System Recovery-Aware Virus Propagation Model and Its Steady-State Analysis

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.

DNA vaccine expressing herpes simplex virus 1 glycoprotein C and D protects mice against herpes simplex keratitis

AIM： To investigate whether DNA vaccine encoding herpes simplex virus 1（HSV-1） glycoprotein C（g C） and glycoprotein D（g D） will achieve better protective effect against herpes simplex keratitis（HSK） than DNA vaccine encoding gD alone. METHODS： DNA vaccine expressing gD or gC combined g D（g D.g C） were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293 T cells by Western-blot. For immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2 wk interval, and two weeks after the final immunization, the specific immune responses and clinical degrees of primary HSK were evaluated. RESULTS： Fusion protein g D.g C could be expressed successfully in cultured 293 T cells. And, p RSC-g C.g DIL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral and cellular immune response in primary HSK mice evidenced by higher levels of specific neutralizing antibody and s Ig A production, enhanced cytotoxicities of splenocytes and nature killer cells（NK）,when compared with those of gD alone or mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice showed least HSK disease. CONCLUSION： gC-based DNA vaccine could effectively prevent the progress of primary HSK, suggesting that this DNA vaccine could be a promising vaccine for HSK treatment in the future.

Comparison of Immune Effect of Four Commercial Marek's Disease Vaccines in Wenchang Chicken

Marek＇s disease（MD） is a lymphoproliferative disease of domestic chickens caused by a highly infectious,oncogenic alpha-herpesvirus known as Marek＇s disease virus（MDV）.The aim of this study was to compare the efficacy of four commercial MDV vaccines in Wenchang chicken.The 1-day old Wenchang chickens tested were injected with one of four different vaccines or not unvaccinated as control;five days later,they were then challenged by virulent MDV strain MD5.The results showed that,in comparison with HVT vaccines,the CVI988 vaccine gave the immunized chickens more potent immunities against challenges of MDV strain MD5.

Conservation of T cell epitopes between seasonal influenza viruses and the novel influenza A H7N9 virus

A novel avian influenza A(H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as H5N1 and H9N2. While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. Here we demonstrate that a number of T cell epitopes are conserved between endemic H1N1 and H3N2 viruses and H7N9 virus. Most of these conserved epitopes are from viral internal proteins. The extent of conservation between endemic human seasonal influenza and avian influenza H7N9 was comparable to that with the highly pathogenic avian influenza H5N1. Thus, the ease of inter-species transmission of H7N9 viruses(compared with avian H5N1 viruses) cannot be attributed to the lack of conservation of such T cell epitopes. On the contrary, our findings predict significant T-cell based cross-reactions in the human population to the novel H7N9 virus. Our findings also have implications for H7N9 virus vaccine design.

Host genetic factors affecting hepatitis B infection outcomes:Insights from genome-wide association studies

The clinical outcome of hepatitis B virus(HBV) infection depends on the success or failure of the immune responses to HBV,and varies widely among individuals,ranging from asymptomatic self-limited infection,inactive carrier state,chronic hepatitis,cirrhosis,hepatocellular carcinoma,to liver failure,depending on the success or failure of immune response to HBV.Genome-wide association studies(GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits.In this review,we discuss GWAS for persistence of HBV infection,antibody response to hepatitis B vaccine,and HBV-related advanced liver diseases.HBV persistence is associated with multiple genes with diverse roles in immune mechanisms.The strongest associations are found within the classical human leukocyte antigen(HLA) genes,highlighting the central role of antigen presentation in the immune response to HBV.Associated variants affect both epitope binding specificities and expression levels of HLA molecules.Several other susceptibility genes regulate the magnitude of adaptive immune responses,determining immunity vs tolerance.HBV persistence and nonresponse to vaccine share the same risk variants,implying overlapping genetic bases.On the other hand,the risk variants for HBV-related advanced liver diseases are largely different,suggesting different host-virus dynamics in acute vs chronic HBV infections.The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.

