Sample records for viral genetic material

  1. Linking Dynamical and Population Genetic Models of Persistent Viral Infection

    E-print Network

    Kelly, John K.; Williamson, Scott; Orive, Maria E.; Smith, Marilyn S.; Holt, Robert D.

    2003-07-01

    This article develops a theoretical framework to link dynamical and population genetic models of persistent viral infection. This linkage is useful because, while the dynamical and population genetic theories have developed ...

  2. Genetic Heterogeneity of Bovine Viral Diarrhoea Virus In Italy

    Microsoft Academic Search

    E. Falcone; P. Cordioli; M. Tarantino; M. Muscillo; G. La Rosa; M. Tollis

    2003-01-01

    The genetic characteristics, of 38 field isolates of bovine viral diarrhoea virus (BVDV) collected in 1999 from sick or healthy and persistently infected cattle of dairy farms situated in northern Italy, were investigated. A partial 5'-untranslated region (5'-UTR) sequence of each isolate was determined and a phylogenetic analysis was performed. All the isolates were classified as belonging to the BVDV-1

  3. Viral Tracing of Genetically Defined Neural Circuitry

    PubMed Central

    Beier, Kevin; Cepko, Constance

    2012-01-01

    Classical methods for studying neuronal circuits are fairly low throughput. Transsynaptic viruses, particularly the pseudorabies (PRV) and rabies virus (RABV), and more recently vesicular stomatitis virus (VSV), for studying circuitry, is becoming increasingly popular. These higher throughput methods use viruses that transmit between neurons in either the anterograde or retrograde direction. Recently, a modified RABV for monosynaptic retrograde tracing was developed. (Figure 1A). In this method, the glycoprotein (G) gene is deleted from the viral genome, and resupplied only in targeted neurons. Infection specificity is achieved by substituting a chimeric G, composed of the extracellular domain of the ASLV-A glycoprotein and the cytoplasmic domain of the RABV-G (A/RG), for the normal RABV-G1. This chimeric G specifically infects cells expressing the TVA receptor1. The gene encoding TVA can been delivered by various methods2-8. Following RABV-G infection of a TVA-expressing neuron, the RABV can transmit to other, synaptically connected neurons in a retrograde direction by nature of its own G which was co-delivered with the TVA receptor. This technique labels a relatively large number of inputs (5-10%)2 onto a defined cell type, providing a sampling of all of the inputs onto a defined starter cell type. We recently modified this technique to use VSV as a transsynaptic tracer9. VSV has several advantages, including the rapidity of gene expression. Here we detail a new viral tracing system using VSV useful for probing microcircuitry with increased resolution. While the original published strategies by Wickersham et al.4 and Beier et al.9 permit labeling of any neurons that project onto initially-infected TVA-expressing-cells, here VSV was engineered to transmit only to TVA-expressing cells (Figure 1B). The virus is first pseudotyped with RABV-G to permit infection of neurons downstream of TVA-expressing neurons. After infecting this first population of cells, the virus released can only infect TVA-expressing cells. Because the transsynaptic viral spread is limited to TVA-expressing cells, presence of absence of connectivity from defined cell types can be explored with high resolution. An experimental flow chart of these experiments is shown in Figure 2. Here we show a model circuit, that of direction-selectivity in the mouse retina. We examine the connectivity of starburst amacrine cells (SACs) to retinal ganglion cells (RGCs). PMID:23117695

  4. Host genetic susceptibility, dysbiosis and viral triggers in IBD

    PubMed Central

    Sun, Lulu; Nava, Gerardo M.; Stappenbeck, Thaddeus S.

    2014-01-01

    Purpose of Review Inflammatory bowel disease (IBD) is thought to occur in genetically susceptible individuals. However, environmental factors, potentially including shifts in commensal microbiota, are also required to trigger disease. This review discusses some of the recent discoveries in host susceptibility and interaction with the microbial environment, and pinpoints key areas for advancement in our understanding of IBD pathogenesis. Recent findings Meta-analyses of genome wide association studies have uncovered many new exciting genes associated with susceptibility loci. In addition, improved methods to analyze the commensal microbiota path the way to better define dysbiosis and its potential role in disease. Lastly, identification of viral triggers in experimental systems of IBD suggests a potential role in IBD. Summary Understanding the precise microbial and immune triggers of IBD in a genetic context will hopefully lead to a better understanding of the pathogenesis of this disease and the discovery of novel therapeutic approaches including vaccines for specific viruses. PMID:21483258

  5. Materials for Non-Viral Gene Delivery

    NASA Astrophysics Data System (ADS)

    Segura, Tatiana; Shea, Lonnie D.

    2001-08-01

    Novel therapeutic strategies can be envisioned based on altering the expression level of target genes involved in cellular processes and disease progression; however, our ability to efficiently manipulate gene expression is limited. Non-viralbased gene therapy provides a relatively safe approach to increase or decrease the expression of a specific gene using DNA or antisense sequences; however, synthetic systems are required to direct plasmids and oligonucleotides to a specific tissue and to enhance cellular uptake and intracellular trafficking. Numerous materials are being developed that interact with DNA to enhance its properties (e.g. stability, charge density) and thus direct its biodistribution and facilitate cellular interactions. The development of synthetic delivery systems to manipulate gene expression efficiently is a powerful tool that will ultimately lead to novel therapeutic strategies for the treatment of numerous disorders.

  6. Genetic typing of bovine viral diarrhoea virus: evidence of an increasing number of variants in Italy

    Microsoft Academic Search

    Sara Ciulli; Elena Galletti; Mara Battilani; Alessandra Scagliarini; Arcangelo Gentile; Luigi Morganti; Santino Prosperi

    2008-01-01

    Bovine Viral Diarrhoea Virus (BVDV) is responsible worldwide for severe economic losses on cattle farms. BVDV is an RNA virus with a high genome variability having practical consequences on epidemiology, diagnosis and disease control. Genetic monitoring was suggested as the first step in BVDV control. Thirty-seven Bovine Viral Diarrhoea Viruseswereidentifiedinpersistentlyinfectedcattle,mucosaldisease-affectedanimalsandinbulkmilk,andwerechar - acterised genetically. The 5'UTR region was amplified and sequenced,

  7. AndreGratia: A Forerunner in Microbial and Viral Genetics

    Microsoft Academic Search

    James F. Crow; William F. Dove; Jean-Pierre Gratia

    riophages in connection with the study of viruses and cell biology; and (e) unknown aspects of lysogeny and When people spoke of microbes in the early 1900s, colicinogeny described long ago and possibly connected they were thinking almost exclusively of bacterial (and with new findings on imprinting in bacteria. viral) pathogens affecting humans. Of course, Antonie Microbiology has undeniably played

  8. Emergence of viral hemorrhagic septicemia virus in the North American Great Lakes region is associated with low viral genetic diversity

    USGS Publications Warehouse

    Thompson, T.M.; Batts, W.N.; Faisal, M.; Bowser, P.; Casey, J.W.; Phillips, K.; Garver, K.A.; Winton, J.; Kurath, G.

    2011-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a fish rhabdovirus that causes disease in a broad range of marine and freshwater hosts. The known geographic range includes the Northern Atlantic and Pacific Oceans, and recently it has invaded the Great Lakes region of North Ame­rica. The goal of this work was to characterize genetic diversity of Great Lakes VHSV isolates at the early stage of this viral emergence by comparing a partial glycoprotein (G) gene sequence (669 nt) of 108 isolates collected from 2003 to 2009 from 31 species and at 37 sites. Phylogenetic analysis showed that all isolates fell into sub-lineage IVb within the major VHSV genetic group IV. Among these 108 isolates, genetic diversity was low, with a maximum of 1.05% within the 669 nt region. There were 11 unique sequences, designated vcG001 to vcG011. Two dominant sequence types, vcG001 and vcG002, accounted for 90% (97 of 108) of the isolates. The vcG001 isolates were most widespread. We saw no apparent association of sequence type with host or year of isolation, but we did note a spatial pattern, in which vcG002 isolates were more prevalent in the easternmost sub-regions, including inland New York state and the St. Lawrence Seaway. Different sequence types were found among isolates from single disease outbreaks, and mixtures of types were evident within 2 isolates from ­individual fish. Overall, the genetic diversity of VHSV in the Great Lakes region was found to be extremely low, consistent with an introduction of a new virus into a geographic region with ­previously naïve host populations.

  9. Emergence of Viral hemorrhagic septicemia virus in the North American Great Lakes region is associated with low viral genetic diversity.

    PubMed

    Thompson, Tarin M; Batts, William N; Faisal, Mohamed; Bowser, Paul; Casey, James W; Phillips, Kenneth; Garver, Kyle A; Winton, James; Kurath, Gael

    2011-08-29

    Viral hemorrhagic septicemia virus (VHSV) is a fish rhabdovirus that causes disease in a broad range of marine and freshwater hosts. The known geographic range includes the Northern Atlantic and Pacific Oceans, and recently it has invaded the Great Lakes region of North America. The goal of this work was to characterize genetic diversity of Great Lakes VHSV isolates at the early stage of this viral emergence by comparing a partial glycoprotein (G) gene sequence (669 nt) of 108 isolates collected from 2003 to 2009 from 31 species and at 37 sites. Phylogenetic analysis showed that all isolates fell into sub-lineage IVb within the major VHSV genetic group IV. Among these 108 isolates, genetic diversity was low, with a maximum of 1.05% within the 669 nt region. There were 11 unique sequences, designated vcG001 to vcG011. Two dominant sequence types, vcG001 and vcG002, accounted for 90% (97 of 108) of the isolates. The vcG001 isolates were most widespread. We saw no apparent association of sequence type with host or year of isolation, but we did note a spatial pattern, in which vcG002 isolates were more prevalent in the easternmost sub-regions, including inland New York state and the St. Lawrence Seaway. Different sequence types were found among isolates from single disease outbreaks, and mixtures of types were evident within 2 isolates from individual fish. Overall, the genetic diversity of VHSV in the Great Lakes region was found to be extremely low, consistent with an introduction of a new virus into a geographic region with previously naive host populations. PMID:21991663

  10. Genetic disruption of KSHV major latent nuclear antigen LANA enhances viral lytic transcriptional program

    SciTech Connect

    Li Qiuhua [Tumor Virology Program, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229 (United States); Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229 (United States); Zhou Fuchun; Ye Fengchun [Tumor Virology Program, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229 (United States); Department of Pediatrics, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229 (United States); Gao Shoujiang [Tumor Virology Program, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229 (United States); Department of Pediatrics, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229 (United States); Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229 (United States); Department of Medicine, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229 (United States); Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229 (United States); Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229 (United States); Tumor Virology Group, Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiaohongshan, Wuhan (China)], E-mail: gaos@uthscsa.edu

    2008-09-30

    Following primary infection, KSHV establishes a lifelong persistent latent infection in the host. The mechanism of KSHV latency is not fully understood. The latent nuclear antigen (LANA or LNA) encoded by ORF73 is one of a few viral genes expressed during KSHV latency, and is consistently detected in all KSHV-related malignancies. LANA is essential for KSHV episome persistence, and regulates the expression of viral lytic genes through epigenetic silencing, and inhibition of the expression and transactivation function of the key KSHV lytic replication initiator RTA (ORF50). In this study, we used a genetic approach to examine the role of LANA in regulating KSHV lytic replication program. Deletion of LANA did not affect the expression of its adjacent genes vCyclin (ORF72) and vFLIP (ORF71). In contrast, the expression levels of viral lytic genes including immediate-early gene RTA, early genes MTA (ORF57), vIL-6 (ORF-K2) and ORF59, and late gene ORF-K8.1 were increased before and after viral lytic induction with 12-O-tetradecanoyl-phorbol-13-acetate and sodium butyrate. This enhanced expression of viral lytic genes was also observed following overexpression of RTA with or without simultaneous chemical induction. Consistent with these results, the LANA mutant cells produced more infectious virions than the wild-type virus cells did. Furthermore, genetic repair of the mutant virus reverted the phenotypes to those of wild-type virus. Together, these results have demonstrated that, in the context of viral genome, LANA contributes to KSHV latency by regulating the expression of RTA and its downstream genes.

