基于免疫原理的可执行文件签名验证模型的研究

病毒发现和防治策略是操作系统安全框架的重要组成部分。目前通过特征码匹配进行查杀病毒的方法通常落后于计算机病毒的发展,已经不能满足日益迫切的安全需求。文章根据生物体免疫系统检测病毒的机理,提出了一种对可执行文件签名验证的模型,通过文件签名界定“自我”和“非我”,并以此为依据完成系统中恶意代码的发现。最后介绍了在Windows操作系统下开发的基于可执行文件签名验证模型的病毒检测系统。

猪弓形虫病诊断与防治研究

凌源劳改分局下属养猪场,xx年4月30日发生以高热、呼吸困难为主症的疫病,至7月10日陆续发病101头,发病率59.41%(101/170);死亡61头,病死率60.40%(61/101);特征性病理变化为胸、腹水增多,肺水肿;病料直接涂片姬姆萨染色可检出弓形虫(滋养体),初诊为猪弓形虫病;采取对症治疗、预防的同时进行流行病学调查,临床、病理检查,小白鼠继代培养,人工接种动物发病等试验复制出具有典型症状、病理变化和病原体的病猪、羊、鸡、兔、豚鼠;排除了细菌病和猪瘟,确诊为猪弓形虫病;磺胺类药物治疗有效率达92.50%(37/40),预防有效率达97.10%(67/69)。

Neutralizing antibodies in hepatitis C virus infection

Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodiesfor control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.

Characterization of the Receptor-binding Domain of Ebola Glycoprotein in Viral Entry

Ebola virus infection causes severe hemorrhagic fever in human and non-human primates with high mortality. Viral entry/infection is initiated by binding of glycoprotein GP protein on Ebola virion to host cells, followed by fusion of virus-cell membrane also mediated by GP. Using an human immunodeficiency virus (HIV)-based pseudotyping system, the roles of 41 Ebola GP1 residues in the receptor-binding domain in viral entry were studied by alanine scanning substitutions. We identified that four residues appear to be involved in protein folding/structure and four residues are important for viral entry. An improved entry interference assay was developed and used to study the role of these residues that are important for viral entry. It was found that R64 and K95 are involved in receptor binding. In contrast, some residues such as I170 are important for viral entry, but do not play a major role in receptor binding as indicated by entry interference assay and/or protein binding data, suggesting that these residues are involved in post-binding steps of viral entry. Furthermore, our results also suggested that Ebola and Marburg viruses share a common cellular molecule for entry.

Baculovirus Host-Range

Baculoviruses are used as microbial insecticides, protein expression vectors, epitope display platforms, and most recently as vectors for gene therapy. Understanding the mechanisms that control baculovirus host-range and tissue tropisms are important for assessing their safety and for improving their properties for these biotechnology applications. In the past two decades some progress has been made and several baculovirus genes that influence host-range have been identified. Despite this progress, our understanding of the underlying mechanisms that restrict baculovirus host-range is still limited. Here we review what is currently known about baculovirus genes that influence virus host-range.

Targeting host factors:A novel rationale for the management of hepatitis C virus

Hepatitis C is recognized as a major threat to global public health. The current treatment of patients with chronic hepatitis C is the addition of ribavirin to interferon-based therapy which has limited efficacy, poor tolerability, and significant expense. New treatment options that are more potent and less toxic are much needed. Moreover, more effective treatment is an urgent priority for those who relapse or do not respond to current regimens. A major obstacle in combating hepatitis C virus （HCV） infection is that the fidelity of the viral replication machinery is notoriously low, thus enabling the virus to quickly develop mutations that resist compounds targeting viral enzymes. Therefore, an approach targeting the host cofactors, which are indispensable for the propagation of viruses, may be an ideal target for the development of antiviral agents because they have a lower rate of mutation than that of the viral genome, as long as they have no side effects to patients. Drugs targeting, for example, receptors of viral entry, host metabolism or nuclear receptors, which are factors required to complete the HCV life cycle, may be more effective in combating the viral infection. Targeting host cofactors of the HCV life cycle is an attractive concept because it imposes a higher genetic barrier for resistance than direct antiviral compounds. However the principle drawback of this strategy is the greater potential for cellular toxicity.

Causal role of Helicobacter pylori infection in gastric cancer

Gastric cancer is the second most frequent cancer in the world, accounting for a large proportion of all cancer cases in Asia, Latin America, and some countries in Europe. Helicobacter pylori（H pylori） is regarded as playing a specific role in the development of atrophic gastritis, which represents the most recognized pathway in multistep intestinal-type gastric carcinogenesis. Recent studies suggest that a combination of host genetic factors, bacterial virulence factors, and environmental and lifestyle factors determine the severity of gastric damage and the eventual clinical outcome of H pylori infection. The seminal discovery of Hpylori as the leading cause of gastric cancer should lead to effective eradication strategies. Prevention of gastric cancer requires better screening strategies to identify candidates for eradication.