Chinese Herbal Medicine for the Treatment of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome-Associated Diarrhea: A Protocol for the Systematic Review and Meta-Analysis of Randomized Clinical Trials

Diarrhea can occur at an early or advanced stage of acquired immunodeficiency syndrome(AIDS)as a usual symptom in people with human immunodeficiency virus(HIV)infection.While it is usually not fatal,it can influence patients’quality of life seriously.It has shown to be efficacious and improves people’s immune status to a certain extent to treat HIV/AIDS-related diarrhea on the basis of syndrome differentiation and treatment or Chinese herbs plus conventional treatment.Therefore,it may have a good application potential.Here,we outline a protocol for the systematic review of this health-care intervention,with the aim to evaluate the beneficial effects and safety of Traditional Chinese Medicine(TCM)for patients who suffer from HIV/AIDS-associated diarrhea.Randomized controlled trials that compare Chinese herbs with placebo or other effective treatments will be searched and included,in spite of publication status or language.The primary outcomes include diarrhea frequency and fecal character.The databases we will search as follows:China Science and Technology Journal Database(VIP),Chinese Biomedical Literature Database(Sino Med),Wanfang Data,China National Knowledge Infrastructure,Pub Med and the CENTRAL in Cochrane Library.Two authors will respectively conduct the screening of trials,data extraction,and use the Cochrane risk of bias tool to assess the methodological quality.We will analyze the data and perform a meta-analysis if possible.We intend to identify potential therapeutic modalities that may be of benefit to inform clinical practice by supplying existing evidence of the helpful effects and safety of TCM to treat patients suffering from HIV/AIDS-associated diarrhea.

An update: Epstein-Barr virus and immune evasion via microRNA regulation

Epstein-Barr virus(EBV) is an oncogenic virus that ubiquitously establishes life-long persistence in humans. To ensure its survival and maintain its B cell transformation function, EBV has developed powerful strategies to evade host immune responses. Emerging evidence has shown that micro RNAs(mi RNAs) are powerful regulators of the maintenance of cellular homeostasis. In this review, we summarize current progress on how EBV utilizes mi RNAs for immune evasion. EBV encodes mi RNAs targeting both viral and host genes involved in the immune response. The mi RNAs are found in two gene clusters, and recent studies have demonstrated that lack of these clusters increases the CD4^+ and CD8^+ T cell response of infected cells. These reports strongly indicate that EBV mi RNAs are critical for immune evasion. In addition, EBV is able to dysregulate the expression of a variety of host mi RNAs, which influence multiple immune-related molecules and signaling pathways. The transport via exosomes of EBV-regulated mi RNAs and viral proteins contributes to the construction and modification of the inflammatory tumor microenvironment.During EBV immune evasion, viral proteins, immune cells, chemokines, pro-inflammatory cytokines, and pro-apoptosis molecules are involved. Our increasing knowledge of the role of mi RNAs in immune evasion will improve the understanding of EBV persistence and help to develop new treatments for EBV-associated cancers and other diseases.

Retroviral integrase protein and intasome nucleoprotein complex structures

Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase(IN) protein. IN catalyzes two distinct chemical reactions: 3'-processing, whereby the viral DNA is recessed by a di- or trinucleotide at its 3'-ends, and strand transfer, in which the processed viral DNA ends are inserted into host chromosomal DNA. Although IN has been studied as a recombinant protein since the 1980 s, detailed structural understanding of its catalytic functions awaited high resolution structures of functional IN-DNA complexes or intasomes, initially obtained in 2010 for the spumavirus prototype foamy virus(PFV). Since then, two additional retroviral intasome structures, from the α-retrovirus Rous sarcoma virus(RSV) and β-retrovirus mouse mammary tumor virus(MMTV), have emerged. Here, we briefly review the history of IN structural biology prior to the intasome era, and then compare the intasome structures of PFV, MMTV and RSV in detail. Whereas the PFV intasome is characterized by a tetrameric assembly of IN around the viral DNA ends, the newer structures harbor octameric IN assemblies. Although the higher order architectures of MMTV and RSV intasomes differ from that of the PFV intasome, they possess remarkably similar intasomal core structures. Thus, retroviral integration machineries have adapted evolutionarily to utilize disparate IN elements to construct convergent intasome core structures for catalytic function.