  11. Genetic disruption of KSHV major latent nuclear antigen LANA enhances viral lytic transcriptional program.

    PubMed

    Li, Qiuhua; Zhou, Fuchun; Ye, Fengchun; Gao, Shou-Jiang

    2008-09-30

    Following primary infection, KSHV establishes a lifelong persistent latent infection in the host. The mechanism of KSHV latency is not fully understood. The latent nuclear antigen (LANA or LNA) encoded by ORF73 is one of a few viral genes expressed during KSHV latency, and is consistently detected in all KSHV-related malignancies. LANA is essential for KSHV episome persistence, and regulates the expression of viral lytic genes through epigenetic silencing, and inhibition of the expression and transactivation function of the key KSHV lytic replication initiator RTA (ORF50). In this study, we used a genetic approach to examine the role of LANA in regulating KSHV lytic replication program. Deletion of LANA did not affect the expression of its adjacent genes vCyclin (ORF72) and vFLIP (ORF71). In contrast, the expression levels of viral lytic genes including immediate-early gene RTA, early genes MTA (ORF57), vIL-6 (ORF-K2) and ORF59, and late gene ORF-K8.1 were increased before and after viral lytic induction with 12-O-tetradecanoyl-phorbol-13-acetate and sodium butyrate. This enhanced expression of viral lytic genes was also observed following overexpression of RTA with or without simultaneous chemical induction. Consistent with these results, the LANA mutant cells produced more infectious virions than the wild-type virus cells did. Furthermore, genetic repair of the mutant virus reverted the phenotypes to those of wild-type virus. Together, these results have demonstrated that, in the context of viral genome, LANA contributes to KSHV latency by regulating the expression of RTA and its downstream genes. PMID:18684478

  12. Host and Viral Genetic Correlates of Clinical Definitions of HIV-1 Disease Progression

    PubMed Central

    Rauch, Andri; Martínez, Raquel; Günthard, Huldrych F.; Garcia, Soledad; Rodríguez, Carmen; del Romero, Jorge; Telenti, Amalio; López-Galíndez, Cecilio

    2010-01-01

    Background Various patterns of HIV-1 disease progression are described in clinical practice and in research. There is a need to assess the specificity of commonly used definitions of long term non-progressor (LTNP) elite controllers (LTNP-EC), viremic controllers (LTNP-VC), and viremic non controllers (LTNP-NC), as well as of chronic progressors (P) and rapid progressors (RP). Methodology and Principal Findings We re-evaluated the HIV-1 clinical definitions, summarized in Table 1, using the information provided by a selected number of host genetic markers and viral factors. There is a continuous decrease of protective factors and an accumulation of risk factors from LTNP-EC to RP. Statistical differences in frequency of protective HLA-B alleles (p-0.01), HLA-C rs9264942 (p-0.06), and protective CCR5/CCR2 haplotypes (p-0.02) across groups, and the presence of viruses with an ancestral genotype in the “viral dating” (i.e., nucleotide sequences with low viral divergence from the most recent common ancestor) support the differences among principal clinical groups of HIV-1 infected individuals. Conclusions A combination of host genetic and viral factors supports current clinical definitions that discriminate among patterns of HIV-1 progression. The study also emphasizes the need to apply a standardized and accepted set of clinical definitions for the purpose of disease stratification and research. PMID:20552027

  13. Viral Genome Segmentation Can Result from a Trade-Off between Genetic Content and Particle Stability

    PubMed Central

    Ojosnegros, Samuel; García-Arriaza, Juan; Escarmís, Cristina; Manrubia, Susanna C.; Perales, Celia; Arias, Armando; Mateu, Mauricio García; Domingo, Esteban

    2011-01-01

    The evolutionary benefit of viral genome segmentation is a classical, yet unsolved question in evolutionary biology and RNA genetics. Theoretical studies anticipated that replication of shorter RNA segments could provide a replicative advantage over standard size genomes. However, this question has remained elusive to experimentalists because of the lack of a proper viral model system. Here we present a study with a stable segmented bipartite RNA virus and its ancestor non-segmented counterpart, in an identical genomic nucleotide sequence context. Results of RNA replication, protein expression, competition experiments, and inactivation of infectious particles point to a non-replicative trait, the particle stability, as the main driver of fitness gain of segmented genomes. Accordingly, measurements of the volume occupation of the genome inside viral capsids indicate that packaging shorter genomes involves a relaxation of the packaging density that is energetically favourable. The empirical observations are used to design a computational model that predicts the existence of a critical multiplicity of infection for domination of segmented over standard types. Our experiments suggest that viral segmented genomes may have arisen as a molecular solution for the trade-off between genome length and particle stability. Genome segmentation allows maximizing the genetic content without the detrimental effect in stability derived from incresing genome length. PMID:21437265

  14. Bovine viral diarrhoea virus genotype 1 can be separated into at least eleven genetic groups

    Microsoft Academic Search

    Š. Vil?ek; D. J. Paton; B. Durkovic; L. Strojny; G. Ibata; A. Moussa; A. Loitsch; W. Rossmanith; S. Vega; M. T. Scicluna; V. Palfi

    2001-01-01

    Summary.  ?Seventy-eight bovine viral diarrhoea viruses (BVDV) recently collected in Austria, France, Hungary, Italy, Slovakia, Spain\\u000a and UK were genetically typed in the 5?-untranslated (5?UTR) and autoprotease (Npro) regions of the pestivirus genome. Seventy-six of the isolates were BVDV-1 and two French isolates were of the BVDV-2 genotype.\\u000a Phylogenetic analysis of the 5?UTR (245?nt), including additional BVDV-1 sequences from USA, Canada,

  15. Genetic typing of bovine viral diarrhoea virus: most Slovenian isolates are of genotypes 1d and 1f

    Microsoft Academic Search

    Ivan Toplak; Torstein Sandvik; Darja Barli?-Maganja; Jože Grom; David J Paton

    2004-01-01

    A selection of 43 bovine viral diarrhoea viruses isolated from mainly persistently infected cattle on 23 Slovenian farms between 1997 and 2001 were characterised genetically. Viral RNA was extracted from infected cell cultures, reverse transcribed and amplified by PCR with primers targeting the 5?-UTR and the Npro gene, followed by direct sequencing of purified PCR products obtained for both genomic

  16. Challenges and opportunities in estimating viral genetic diversity from next-generation sequencing data

    PubMed Central

    Beerenwinkel, Niko; Günthard, Huldrych F.; Roth, Volker; Metzner, Karin J.

    2012-01-01

    Many viruses, including the clinically relevant RNA viruses HIV (human immunodeficiency virus) and HCV (hepatitis C virus), exist in large populations and display high genetic heterogeneity within and between infected hosts. Assessing intra-patient viral genetic diversity is essential for understanding the evolutionary dynamics of viruses, for designing effective vaccines, and for the success of antiviral therapy. Next-generation sequencing (NGS) technologies allow the rapid and cost-effective acquisition of thousands to millions of short DNA sequences from a single sample. However, this approach entails several challenges in experimental design and computational data analysis. Here, we review the entire process of inferring viral diversity from sample collection to computing measures of genetic diversity. We discuss sample preparation, including reverse transcription and amplification, and the effect of experimental conditions on diversity estimates due to in vitro base substitutions, insertions, deletions, and recombination. The use of different NGS platforms and their sequencing error profiles are compared in the context of various applications of diversity estimation, ranging from the detection of single nucleotide variants (SNVs) to the reconstruction of whole-genome haplotypes. We describe the statistical and computational challenges arising from these technical artifacts, and we review existing approaches, including available software, for their solution. Finally, we discuss open problems, and highlight successful biomedical applications and potential future clinical use of NGS to estimate viral diversity. PMID:22973268

  17. The recombination of genetic material

    SciTech Connect

    Low, K.B.

    1988-01-01

    Genetic recombination is the major mechanism by which new arrangements of genetic elements are produced in all living organisms, from the simplest bacterial viruses to humans. This volume presents an overview of the types of recombination found in prokaryotes and eukaryotes.

  18. A Novel Approach to Identify Candidate Prognostic Factors for Hepatitis C Treatment Response Integrating Clinical and Viral Genetic Data

    PubMed Central

    Amadoz, Alicia; González-Candelas, Fernando

    2015-01-01

    The combined therapy of pegylated interferon (IFN) plus ribavirin (RBV) has been for a long time the standard treatment for patients infected with hepatitis C virus (HCV). In the case of genotype 1, only 38%–48% of patients have a positive response to the combined treatment. In previous studies, viral genetic information has been occasionally included as a predictor. Here, we consider viral genetic variation in addition to 11 clinical and 19 viral populations and evolutionary parameters to identify candidate baseline prognostic factors that could be involved in the treatment outcome. We obtained potential prognostic models for HCV subtypes la and lb in combination as well as separately. We also found that viral genetic information is relevant for the combined treatment assessment of patients, as the potential prognostic model of joint subtypes includes 9 viral-related variables out of 11. Our proposed methodology fully characterizes viral genetic information and finds a combination of positions that modulate inter-patient variability. PMID:25780333

  19. HIV-1 neutralizing antibody response and viral genetic diversity characterized with next generation sequencing.

    PubMed

    Carter, Christoph C; Wagner, Gabriel A; Hightower, George K; Caballero, Gemma; Phung, Pham; Richman, Douglas D; Pond, Sergei L Kosakovsky; Smith, Davey M

    2015-01-01

    To better understand the dynamics of HIV-specific neutralizing antibody (NAb), we examined associations between viral genetic diversity and the NAb response against a multi-subtype panel of heterologous viruses in a well-characterized, therapy-naïve primary infection cohort. Using next generation sequencing (NGS), we computed sequence-based measures of diversity within HIV-1 env, gag and pol, and compared them to NAb breadth and potency as calculated by a neutralization score. Contemporaneous env diversity and the neutralization score were positively correlated (p=0.0033), as were the neutralization score and estimated duration of infection (EDI) (p=0.0038), and env diversity and EDI (p=0.0005). Neither early env diversity nor baseline viral load correlated with future NAb breadth and potency (p>0.05). Taken together, it is unlikely that neutralizing capability in our cohort was conditioned on viral diversity, but rather that env evolution was driven by the level of NAb selective pressure. PMID:25463602

  20. Manipulating Genetic Material in Bacteria

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Lisa Crawford, a graduate research assistant from the University of Toledo, works with Laurel Karr of Marshall Space Flight Center (MSFC) in the molecular biology laboratory. They are donducting genetic manipulation of bacteria and yeast for the production of large amount of desired protein. Photo credit: NASA/Marshall Space Flight Center (MSFC)

  1. Solving the Material Interface Reconstruction Problem using Genetic Programming

    E-print Network

    Fernandez, Thomas

    Solving the Material Interface Reconstruction Problem using Genetic Programming Jeremy Meredith-422-1197 Abstract: This paper develops enhanced material interface reconstruction techniques using genetic programming. Material interface reconstruction is the attempt to recreate high resolution material placement

  2. The Nature of Genetic Material Online Module

    NSDL National Science Digital Library

    Center for Educational Outreach and Center for Collaborative and Interactive Technologies * (Baylor College of Medicine; )

    2010-05-27

    The Nature of Genetic Material, a new resource from Baylor College of Medicineâ??s comprehensive website, BioEd Online, is one module of a three-part, interactive Web-based course called Genes, Health and Society. [The course, which explores the rapidly evolving world of genetics and genomics, can be taken free of charge for professional or personal development. Each module stands alone. Educators can work through the modules in sequence or move freely among them.

  3. Viral transduction of the neonatal brain delivers controllable genetic mosaicism for visualizing and manipulating neuronal circuits in vivo

    PubMed Central

    Kim, Ji-Yoen; Ash, Ryan T.; Ceballos-Diaz, Carolina; Levites, Yona; Golde, Todd E.; Smirnakis, Stelios M.; Jankowsky, Joanna L.

    2012-01-01

    Neonatal intraventricular injection of adeno-associated virus has been shown to transduce neurons widely throughout the brain, but its full potential for experimental neuroscience has not been adequately explored. We report a detailed analysis of the method’s versatility with an emphasis on experimental applications where tools for genetic manipulation are currently lacking. Viral injection into the neonatal mouse brain is fast, easy, and accesses regions of the brain including cerebellum and brain stem that have been difficult to target with other techniques such as electroporation. We show that viral transduction produces an inherently mosaic expression pattern that can be exploited by varying the titer to transduce isolated neurons or densely-packed populations. We demonstrate that expression of virally-encoded proteins is active much sooner than previously believed, allowing genetic perturbation during critical periods of neuronal plasticity, but is also long-lasting and stable, allowing chronic studies of aging. We harness these features to visualize and manipulate neurons in the hindbrain that have been recalcitrant to approaches commonly applied in the cortex. We show that viral labeling aids the analysis of postnatal dendritic maturation in cerebellar Purkinje neurons by allowing individual cells to be readily distinguished, and then demonstrate that the same sparse labeling allows live in vivo imaging of mature Purkinje neurons at resolution sufficient for complete analytical reconstruction. Given the rising availability of viral constructs, packaging services, and genetically modified animals, these techniques should facilitate a wide range of experiments into brain development, function, and degeneration. PMID:23347239

  4. Patenting human genetic material: refocusing the debate

    Microsoft Academic Search

    Timothy Caulfield; E. Richard Gold; Mildred K. Cho

    2000-01-01

    The biotechnology industry has become firmly established over the past twenty years and gene patents have played an important part in this phenomenon. However, concerns have been raised over the patentability of human genetic material, through public protests and international statements, but to little effect. Here we discuss some of these concerns, the patent authorities' response to them, and ways

  5. Genetic Imprint of Vaccination on Simian/Human Immunodeficiency Virus Type 1 Transmitted Viral Genomes in Rhesus Macaques

    PubMed Central

    Varela, Mariana; Verschoor, Ernst; Lai, Rachel P. J.; Hughes, Joseph; Mooj, Petra; McKinley, Trevelyan J.; Fitzmaurice, Timothy J.; Landskron, Lisa; Willett, Brian J.; Frost, Simon D. W.; Bogers, Willy M.; Heeney, Jonathan L.

    2013-01-01

    Understanding the genetic, antigenic and structural changes that occur during HIV-1 infection in response to pre-existing immunity will facilitate current efforts to develop an HIV-1 vaccine. Much is known about HIV-1 variation at the population level but little with regard to specific changes occurring in the envelope glycoprotein within a host in response to immune pressure elicited by antibodies. The aim of this study was to track and map specific early genetic changes occurring in the viral envelope gene following vaccination using a highly controlled viral challenge setting in the SHIV macaque model. We generated 449 full-length env sequences from vaccinees, and 63 from the virus inoculum. Analysis revealed a different pattern in the distribution and frequency of mutations in the regions of the envelope gene targeted by the vaccine as well as different patterns of diversification between animals in the naïve control group and vaccinees. Given the high stringency of the model it is remarkable that we were able to identify genetic changes associated with the vaccination. This work provides insight into the characterization of breakthrough viral populations in less than fully efficacious vaccines and illustrates the value of HIV-1 Env SHIV challenge model in macaques to unravel the mechanisms driving HIV-1 envelope genetic diversity in the presence of vaccine induced-responses. PMID:23967111

  6. Genetic materials at the gene engineering division, RIKEN BioResource Center.

    PubMed

    Yokoyama, Kazunari K; Murata, Takehide; Pan, Jianzhi; Nakade, Koji; Kishikawa, Shotaro; Ugai, Hideyo; Kimura, Makoto; Kujime, Yukari; Hirose, Megumi; Masuzaki, Satoko; Yamasaki, Takahito; Kurihara, Chitose; Okubo, Masato; Nakano, Yuri; Kusa, Yuka; Yoshikawa, Akiko; Inabe, Kumiko; Ueno, Kazuko; Obata, Yuichi

    2010-01-01

    Genetic materials are one of the most important and fundamental research resources for studying biological phenomena. Scientific need for genetic materials has been increasing and will never cease. Ever since it was established as RIKEN DNA Bank in 1987, the Gene Engineering Division of RIKEN BioResource Center (BRC) has been engaged in the collection, maintenance, storage, propagation, quality control, and distribution of genetic resources developed mainly by the Japanese research community. When RIKEN BRC was inaugurated in 2001, RIKEN DNA Bank was incorporated as one of its six Divisions, the Gene Engineering Division. The Gene Engineering Division was selected as a core facility for the genetic resources of mammalian and microbe origin by the National BioResource Project (NBRP) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan in 2002. With support from the scientific community, the Division now holds over 3 million clones of genetic materials for distribution. The genetic resources include cloned DNAs, gene libraries (e.g., cDNA and genomic DNA cloned into phage, cosmid, BAC, phosmid, and YAC), vectors, hosts, recombinant viruses, and ordered library sets derived from animal cells, including human and mouse cells, microorganisms, and viruses. Recently genetic materials produced by a few MEXT national research projects were transferred to the Gene Engineering Division for further dissemination. The Gene Engineering Division performs rigorous quality control of reproducibility, restriction enzyme mapping and nucleotide sequences of clones to ensure the reproducibility of in vivo and in vitro experiments. Users can easily access our genetic materials through the internet and obtain the DNA resources for a minimal fee. Not only the materials, but also information of features and technology related to the materials are provided via the web site of RIKEN BRC. Training courses are also given to transfer the technology for handling viral vectors. RIKEN BRC supports scientists around the world in the use of valuable genetic materials. PMID:20484845

  7. [Genetic analysis of Echovirus 11 isolated from patients with viral encephalitis in Longyan, China].