Pathogenetic Consequences of Cytomegalovirus-Host Co-evolution

Co-evolution has been shown to result in an adaptive reciprocal modification in the respective behaviors of interacting populations over time. In the case of host-parasite co-evolution,the adaptive behavior is most evident from the reciprocal change in fitness of host and parasite-manifested in terms of pathogen survival versus host resistance. Cytomegaloviruses and their hosts represent a pairing of populations that has co-evolved over hundreds of years. This review explores the pathogenetic consequences emerging from the behavioral changes caused by co-evolutionary forces on the virus and its host.

Interplay among cellular polarization,lipoprotein metabolism and hepatitis C virus entry

Hepatitis C virus (HCV) infects more than three million new individuals worldwide each year. In a high percent age of patients, acute infections become chronic, eventually progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Given the lack of effective prophylactic or therapeutic vaccines, and the limited sustained virological response rates to current therapies, new approaches are needed to prevent, control, and clear HCV infection.Entry into the host cell, being the first step of the viral cycle, is a potential target for the design of new antiviral compounds. Despite the recent discovery of the tight junction-associated proteins claudin-1 and occludin as HCV co-receptors, which is an important step towards the understanding of HCV entry, the precise mechanisms are still largely unknown. In addition, increasing evidence indicates that tools that are broadly employed to study HCV infection do not accurately reflect the real process in terms of viral particle composition and host cell phenotype. Thus, systems that more closely mimic natural infection are urgently required to elucidate the mechanisms of HCV entry, which will in turn help to design antiviral strategies against this part of the infection process.

Host Cell Protein C9orf9 Promotes Viral Proliferation via Interaction with HSV-1 UL25 Protein

In light of the scarcity of reports on the interaction between HSV-1 nucleocapsid protein UL25 and its host cell proteins,the purpose of this study is to use yeast two-hybrid screening to search for cellular proteins that can interact with the UL25 protein.C9orf69,a protein of unknown function was identified.The interaction between the two proteins under physiological conditions was also confirmed by biological experiments including co-localization by fluorescence and immunoprecipitation.A preliminary study of the function of C9orf69 showed that it promotes viral proliferation.Further studies showed that C9orf69 did not influence viral multiplication efficiency by transcriptional regulation of viral genes,but indirectly promoted proliferation via interaction with UL25.

Host cellular signaling induced by influenza virus

A wide range of host cellular signal transduction pathways can be stimulated by influenza virus infection. Some of these signal transduction pathways induce the host cell's innate immune response against influenza virus, while others are essential for efficient influenza virus replication. This review examines the cellular signaling induced by influenza virus infection in host cells, including host pattern recognition receptor (PRR)-related signaling, protein kinase C (PKC), Raf/MEK/ERK and phosphatidylinositol-3-kinase (PI3K)/Akt signaling, and the corresponding effects on the host cell and/or virus, such as recognition of virus by the host cell, viral absorption and entry, viral ribonucleoprotein (vRNP) export, translation control of cellular and viral proteins, and virus-induced cell apoptosis. Research into influenza virus-induced cell signaling promotes a clearer understanding of influenza virus-host interactions and assists in the identification of novel antiviral targets and antiviral strategies.

Viral suppression of RNA silencing

Gene silencing (RNA silencing) plays a fundamental role in antiviral defense in plants, fungi and invertebrates. Viruses encode proteins that suppress gene silencing to counter host defense. Viral suppressors of RNA silencing (VSRs) have been identified from almost all plant virus genera and some viruses of insects and mammals. Recent studies have revealed that VSRs counter host defense and interfere with host gene regulation by interacting with RNA or important components of the RNA silencing pathway. Here, we review the current understanding of the complex mechanisms of VSRs that have been revealed by recent studies.

The role of virus-derived small interfering RNAs in RNA silencing in plants

Antiviral defense is one of the important roles of RNA silencing in plants. Virus-derived small interfering RNAs (vsiRNAs) are found in the infected host cells, indicating that the host RNA silencing machinery can target viral RNAs for destruction. With the development of high-throughput sequencing of vsiRNAs, recent genetic studies have shed light on the origin and composition of vsiRNAs and their potential functions in the regulation of gene expression. Here, we briefly describe the origin and biogenesis of vsiRNAs, and review the recent discoveries regarding vsiRNA-mediated RNA silencing of viral genomes and host transcripts. This will better our understanding of virus pathogenicity and RNA silencing-related host-pathogen inter- actions in plants.

