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Innate immune responses in RNA viral infection

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Frontiers of Medicine 2021年第3期15卷 333-346页

作者： Qian Xu Yuting Tang Gang Huang Divisions of Pathology and Experimental Hematology and Cancer Biology Cincinnati Children’s Hospital Medical CenterCincinnatiOH 45229USA Department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

RNA viruses cause a multitude of human diseases,including several pandemic events in the past *** viral invasion,the innate immune system responds rapidly and plays a key role in activating the adaptive immune *** the innate immune system,the interactions between pathogen-associated molecular patterns and host pattern recognition receptors activate multiple signaling pathways in immune cells and induce the production of pro-inflammatory cytokines and interferons to elicit antiviral ***,dendritic cells,and natural killer cells are the principal innate immune components that exert antiviral *** this review,the current understanding of innate immunity contributing to the restriction of RNA viral infections was briefly *** the main role of immune cells in combating viral infection,the intercellular transfer of pathogen and host-derived materials and their epigenetic and metabolic interactions associated with innate immunity was *** knowledge provides an enhanced understanding of the innate immune response to RNA viral infections in general and aids in the preparation for the existing and next emerging viral infections.

关键词： innate immune viral infection intercellular signaling metabolic changes epigenetic changes

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RNAi,a new therapeutic strategy against viral infection

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Cell Research 2004年第6期14卷 460-466页

作者： Fischer L.TAN,James Q.YIN Institute of Biophysics Institute of Biophysics Chinese Academy of Sciences 15 Datun Road Beijing 100101 China. Chinese Academy of Sciences 15 Datun Road Beijing 100101 China.

RNA interference (RNAi) is an adaptive defense mechanism triggered by double-stranded RNA (dsRNA). It is a powerful reverse genetic tool that has been widely employed to silence gene expression in mammalian and human cells. RNAi-based gene therapies, especially in viral diseases have become more and more interesting and promising. Recently, small interfering RNA (siRNA) can be used to protect host from viral infection, inhibit the expression of viral antigen and accessory genes, control the transcription and replication of viral genome, hinder the assembly of viral particles, and display influences in virus-host interactions. In this review, we attempt to present recent progresses of this breakthrough technology in the above fields and summarize the possibilities of siRNA-based drugs.

关键词： RNAi siRNA viral infection gene therapy.

New animal models for hepatitis C viral infection and pathogenesis studies

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World Journal of Gastroenterology 2007年第17期13卷 2427-2435页

作者： Dina Kremsdorf Nicolas Brezillon INSERM U812 ParisFrance Pasteur Institute Paris France Université Paris Descartes Faculté de Médecine René Descartes CHU Necker Paris 75015France

Hepatitis C virus （HCV） is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma （HCC）. In man, the pathobiological changes associated with HCV infection have been attributed to both the immune system and direct viral cytopathic effects. Until now, the lack of simple culture systems to infect and propagate the virus has hampered progress in understanding the viral life cycle and pathogenesis of HCV infection, including the molecular mechanisms implicated in HCV-induced HCC. This clearly demonstrates the need to develop small animal models for the study of HCV-associated pathogenesis. This review describes and discusses the development of new HCV animal models to study viral infection and investigate the direct effects of viral protein expression on liver disease.

关键词： Hepatitis C virus viral infection Transgenicmice Pathogenesis

Memory CD8+ T cell differentiation in viral infection: A cell for all seasons

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World Journal of Gastroenterology 2007年第36期13卷 4848-4857页

作者： Henry Radziewicz Luke Uebelhoer Bertram Bengsch Arash Grakoui Emory Vaccine Center and Department of Microbiology and Immunology Department of Medicine Emory University School of Medicine Atlanta GA 30322 United States Department of Medicine University Hospital Freiburg Freiburg 79106 Germany

Chronic viral infections such as hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are major global health problems affecting more than 500 million people worldwide. Virus-specific CD8+ T cells play an important role in the course and outcome of these viral infections and it is hypothesized that altered or impaired differentiation of virus- specific CD8+ T cells contributes to the development of persistence and/or disease progression. A deeper understanding of the mechanisms responsible for functional differentiation of CD8+ T cells is essential for the generation of successful therapies aiming to strengthen the adaptive component of the immune system.