    PubMed

    Chen, Qianjin; Cao, Chunyuan; Zhang, Yanfeng; He, Chunrong; Luo, Zhaofu; He, Yun; Liao, Yihong; Wu, Shuixin

    2015-01-01

    This study aimed to analyse the genetically characterize isolates of Echovirus 11 from Longyan City,Fujian Province,and to reveal their genetic relationships with other isolates from China and abroad. Cerebrospinal fluid specimens from patients diagnosed with viral encephalitis or central nervous system (CNS) infections were collected from Longyan First Hospital between January and December 2011. Seven Echo11 strains were isolated and identified using the RIMV serum panel. The entire VP1 coding regions of four strains were sequenced and typed as Echo11 by an online blast program and,subsequently, phylogenet- ic analyses of the VP1 sequences of these stains and others published on GenBank were conducted. There were 600 nucleotides (nt) in each complete VP1 coding region that encoded 200 amino acids (aa). Among those four Echo11 strains, the sequence identities of nt and aa were 100% and 99%-100% respectively. And phylogenetic analyses indicate belong to subtype DS, the homology compared with DS strain (GU393713) were 93% (nt) and 99% (aa). The sequence identities for the nt and aa were 75%-76% and 90%, respectively, between the current isolates from Longyan and the Gregory prototype strain found in 1953. The sequence identity of nt and aa between the Longyan virus strains and the domestic Shandong strains isolated in 2010 were lower, at 74% and 88%-89%, respectively. However,the highest level of ho- mology was found when the Longyan strains were compared with the Netherlands strain (GU393773) found in 2007 (nt and aa identity: 94%-95% and 98%-99%, respectively). The relatively low levels of similarity between domestic isolates suggest that different transmission routes exist for Echo11 in mainland China. PMID:25997328

  8. Ring finger protein 39 genetic variants associate with HIV-1 plasma viral loads and its replication in cell culture

    PubMed Central

    2014-01-01

    Background The human immunodeficiency virus (HIV-1) exploits host proteins to complete its life cycle. Genome-wide siRNA approaches suggested that host proteins affect HIV-1 replication. However, the results barely overlapped. RING finger protein 39 (RNF39) has been identified from genome-wide association studies. However, its function during HIV-1 replication remains unclear. Methods and results We investigated the relationship between common RNF39 genetic variants and HIV-1 viral loads. The effect of RNF39 protein knockdown or overexpression on HIV-1 replication was then investigated in different cell lines. Two genetic variants were associated with HIV-1 viral loads. Patients with the ht1-GG/GG haplotype presented lower RNF39 expression levels and lower HIV-1 viral load. RNF39 knockdown inhibited HIV-1 expression. Conclusions RNF39 protein may be involved in HIV-1 replication as observed in genetic studies on patients with HIV-1 and in in vitro cell cultures. PMID:25126410

  9. Genetic Analysis and Expression of NS3 Gene of Bovine Viral Diarrhoea Virus 1 from India for Detection of Antibodies in Cattle

    Microsoft Academic Search

    N. Mishra; S. S. Pitale; H. K. Pradhan

    2008-01-01

    Mishra, N., Pitale, S.S. and Pradhan, H.K. 2008. Genetic analysis and expression of NS3 gene of bovine viral diarrhoea virus 1 from India for detection of antibodies in cattle. J. Appl. Anim. Res., 33: 99–103.Considering the importance of NS3 antigen in diagnosis of bovine viral diarrhea virus (BVDV) infection, we analysed genetically selected Indian isolates in NS3 gene region and

  10. Genetic Variability of Bovine Viral Diarrhea Virus and Evidence for a Possible Genetic Bottleneck during Vertical Transmission in Persistently Infected Cattle

    PubMed Central

    Orsel, Karin; van Marle, Guido; van der Meer, Frank

    2015-01-01

    Bovine viral diarrhea virus (BVDV), a Pestivirus in the family Flaviviridae, is an economically important pathogen of cattle worldwide. The primary propagators of the virus are immunotolerant persistently infected (PI) cattle, which shed large quantities of virus throughout life. Despite the absence of an acquired immunity against BVDV in these PI cattle there are strong indications of viral variability that are of clinical and epidemiological importance. In this study the variability of E2 and NS5B sequences in multiple body compartments of PI cattle were characterized using clonal sequencing. Phylogenetic analyses revealed that BVDV exists as a quasispecies within PI cattle. Viral variants were clustered by tissue compartment significantly more often than expected by chance alone with the central nervous system appearing to be a particularly important viral reservoir. We also found strong indications for a genetic bottleneck during vertical transmission from PI animals to their offspring. These quasispecies analyses within PI cattle exemplify the role of the PI host in viral propagation and highlight the complex dynamics of BVDV pathogenesis, transmission and evolution. PMID:26132819

  11. A Drosophila Model for Genetic Analysis of Influenza Viral/Host Interactions

    PubMed Central

    Adamson, Amy L.; Chohan, Kultaran; Swenson, Jennifer; LaJeunesse, Dennis

    2011-01-01

    Influenza viruses impose a constant threat to vertebrates susceptible to this family of viruses. We have developed a new tool to study virus–host interactions that play key roles in viral replication and to help identify novel anti-influenza drug targets. Via the UAS/Gal4 system we ectopically expressed the influenza virus M2 gene in Drosophila melanogaster and generated dose-sensitive phenotypes in the eye and wing. We have confirmed that the M2 proton channel is properly targeted to cell membranes in Drosophila tissues and functions as a proton channel by altering intracellular pH. As part of the efficacy for potential anti-influenza drug screens, we have also demonstrated that the anti-influenza drug amantadine, which targets the M2 proton channel, suppressed the UAS-M2 mutant phenotype when fed to larvae. In a candidate gene screen we identified mutations in components of the vacuolar V1V0 ATPase that modify the UAS-M2 phenotype. Importantly, in this study we demonstrate that Drosophila genetic interactions translate directly to physiological requirements of the influenza A virus for these components in mammalian cells. Overexpressing specific V1 subunits altered the replication capacity of influenza virus in cell culture and suggests that drugs targeting the enzyme complex via these subunits may be useful in anti-influenza drug therapies. Moreover, this study adds credence to the idea of using the M2 “flu fly” to identify new and previously unconsidered cellular genes as potential drug targets and to provide insight into basic mechanisms of influenza virus biology. PMID:21775472

  12. Re-emergence of vesicular stomatitis in the western United States is associated with distinct viral genetic lineages.

    PubMed

    Rodriguez, L L; Bunch, T A; Fraire, M; Llewellyn, Z N

    2000-05-25

    Phylogenetic analysis of partial phosphoprotein and glycoprotein gene sequences showed that a single genetic lineage of vesicular stomatitis virus (VSV) serotype New Jersey (NJ) caused the 1995 and 1997 outbreaks of vesicular stomatitis (VS) in the western United States. While distinct from VSV-NJ strains causing previous outbreaks in the western United States and those circulating in feral swine in the southeastern United States, this lineage was closely related to viral lineages circulating in the Mexican states of Guerrero, Veracruz, and Oaxaca in 1996, 1989, and 1984 respectively. In 1997 and 1998, VSV serotype Indiana 1 (IN1) re-emerged in the western United States after 30 years. Viruses causing these outbreaks grouped within a single genetic lineage distinct from VSV-IN1 isolates causing outbreaks in the western United States in 1929 and 1956 but closely related to a strain circulating in the state of Colima in central Mexico in 1997. Our data showed that sporadic VS outbreaks in the western United States are caused by genetically distinct viral lineages closer to those circulating in enzootic areas of central and southern Mexico than to those causing previous outbreaks in the United States. The genetic evidence and temporal distribution of outbreaks are not consistent with a pattern of long-term maintenance of VSV in the western United States. PMID:10814582

  13. Natural and genetically engineered viral agents for oncolysis and gene therapy of human cancers

    Microsoft Academic Search

    Joseph G. Sinkovics; Joseph C. Horvath

    2008-01-01

    Based on personal acquaintances and experience dating back to the early 1950s, the senior author reviews the history of viral\\u000a therapy of cancer. He points out the difficulties encountered in the treatment of human cancers, as opposed by the highly\\u000a successful viral therapy of experimentally maintained tumors in laboratory animals, especially that of ascites carcinomas\\u000a in mice. A detailed account

  14. Polymorphic genetic characterization of E2 gene of bovine viral diarrhea virus in China.

    PubMed

    Lang, Yifei; Gao, Shandian; Du, Junzheng; Shao, Junjun; Cong, Guozheng; Lin, Tong; Zhao, Furong; Liu, Lihong; Chang, Huiyun

    2014-12-01

    Bovine viral diarrhea virus (BVDV) is one of the wide distributed pathogenic viruses of livestock and wild animals worldwide. E2 glycoprotein is a major structural component of the BVDV virion and plays a key role in viral attachment to host cells and inducing immune responses against viral infection. In order to gain detailed information of the E2 coding region of BVDV circulating in China, 46 positive samples were tested by RT-PCR for the E2 coding region. The 1122 nt nucleotide sequences of full-length E2 were harvested and analyzed. The results suggested that full-length E2 was an ideal target for BVDV genotyping and divided the domestic BVDV isolates into 9 subgenotypes, namely BVDV-1a, -1b1, -1c, -1d, -1o, -1m, -1p, -1q and BVDV-2a, showing great diversity. The difference of nonsynonymous and synonymous substitution rates (dN-dS) inferred both positive and purifying selection of the E2. However, combination of positive and purifying selection at different points indicated purifying selection within the complete E2. Protein properties analysis based on glycosylation sites and epitope prediction demonstrated that the biological character of E2 among individual BVDV subgenotype was similar, but may alter due to amino acid changes. For the first time, the comprehensive collection of E2 sequences of Chinese BVDV isolates was elucidated, which would provide information for future vaccine design and BVD control in China. PMID:25465669

  15. Genetic Modification of Cancer Cells Using Non-Viral, Episomal S/MAR Vectors for In Vivo Tumour Modelling

    PubMed Central

    Gowers, Kate; Harbottle, Richard Paul

    2012-01-01

    The development of genetically marked animal tumour xenografts is an area of ongoing research to enable easier and more reliable testing of cancer therapies. Genetically marked tumour models have a number of advantages over conventional tumour models, including the easy longitudinal monitoring of therapies and the reduced number of animals needed for trials. Several different methods have been used in previous studies to mark tumours genetically, however all have limitations, such as genotoxicity and other artifacts related to the usage of integrating viral vectors. Recently, we have generated an episomally maintained plasmid DNA (pDNA) expression system based on Scaffold/Matrix Attachment Region (S/MAR), which permits long-term luciferase transgene expression in the mouse liver. Here we describe a further usage of this pDNA vector with the human Ubiquitin C promoter to create stably transfected human hepatoma (Huh7) and human Pancreatic Carcinoma (MIA-PaCa2) cell lines, which were delivered into “immune deficient” mice and monitored longitudinally over time using a bioluminometer. Both cell lines revealed sustained episomal long-term luciferase expression and formation of a tumour showing the pathological characteristics of hepatocellular carcinoma (HCC) and pancreatic carcinoma (PaCa), respectively. This is the first demonstration that a pDNA vector can confer sustained episomal luciferase transgene expression in various mouse tumour models and can thus be readily utilised to follow tumour formation without interfering with the cellular genome. PMID:23110132

  16. Putting Synthesis into Biology – A Viral View of Genetic Engineering Through de novo Gene and Genome synthesis

    PubMed Central

    Mueller, Steffen; Coleman, J. Robert; Wimmer, Eckard

    2009-01-01

    The rapid improvements in DNA synthesis technology hold the potential to revolutionize biosciences in the near future. Traditional genetic engineering methods are template dependent and make extensive but laborious use of site-directed mutagenesis to explore the impact of small variations on an existing sequence “theme”. De novo gene and genome synthesis frees the investigator from the restrictions of the pre-existing template and allows for the rational design of any conceivable new sequence theme. Viruses, being amongst the simplest replicating entities, have been at the forefront of the advancing biosciences since the dawn of molecular biology. Viral genomes, especially those of RNA viruses, are relatively short, often less than 10,000 bases long, making them amenable to whole genome synthesis with the currently available technology. For this reason viruses are once again poised to lead the way in the budding field of synthetic biology – for better or worse. PMID:19318214

  17. Genetic reference materials and their application to haematology

    Microsoft Academic Search

    J. R. Hawkins; M. Hawkins; J. Boyle; E. Gray; P. Matejtschuk; P. Metcalfe

    2010-01-01

    Genetic investigations are becoming increasingly useful and widespread in many areas of human health. However, there is a worldwide lack of certified reference materials for use in genetic testing, meaning that tests are being run without well validated controls and new assays are more difficult to develop and validate. We have responded to this challenge by starting a programme of

  18. Analysis of viral (zucchini yellow mosaic virus) genetic diversity during systemic movement through a Cucurbita pepo vine.

