Background A series of public health preventive measures has been widely implemented in Beijing to control the corona-virus disease-19(COVID-19)pandemic since January 2020.An evaluation of the effects of these preventive measures on the spread of other respiratory viruses is necessary.Methods Respiratory specimens collected from children with acute respiratory infections were tested by NxTAGTN,respiratory pathogen panel assays during January 2017 and December 2020.Specimens characterized as rhinoviruses(RVs)were sequenced to identify the RV species and types.Then,the epidemiology results of respiratory pathogens in 2020 were compared with those from 2017 to 2019 using SPSS statistics 22.0.Results The positive rates of adenovirus(ADV),influenza virus(flu),RVs,and respiratory syncytial virus(RSV)dropped abruptly by 86.31%,94.679c,94.59%,and 92.17%,respectively,from February to May 2020,compared with the average level in the same period during 2017-2019.Positive rates of RVs then steeply increased from June 2020(13.77%),to an apex(37.25%)in August 2020,significantly higher than the average rates(22.51%)in August 2017-2019(7^=0.005).The increase,especially in group>3 years,was accompanied by the reopening of schools and kindergartens after the 23rd and 24th week of 2020 in Beijing.Conclusions Whereas the abrupt drop in viral pathogen positive rates from February to May 2020 revealed the remarkable effects of the COVID-19 preventive measures,the sharp increase in positive rates of RVs from the 23rd week of 2020 might be explained by the reopening of schools and kindergartens in Beijing.
基金supported by the National Key Research and Development Program(2018YFA0900801)National Science Foundation of China(31800145)+1 种基金the State Key Laboratory of Veterinary Etiological Biology,Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences and the seed Foundation of Innovation and Creation for Graduate Students in Northwestern Polytechnical University ZZ2019279sponsored by the Youth Innovation Promotion Association at the Chinese Academy of Sciences。
文摘Human rhinoviruses(HRVs)are the predominant infectious agents for the common cold worldwide.The HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma.3C protease,a highly conserved enzyme,cleaves the viral polyprotein during replication and assists the virus in escaping the host immune system.These key roles make 3C protease an important drug target.A few structures of 3Cs complexed with an irreversible inhibitor rupintrivir have been determined.These structures shed light on the determinants of drug specificity.Here we describe the structures of HRV-C153C in free and inhibitor-bound forms.The volume-decreased S1'subsite and half-closed S2 subsite,which were thought to be unique features of enterovirus A 3C proteases,appear in the HRV-C 3C protease.Rupintrivir assumes an“intermediate”conformation in the complex,which might open up additional avenues for the design of potent antiviral inhibitors.Analysis of the features of the three-dimensional structures and the amino acid sequences of 3C proteases suggest new applications for existing drugs.
基金This work was supported by the China MegaProject for Infectious Disease(2018ZX10102001,2018ZX10711001,2018ZX10734401 and 2018ZX10734404)the SKLID Development Grant(2011SKLID104).
文摘Human rhinovirus(HRV)is one of the most important cold-causing pathogens in humans.Piwi-interacting RNAs(piRNAs)are a recently discovered class of small non-coding RNAs whose best-understood function is to repress mobile element(ME)activity in animal germline.However,the profile of human/host piRNA during HRV infection is largely unknown.Here we performed high-throughput sequencing of piRNAs from H1-HeLa cells infected with HRV16 at 12 h,24 h,and 36 h.The results showed that 22,151,664,24,362,486 and 22,726,546 piRNAs displayed differential expression after HRV16 infection for three time points.A significant differential expression of 21 piRNAs was found in all time points and further verified by RT-qPCR,including 7 known piRNAs and 14 newly found piRNAs.In addition,piRNA prediction was performed on Piano using the SVM algorithm and transposon information.It found that novel_pir78110,novel_pir78107,novel_pir78097,novel_pir78094 and novel_pir76584 are associated with the DNA/hobo of Drosophila,Ac of maize and Tam3 of snapdragon(hAT)-Charlie transposon.The novel_pir97924,novel_pir105705 and novel_pir105700 recognize long interspersed nuclear elements 1(LINE-1).The novel_pir33182 and novel_pir46604 are related to the long terminal repeat(LTR)/(Endogenous Retrovirus1)ERV1 repetitive element.The novel_pir73855 is related to the LTR/ERVK repetitive element.Both novel_pir70108 and novel_pir70106 are associated with the LTR/ERVL-MaLR repetitive element.The novel_pir15900 is associated with the DNA/hAT-Tip100 repetitive element.Overall,our results indicated that rhinovirus infection could reduce the expression of some piRNAs to facilitate upregulation of LINE-1 transcription or retrotransposons'expression,which is helpful to further explore the mechanism of rhinovirus infection.
