The severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)belongs to the genus Beta coronavirus and the family of Coronaviridae.It is a positive-sense,non-segmented single-strand RNA virus.Four common types of hu...The severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)belongs to the genus Beta coronavirus and the family of Coronaviridae.It is a positive-sense,non-segmented single-strand RNA virus.Four common types of human coronaviruses circulate globally,particularly in the fall and winter seasons.They are responsible for 10%-30% of all mild upper respiratory tract infections in adults.These are 229E,NL63 of the Alfacoronaviridae family,OC43,and HKU1 of the Betacoronaviridae family.However,there are three highly pathogenic human coronaviruses:SARS-CoV-2,Middle East respiratory syndrome coronavirus,and the latest pandemic caused by the SARS-CoV-2 infection.All viruses,including SARS-CoV-2,have the inherent tendency to evolve.SARS-CoV-2 is still evolving in humans.Additionally,due to the development of herd immunity,prior infection,use of medication,vaccination,and antibodies,the viruses are facing immune pressure.During the replication process and due to immune pressure,the virus may undergo mutations.Several SARS-CoV-2 variants,including the variants of concern(VOCs),such as B.1.1.7(Alpha),B.1.351(Beta),B.1.617/B.1.617.2(Delta),P.1(Gamma),and B.1.1.529(Omicron)have been reported from various parts of the world.These VOCs contain several important mutations;some of them are on the spike proteins.These mutations may lead to enhanced infectivity,transmissibility,and decreased neutralization efficacy by monoclonal antibodies,convalescent sera,or vaccines.Mutations may also lead to a failure of detection by molecular diagnostic tests,leading to a delayed diagnosis,increased community spread,and delayed treatment.We searched PubMed,EMBASE,Covariant,the Stanford variant Database,and the CINAHL from December 2019 to February 2023 using the following search terms:VOC,SARS-CoV-2,Omicron,mutations in SARS-CoV-2,etc.This review discusses the various mutations and their impact on infectivity,transmissibility,and neutralization efficacy.展开更多
As the world is closely watching the current 2009 H1N1 pandemic unfold, there is a great interest and need in understanding its origin, genetic structures, virulence, and pathogenicity. The two surface proteins, hemag...As the world is closely watching the current 2009 H1N1 pandemic unfold, there is a great interest and need in understanding its origin, genetic structures, virulence, and pathogenicity. The two surface proteins, hemagglutinin (HA) and neuraminidase (NA), of the influenza virus have been the focus of most flu research due to their crucial biological functions. In our previous study on 2009 H1N1, three aspects of NA were investigated: the mutations and co-mutations, the stalk motifs, and the phylogenetic analysis. In this study, we turned our attention to HA and the interaction between HA and NA. The 118 mutations of 2009 H1N1 HA were found and mapped to the 3D homology model of H1, and the mutations on the five epitope regions on H1 were identified. This information is essential for developing new drugs and vaccine. The distinct response patterns of HA to the changes of NA stalk motifs were discovered, illustrating the functional dependence between HA and NA. With help from our previous results, two co-mutation networks were uncovered, one in HA and one in NA, where each mutation in one network co-mutates with the mutations in the other network across the two proteins HA and NA. These two networks residing in HA and NA separately may provide a functional linkage between the mutations that can impact the drug binding sites in NA and those that can affect the host immune response or vaccine efficacy in HA. Our findings demonstrated the value of conducting timely analysis on the 2009 H1N1 virus and of the integrated approach to studying both surface proteins HA and NA together to reveal their interdependence, which could not be accomplished by studying them individually.展开更多
The NP, PA, PB1, and PB2 proteins of influenza viruses together are responsible for the transcription and replication of viral RNA, and the latter three proteins comprise the viral polymerase. Two recent reports indic...The NP, PA, PB1, and PB2 proteins of influenza viruses together are responsible for the transcription and replication of viral RNA, and the latter three proteins comprise the viral polymerase. Two recent reports indicated that the mutation at site 627 of PB2 plays a key role in host range and increased virulence of influenza viruses, and could be compensated by multiple mutations at other sites of PB2, suggesting the association of this mutation with those at other sites. The objective of this study was to analyze the co-mutated sites within and between these important proteins of influenza. With mutual information, a set of statistically significant co- mutated position pairs (P value = 0) in NP, PA, PB1, and PB2 of avian, human, pandemic 2009 H1N1, and swine influenza were identified, based on which several highly connected networks of correlated sites in NP, PA, PB1, and PB2 were discovered. These correlation networks further illustrated the inner functional dependence of the four proteins that are critical for host adaptation and pathogenicity. Mutual information was also applied to quantify the correlation of sites within each individual protein and between proteins. In general, the inter protein correlation of the four proteins was stronger than the intra protein correlation. Finally, the correlation patterns of the four proteins of pandemic 2009 H1N1 were found to be closer to those of avian and human than to swine influenza, thus rendering a novel insight into the interaction of the four proteins of the pandemic 2009 H1N1 virus when compared to avian, human, and swine influenza and how the origin of these four proteins might affect the correlation patterns uncovered in this analysis.展开更多