    PubMed

    Dunham, J P; Simmons, H E; Holmes, E C; Stephenson, A G

    2014-10-13

    Determining the extent and structure of intra-host genetic diversity and the magnitude and impact of population bottlenecks is central to understanding the mechanisms of viral evolution. To determine the nature of viral evolution following systemic movement through a plant, we performed deep sequencing of 23 leaves that grew sequentially along a single Cucurbita pepo vine that was infected with zucchini yellow mosaic virus (ZYMV), and on a leaf that grew in on a side branch. Strikingly, of 112 genetic (i.e. sub-consensus) variants observed in the data set as a whole, only 22 were found in multiple leaves. Similarly, only three of the 13 variants present in the inoculating population were found in the subsequent leaves on the vine. Hence, it appears that systemic movement is characterized by sequential population bottlenecks, although not sufficient to reduce the population to a single virion as multiple variants were consistently transmitted between leaves. In addition, the number of variants within a leaf increases as a function of distance from the inoculated (source) leaf, suggesting that the circulating sap may serve as a continual source of virus. Notably, multiple mutational variants were observed in the cylindrical inclusion (CI) protein (known to be involved in both cell-to-cell and systemic movement of the virus) that were present in multiple (19/24) leaf samples. These mutations resulted in a conformational change, suggesting that they might confer a selective advantage in systemic movement within the vine. Overall, these data reveal that bottlenecks occur during systemic movement, that variants circulate in the phloem sap throughout the infection process, and that important conformational changes in CI protein may arise during individual infections. PMID:25107623

  19. Virulent Marek's Disease Virus Generated from Infectious Bacterial Artificial Chromosome Clones with Complete DNA Sequence and Implication of Viral Genetic Homogeniety in Pathogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic homogeneity of a test population is essential to precisely associate a viral genome sequence and its phenotype at the nucleotide level. However, homogeneity is not easy to achieve for Marek’s disease virus (MDV) due to its strictly cell-associated replication. To address this problem, two vi...

  20. Molecular bases of hepatic fibrogenesis - genetic and therapeutical implications in chronic viral C hepatitis.

    PubMed

    Rogoveanu, I; S?ndulescu, Daniela Larisa; Gheonea, D I; Ciurea, T; Com?nescu, Violeta

    2008-01-01

    Hepatitis C virus represents one of the major health problems of actual world, as almost 170 million of world population and 1 million persons in Romania are infected with HCV. Considering the increasing importance of HCV, it is imposed that we elucidate the molecular mechanisms, which are the base of hepatic fibrogenesis and potential targets for therapy, for diminishing progression to cirrhosis and avoid the appearance of complications. Activation of stellate cells is the main event in hepatic fibrosis. They also express almost all key components needed for the pathological degradation of matrix and that is why they play an important role not only in the production, but also in the degradation of the matrix. Recently, the worldwide research has also been oriented towards another type of cells with possible function in fibrogenesis and response to antiviral therapy: hepatic progenitor cells. The presence of hepatic progenitor cells in chronic C viral hepatitis is associated with severity of the disease, grade of fibrosis and the risk of hepatocarcinoma. Traditionally perceived as irreversible, reversibility of advanced fibrosis has been described recently in antiviral therapy trials for chronic C viral hepatitis. The favorable effect of interferon therapy on hepatic histology, including fibrosis, has been shown even in patients without sustained virusological response. During the last years, the advantages of the so-called support therapy using interferon have been demonstrated in patients with an increased rate in progression of fibrosis. Further research of the factors associated with progression of fibrosis will allow optimization of criteria for patient's antiviral therapy. PMID:18273498

  1. In Vivo Adeno-Associated Viral Vector–Mediated Genetic Engineering of White and Brown Adipose Tissue in Adult Mice

    PubMed Central

    Jimenez, Veronica; Muñoz, Sergio; Casana, Estefania; Mallol, Cristina; Elias, Ivet; Jambrina, Claudia; Ribera, Albert; Ferre, Tura; Franckhauser, Sylvie; Bosch, Fatima

    2013-01-01

    Adipose tissue is pivotal in the regulation of energy homeostasis through the balance of energy storage and expenditure and as an endocrine organ. An inadequate mass and/or alterations in the metabolic and endocrine functions of adipose tissue underlie the development of obesity, insulin resistance, and type 2 diabetes. To fully understand the metabolic and molecular mechanism(s) involved in adipose dysfunction, in vivo genetic modification of adipocytes holds great potential. Here, we demonstrate that adeno-associated viral (AAV) vectors, especially serotypes 8 and 9, mediated efficient transduction of white (WAT) and brown adipose tissue (BAT) in adult lean and obese diabetic mice. The use of short versions of the adipocyte protein 2 or uncoupling protein-1 promoters or micro-RNA target sequences enabled highly specific, long-term AAV-mediated transgene expression in white or brown adipocytes. As proof of concept, delivery of AAV vectors encoding for hexokinase or vascular endothelial growth factor to WAT or BAT resulted in increased glucose uptake or increased vessel density in targeted depots. This method of gene transfer also enabled the secretion of stable high levels of the alkaline phosphatase marker protein into the bloodstream by transduced WAT. Therefore, AAV-mediated genetic engineering of adipose tissue represents a useful tool for the study of adipose pathophysiology and, likely, for the future development of new therapeutic strategies for obesity and diabetes. PMID:24043756

  2. Globalisation and global trade influence molecular viral population genetics of Torque Teno Sus Viruses 1 and 2 in pigs.

    PubMed

    Cortey, Martí; Pileri, Emanuela; Segalés, Joaquim; Kekarainen, Tuija

    2012-04-23

    Globalisation, in terms of the rapid and free movement of people, animals and food, has created a new paradigm, increasing the range and rate of distribution of many pathogens. In the present study, Torque teno sus viruses (TTSuVs) have been used as a model to evaluate the effects of global trade on viral heterogeneity, and how the movement of live pigs can affect the distribution and composition of virus populations. Seventeen countries from different parts of the world have been screened for TTSuV1 and TTSuvV2. High levels of genetic diversity have been found as well as two new TTSuV subtypes. A small fraction of this diversity (<5%) was related with spatial structure; however the majority (>50%) was best explained by the exchange of live pigs among countries, pointing to the direct relationship between the movement of hosts and the diversity of their accompanying viruses. Taking TTSuVs as sentinels, this study revealed that the distribution and diversity of comensal microflora in live animals subjected to global trade is shaped by the commercial movements among countries. In the case of TTSuVs, it appears that commercial movements of animals are eroding the genetic composition of the virus populations that may have been present in pig herds since their domestication. PMID:22101091

  3. Unit: Genetics, Inspection Set, First Trial Materials.

    ERIC Educational Resources Information Center

    Australian Science Education Project, Toorak, Victoria.

    Most of the activities suggested in this trial version of the Genetics unit produced by the Australian Science Education Project rely on second-hand data, although one of the introductory activities suggested is based on results of a mouse breeding experiment. The unit is, therefore, expected to be suitable only for students who are capable of…

  4. Genetic diversity of recent bovine viral diarrhoea viruses from the southeast of Austria (Styria)

    Microsoft Academic Search

    Stefan Vilcek; Irene Greiser-Wilke; Branislav Durkovic; Walter Obritzhauser; Armin Deutz; Josef Köfer

    2003-01-01

    To characterise the bovine virus diarrhoea virus (BVDV) isolates circulating in the southeastern region of Austria, namely in the province of Styria, 71 blood samples collected between 1998 and 2000 from persistently infected cattle in 62 herds were subjected to genetic typing. For this, 288bp fragments from the 5? untranslated region (5?-UTR) were amplified by polymerase chain reaction after reverse

  5. Promoter Hypermethylation Profiling Identifies Subtypes of Head and Neck Cancer with Distinct Viral, Environmental, Genetic and Survival Characteristics

    PubMed Central

    Choudhury, Javed Hussain; Ghosh, Sankar Kumar

    2015-01-01

    Background Epigenetic and genetic alteration plays a major role to the development of head and neck squamous cell carcinoma (HNSCC). Consumption of tobacco (smoking/chewing) and human papilloma virus (HPV) are also associated with an increase the risk of HNSCC. Promoter hypermethylation of the tumor suppression genes is related with transcriptional inactivation and loss of gene expression. We investigated epigenetic alteration (promoter methylation of tumor-related genes/loci) in tumor tissues in the context of genetic alteration, viral infection, and tobacco exposure and survival status. Methodology The study included 116 tissue samples (71 tumor and 45 normal tissues) from the Northeast Indian population. Methylation specific polymerase chain reaction (MSP) was used to determine the methylation status of 10 tumor-related genes/loci (p16, DAPK, RASSF1, BRAC1, GSTP1, ECAD, MLH1, MINT1, MINT2 and MINT31). Polymorphisms of CYP1A1, GST (M1 & T1), XRCC1and XRCC2 genes were studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex-PCR respectively. Principal Findings Unsupervised hierarchical clustering analysis based on methylation pattern had identified two tumor clusters, which significantly differ by CpG island methylator phenotype (CIMP), tobacco, GSTM1, CYP1A1, HPV and survival status. Analyzing methylation of genes/loci individually, we have found significant higher methylation of DAPK, RASSF1, p16 and MINT31genes (P = 0.031, 0.013, 0.031 and 0.015 respectively) in HPV (+) cases compared to HPV (-). Furthermore, a CIMP-high and Cluster-1 characteristic was also associated with poor survival. Conclusions Promoter methylation profiles reflecting a correlation with tobacco, HPV, survival status and genetic alteration and may act as a marker to determine subtypes and patient outcome in HNSCC. PMID:26098903

  6. Horizontal Transfer of Genetic Material among Saccharomyces Yeasts

    PubMed Central

    Marinoni, Gaelle; Manuel, Martine; Petersen, Randi Føns; Hvidtfeldt, Jeanne; Sulo, Pavol; Piškur, Jure

    1999-01-01

    The genus Saccharomyces consists of several species divided into the sensu stricto and the sensu lato groups. The genomes of these species differ in the number and organization of nuclear chromosomes and in the size and organization of mitochondrial DNA (mtDNA). In the present experiments we examined whether these yeasts can exchange DNA and thereby create novel combinations of genetic material. Several putative haploid, heterothallic yeast strains were isolated from different Saccharomyces species. All of these strains secreted an a- or ?-like pheromone recognized by S. cerevisiae tester strains. When interspecific crosses were performed by mass mating between these strains, hybrid zygotes were often detected. In general, the less related the two parental species were, the fewer hybrids they gave. For some crosses, viable hybrids could be obtained by selection on minimal medium and their nuclear chromosomes and mtDNA were examined. Often the frequency of viable hybrids was very low. Sometimes putative hybrids could not be propagated at all. In the case of sensu stricto yeasts, stable viable hybrids were obtained. These contained both parental sets of chromosomes but mtDNA from only one parent. In the case of sensu lato hybrids, during genetic stabilization one set of the parental chromosomes was partially or completely lost and the stable mtDNA originated from the same parent as the majority of the nuclear chromosomes. Apparently, the interspecific hybrid genome was genetically more or less stable when the genetic material originated from phylogenetically relatively closely related parents; both sets of nuclear genetic material could be transmitted and preserved in the progeny. In the case of more distantly related parents, only one parental set, and perhaps some fragments of the other one, could be found in genetically stabilized hybrid lines. The results obtained indicate that Saccharomyces yeasts have a potential to exchange genetic material. If Saccharomyces isolates could mate freely in nature, horizontal transfer of genetic material could have occurred during the evolution of modern yeast species. PMID:10515941

  7. Interactions between Multiple Genetic Determinants in the 5? UTR and VP1 Capsid Control Pathogenesis of Chronic Post-Viral Myopathy caused by Coxsackievirus B1

    PubMed Central

    Sandager, Maribeth M.; Nugent, Jaime L.; Schulz, Wade L.; Messner, Ronald P.; Tam, Patricia E.

    2008-01-01

    Mice infected with coxsackievirus B1 Tucson (CVB1T) develop chronic, post-viral myopathy (PVM) with clinical manifestations of hind limb muscle weakness and myositis. The objective of the current study was to establish the genetic basis of myopathogenicity in CVB1T. Using a reverse genetics approach, full attenuation of PVM could only be achieved by simultaneously mutating four sites located at C706U in the 5? untranslated region (5? UTR) and at Y87F, V136A, and T276A in the VP1 capsid. Engineering these four myopathic determinants into an amyopathic CVB1T variant restored the ability to cause PVM. Moreover, these same four determinants controlled PVM expression in a second strain of mice, indicating that the underlying mechanism is operational in mice of different genetic backgrounds. Modeling studies predict that C706U alters both local and long-range pairing in the 5? UTR, and that VP1 determinants are located on the capsid surface. However, these differences did not affect viral titers, temperature stability, pH stability, or the antibody response to virus. These studies demonstrate that PVM develops from a complex interplay between viral determinants in the 5? UTR and VP1 capsid and have uncovered intriguing similarities between genetic determinants that cause PVM and those involved in pathogenesis of other enteroviruses. PMID:18029287

  8. Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds.

    PubMed

    Yang, Wan-Lin; Kouyos, Roger D; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Scherrer, Alexandra U; Shilaih, Mohaned; Hinkley, Trevor; Petropoulos, Christos; Bonhoeffer, Sebastian; Günthard, Huldrych F

    2015-03-01

    Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS). All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR) determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities) and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V) to 2.7/100-person-years;[0.7, 10.9] (for 215D). RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs). When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation. PMID:25798934

  9. Review of Climate, Landscape, and Viral Genetics as Drivers of the Japanese Encephalitis Virus Ecology

    PubMed Central

    Le Flohic, Guillaume; Porphyre, Vincent; Gonzalez, Jean-Paul

    2013-01-01

    The Japanese encephalitis virus (JEV), an arthropod-born Flavivirus, is the major cause of viral encephalitis, responsible for 10,000–15,000 deaths each year, yet is a neglected tropical disease. Since the JEV distribution area has been large and continuously extending toward new Asian and Australasian regions, it is considered an emerging and reemerging pathogen. Despite large effective immunization campaigns, Japanese encephalitis remains a disease of global health concern. JEV zoonotic transmission cycles may be either wild or domestic: the first involves wading birds as wild amplifying hosts; the second involves pigs as the main domestic amplifying hosts. Culex mosquito species, especially Cx. tritaeniorhynchus, are the main competent vectors. Although five JEV genotypes circulate, neither clear-cut genotype-phenotype relationship nor clear variations in genotype fitness to hosts or vectors have been identified. Instead, the molecular epidemiology appears highly dependent on vectors, hosts' biology, and on a set of environmental factors. At global scale, climate, land cover, and land use, otherwise strongly dependent on human activities, affect the abundance of JEV vectors, and of wild and domestic hosts. Chiefly, the increase of rice-cultivated surface, intensively used by wading birds, and of pig production in Asia has provided a high availability of resources to mosquito vectors, enhancing the JEV maintenance, amplification, and transmission. At fine scale, the characteristics (density, size, spatial arrangement) of three landscape elements (paddy fields, pig farms, human habitations) facilitate or impede movement of vectors, then determine how the JEV interacts with hosts and vectors and ultimately the infection risk to humans. If the JEV is introduced in a favorable landscape, either by live infected animals or by vectors, then the virus can emerge and become a major threat for human health. Multidisciplinary research is essential to shed light on the biological mechanisms involved in the emergence, spread, reemergence, and genotypic changes of JEV. PMID:24069463

  10. Genetic variation of viral protein 1 genes of field strains of waterfowl parvoviruses and their attenuated derivatives.

