Objective Unbiased next generation sequencing（NGS） is susceptible to interference from host or environmental sequences. Consequently, background depletion and virome enrichment techniques are usually needed for clin...Objective Unbiased next generation sequencing（NGS） is susceptible to interference from host or environmental sequences. Consequently, background depletion and virome enrichment techniques are usually needed for clinical samples where viral load is much lower than background sequences. Methods A viral Sequence Independent Targeted Amplification（VSITA） approach using a set of non-ribosomal and virus-enriched octamers（V8） was developed and compared with traditionally used random hexamers（N6）. Forty-five archived clinical samples of different types were used in parallel to compare the V8 and N6 enrichment performance of viral sequences and removal performance of ribosomal sequences in the step of reverse transcription followed by quantitative PCR（qP CR）. Ten sera samples from patients with fever of unknown origin and 10 feces samples from patients with diarrhea of unknown origin were used in comparison of V8 and N6 enrichment performance following NGS analysis. Results A minimum 30 hexamers matching to viral reference sequences（sense and antisense） were selected from a dataset of random 4,096（4~6） hexamers（N6）. Two random nucleotides were added to the 5＇ end of the selected hexamers, and 480（30 × 4~2） octamers（V8） were obtained. In general, VSITA approach showed higher enrichment of virus-targeted c DNA and enhanced ability to remove unwanted ribosomal sequences in the majorities of 45 predefined clinical samples. Moreover, VSITA combined with NGS enabled to detect not only more viruses but also achieve more viral reads hit and higher viral genome coverage in 20 clinical samples with diarrhea or fever of unknown origin. Conclusion The VSITA approach designed in this study is demonstrated to possess higher sensitivity and broader genome coverage than traditionally used random hexamers in the NGS-based identification of viral pathogens directly from clinical samples.展开更多
High genetic variability of human immunodeficiency virus(HIV)has been a major intractable challenge to the practical design of vaccines.But a recent pioneer study published in PNAS Xenobots,is likely to revolutionize ...High genetic variability of human immunodeficiency virus(HIV)has been a major intractable challenge to the practical design of vaccines.But a recent pioneer study published in PNAS Xenobots,is likely to revolutionize HIV prevention as it presented the world's first living robot made of cells.In the advent of this discovery,we herein discuss the possibility of using living biological cell robots to target HIV-infected T lymphocytes,and the prospects of this approach being a new HIV vaccine.We capture the current research status and trend of advances in biological cell robots'design as a new HIV vaccine.The key differences between this novel vaccine and other HIV vaccines are highlighted.展开更多
Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved t...Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.展开更多
Network structures and human behaviors are considered as two important factors in virus defense currently. However, due to ignorance of network security, normal users usually take simple activities, such as reinstalli...Network structures and human behaviors are considered as two important factors in virus defense currently. However, due to ignorance of network security, normal users usually take simple activities, such as reinstalling computer system, or using the computer recovery system to clear virus. How system recovery influences virus spreading is not taken into consideration currently. In this paper, a new virus propagation model considering the system recovery is proposed first, and then in its steady-state analysis, the virus propagation steady time and steady states are deduced. Experiment results show that models considering system recovery can effectively restrain virus propagation. Furthermore, algorithm with system recovery in BA scale-free network is proposed. Simulation result turns out that target immunization strategy with system recovery works better than traditional ones in BA network.展开更多
The recent outbreak of the human Zaire ebolavirus(EBOV)epidemic is spiraling out of control in West Africa.Human EBOV hemorrhagic fever has a case fatality rate of up to 90%.The EBOV is classified as a biosafety level...The recent outbreak of the human Zaire ebolavirus(EBOV)epidemic is spiraling out of control in West Africa.Human EBOV hemorrhagic fever has a case fatality rate of up to 90%.The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention,with no approved therapies and vaccines available for its treatment apart from supportive care.Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial,the current epidemic might be outpacing the speed at which drugs and vaccines can be produced.Like all viruses,the EBOV largely relies on host cell factors and physiological processes for its entry,replication,and egress.We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies.Most of the therapeutic agents in this review are directed against non-mutable targets of the host,which is independent of viral mutation.These medications are approved by the Food and Drug Administration(FDA)for the treatment of other diseases.They are available and stockpileable for immediate use.They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.展开更多