关键词： viral infection Hepatitis C virus Memory T cell phenotype Differentiation

CD49a^(+)CD49b^(+) NK cells induced by viral infection reflect an activated state of conventional NK cells

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Science China(Life Sciences) 2020年第11期63卷 1725-1733页

作者： Wenhan Li Jing Zhou Xianwei Wang Yuzhang Wu Lilin Ye Haiming Wei Rui Sun Zhigang Tian Hui Peng Division of Molecular Medicine Hefei National Laboratory for Physical Sciences at Microscalethe CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Life SciencesUniversity of Science and Technology of ChinaHefei 230027China Institue of Immunology University of Science and Technology of ChinaHefei 230027China Institute of Immunology Third Military Medical UniversityChongqing 400038China

Natural killer(NK) cells are important innate effectors that play a pivotal role in the defense against tumors and infections and participate in regulating adaptive immunity. Recent studies have revealed phenotypic and functional heterogeneity of NK ***, using murine models of acute and chronic lymphocytic choriomeningitis virus infection, we observed that a CD49a^(+)CD49b^(+) NK cell subset emerged in the liver and other tissues, and underwent vigorous expansion following viral infection,before progressively decreasing in cell number. These viral infection-induced CD49a^(+)CD49b^(+) NK cells displayed an activated and mature phenotype. Moreover, compared with liver-resident NK cells and conventional NK(cNK) cells, CD49a^(+)CD49b^(+) NK cells showed increased functional competence, as evidenced by higher amounts of IFN-γ production and stronger cytotoxic capabilities during viral infection. Generation of these CD49a^(+)CD49b^(+) NK cells was shown to be independent of the T-bet transcription factor. Adoptive transfer experiments revealed that c NK cells could convert into CD49a^(+)CD49b^(+) NK cells following viral infection. Collectively, these results suggest that viral infection-induced CD49a^(+)CD49b^(+) NK cells represent a transiently activated state of cNK cells.

关键词： NK cells liver viral infection cell activation effector function

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DVsc:An Automated Framework for Efficiently Detecting viral infection from Single-cell Transcriptomics Data

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 189-200页

作者： Fei Leng Song Mei Xiaolin Zhou Xuanshi Liu Yefeng Yuan Wenjian Xu Chongyi Hao Ruolan Guo Chanjuan Hao Wei Li Peng Zhang Beijing Key Laboratory for Genetics of Birth Defects Beijing Pediatric Research Institute/MOE Key Laboratory of Major Diseases in Children/Rare Disease CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Institute of Biomedical Engineering University of TorontoTorontoM5S 3G9Canada

Single-cell RNA sequencing(scRNA-seq)has emerged as a valuable tool for studying cellular heterogeneity in various fields,particularly in virological *** studying the viral and cellular transcriptomes,the dynamics of viral infection can be investigated at a single-cell ***,limited studies have been conducted to investigate whether RNA transcripts from clinical samples contain substantial amounts of viral RNAs,and a specific computational framework for efficiently detecting viral reads based on scRNA-seq data has not been ***,we introduce DVsc,an open-source framework for precise quantitative analysis of viral infection from single-cell transcriptomics *** applied to approximately 200 diverse clinical samples that were infected by more than 10 different viruses,DVsc demonstrated high accuracy in systematically detecting viral infection across a wide array of cell *** innovative bioinformatics pipeline could be crucial for addressing the potential effects of surreptitiously invading viruses on certain illnesses,as well as for designing novel medicines to target viruses in specific host cell subsets and evaluating the efficacy of *** supports the FASTQ format as an input and is compatible with multiple single-cell sequencing ***,it could also be applied to sequences from bulk RNA sequencing *** is available at http://62.***.32.33:5000/DVsc.