    PubMed

    Tsai, Hsiang-Jung; Tseng, Chun-hsien; Chang, Poa-chun; Mei, Kai; Wang, Shih-Chi

    2004-09-01

    To understand the genetic variations between the field strains of waterfowl parvoviruses and their attenuated derivatives, we analyzed the complete nucleotide sequences of the viral protein 1 (VP1) genes of nine field strains and two vaccine strains of waterfowl parvoviruses. Sequence comparison of the VP1 proteins showed that these viruses could be divided into goose parvovirus (GPV) related and Muscovy duck parvovirus (MDPV) related groups. The amino acid difference between GPV- and MDPV-related groups ranged from 13.1% to 15.8%, and the most variable region resided in the N terminus of VP2. The vaccine strains of GPV and MDPV exhibited only 1.2% and 0.3% difference in amino acid when compared with their parental field strains, and most of these differences resided in residues 497-575 of VP1, suggesting that these residues might be important for the attenuation of GPV and MDPV. When the GPV strains isolated in 1982 (the strain 82-0308) and in 2001 (the strain 01-1001) were compared, only 0.3% difference in amino acid was found, while MDPV strains isolated in 1990 (the strain 90-0219) and 1997 (the strain 97-0104) showed only 0.4% difference in amino acid. The result indicates that the genome of waterfowl parvovirus had remained highly stable in the field. PMID:15529973

  11. Multiplexed supramolecular self-assembly for non-viral gene delivery Nathan P. Gabrielson, Jianjun Cheng*

    E-print Network

    Cheng, Jianjun

    the underlying genetic causes. However, nearly 20 years since the technique was first applied in a human clinical Cheng* Department of Materials Science and Engineering, University of Illinois at Urbanae is the lack of a safe and efficient method to deliver genetic material to patient cells. While viral vectors

  12. Origin of genetic variation mutation = raw material of evolution

    E-print Network

    Dever, Jennifer A.

    is random - the chance that a particular mutation will occur is NOT influenced by whether1 Origin of genetic variation mutation = raw material of evolution Mutations generate variation without regard to their consequences for fitness Review ­ Genome, Genes & Gene expression · Genome · DNA

  13. Genetic optimization of two-material composite laminates Laurent Grosset

    E-print Network

    Coello, Carlos A. Coello

    Genetic optimization of two-material composite laminates Laurent Grosset , Satchi Venkataraman@aero.ufl.edu) Post-Doctoral Associate (satchi@aero.ufl.edu) Distinguished Professor, Fellow AIAA (haftka & Engineering Science, University of Florida, P.O.Box 116250, Gainesville, FL 32611, USA Satchi Venkataraman

  14. A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity

    USGS Publications Warehouse

    Ammayappan, Arun; Kurath, Gael; Thompson, Tarin M.; Vakharia, Vikram N.

    2011-01-01

    Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus in the family of Rhabdoviridae, causes a highly contagious disease of fresh and saltwater fish worldwide. Recently, a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. An efficient reverse genetics system was developed to generate a recombinant VHSV of genotype IVb from cloned cDNA. The recombinant VHSV (rVHSV) was comparable to the parental wild-type strain both in vitro and in vivo, causing high mortality in yellow perch (Perca flavescens). A modified recombinant VHSV was generated in which the NV gene was substituted with an enhanced green fluorescent protein gene (rVHSV-?NV-EGFP), and another recombinant was made by inserting the EGFP gene into the full-length viral clone between the P and M genes (rVHSV-EGFP). The in vitro replication kinetics of rVHSV-EGFP was similar to rVHSV; however, the rVHSV-?NV-EGFP grew 2 logs lower. In yellow perch challenges, wtVHSV and rVHSV induced 82-100% cumulative per cent mortality (CPM), respectively, whereas rVHSV-EGFP produced 62% CPM and rVHSV-?NV-EGFP caused only 15% CPM. No reversion of mutation was detected in the recovered viruses and the recombinant viruses stably maintained the foreign gene after several passages. These results indicate that the NV gene of VHSV is not essential for viral replication in vitro and in vivo, but it plays an important role in viral replication efficiency and pathogenicity. This system will facilitate studies of VHSV replication, virulence, and production of viral vectored vaccines.

  15. A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity.

    PubMed

    Ammayappan, Arun; Kurath, Gael; Thompson, Tarin M; Vakharia, Vikram N

    2011-08-01

    Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus in the family of Rhabdoviridae, causes a highly contagious disease of fresh and saltwater fish worldwide. Recently, a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. An efficient reverse genetics system was developed to generate a recombinant VHSV of genotype IVb from cloned cDNA. The recombinant VHSV (rVHSV) was comparable to the parental wild-type strain both in vitro and in vivo, causing high mortality in yellow perch (Perca flavescens). A modified recombinant VHSV was generated in which the NV gene was substituted with an enhanced green fluorescent protein gene (rVHSV-?NV-EGFP), and another recombinant was made by inserting the EGFP gene into the full-length viral clone between the P and M genes (rVHSV-EGFP). The in vitro replication kinetics of rVHSV-EGFP was similar to rVHSV; however, the rVHSV-?NV-EGFP grew 2 logs lower. In yellow perch challenges, wtVHSV and rVHSV induced 82-100% cumulative per cent mortality (CPM), respectively, whereas rVHSV-EGFP produced 62% CPM and rVHSV-?NV-EGFP caused only 15% CPM. No reversion of mutation was detected in the recovered viruses and the recombinant viruses stably maintained the foreign gene after several passages. These results indicate that the NV gene of VHSV is not essential for viral replication in vitro and in vivo, but it plays an important role in viral replication efficiency and pathogenicity. This system will facilitate studies of VHSV replication, virulence, and production of viral vectored vaccines. PMID:20936318

  16. Generation of pluripotent stem cells without the use of genetic material.

    PubMed

    Higuchi, Akon; Ling, Qing-Dong; Kumar, S Suresh; Munusamy, Murugan A; Alarfaj, Abdullah A; Chang, Yung; Kao, Shih-Hsuan; Lin, Ke-Chen; Wang, Han-Chow; Umezawa, Akihiro

    2015-01-01

    Induced pluripotent stem cells (iPSCs) provide a platform to obtain patient-specific cells for use as a cell source in regenerative medicine. Although iPSCs do not have the ethical concerns of embryonic stem cells, iPSCs have not been widely used in clinical applications, as they are generated by gene transduction. Recently, iPSCs have been generated without the use of genetic material. For example, protein-induced PSCs and chemically induced PSCs have been generated by the use of small and large (protein) molecules. Several epigenetic characteristics are important for cell differentiation; therefore, several small-molecule inhibitors of epigenetic-modifying enzymes, such as DNA methyltransferases, histone deacetylases, histone methyltransferases, and histone demethylases, are potential candidates for the reprogramming of somatic cells into iPSCs. In this review, we discuss what types of small chemical or large (protein) molecules could be used to replace the viral transduction of genes and/or genetic reprogramming to obtain human iPSCs. PMID:25365202

  17. Relevance of Baseline Viral Genetic Heterogeneity and Host Factors for Treatment Outcome Prediction in Hepatitis C Virus 1b-Infected Patients

    PubMed Central

    Saludes, Verónica; Bascuñana, Elisabet; Jordana-Lluch, Elena; Casanovas, Sònia; Ardèvol, Mercè; Soler, Esther; Planas, Ramón; Ausina, Vicente; Martró, Elisa

    2013-01-01

    Background Only about 50% of patients chronically infected with HCV genotype 1 (HCV-1) respond to treatment with pegylated interferon-alfa and ribavirin (dual therapy), and protease inhibitors have to be administered together with these drugs increasing costs and side-effects. We aimed to develop a predictive model of treatment response based on a combination of baseline clinical and viral parameters. Methodology Seventy-four patients chronically infected with HCV-1b and treated with dual therapy were studied (53 retrospectively ?training group?, and 21 prospectively ?validation group?). Host and viral-related factors (viral load, and genetic variability in the E1–E2, core and Interferon Sensitivity Determining Region) were assessed. Multivariate discriminant analysis and decision tree analysis were used to develop predictive models on the training group, which were then validated in the validation group. Principal Findings A multivariate discriminant predictive model was generated including the following variables in decreasing order of significance: the number of viral variants in the E1–E2 region, an amino acid substitution pattern in the viral core region, the IL28B polymorphism, serum GGT and ALT levels, and viral load. Using this model treatment outcome was accurately predicted in the training group (AUROC?=?0.9444; 96.3% specificity, 94.7% PPV, 75% sensitivity, 81% NPV), and the accuracy remained high in the validation group (AUROC?=?0.8148, 88.9% specificity, 90.0% PPV, 75.0% sensitivity, 72.7% NPV). A second model was obtained by a decision tree analysis and showed a similarly high accuracy in the training group but a worse reproducibility in the validation group (AUROC?=?0.9072 vs. 0.7361, respectively). Conclusions and Significance The baseline predictive models obtained including both host and viral variables had a high positive predictive value in our population of Spanish HCV-1b treatment naïve patients. Accurately identifying those patients that would respond to the dual therapy could help reducing implementation costs and additional side effects of new treatment regimens. PMID:24015264

  18. HIV-1 Genetic Diversity and Its Impact on Baseline CD4+T Cells and Viral Loads among Recently Infected Men Who Have Sex with Men in Shanghai, China

    PubMed Central

    Zhou, Leiming; Ning, Zhen; Wang, Xuqin; Yu, Xiaolei; Zhang, Wei; Shen, Fangwei; Zheng, Xiaohong; Gai, Jing; Li, Xiaoshan; Kang, Laiyi; Nyambi, Phillipe; Wang, Ying; Zhuang, Minghua; Pan, Qichao; Zhuang, Xun; Zhong, Ping

    2015-01-01

    The HIV-1 epidemic among men who have sex with men (MSM) has been spreading throughout China. Shanghai, a central gathering place for MSM, is facing a continuously increasing incidence of HIV-1 infection. In order to better understand the dynamics of HIV-1 diversity and its influence on patient’s immune status at baseline on diagnosis, 1265 newly HIV-1-infected MSM collected from January 2009 to December 2013 in Shanghai were retrospectively analyzed for genetic subtyping, CD4+T cell counts, and viral loads. HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (62.13%), CRF07_BC (24.51%), subtype B (8.06%), CRF55_01B (3.24%), CER67_01B (0.95%), CRF68_01B (0.4%), CRF08_BC (0.08%) and CRF59_01B (0.08%). Twenty-four unique recombination forms (URFs) (1.98%) were identified as well. Bayesian inference analysis indicated that the introduction of CRF01_AE strain (1997) was earlier than CRF07_BC strain (2001) into MSM population in Shanghai based on the time of the most recent common ancestor (tMRCA). Three epidemic clusters and five sub-clusters were found in CRF01_AE. Significantly lower CD4+T cell count was found in individuals infected with CRF01_AE than in those infected with CRF07_BC infection (P<0.01), whereas viral load was significantly higher those infected with CRF01_AE than with CRF07_BC (P<0.01). In addition, the patients with >45 years of age were found to have lower CD4+T cell counts and higher viral loads than the patients with <25 years of age (P<0.05). This study reveals the presence of HIV-1 subtype diversity in Shanghai and its remarkable influence on clinical outcome. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster, patient’s baseline CD4+T cell count and viral load would be of great value to monitoring of disease progression, intervention for transmission, improvement of antiretroviral therapy strategy and design of vaccines. PMID:26121491

  19. [Genetic variability of hepatitis C virus in the health area of Elche (Spain). Correlation between core antigen and viral load].

    PubMed

    Rodríguez, J C; García, J; Moya, I; Ayelo, A; Vázquez, N; Sillero, C; Royo, G

    2003-01-01

    We investigated the prevalence of the various genotypes of hepatitis C virus (HCV) in 281 patients evaluated between March, 2000 and March, 2002 in the health area of Elche. Of these patients, 55 were coinfected with human immunodeficiency virus (HIV). The genotype was related to viral load and the co-existence of HIV infection. Likewise, the relationship between these parameters and the presence of the HCV core antigen was established. The results indicate that genotype 1b was the most prevalent (38.4%) followed by genotype 3a (23.1%). Patients coinfected with HIV presented fewer infections due to group 1 genotypes (p < 0.05).Patients with HIV presented a greater viral load in all the genotypes, with genotype 3 presenting a high viral load. Detection of the HCV core antigen showed a close correlation with viral load determinations. Although not yet sufficiently assessed, determination of the HCV core antigen constitutes a simple technique that could eventually contribute to improving the management of patients with chronic HCV hepatitis. PMID:12887853

  20. Pharyngitis - viral

    MedlinePLUS

    ... pharyngitis. Pharyngitis may occur as part of a viral infection that also involves other organs, such as the ... when a sore throat is due to a viral infection. The antibiotics will not help. Using them to ...