基金supported by grants from the National key research and development plan of China[2016TFC1202700,2016YFC1200903,and 2017YFC1200503]China Mega-Project for Infectious Disease[2017ZX10302301-004,2017ZX100101,and 2017ZX10104001]
文摘Objective Unbiased next generation sequencing（NGS） is susceptible to interference from host or environmental sequences. Consequently, background depletion and virome enrichment techniques are usually needed for clinical samples where viral load is much lower than background sequences. Methods A viral Sequence Independent Targeted Amplification（VSITA） approach using a set of non-ribosomal and virus-enriched octamers（V8） was developed and compared with traditionally used random hexamers（N6）. Forty-five archived clinical samples of different types were used in parallel to compare the V8 and N6 enrichment performance of viral sequences and removal performance of ribosomal sequences in the step of reverse transcription followed by quantitative PCR（qP CR）. Ten sera samples from patients with fever of unknown origin and 10 feces samples from patients with diarrhea of unknown origin were used in comparison of V8 and N6 enrichment performance following NGS analysis. Results A minimum 30 hexamers matching to viral reference sequences（sense and antisense） were selected from a dataset of random 4,096（4~6） hexamers（N6）. Two random nucleotides were added to the 5＇ end of the selected hexamers, and 480（30 × 4~2） octamers（V8） were obtained. In general, VSITA approach showed higher enrichment of virus-targeted c DNA and enhanced ability to remove unwanted ribosomal sequences in the majorities of 45 predefined clinical samples. Moreover, VSITA combined with NGS enabled to detect not only more viruses but also achieve more viral reads hit and higher viral genome coverage in 20 clinical samples with diarrhea or fever of unknown origin. Conclusion The VSITA approach designed in this study is demonstrated to possess higher sensitivity and broader genome coverage than traditionally used random hexamers in the NGS-based identification of viral pathogens directly from clinical samples.
基金AIDS Association of Inner Mongolia University for Nationalities,No.IMUN20190908.
文摘High genetic variability of human immunodeficiency virus(HIV)has been a major intractable challenge to the practical design of vaccines.But a recent pioneer study published in PNAS Xenobots,is likely to revolutionize HIV prevention as it presented the world's first living robot made of cells.In the advent of this discovery,we herein discuss the possibility of using living biological cell robots to target HIV-infected T lymphocytes,and the prospects of this approach being a new HIV vaccine.We capture the current research status and trend of advances in biological cell robots'design as a new HIV vaccine.The key differences between this novel vaccine and other HIV vaccines are highlighted.
文摘Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.
基金supported by China NSF(61572222, 61272405, 61272033, 61272451, 61472121)Fundamental Research Funds for the Central Universities and the open research fund of Zhejiang Provincial Key Lab of Data StorageTransmission Technology, Hangzhou Dianzi University(No. 201301)
文摘Network structures and human behaviors are considered as two important factors in virus defense currently. However, due to ignorance of network security, normal users usually take simple activities, such as reinstalling computer system, or using the computer recovery system to clear virus. How system recovery influences virus spreading is not taken into consideration currently. In this paper, a new virus propagation model considering the system recovery is proposed first, and then in its steady-state analysis, the virus propagation steady time and steady states are deduced. Experiment results show that models considering system recovery can effectively restrain virus propagation. Furthermore, algorithm with system recovery in BA scale-free network is proposed. Simulation result turns out that target immunization strategy with system recovery works better than traditional ones in BA network.
文摘The recent outbreak of the human Zaire ebolavirus(EBOV)epidemic is spiraling out of control in West Africa.Human EBOV hemorrhagic fever has a case fatality rate of up to 90%.The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention,with no approved therapies and vaccines available for its treatment apart from supportive care.Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial,the current epidemic might be outpacing the speed at which drugs and vaccines can be produced.Like all viruses,the EBOV largely relies on host cell factors and physiological processes for its entry,replication,and egress.We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies.Most of the therapeutic agents in this review are directed against non-mutable targets of the host,which is independent of viral mutation.These medications are approved by the Food and Drug Administration(FDA)for the treatment of other diseases.They are available and stockpileable for immediate use.They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.