The influenza A viruses have three gene segments, M, NS, and PB1, which code for more than one protein. The overlapping genes from the same segment entail their interdependence, which could be reflected in the evoluti...The influenza A viruses have three gene segments, M, NS, and PB1, which code for more than one protein. The overlapping genes from the same segment entail their interdependence, which could be reflected in the evolutionary constraints, host distinction, and co-mutations of influenza. Most previous studies of overlapping genes focused on their unique evolutionary constraints, and very little was achieved to assess the potential impact of the overlap on other biological aspects of influenza. In this study, our aim was to explore the mutual dependence in host differentiation and co-mutations in M, NS, and PB1 of avian, human, 2009 H1N1, and swine viruses, with Random Forests, information entropy, and mutual information. The host markers and highly co-mutated individual sites and site pairs (P values < 0.035) in the three gene segments were identified with their relative significance between the overlapping genes calculated. Further, Random Forests predicted that among the three stop codons in the current PB1-F2 gene of 2009 H1N1, the significance of a mutation at these sites for host differentiation was, in order from most to least, that at 12, 58, and 88, i.e., the closer to the start of the gene the more important the mutation was. Finally, our sequence analysis surprisingly revealed that the full-length PB1-F2, if the three stop codons were all mutated, would function more as a swine protein than a human protein, although the PB1 of 2009 H1N1 was derived from human H3N2.展开更多
The maize pollens were implanted with seven different doses of 30 keV N+ beam respectively, The genomic DNA polymorphism from treated pollens were analyzed with 104 primers by using RAPD respectively. The results sho...The maize pollens were implanted with seven different doses of 30 keV N+ beam respectively, The genomic DNA polymorphism from treated pollens were analyzed with 104 primers by using RAPD respectively. The results showed that N^+ beam-induced mutation of maize pollens can result in the change of their DNA bases. The mutation is not properly random and its frequency increases with a rise in 30 keV N+ beam doses. It is conformed with A-G transformation, which is one of the most important factors in DNA bases induced by N+ beam.展开更多
As we enter the year of 2011, the 2009 H1N1 pandemic influenza virus is in the news again. At least 20 people have died of this virus in China since the beginning of 2011 and it is now the predominant flu strain in th...As we enter the year of 2011, the 2009 H1N1 pandemic influenza virus is in the news again. At least 20 people have died of this virus in China since the beginning of 2011 and it is now the predominant flu strain in the country. Although this novel virus was quite stable during its run in the flu season of 2009-2010, a genetic variant of this virus was found in Singapore in early 2010, and then in Australia and New Zealand during their 2010 winter influenza season. Several critical mutations in the HA protein of this variant were uncovered in the strains collected from January 2010 to April 2010. Moreover, a structural homology model of HA from the A/Brisbane/10/2010(H1N1) strain was made based on the structure of A/California/04/2009 (H1N1). The purpose of this study was to investigate mutations in the HA protein of 2009 H1N1 from sequence data collected worldwide from May 2010 to February 2011. A fundamental problem in bioinformatics and biology is to find the similar gene sequences for a given gene sequence of interest. Here we proposed the inverse problem, i.e., finding the exemplars from a group of related gene sequences. With a clustering algorithm affinity propagation, six exemplars of the HA sequences were identified to represent six clusters. One of the clusters contained strain A/Brisbane/12/2010(H1N1) that only differed from A/Brisbane/10/2010 in the HA sequence at position 449. Based on the sequence identity of the six exemplars, nine mutations in HA were located that could be used to distinguish these six clusters. Finally, we discovered the change of correlation patterns for the HA and NA of 2009 H1N1 as a result of the HA receptor binding specificity switch, revealing the balanced interplay between these two surface proteins of the virus.展开更多