  1. Extended Genetic Diversity of Bovine Viral Diarrhea Virus and Frequency of Genotypes and Subtypes in Cattle in Italy between 1995 and 2013

    PubMed Central

    Lauzi, Stefania; Ebranati, Erika; Giammarioli, Monica; Cannella, Vincenza; Masoero, Loretta; Canelli, Elena; Guercio, Annalisa; Caruso, Claudio; Ciccozzi, Massimo; De Mia, Gian Mario; Acutis, Pier Luigi; Zehender, Gianguglielmo

    2014-01-01

    Genetic typing of bovine viral diarrhea virus (BVDV) has distinguished BVDV-1 and BVDV-2 species and an emerging putative third species (HoBi-like virus), recently detected in southern Italy, signaling the occurrence of natural infection in Europe. Recognizing the need to update the data on BVDV genetic variability in Italy for mounting local and European alerts, a wide collection of 5? UTR sequences (n = 371) was selected to identify the frequency of genotypes and subtypes at the herd level. BVDV-1 had the highest frequency, followed by sporadic BVDV-2. No novel HoBi-like viruses were identified. Four distribution patterns of BVDV-1 subtypes were observed: highly prevalent subtypes with a wide temporal-spatial distribution (1b and 1e), low prevalent subtypes with a widespread geographic distribution (1a, 1d, 1g, 1h, and 1k) or a restricted geographic distribution (1f), and sporadic subtypes detected only in single herds (1c, 1j, and 1l). BVDV-1c, k, and l are reported for the first time in Italy. A unique genetic variant was detected in the majority of herds, but cocirculation of genetic variants was also observed. Northern Italy ranked first for BVDV introduction, prevalence, and dispersion. Nevertheless, the presence of sporadic variants in other restricted areas suggests the risk of different routes of BVDV introduction. PMID:25045658

  2. Molecular piracy: the viral link to carcinogenesis.

    PubMed

    Flaitz, C M; Hicks, M J

    1998-11-01

    The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous cell carcinoma development by enhancing activation, amplification, and overexpression of pre-existing oncogenes within neoplastic tissues. Because of the integral role of viruses in malignant transformation of host cells, innovative antiviral therapy may prevent tumour development, involute neoplastic proliferations, or arrest malignant progression. PMID:9930354

  3. Raw Sewage Harbors Diverse Viral Populations

    PubMed Central

    Cantalupo, Paul G.; Calgua, Byron; Zhao, Guoyan; Hundesa, Ayalkibet; Wier, Adam D.; Katz, Josh P.; Grabe, Michael; Hendrix, Roger W.; Girones, Rosina; Wang, David; Pipas, James M.

    2011-01-01

    ABSTRACT At this time, about 3,000 different viruses are recognized, but metagenomic studies suggest that these viruses are a small fraction of the viruses that exist in nature. We have explored viral diversity by deep sequencing nucleic acids obtained from virion populations enriched from raw sewage. We identified 234 known viruses, including 17 that infect humans. Plant, insect, and algal viruses as well as bacteriophages were also present. These viruses represented 26 taxonomic families and included viruses with single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), positive-sense ssRNA [ssRNA(+)], and dsRNA genomes. Novel viruses that could be placed in specific taxa represented 51 different families, making untreated wastewater the most diverse viral metagenome (genetic material recovered directly from environmental samples) examined thus far. However, the vast majority of sequence reads bore little or no sequence relation to known viruses and thus could not be placed into specific taxa. These results show that the vast majority of the viruses on Earth have not yet been characterized. Untreated wastewater provides a rich matrix for identifying novel viruses and for studying virus diversity. Importance At this time, virology is focused on the study of a relatively small number of viral species. Specific viruses are studied either because they are easily propagated in the laboratory or because they are associated with disease. The lack of knowledge of the size and characteristics of the viral universe and the diversity of viral genomes is a roadblock to understanding important issues, such as the origin of emerging pathogens and the extent of gene exchange among viruses. Untreated wastewater is an ideal system for assessing viral diversity because virion populations from large numbers of individuals are deposited and because raw sewage itself provides a rich environment for the growth of diverse host species and thus their viruses. These studies suggest that the viral universe is far more vast and diverse than previously suspected. PMID:21972239

  4. Viral infection

    PubMed Central

    Puigdomènech, Isabel; de Armas-Rillo, Laura; Machado, José-David

    2011-01-01

    Viruses have developed different survival strategies in host cells by crossing cell-membrane compartments, during different steps of their viral life cycle. In fact, the non-regenerative viral membrane of enveloped viruses needs to encounter the dynamic cell-host membrane, during early steps of the infection process, in which both membranes fuse, either at cell-surface or in an endocytic compartment, to promote viral entry and infection. Once inside the cell, many viruses accomplish their replication process through exploiting or modulating membrane traffic, and generating specialized compartments to assure viral replication, viral budding and spreading, which also serve to evade the immune responses against the pathogen. In this review, we have attempted to present some data that highlight the importance of membrane dynamics during viral entry and replicative processes, in order to understand how viruses use and move through different complex and dynamic cell-membrane structures and how they use them to persist. PMID:21966556

  5. Reinvestigation of the role of the rabies virus glycoprotein in viral pathogenesis using a reverse genetics approach.

    PubMed

    Morimoto, K; Foley, H D; McGettigan, J P; Schnell, M J; Dietzschold, B

    2000-10-01

    The rabies virus glycoprotein (G) gene of the highly neuroinvasive and neurotropic strains SHBRV-18, CVS-N2c, and CVS-B2c was introduced into the non-neuroinvasive and less neurotropic SN-10 strain to provide further insight into the role of G in the pathogenesis of rabies. Phenotypic analyses of the recombinant viruses revealed, as expected, that the neurotropism of a particular rabies virus strain was a function of its G. Nevertheless, the pathogenicity of the recombinant viruses was, in every case, markedly lower than that of the wild-type viruses suggesting that while the G dictates neurotropism, other viral attributes are also important in pathogenesis. The low pathogenicity of the recombinant viruses is at least in part due to a strong increase in transcription activity. On the other hand, the production of infectious virus by the R-SHB18 recombinant virus-infected cells was significantly delayed by comparison with SHBRV-18 wild-type virus infected-cells. Replacement of the R-SHB18 G cytoplasmic domain, transmembrane domain, and stem region with its SN-10 G counterparts neither results in a significant increase in budding efficiency nor an increase in pathogenicity. These results suggest that an optimal match of the cytoplasmic domain of G with the matrix protein may not be sufficient for maximal virus budding efficiency, which is evidently a major factor of virus pathogenicity. Our studies indicate that to maintain pathogenicity, the interactions between various structural elements of rabies virus must be highly conserved and the expression of viral proteins, in particular the G protein, must be strictly controlled. PMID:11031690

  6. Re-emergence of Vesicular Stomatitis in the Western United States Is Associated with Distinct Viral Genetic Lineages

    Microsoft Academic Search

    Luis L. Rodriguez; Thomas A. Bunch; Moises Fraire; Zara N. Llewellyn

    2000-01-01

    Phylogenetic analysis of partial phosphoprotein and glycoprotein gene sequences showed that a single genetic lineage of vesicular stomatitis virus (VSV) serotype New Jersey (NJ) caused the 1995 and 1997 outbreaks of vesicular stomatitis (VS) in the western United States. While distinct from VSV-NJ strains causing previous outbreaks in the western United States and those circulating in feral swine in the

  7. Genetic predisposition factors and nasopharyngeal carcinoma risk: a review of epidemiological association studies, 2000-2011: Rosetta Stone for NPC: genetics, viral infection, and other environmental factors.

    PubMed

    Hildesheim, Allan; Wang, Cheng-Ping

    2012-04-01

    While infection with Epstein-Barr virus (EBV) is known to be an essential risk factor for the development of nasopharyngeal carcinoma (NPC), other co-factors including genetic factors are thought to play an important role. In this review, we summarize association studies conducted over the past decade to evaluate the role of genetic polymorphisms in NPC development. A review of the literature identified close to 100 studies, including 3 genome-wide association studies (GWAS), since 2000 that evaluated genetic polymorphisms and NPC risk in at least 100 NPC cases and 100 controls. Consistent evidence for associations were reported for a handful of genes, including immune-related HLA Class I genes, DNA repair gene RAD51L1, cell cycle control genes MDM2 and TP53, and cell adhesion/migration gene MMP2. However, for most of the genes evaluated, there was no effort to replicate findings and studies were largely modest in size, typically consisting of no more than a few hundred cases and controls. The small size of most studies, and the lack of attempts at replication have limited progress in understanding the genetics of NPC. Moving forward, if we are to advance our understanding of genetic factors involved in the development of NPC, and of the impact of gene-gene and gene-environment interations in the development of this disease, consortial efforts that pool across multiple, well-designed and coordinated efforts will most likely be required. PMID:22300735

  8. Neuroanatomy goes viral!

    PubMed Central

    Nassi, Jonathan J.; Cepko, Constance L.; Born, Richard T.; Beier, Kevin T.

    2015-01-01

    The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist’s toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic spread, and extending the range of species that can be studied.

  9. Applications of viral nanoparticles in medicine

    PubMed Central

    Yildiz, Ibrahim; Shukla, Sourabh; Steinmetz, Nicole F.

    2011-01-01

    Several nanoparticle platforms are currently being developed for applications in medicine, including both synthetic materials and naturally-occurring bionanomaterials such as viral nanoparticles (VNPs) and their genome-free counterparts, virus-like particles (VLPs). A broad range of genetic and chemical engineering methods have been established that allow VNP/VLP formulations to carry large payloads of imaging reagents or drugs. Furthermore, targeted VNPs and VLPs can be generated by including peptide ligands on the particle surface. In this article, we highlight state-of-the-art virus engineering principles and discuss recent advances that bring potential biomedical applications a step closer. Viral nanotechnology has now come of age and it will not be long before these formulations assume a prominent role in the clinic. PMID:21592772

  10. Viral Perturbations of Host Networks Reflect Disease Etiology

    Microsoft Academic Search

    Natali Gulbahce; Han Yan; Amélie Dricot; Megha Padi; Danielle Byrdsong; Rachel Franchi; Deok-Sun Lee; Orit Rozenblatt-Rosen; Jessica C. Mar; Michael A. Calderwood; Amy Baldwin; Bo Zhao; Balaji Santhanam; Pascal Braun; Nicolas Simonis; Kyung-Won Huh; Karin Hellner; Miranda Grace; Alyce Chen; Renee Rubio; Jarrod A. Marto; Nicholas A. Christakis; Elliott Kieff; Frederick P. Roth; Jennifer Roecklein-Canfield; James A. DeCaprio; Michael E. Cusick; John Quackenbush; David E. Hill; Karl Münger; Marc Vidal; Albert-László Barabási

    2012-01-01

    Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus

  11. Viral Infections

    MedlinePLUS

    ... much smaller than bacteria. Viruses cause familiar infectious diseases such as the common cold, flu and warts. ... can help prevent you from getting many viral diseases. NIH: National Institute of Allergy and Infectious Diseases

  12. Preservation of viral genomes in 700-y-old caribou feces from a subarctic ice patch.

    PubMed

    Ng, Terry Fei Fan; Chen, Li-Fang; Zhou, Yanchen; Shapiro, Beth; Stiller, Mathias; Heintzman, Peter D; Varsani, Arvind; Kondov, Nikola O; Wong, Walt; Deng, Xutao; Andrews, Thomas D; Moorman, Brian J; Meulendyk, Thomas; MacKay, Glen; Gilbertson, Robert L; Delwart, Eric

    2014-11-25

    Viruses preserved in ancient materials provide snapshots of past viral diversity and a means to trace viral evolution through time. Here, we use a metagenomics approach to identify filterable and nuclease-resistant nucleic acids preserved in 700-y-old caribou feces frozen in a permanent ice patch. We were able to recover and characterize two viruses in replicated experiments performed in two different laboratories: a small circular DNA viral genome (ancient caribou feces associated virus, or aCFV) and a partial RNA viral genome (Ancient Northwest Territories cripavirus, or aNCV). Phylogenetic analysis identifies aCFV as distantly related to the plant-infecting geminiviruses and the fungi-infecting Sclerotinia sclerotiorum hypovirulence-associated DNA virus 1 and aNCV as within the insect-infecting Cripavirus genus. We hypothesize that these viruses originate from plant material ingested by caribou or from flying insects and that their preservation can be attributed to protection within viral capsids maintained at cold temperatures. To investigate the tropism of aCFV, we used the geminiviral reverse genetic system and introduced a multimeric clone into the laboratory model plant Nicotiana benthamiana. Evidence for infectivity came from the detection of viral DNA in newly emerged leaves and the precise excision of the viral genome from the multimeric clones in inoculated leaves. Our findings indicate that viral genomes may in some circumstances be protected from degradation for centuries. PMID:25349412

  13. Preservation of viral genomes in 700-y-old caribou feces from a subarctic ice patch

    PubMed Central

    Chen, Li-Fang; Zhou, Yanchen; Shapiro, Beth; Stiller, Mathias; Varsani, Arvind; Kondov, Nikola O.; Wong, Walt; Deng, Xutao; Andrews, Thomas D.; Moorman, Brian J.; Meulendyk, Thomas; MacKay, Glen; Gilbertson, Robert L.; Delwart, Eric

    2014-01-01

    Viruses preserved in ancient materials provide snapshots of past viral diversity and a means to trace viral evolution through time. Here, we use a metagenomics approach to identify filterable and nuclease-resistant nucleic acids preserved in 700-y-old caribou feces frozen in a permanent ice patch. We were able to recover and characterize two viruses in replicated experiments performed in two different laboratories: a small circular DNA viral genome (ancient caribou feces associated virus, or aCFV) and a partial RNA viral genome (Ancient Northwest Territories cripavirus, or aNCV). Phylogenetic analysis identifies aCFV as distantly related to the plant-infecting geminiviruses and the fungi-infecting Sclerotinia sclerotiorum hypovirulence-associated DNA virus 1 and aNCV as within the insect-infecting Cripavirus genus. We hypothesize that these viruses originate from plant material ingested by caribou or from flying insects and that their preservation can be attributed to protection within viral capsids maintained at cold temperatures. To investigate the tropism of aCFV, we used the geminiviral reverse genetic system and introduced a multimeric clone into the laboratory model plant Nicotiana benthamiana. Evidence for infectivity came from the detection of viral DNA in newly emerged leaves and the precise excision of the viral genome from the multimeric clones in inoculated leaves. Our findings indicate that viral genomes may in some circumstances be protected from degradation for centuries. PMID:25349412