The Rhinolophus affinis bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2

Bat coronavirus(CoV)RaTG13 shares the highest genome sequence identity with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)among all known coronaviruses,and also uses human angiotensin converting enzyme 2(hACE2)for virus entry.Thus,SARS-CoV-2 is thought to have originated from bat.However,whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains elusive.Here,we found that Rhinolophus affinis bat ACE2(Ra ACE2)is an entry receptor for both SARSCoV-2 and Ra TG13,although the binding of Ra ACE2 to the receptor-binding domain(RBD)of SARSCoV-2 is markedly weaker than that of h ACE2.We further evaluated the receptor activities of ACE2 s from additional 16 diverse animal species for Ra TG13,SARS-CoV,and SARS-CoV-2 in terms of S protein binding,membrane fusion,and pseudovirus entry.We found that the Ra TG13 spike(S)protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2,and seven out of sixteen different ACE2 s function as entry receptors for all three viruses,indicating that all three viruses might have broad host rages.Of note,Ra TG13 S pseudovirions can use mouse,but not pangolin ACE2,for virus entry,whereas SARS-CoV-2 S pseudovirions can use pangolin,but not mouse,ACE2 enter cells efficiently.Mutagenesis analysis revealed that residues 484 and 498 in Ra TG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2 s.Finally,two polymorphous Rhinolophous sinicus bat ACE2 s showed different susceptibilities to virus entry by Ra TG13 and SARS-CoV-2 S pseudovirions,suggesting possible coevolution.Our results offer better understanding of the mechanism of coronavirus entry,host range,and virushost coevolution.

Uncovering the mystery of Ebola virus entry: Lock and key

How Ebola virus(EBOV)enters a host cell remains intriguingly mysterious to the public.Recently,a study led by George F Gao and his colleagues has unveiled how the primed glycoprotein on the envelope of EBOV binds to its endosomal receptor Niemann-Pick C1(NPC1)molecule during the process of virus membrane fusion with the host cells,an essential step for viral entry(Wang et al.,2016).This fine resolution of the viral glycoprotein with NPC1 at the atomic level sheds light on the development of therapeutic inhibitors against EBOV infection.

Ecology of avian influenza viruses in migratory birds wintering within the Yangtze River wetlands

Migratory birds are considered natural reservoirs of avian influenza A viruses(AIVs).To further our viral ecology knowledge and understand the subsequent risk posed by wild birds,we conducted a 4-year surveillance study of AIVs in the bird wintering wetlands of the Yangtze River,China.We collected over8000 samples and isolated 122 AIV strains.Analyses were then carried out with 108 novel sequenced genomes and data were deposited in GISAID and other public databases.The results showed that the Yangtze River wintering wetlands functioned as a mixing ground,where various subtypes of AIVs were detected harboring a high diversity of nucleotide sequences;moreover,a portion of AIV gene segments were persistent inter-seasonally.Phylogenetic incongruence presented complex reassortment events and distinct patterns among various subtypes.In addition,we observed that viral gene segments in wintering wetlands were closely related to known North American isolates,indicating that intercontinental gene flow occurred.Notably,highly pathogenic H5 and low pathogenic H9 viruses,which usually circulate in poultry,were found to have crossed the poultry/wild bird interface,with the viruses introduced to wintering birds.Overall,this study represented the largest AIV surveillance effort of wild birds within the Yangtze River wintering wetlands.Surveillance data highlighted the important role of wintering wild birds in the ecology of AIVs and may enable future early warnings of novel AIV emergence.

Viral proteomics: The emerging cutting-edge of virus research

Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment.They encode a wide spectrum of multifunctional proteins,which interplay with and modify proteins in host cells.Viral genomes were chronologically the first to be sequenced.However,the corresponding viral proteomes,the alterations of host proteomes upon viral infection,and the dynamic nature of proteins,such as post-translational modifications,enzymatic cleavage,and activation or destruction by proteolysis,remain largely unknown.Emerging high-throughput techniques,in particular quantitative or semi-quantitative mass spectrometry-based proteomics analysis of viral and cellular proteomes,have been applied to define viruses and their interactions with their hosts.Here,we review the major areas of viral proteomics,including virion proteomics,structural proteomics,viral protein interactomics,and changes to the host cell proteome upon viral infection.

Virus genomes and virus-host interactions in aquaculture animals

Over the last 30 years,aquaculture has become the fastest growing form of agriculture production in the world,but its development has been hampered by a diverse range of pathogenic viruses.During the last decade,a large number of viruses from aquatic animals have been identified,and more than 100 viral genomes have been sequenced and genetically characterized.These advances are leading to better understanding about antiviral mechanisms and the types of interaction occurring between aquatic viruses and their hosts.Here,based on our research experience of more than 20 years,we review the wealth of genetic and genomic information from studies on a diverse range of aquatic viruses,including iridoviruses,herpesviruses,reoviruses,and rhabdoviruses,and outline some major advances in our understanding of virus–host interactions in animals used in aquaculture.

Sensitive semi-quantitative detection of respiratory syncytial virus by dark-field light scattering imaging of the infected host cells

A novel sensitive semi-quantitative virus detection technique was developed using the respiratory syncytial virus(RSV) as an example, through dark-field light scattering imaging of the surface state of the virusinvaded host cells. In this method, anti-RSV-antibody modified gold nanoparticles(Au NPs) could bind with the invading virus on the cell membrane of the infected host cells through the specific antibody-antigen binding. Then,the host cells could be imaged by the localized surface plasmon resonance light scattering properties of Au NPs under a dark-field light scattering microscopy, which could be further used to semi-quantify the invading virus.