Researchers have been searching for molecular features that could make avian H5N1 influenza transmissible among people since the first report of human infections with this virus in 1997. A recent study surprisingly de...Researchers have been searching for molecular features that could make avian H5N1 influenza transmissible among people since the first report of human infections with this virus in 1997. A recent study surprisingly demonstrated that only five mutations, fewer than previously estimated, are needed to make avian H5N1 influenza transmissible between ferrets through the air, raising fears that a human pandemic is possible if this virus escapes from the lab. Of the five mutations found, four of them are located in the HA gene that is responsible for the viral entry into the host cells. A crucial step for avian influenza to go across the species boundary to infect humans is the switch of its receptor binding specificity from avian to human types. The first task of this study was to quantify the individual as well as the collective effect of the known HA mutations from the previous research on receptor binding selection. Our second task was to identify new combinations of HA mutations that could change the receptor binding preference of H5N1 from avian to human types. Our findings thus deepened our understanding of the previous research and also extended its results by discovering new combinations of mutations that could enhance the binding of avian H5N1 to human type receptors while reduce that to avian types.展开更多
Objectif L＇objectif de ce travail est d＇etablir une méthode d＇analyse du polymorphisme de la conformation monochaine （ PCMC ）, capable de détecter la mutation ponctuelle du géne hMLH1 dans le cance...Objectif L＇objectif de ce travail est d＇etablir une méthode d＇analyse du polymorphisme de la conformation monochaine （ PCMC ）, capable de détecter la mutation ponctuelle du géne hMLH1 dans le cancer colique en utilisant l＇ l ctrophor se capillaire associée a it la fluorescence laser-induite （FLI-EC）. Méthodes Les exons 12 du gdne hMLH1 du sang périphérique de 42 patients de cancer colo-rectal sporadique et 20 sujets sains témoins sont amplifies par la PCR. Le PCMC des produits du PCR est analysé par FLI-EC. Les échantillons anormaux ont été confirmés par séquen age EC. Les effets de la concentration du milieu （ LPA ） , de la temperature de séparationéet du voltage de séparation sur le comportement de EC ont été aussi etudiés. Résultats L＇analyse de PCMC par la methode FLI-EC a retrouvé une mutation hétérozygote chez 4 des 42 patients. La mutation ponctuelle de Tl l51A a été objectivée par la séquen age EC de ces échantillons, aucune mutation n＇a été retrouvée chez les 20 sujets sains témoins. La séparation des pics d＇ADN monochainaux a été facilitée par une légdre augmentation de la concentration de LPA （4%-6%）, une légdre baisse de la temperature de séparation （20℃） et une légére élévation du voltage de séparation （9kV）. Conclusion Une concentration adequate de LPA, une temperature de séparation appropriée et un voltage de séparation bien approprié améliorent considérablement l＇efficacité du FLI-EC. L＇application de cette méthode pour détecter la mutation ponctuelle du géne hMLH1 est d＇une rapiditY, d＇une efficacité, et d＇uneéreproductivit consid rables. Cette méthode de réalisation facile reste trés prometteur pour le dépistage rapide et massive des mutations génétiques.展开更多
文摘The severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)belongs to the genus Beta coronavirus and the family of Coronaviridae.It is a positive-sense,non-segmented single-strand RNA virus.Four common types of human coronaviruses circulate globally,particularly in the fall and winter seasons.They are responsible for 10%-30% of all mild upper respiratory tract infections in adults.These are 229E,NL63 of the Alfacoronaviridae family,OC43,and HKU1 of the Betacoronaviridae family.However,there are three highly pathogenic human coronaviruses:SARS-CoV-2,Middle East respiratory syndrome coronavirus,and the latest pandemic caused by the SARS-CoV-2 infection.All viruses,including SARS-CoV-2,have the inherent tendency to evolve.SARS-CoV-2 is still evolving in humans.Additionally,due to the development of herd immunity,prior infection,use of medication,vaccination,and antibodies,the viruses are facing immune pressure.During the replication process and due to immune pressure,the virus may undergo mutations.Several SARS-CoV-2 variants,including the variants of concern(VOCs),such as B.1.1.7(Alpha),B.1.351(Beta),B.1.617/B.1.617.2(Delta),P.1(Gamma),and B.1.1.529(Omicron)have been reported from various parts of the world.These VOCs contain several important mutations;some of them are on the spike proteins.These mutations may lead to enhanced infectivity,transmissibility,and decreased neutralization efficacy by monoclonal antibodies,convalescent sera,or vaccines.Mutations may also lead to a failure of detection by molecular diagnostic tests,leading to a delayed diagnosis,increased community spread,and delayed treatment.We searched PubMed,EMBASE,Covariant,the Stanford variant Database,and the CINAHL from December 2019 to February 2023 using the following search terms:VOC,SARS-CoV-2,Omicron,mutations in SARS-CoV-2,etc.This review discusses the various mutations and their impact on infectivity,transmissibility,and neutralization efficacy.