  14. Prevalence Study and Genetic Typing of Bovine Viral Diarrhea Virus (BVDV) in Four Bovine Species in China

    PubMed Central

    Deng, Mingliang; Ji, Sukun; Fei, Wentao; Raza, Sohail; He, Chenfei; Chen, Yingyu; Chen, Huanchun; Guo, Aizhen

    2015-01-01

    To determine the nationwide status of persistent BVDV infection in different bovine species in China and compare different test methods, a total of 1379 serum samples from clinical healthy dairy cattle, beef cattle, yaks (Bos grunniens), and water buffalo (Bubalus bubalis) were collected in eight provinces of China from 2010 to 2013. The samples were analyzed using commercial antibody (Ab) and antigen (Ag) detection kits, and RT-PCR based on the 5’-UTR and Npro gene sequencing. Results showed that the overall positive rates for BVDV Ab, Ag and RT-PCR detection were 58.09% (801/1379), 1.39% (14/1010), and 22.64% (146/645), respectively, while the individual positive rates varied among regions, species, and farms. The average Ab-positive rates for dairy cattle, beef cattle, yaks, and water buffalo were 89.49% (298/333), 63.27% (248/392), 45.38% (236/520), and 14.18% (19/134), respectively, while the Ag-positive rates were 0.00% (0/116), 0.77% (3/392), 0.82% (3/368), and 5.97% (8/134), respectively, and the nucleic acid-positive rates detected by RT-PCR were 32.06% (42/131), 13.00% (26/200), 28.89% (52/180), and 19.40% (26/134), respectively. In addition, the RT-PCR products were sequenced and 124 5’-UTR sequences were obtained. Phylogenetic analysis of the 5’-UTR sequences indicated that all of the 124 BVDV-positive samples were BVDV-1 and subtyped into either BVDV-1b (33.06%), BVDV-1m (49.19%), or a new cluster, designated as BVDV-1u (17.74%). Phylogenetic analysis based on Npro sequences confirmed this novel subtype. In conclusion, this study revealed the prevalence of BVDV-1 in bovine species in China and the dominant subtypes. The high proportion of bovines with detectable viral nucleic acids in the sera, even in the presence of high Ab levels, revealed a serious threat to bovine health. PMID:25849315

  15. Molecular genetic analysis of human herpes virus 8-encoded viral FLICE inhibitory protein-induced NF-kappaB activation.

    PubMed

    Matta, Hittu; Sun, Qinmiao; Moses, Gregory; Chaudhary, Preet M

    2003-12-26

    The human herpes virus 8 (HHV8)-encoded viral FLICE inhibitory protein (vFLIP), also known as K13, is known to activate the NF-kappaB pathway, a property not shared by other vFLIPs. Previous studies have demonstrated that HHV8 vFLIP K13 interacts with several cellular signaling proteins involved in NF-kappaB activation, such as receptor-interacting protein, NF-kappaB-inducing kinase, IkappaB kinase (IKK) 1, IKK2, and NF-kappaB essential modulator (NEMO). In this report we have used cell lines deficient in the above proteins to investigate the mechanism of NF-kappaB activation via HHV8 vFLIP K13. We demonstrate that receptor-interacting protein and NF-kappaB-inducing kinase are dispensable for vFLIP K13-induced NF-kappaB DNA binding and transcriptional activation. On the other hand, vFLIP K13-induced NF-kappaB DNA binding activity is significantly reduced, although not absent, in cells deficient in IKK1, IKK2, and NEMO. Furthermore, vFLIP K13-induced NF-kappaB transcriptional activity is only weakly present in IKK1-deficient cells and almost completely absent in those deficient in IKK2 and NEMO. HHV8 vFLIP K13-induced NF-kappaB activation in IKK1- and IKK2-deficient fibroblasts could be rescued by wild type but not by the kinase-inactive mutants of IKK1 and IKK2, respectively. Consistent with the above results, vFLIP K13-induced NF-kappaB activation could be effectively blocked by chemical inhibitors of the kinase activity of IKK1 and IKK2. Thus, a cooperative interaction of all three subunits of the IKK complex is required for maximal NF-kappaB activation via HHV8 vFLIP K13. Selective inhibitors of the IKK1 kinase activity may have a role in the treatment of disorders caused by abnormal NF-kappaB activation by HHV8 vFLIP K13. PMID:14561765

  16. Viral vectors for gene delivery and gene therapy within the endocrine system

    Microsoft Academic Search

    D Stone; A David; F Bolognani; P R Lowenstein; M G Castro

    2000-01-01

    The transfer of genetic material into endocrine cells and tissues, both in vitro and in vivo, has been identified as critical for the study of endocrine mechanisms and the future treat- ment of endocrine disorders. Classical methods of gene transfer, such as transfection, are inefficient and limited mainly to delivery into actively proliferating cells in vitro. The development of viral

  17. Genetically engineered polypeptides for inorganics: A utility in biological materials science and engineering

    Microsoft Academic Search

    Candan Tamerler; Turgay Kacar; Deniz Sahin; Hanson Fong; Mehmet Sarikaya

    2007-01-01

    Adapting molecular biology to materials science we developed peptide-based protocols for the assembly and formation of hybrid materials and systems. In this approach of generating molecular scale biomimetic materials, peptides are designed, synthesized, genetically tailored and, finally, utilized as potential molecular linkers in self-assembly, ordered organization, and fabrication of inorganics for specific technological applications. The potential areas range from molecular

  18. Privacy and Property? Multi-level Strategies for Protecting Personal Interests in Genetic Material 

    E-print Network

    Laurie, Graeme

    2003-01-01

    The paper builds on earlier medico-legal work by Laurie on privacy in relation to genetic material. In this chapter, the author discusses not only Laurie's views as 'pro-privacy' but the limitations of privacy, particularly once information...

  19. Phytopathological and molecular genetic identification of leaf rust resistance genes in common wheat accessions with alien genetic material

    Microsoft Academic Search

    N. R. Gajnullin; I. F. Lapochkina; A. I. Zhemchuzhina; M. I. Kiseleva; T. M. Kolomiets; E. D. Kovalenko

    2007-01-01

    Leaf rust resistance genes were sought in 23 resistant common wheat accessions with alien genetic material of Aegilops speltoides, Ae. triuncialis, and Triticum kiharae from the Arsenal collection. The genes were identified by common phytopathological tests and PCR analysis with STS markers\\u000a linked with the known Lr genes. None of the methods identified the resistance genes in two accessions. In

  20. Greenberg v. Miami Children 's Hospital: unjust enrichment and the patenting of human genetic material.

    PubMed

    Greenfield, Debra L

    2006-01-01

    Individuals and societal groups are questioning the practice of patenting human genetic material in the context of medical research and health care, where diverse ethical, social, and political objections are being raised by critics. A recent case provides a broad legal theory, the common law cause of action, unjust enrichment, and a precedent for challenging the commercialization and patenting of human genetic material. PMID:17554842

  1. Genetic optimization of two-material composite laminates

    Microsoft Academic Search

    Laurent Grosset; Satchi Venkataraman; Raphael T. Haftka

    This paper describes the optimization of a composite laminate made from two materials. The use of two materials in the laminates design can offer improved designs, as it is possible to combine the desirable properties of the two materials. In this paper, we consider the use of graphite-epox y, which has high stiffness properties, but is expensive, and glass-epoxy, which

  2. The contribution of viral genotype to plasma viral set-point in HIV infection.

    PubMed

    Hodcroft, Emma; Hadfield, Jarrod D; Fearnhill, Esther; Phillips, Andrew; Dunn, David; O'Shea, Siobhan; Pillay, Deenan; Leigh Brown, Andrew J

    2014-05-01

    Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8-8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms. PMID:24789308

  3. Gene therapy for viral hepatitis.

    PubMed

    Gonzalez-Aseguinolaza, Gloria; Crettaz, Julien; Ochoa, Laura; Otano, Itziar; Aldabe, Rafael; Paneda, Astrid

    2006-12-01

    Hepatitis B and C infections are two of the most prevalent viral diseases in the world. Existing therapies against chronic viral hepatitis are far from satisfactory due to low response rates, undesirable side effects and selection of resistant viral strains. Therefore, new therapeutic approaches are urgently needed. This review, after briefly summarising the in vitro and in vivo systems for the study of both diseases and the genetic vehicles commonly used for liver gene transfer, examines the existing status of gene therapy-based antiviral strategies that have been employed to prevent, eliminate or reduce viral infection. In particular, the authors focus on the results obtained in clinical trials and experimental clinically relevant animal models. PMID:17223736

  4. Microfluidic Fabrication of Hydrogel Microparticles Containing Functionalized Viral Nanotemplates

    E-print Network

    Lewis, Christina L.

    We demonstrate rapid microfluidic fabrication of hybrid microparticles composed of functionalized viral nanotemplates directly embedded in polymeric hydrogels. Specifically, genetically modified tobacco mosaic virus (TMV) ...

  5. Genetic algorithms and genetic programming for multiscale modeling: Applications in materials science and chemistry and advances in scalability

    NASA Astrophysics Data System (ADS)

    Sastry, Kumara Narasimha

    2007-03-01

    Effective and efficient rnultiscale modeling is essential to advance both the science and synthesis in a, wide array of fields such as physics, chemistry, materials science; biology, biotechnology and pharmacology. This study investigates the efficacy and potential of rising genetic algorithms for rnultiscale materials modeling and addresses some of the challenges involved in designing competent algorithms that solve hard problems quickly, reliably and accurately. In particular, this thesis demonstrates the use of genetic algorithms (GAs) and genetic programming (GP) in multiscale modeling with the help of two non-trivial case studies in materials science and chemistry. The first case study explores the utility of genetic programming (GP) in multi-timescaling alloy kinetics simulations. In essence, GP is used to bridge molecular dynamics and kinetic Monte Carlo methods to span orders-of-magnitude in simulation time. Specifically, GP is used to regress symbolically an inline barrier function from a limited set of molecular dynamics simulations to enable kinetic Monte Carlo that simulate seconds of real time. Results on a non-trivial example of vacancy-assisted migration on a surface of a face-centered cubic (fcc) Copper-Cobalt (CuxCo 1-x) alloy show that GP predicts all barriers with 0.1% error from calculations for less than 3% of active configurations, independent of type of potentials used to obtain the learning set of barriers via molecular dynamics. The resulting method enables 2--9 orders-of-magnitude increase in real-time dynamics simulations taking 4--7 orders-of-magnitude less CPU time. The second case study presents the application of multiobjective genetic algorithms (MOGAs) in multiscaling quantum chemistry simulations. Specifically, MOGAs are used to bridge high-level quantum chemistry and semiempirical methods to provide accurate representation of complex molecular excited-state and ground-state behavior. Results on ethylene and benzene---two common building blocks in organic chemistry---indicate that MOGAs produce High-quality semiempirical methods that (1) are stable to small perturbations, (2) yield accurate configuration energies on untested and critical excited states, and (3) yield ab initio quality excited-state dynamics. The proposed method enables simulations of more complex systems to realistic, multi-picosecond timescales, well beyond previous attempts or expectation of human experts, and 2--3 orders-of-magnitude reduction in computational cost. While the two applications use simple evolutionary operators, in order to tackle more complex systems, their scalability and limitations have to be investigated. The second part of the thesis addresses some of the challenges involved with a successful design of genetic algorithms and genetic programming for multiscale modeling. The first issue addressed is the scalability of genetic programming, where facetwise models are built to assess the population size required by GP to ensure adequate supply of raw building blocks and also to ensure accurate decision-making between competing building blocks. This study also presents a design of competent genetic programming, where traditional fixed recombination operators are replaced by building and sampling probabilistic models of promising candidate programs. The proposed scalable GP, called extended compact GP (eCGP), combines the ideas from extended compact genetic algorithm (eCGA) and probabilistic incremental program evolution (PIPE) and adaptively identifies, propagates and exchanges important subsolutions of a search problem. Results show that eCGP scales cubically with problem size on both GP-easy and GP-hard problems. Finally, facetwise models are developed to explore limitations of scalability of MOGAs, where the scalability of multiobjective algorithms in reliably maintaining Pareto-optimal solutions is addressed. The results show that even when the building blocks are accurately identified, massive multimodality of the search problems can easily overwhelm the nicher (diversity preserving operator) and l

  6. Material Symmetries from Ultrasonic Velocity Measurements: A Genetic Algorithm Based Blind Inversion Method

    SciTech Connect

    Vardhan, J. Vishnu; Balasubramaniam, Krishnan [Department of Mechanical Engineering, Indian Institute of Technology, Chennai-600 036 (India); Krishnamurthy, C. V. [Center for Nondestructive Evaluation, Indian Institute of Technology, Chennai-600 036 (India)

    2007-03-21

    The determination of material symmetries and principle plane orientations of anisotropic plates, whose planes of symmetries are not known apriori, were calculated using a Genetic Algorithm (GA) based blind inversion method. The ultrasonic phase velocity profiles were used as input data to the inversion. The assumption of a general anisotropy was imposed during the start of each blind inversion. The multi-parameter solution space of the Genetic Algorithm was exploited to identify the 'statistically significant' solution sets of elastic moduli in the geometric coordinate system of the plate, by thresholding the coefficients-of-variation (Cv). Using these ''statistically significant'' elastic moduli, the unknown material symmetry and the principle planes (angles between the geometrical coordinates and the material symmetry coordinates) were evaluated using the method proposed by Cowin and Mehrabadi. This procedure was verified using simulated ultrasonic velocity data sets on material with orthotropic symmetry. Experimental validation was also performed on unidirectional Graphite Epoxy [0]7s fiber reinforced composite plate.