关键词： Single-cell RNA sequencing viral transcriptome Cellular transcriptome viral infection Quantitative analysis Bulk RNA sequencing

Dynamical analysis and optimal control for a delayed viral infection model

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International Journal of Biomathematics 2023年第4期16卷 21-44页

作者： Fei Li Suxia Zhang Xiaxia Xu School of Science Xi'an University of Technology Xi'an710048P.R.China

To describe the interaction between viral infection and immune response,we establish a mathematical model with intracellular delay and investigate an optimal control problem to examine the effect of antiviral *** analysis of the proposed model for the stability of equilibria and Hopf bifurcation is *** results reveal that the dynamical properties are determined by both the immune-inactivated reproduction number and the immune-activated reproduction *** the aim of minimizing the infected cells and viral load with consideration for the treatment costs,the optimal solution is discussed *** simulations are performed to suggest the optimal therapeutic strategy and compare the model-predicted consequences.

关键词： viral infection immune delay Hopf bifurcation optimal control

Global properties of nonlinear humoral immunity viral infection models

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International Journal of Biomathematics 2015年第5期8卷 53-105页

作者： A. M. Elaiw H. A1Shamrani' Department of Mathematics Faculty of Science King Abdulaziz University P. O. Box 80203 Jeddah 21589 Saudi Arabia Department of Mathematics Faculty of Science AI-Azhar University Assiut 71511 Egypt

In this paper, we consider two nonlinear models for viral infection with humoraL immu- nity. The first model contains four compartments; uninfected target cells, actively infected cells, free virus particles and B cells. The second model is a modification of the first one by including the latently infected cells. The incidence rate, removal rate of infected cells, production rate of viruses and the latent-to-active conversion rate are given by more general nonlinear functions. We have established a set of conditions on these general functions and determined two threshold parameters for each model which are sufficient to determine the global dynamics of the models. The global asymptotic stability of all equilibria of the models has been proven by using Lyapunov theory and applying LaSalle＇s invariance principle. We have performed some numerical simulations for the models with specific forms of the general functions. We have shown that, the numerical results are consistent with the theoretical results.

关键词： viral infection global stability humoral immune response Lyapunov func-tion.

Exosomes in viral infection:Effects for pathogenesis and treatment strategies

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BIOCELL 2023年第12期47卷 2597-2608页

作者： FATEMEH HEIDARI REIHANEH SEYEDEBRAHIMI PIAO YANG MOHSEN ESLAMI FARSANI SHIMA ABABZADEH NASER KALHOR HAMED MANOOCHEHRI MOHSEN SHEYKHHASAN MARYAM AZIMZADEH Anatomy Department Faculty of MedicineQom University of Medical SciencesQomIran Cellular and Molecular Research Center Qom University of Medical SciencesQomIran Department of Molecular Genetics College of Arts and SciencesThe Ohio State UniversityColumbusOH43210USA Tissue Engineering Department Faculty of MedicineQom University of Medical SciencesQomIran Department of Mesenchymal Stem Cells Academic Center for EducationCultureand Research(ACECR)Qom BranchQomIran The Persian Gulf Marine Biotechnology Research Center The Persian Gulf Biomedical Sciences Research InstituteBushehr University of Medical SciencesBushehrIran Department of Molecular Medicine and Genetics Research Center for Molecular MedicineHamadan University of Medical SciencesHamadanIran Department of Medical Laboratory Sciences Khomein University of Medical SciencesKhomeinIran Molecular and Medicine Research Center Khomein University of Medical SciencesKhomeinIran

Exosomes are small vesicles that carry molecules from one cell to *** have many features that make them interesting for research,such as their stability,low immunogenicity,size of the nanoscale,toxicity,and selective *** can also interact with viruses in diverse *** research highlights the significant role of exosomes in viral infections,particularly in the context of diseases like COVID-19,HIV,HBV and *** the intricate interplay between exosomes and the human immune system holds great promise for the development of effective antiviral *** important aspect is gaining clarity on how exosomes influence the immune system and enhance viral infectivity through their inherent *** leveraging the innate properties of exosomes,viruses exploit the machinery involved in exosome biogenesis to set replication,facilitate the spread of infection,and eliminate immune *** can either help or hinder viral infection by modulating the immune *** review summarizes the recent findings on how exosomes mediate viral infection and how they can be used for diagnosis or *** could lead to new clinical applications of exosomes in disease management.

关键词： Exosomes viral infection COVID-19 HIV HBV HCV