文摘As the world is closely watching the current 2009 H1N1 pandemic unfold, there is a great interest and need in understanding its origin, genetic structures, virulence, and pathogenicity. The two surface proteins, hemagglutinin (HA) and neuraminidase (NA), of the influenza virus have been the focus of most flu research due to their crucial biological functions. In our previous study on 2009 H1N1, three aspects of NA were investigated: the mutations and co-mutations, the stalk motifs, and the phylogenetic analysis. In this study, we turned our attention to HA and the interaction between HA and NA. The 118 mutations of 2009 H1N1 HA were found and mapped to the 3D homology model of H1, and the mutations on the five epitope regions on H1 were identified. This information is essential for developing new drugs and vaccine. The distinct response patterns of HA to the changes of NA stalk motifs were discovered, illustrating the functional dependence between HA and NA. With help from our previous results, two co-mutation networks were uncovered, one in HA and one in NA, where each mutation in one network co-mutates with the mutations in the other network across the two proteins HA and NA. These two networks residing in HA and NA separately may provide a functional linkage between the mutations that can impact the drug binding sites in NA and those that can affect the host immune response or vaccine efficacy in HA. Our findings demonstrated the value of conducting timely analysis on the 2009 H1N1 virus and of the integrated approach to studying both surface proteins HA and NA together to reveal their interdependence, which could not be accomplished by studying them individually.
文摘The NP, PA, PB1, and PB2 proteins of influenza viruses together are responsible for the transcription and replication of viral RNA, and the latter three proteins comprise the viral polymerase. Two recent reports indicated that the mutation at site 627 of PB2 plays a key role in host range and increased virulence of influenza viruses, and could be compensated by multiple mutations at other sites of PB2, suggesting the association of this mutation with those at other sites. The objective of this study was to analyze the co-mutated sites within and between these important proteins of influenza. With mutual information, a set of statistically significant co- mutated position pairs (P value = 0) in NP, PA, PB1, and PB2 of avian, human, pandemic 2009 H1N1, and swine influenza were identified, based on which several highly connected networks of correlated sites in NP, PA, PB1, and PB2 were discovered. These correlation networks further illustrated the inner functional dependence of the four proteins that are critical for host adaptation and pathogenicity. Mutual information was also applied to quantify the correlation of sites within each individual protein and between proteins. In general, the inter protein correlation of the four proteins was stronger than the intra protein correlation. Finally, the correlation patterns of the four proteins of pandemic 2009 H1N1 were found to be closer to those of avian and human than to swine influenza, thus rendering a novel insight into the interaction of the four proteins of the pandemic 2009 H1N1 virus when compared to avian, human, and swine influenza and how the origin of these four proteins might affect the correlation patterns uncovered in this analysis.
文摘The influenza A viruses have three gene segments, M, NS, and PB1, which code for more than one protein. The overlapping genes from the same segment entail their interdependence, which could be reflected in the evolutionary constraints, host distinction, and co-mutations of influenza. Most previous studies of overlapping genes focused on their unique evolutionary constraints, and very little was achieved to assess the potential impact of the overlap on other biological aspects of influenza. In this study, our aim was to explore the mutual dependence in host differentiation and co-mutations in M, NS, and PB1 of avian, human, 2009 H1N1, and swine viruses, with Random Forests, information entropy, and mutual information. The host markers and highly co-mutated individual sites and site pairs (P values < 0.035) in the three gene segments were identified with their relative significance between the overlapping genes calculated. Further, Random Forests predicted that among the three stop codons in the current PB1-F2 gene of 2009 H1N1, the significance of a mutation at these sites for host differentiation was, in order from most to least, that at 12, 58, and 88, i.e., the closer to the start of the gene the more important the mutation was. Finally, our sequence analysis surprisingly revealed that the full-length PB1-F2, if the three stop codons were all mutated, would function more as a swine protein than a human protein, although the PB1 of 2009 H1N1 was derived from human H3N2.