Testing Point of Care Portable Data Capture in a Hospital HIV Transmission Prevention Programme and Experience from Computerized Patient Management in a Sub-Saharan Clinic Setting

Clinicians involved in HIV/AIDS （Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome） prevention of mother to child transmission （PMTCT） programme and research activities can benefit from the advantages that computerized systems add to medical practice even in resource constrained sub-Saharan clinic settings. Their continued use of paper based systems presents clinical data management and patient care challenges. A portable point of care data capture electronic system and a computerized clinic patient management system （CCPMS） were implemented to remedy these challenges. PMTCT report compilation was easier with the portable data collection system whose data were found to be more complete and accurate with a 0.83% error rate compared to a 4.1% error rate in the paper registers. A resounding majority of clinicians preferred using the new CCPMS with many of the view that it improved drug inventory and general clinic management with a positive effect on patient care.

Induction of T-cell immunity against Epstein-Barr virus-associated tumors by means of adenovirally transduced dendritic cells

Background Dendritic cells (DCs) are the most powerful antigen-presenting cells to induce specific T-cell immunity, which plays an important role in the body’s anti-tumor responses. In this study, we assessed the feasibility and efficacy of inducing T-cell immunity against Epstein-Barr virus (EBV)-associated tumors in vivo using dendritic cells transfected with EBV latent membrane 2A (LMP2A) recombinant adenovirus.Methods Cytokine-activated bone marrow-derived DCs transfected with EBV LMP2A recombinant adenovirus were infused into BALB/c mice. Splenic cytotoxic T-cell responses were evaluated by cytotoxicity and interferon-γ production assays. in vivo immune protection was then assessed in the mice tumor models implanted with tumor cells expressing EBV LMP2A.Results DCs transfected with EBV LMP2A recombinant adenovirus could strongly induce EBV LMP2A-specific cytotoxic T-cell responses and upregulate interferon-γ production in vivo. Vaccination using these DCs led to prolongation of overall survival rates in the mice tumor models and retarded tumor growth. Conclusions The results suggest that DCs transfected with EBV LMP2A recombinant adenovirus can serve as a feasible and effective tool for eliciting LMP2A-specific cytotoxic T-cell responses against EBV LMP2A in vivo in the treatment of EBV-associated tumors.

Genetic variation in the chemokine receptor 5 gene and course of HIV infection;review on genetics and immunological aspect

Chemokines are small protein molecules associated with various physiological events precisely in immune modulation via dhemokine receptors.The chemokine receptors are G-protein coupled receptors express mainly on the cell surface of immune cells.Retrovi-ruses,including HIV in the early stage of infection,primarily target chemokines receptors and get intemalized easily into immune cells;T cell and escape from immune surveillance.HIV glycoprotein selectively develops an affinity for the extracellular domain of chemokines recep-tors and allows the pathogen to intemalize via CCR-5.Now,CCR-5 remains a crucial signaling pathway that can be translated into the therapeutic target by changing the receptor protein environment.Many populations have a mutation in coding and promoter regions of CCR-5,tun-ing a resistance for HIV infection.Natively,there are several mechanisms where the human genome remains in the dynamic state by changing its composition and acquiring variations.Sin-gle nucleotide polymorphism is spontaneous phenomenon responsible for precise and point mutation at the genome.Several studies have demonstrated that European and African Amer-ican populations are enriched in significant CCR5 promoter SNP(CCR5432)in the coding and promoter region as well.Now,such SNP can be an early-stage biomarker in studying HIV and other similar infections.Here,in this study,we have elucidated the role of SNP(both the pro-moter and coding region)and the fate of HIV infections.We also empathized with the genetics of such SNPs,mostly frequency and its immunological impact.