文摘The maize pollens were implanted with seven different doses of 30 keV N+ beam respectively, The genomic DNA polymorphism from treated pollens were analyzed with 104 primers by using RAPD respectively. The results showed that N^+ beam-induced mutation of maize pollens can result in the change of their DNA bases. The mutation is not properly random and its frequency increases with a rise in 30 keV N+ beam doses. It is conformed with A-G transformation, which is one of the most important factors in DNA bases induced by N+ beam.
文摘As we enter the year of 2011, the 2009 H1N1 pandemic influenza virus is in the news again. At least 20 people have died of this virus in China since the beginning of 2011 and it is now the predominant flu strain in the country. Although this novel virus was quite stable during its run in the flu season of 2009-2010, a genetic variant of this virus was found in Singapore in early 2010, and then in Australia and New Zealand during their 2010 winter influenza season. Several critical mutations in the HA protein of this variant were uncovered in the strains collected from January 2010 to April 2010. Moreover, a structural homology model of HA from the A/Brisbane/10/2010(H1N1) strain was made based on the structure of A/California/04/2009 (H1N1). The purpose of this study was to investigate mutations in the HA protein of 2009 H1N1 from sequence data collected worldwide from May 2010 to February 2011. A fundamental problem in bioinformatics and biology is to find the similar gene sequences for a given gene sequence of interest. Here we proposed the inverse problem, i.e., finding the exemplars from a group of related gene sequences. With a clustering algorithm affinity propagation, six exemplars of the HA sequences were identified to represent six clusters. One of the clusters contained strain A/Brisbane/12/2010(H1N1) that only differed from A/Brisbane/10/2010 in the HA sequence at position 449. Based on the sequence identity of the six exemplars, nine mutations in HA were located that could be used to distinguish these six clusters. Finally, we discovered the change of correlation patterns for the HA and NA of 2009 H1N1 as a result of the HA receptor binding specificity switch, revealing the balanced interplay between these two surface proteins of the virus.
文摘Researchers have been searching for molecular features that could make avian H5N1 influenza transmissible among people since the first report of human infections with this virus in 1997. A recent study surprisingly demonstrated that only five mutations, fewer than previously estimated, are needed to make avian H5N1 influenza transmissible between ferrets through the air, raising fears that a human pandemic is possible if this virus escapes from the lab. Of the five mutations found, four of them are located in the HA gene that is responsible for the viral entry into the host cells. A crucial step for avian influenza to go across the species boundary to infect humans is the switch of its receptor binding specificity from avian to human types. The first task of this study was to quantify the individual as well as the collective effect of the known HA mutations from the previous research on receptor binding selection. Our second task was to identify new combinations of HA mutations that could change the receptor binding preference of H5N1 from avian to human types. Our findings thus deepened our understanding of the previous research and also extended its results by discovering new combinations of mutations that could enhance the binding of avian H5N1 to human type receptors while reduce that to avian types.
文摘Objectif L＇objectif de ce travail est d＇etablir une méthode d＇analyse du polymorphisme de la conformation monochaine （ PCMC ）, capable de détecter la mutation ponctuelle du géne hMLH1 dans le cancer colique en utilisant l＇ l ctrophor se capillaire associée a it la fluorescence laser-induite （FLI-EC）. Méthodes Les exons 12 du gdne hMLH1 du sang périphérique de 42 patients de cancer colo-rectal sporadique et 20 sujets sains témoins sont amplifies par la PCR. Le PCMC des produits du PCR est analysé par FLI-EC. Les échantillons anormaux ont été confirmés par séquen age EC. Les effets de la concentration du milieu （ LPA ） , de la temperature de séparationéet du voltage de séparation sur le comportement de EC ont été aussi etudiés. Résultats L＇analyse de PCMC par la methode FLI-EC a retrouvé une mutation hétérozygote chez 4 des 42 patients. La mutation ponctuelle de Tl l51A a été objectivée par la séquen age EC de ces échantillons, aucune mutation n＇a été retrouvée chez les 20 sujets sains témoins. La séparation des pics d＇ADN monochainaux a été facilitée par une légdre augmentation de la concentration de LPA （4%-6%）, une légdre baisse de la temperature de séparation （20℃） et une légére élévation du voltage de séparation （9kV）. Conclusion Une concentration adequate de LPA, une temperature de séparation appropriée et un voltage de séparation bien approprié améliorent considérablement l＇efficacité du FLI-EC. L＇application de cette méthode pour détecter la mutation ponctuelle du géne hMLH1 est d＇une rapiditY, d＇une efficacité, et d＇uneéreproductivit consid rables. Cette méthode de réalisation facile reste trés prometteur pour le dépistage rapide et massive des mutations génétiques.