  7. Efficient Reverse Genetics Reveals Genetic Determinants of Budding and Fusogenic Differences between Nipah and Hendra Viruses and Enables Real-Time Monitoring of Viral Spread in Small Animal Models of Henipavirus Infection

    PubMed Central

    Yun, Tatyana; Park, Arnold; Hill, Terence E.; Pernet, Olivier; Beaty, Shannon M.; Juelich, Terry L.; Smith, Jennifer K.; Zhang, Lihong; Wang, Yao E.; Vigant, Frederic; Gao, Junling; Wu, Ping

    2014-01-01

    ABSTRACT Nipah virus (NiV) and Hendra virus (HeV) are closely related henipaviruses of the Paramyxovirinae. Spillover from their fruit bat reservoirs can cause severe disease in humans and livestock. Despite their high sequence similarity, NiV and HeV exhibit apparent differences in receptor and tissue tropism, envelope-mediated fusogenicity, replicative fitness, and other pathophysiologic manifestations. To investigate the molecular basis for these differences, we first established a highly efficient reverse genetics system that increased rescue titers by ?3 log units, which offset the difficulty of generating multiple recombinants under constraining biosafety level 4 (BSL-4) conditions. We then replaced, singly and in combination, the matrix (M), fusion (F), and attachment glycoprotein (G) genes in mCherry-expressing recombinant NiV (rNiV) with their HeV counterparts. These chimeric but isogenic rNiVs replicated well in primary human endothelial and neuronal cells, indicating efficient heterotypic complementation. The determinants of budding efficiency, fusogenicity, and replicative fitness were dissociable: HeV-M budded more efficiently than NiV-M, accounting for the higher replicative titers of HeV-M-bearing chimeras at early times, while the enhanced fusogenicity of NiV-G-bearing chimeras did not correlate with increased replicative fitness. Furthermore, to facilitate spatiotemporal studies on henipavirus pathogenesis, we generated a firefly luciferase-expressing NiV and monitored virus replication and spread in infected interferon alpha/beta receptor knockout mice via bioluminescence imaging. While intraperitoneal inoculation resulted in neuroinvasion following systemic spread and replication in the respiratory tract, intranasal inoculation resulted in confined spread to regions corresponding to olfactory bulbs and salivary glands before subsequent neuroinvasion. This optimized henipavirus reverse genetics system will facilitate future investigations into the growing numbers of novel henipavirus-like viruses. IMPORTANCE Nipah virus (NiV) and Hendra virus (HeV) are recently emergent zoonotic and highly lethal pathogens with pandemic potential. Although differences have been observed between NiV and HeV replication and pathogenesis, the molecular basis for these differences has not been examined. In this study, we established a highly efficient system to reverse engineer changes into replication-competent NiV and HeV, which facilitated the generation of reporter-expressing viruses and recombinant NiV-HeV chimeras with substitutions in the genes responsible for viral exit (the M gene, critical for assembly and budding) and viral entry (the G [attachment] and F [fusion] genes). These chimeras revealed differences in the budding and fusogenic properties of the M and G proteins, respectively, which help explain previously observed differences between NiV and HeV. Finally, to facilitate future in vivo studies, we monitored the replication and spread of a bioluminescent reporter-expressing NiV in susceptible mice; this is the first time such in vivo imaging has been performed under BSL-4 conditions. PMID:25392218

  8. Viral Hijackers

    NSDL National Science Digital Library

    2014-09-18

    Students learn how viruses invade host cells and hijack the hosts' cell-reproduction mechanisms in order to make new viruses, which can in turn attack additional host cells. Students also learn how the immune system responds to a viral invasion, eventually defeating the viruses—if all goes well. Finally, they consider the special case of HIV, in which the virus' host cell is a key component of the immune system itself, severely crippling it and ultimately leading to AIDS. The associated activity sets the stage for this lesson with a dramatic simulation that allows students to see for themselves how quickly a virus can spread through a population, and then challenges students to determine who the initial bearers of the virus were.

  9. Electronic Supplementary Material Kolbe et al. "Admixture determines genetic diversity and population differentiation

    E-print Network

    Losos, Jonathan B.

    1 Electronic Supplementary Material Kolbe et al. "Admixture determines genetic diversity and Houston in Texas, New Orleans, Louisiana, USA, and George Town, Grand Cayman (Kolbe et al. 2007). We also), Portillo (N=11), Soroa (N=6), and S. Esmeralda (N=6) in Cuba (Kolbe et al. 2004). These represent all

  10. Liposome technology. Volume II: Incorporation of drugs, proteins and genetic material

    SciTech Connect

    Gregoriadis, G.

    1984-01-01

    These three volumes cover liposome technology in pharmacology and medicine. Contributors emphasize methodology used in their own laboratories, and include a brief introduction, coverage of relevant literature, applications and critical evaluations for the methods they describe. Volume II presents procedures for the entrapment of a number of drugs, including genetic material, into selected types of liposomes.

  11. Genetics

    MedlinePLUS

    Homozygous; Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  12. Mechanical oscillations of a viral capsid

    NASA Astrophysics Data System (ADS)

    Benson, Daryn; Sankey, Otto; Dykeman, Eric

    2010-03-01

    Viruses are sub-microscopic infectious agents that infect almost every living creature on Earth. They are unable to grow or reproduce outside of a host cell and are therefore parasitic in nature. A virus' internal genetic material is protected by an external protein coat (capsid). We developed a theoretical model which uses the interaction of light with a viral capsid to create large amplitude motions within the capsid. This work displays the results of the model on the tobacco mosaic virus (TMV) with attached RNA genome. The development of this model was motivated by the experimental work of Tsen et. al. [1] who used ultra-short laser pulses to inactivate viruses. [1] K-T. Tsen et al., J. of Physics -- Cond. Mat. 19, 472201 (2007).

  13. Development of a certified reference material for genetically modified potato with altered starch composition.

    PubMed

    Broothaerts, Wim; Corbisier, Philippe; Emons, Hendrik; Emteborg, Håkan; Linsinger, Thomas P J; Trapmann, Stefanie

    2007-06-13

    The presence of genetically modified organisms (GMOs) in food and feed products is subject to regulation in the European Union (EU) and elsewhere. As part of the EU authorization procedure for GMOs intended for food and feed use, reference materials must be produced for the quality control of measurements to quantify the GMOs. Certified reference materials (CRMs) are available for a range of herbicide- and insect-resistant genetically modified crops such as corn, soybean, and cotton. Here the development of the first CRM for a GMO that differs from its non-GMO counterpart in a major compositional constituent, that is, starch, is described. It is shown that the modification of the starch composition of potato (Solanum tuberosum L.) tubers, together with other characteristics of the delivered materials, have important consequences for the certification strategy. Moreover, the processing and characterization of the EH92-527-1 potato material required both new and modified procedures, different from those used routinely for CRMs produced from genetically modified seeds. PMID:17508757

  14. Genetic heterogeneity in psoriasis vulgaris based on linkage analyses of a large family material

    SciTech Connect

    Wahlstroem, J.; Swanbeck, G.; Inerot, A. [ Univ. of Goeteborg (Sweden)] [and others

    1994-09-01

    Information on psoriasis among parents and siblings in 14,008 families has been collected. On the basis of this material, evidence for monogenetic autosomal recessive inheritance of psoriasis has recently been presented. Indications from more than one type of non-pustular psoriasis has been obtained from the population genetic data. Molecular genetic linkage analysis of psoriasis to a number of polymorphic genetic markers for a large number of families has been made. It is apparent that there is genetic heterogeneity in a psoriasis population with regard to psoriasis genes. Using the computer program Linkage 5.0 and a formula for heterogeneity, a lodscore over 3.0 for one locus has been obtained. This locus has further been confirmed by several other markers in the vicinity. The locus found is linked to slightly over half of the families, indicating that there are more genetically independent types of psoriasis. The age at onset of those families that are apparently linked to this locus have a slightly higher age at onset than those not linked to that locus but with a considerable overlap. In spite of close coverage of the whole chromosomes number 6 and 17, no linkage has been found in this regions. This indicates that neither the HLA region nor the region earlier found to be involved in one family with psoriasis are primarily involved in our families.

  15. Viral Oncolysis for Malignant Liver Tumors

    Microsoft Academic Search

    John T. Mullen; Kenneth K. Tanabe

    2003-01-01

    Viral oncolysis represents a unique strategy to exploit the natural process of viral replication to kill tumor cells. Although\\u000a this concept dates back nearly a century, recent advances in the fields of molecular biology and virology have enabled investigators\\u000a to genetically engineer viruses with greater potency and tumor specificity. In this article we review the general mechanisms\\u000a by which oncolytic

  16. Viral perturbations of host networks reflect disease etiology.

    PubMed

    Gulbahce, Natali; Yan, Han; Dricot, Amélie; Padi, Megha; Byrdsong, Danielle; Franchi, Rachel; Lee, Deok-Sun; Rozenblatt-Rosen, Orit; Mar, Jessica C; Calderwood, Michael A; Baldwin, Amy; Zhao, Bo; Santhanam, Balaji; Braun, Pascal; Simonis, Nicolas; Huh, Kyung-Won; Hellner, Karin; Grace, Miranda; Chen, Alyce; Rubio, Renee; Marto, Jarrod A; Christakis, Nicholas A; Kieff, Elliott; Roth, Frederick P; Roecklein-Canfield, Jennifer; Decaprio, James A; Cusick, Michael E; Quackenbush, John; Hill, David E; Münger, Karl; Vidal, Marc; Barabási, Albert-László

    2012-01-01

    Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia. PMID:22761553

  17. Literature mining of genetic variants for curation: quantifying the importance of supplementary material.

    PubMed

    Jimeno Yepes, Antonio; Verspoor, Karin

    2014-01-01

    A major focus of modern biological research is the understanding of how genomic variation relates to disease. Although there are significant ongoing efforts to capture this understanding in curated resources, much of the information remains locked in unstructured sources, in particular, the scientific literature. Thus, there have been several text mining systems developed to target extraction of mutations and other genetic variation from the literature. We have performed the first study of the use of text mining for the recovery of genetic variants curated directly from the literature. We consider two curated databases, COSMIC (Catalogue Of Somatic Mutations In Cancer) and InSiGHT (International Society for Gastro-intestinal Hereditary Tumours), that contain explicit links to the source literature for each included mutation. Our analysis shows that the recall of the mutations catalogued in the databases using a text mining tool is very low, despite the well-established good performance of the tool and even when the full text of the associated article is available for processing. We demonstrate that this discrepancy can be explained by considering the supplementary material linked to the published articles, not previously considered by text mining tools. Although it is anecdotally known that supplementary material contains 'all of the information', and some researchers have speculated about the role of supplementary material (Schenck et al. Extraction of genetic mutations associated with cancer from public literature. J Health Med Inform 2012;S2:2.), our analysis substantiates the significant extent to which this material is critical. Our results highlight the need for literature mining tools to consider not only the narrative content of a publication but also the full set of material related to a publication. PMID:24520105

  18. Genetically expressed HIV-1 viral proteins attenuate nicotine-induced behavioral sensitization and alter mesocorticolimbic ERK and CREB signaling in rats

    PubMed Central

    Midde, Narasimha M.; Gomez, Adrian M.; Harrod, Steven B.; Zhu, Jun

    2011-01-01

    The prevalence of tobacco smoking in HIV-1 positive individuals is 3-fold greater than that in the HIV-1 negative population; however, whether HIV-1 viral proteins and nicotine together produce molecular changes in mesolimbic structures that mediate psychomotor behavior has not been studied. This study determined whether HIV-1 viral proteins changed nicotine-induced behavioral sensitization in HIV-1 transgenic (HIV-1Tg) rats. Further, we examined cAMP response element binding protein (CREB) and extracellular regulated kinase (ERK1/2) signaling in the prefrontal cortex (PFC), nucleus accumbens (NAc) and ventral tegmental area (VTA). HIV-1Tg rats exhibited a transient decrease of activity during habituation, but showed attenuated nicotine (0.35 mg/kg, s.c.)-induced behavioral sensitization compared to Fisher 344 (F344) rats. The basal levels of phosphorylated CREB and ERK2 were lower in the PFC of HIV-1Tg rats, but not in the NAc and VTA, relative to the controls. In the nicotine-treated groups, the levels of phosphorylated CREB and ERK2 in the PFC were increased in HIV-1Tg rats, but decreased in F344 animals. Moreover, repeated nicotine administration reduced phosphorylated ERK2 in the VTA of HIV-1Tg rats and in the NAc of F344 rats, but had no effect on phosphorylated CREB, indicating a region-specific change of intracellular signaling. These results demonstrate that HIV-1 viral proteins produce differences in basal and nicotine-induced alterations in CREB and ERK signaling that may contribute to the alteration in psychomotor sensitization. Thus, HIV-1 positive smokers are possibly more vulnerable to alterations in CREB and ERK signaling and this has implications for motivated behavior, including tobacco smoking, in HIV-1 positive individuals who self-administer nicotine. PMID:21420997

  19. The Application of a Genetic Algorithm to Estimate Material Properties for Fire Modeling from Bench-Scale Fire Test Data 

    E-print Network

    Lautenberger, Chris; Rein, Guillermo; Fernandez-Pello, Carlos

    A methodology based on an automated optimization technique that uses a genetic algorithm (GA) is developed to estimate the material properties needed for CFD-based fire growth modeling from bench-scale fire test data. ...

  20. Evolution of Cyanobacteria by Exchange of Genetic Material among Phyletically Related Strains

    PubMed Central

    Rudi, Knut; Skulberg, Olav M.; Jakobsen, Kjetill S.

    1998-01-01

    The cyanobacterial radiation consists of several lineages of phyletically (morphologically and genetically) related organisms. Several of these organisms show a striking resemblance to fossil counterparts. To investigate the molecular mechanisms responsible for stabilizing or homogenizing cyanobacterial characters, we compared the evolutionary rates and phylogenetic origins of the small-subunit rRNA-encoding DNA (16S rDNA), the conserved gene rbcL (encoding d-ribulose 1,5-bisphosphate carboxylase-oxygenase large subunit), and the less conserved gene rbcX. This survey includes four categories of phyletically related organisms: 16 strains of Microcystis, 6 strains of Tychonema, 10 strains of Planktothrix, and 12 strains of Nostoc. Both rbcL and rbcX can be regarded as neutrally evolving genes, with 95 to 100% and 50 to 80% synonymous nucleotide substitutions, respectively. There is generally low sequence divergence within the Microcystis, Tychonema, and Planktothrix categories both for rbcLX and 16S rDNA. The Nostoc category, on the other hand, consists of three genetically clustered lineages for these loci. The 16S rDNA and rbcLX phylogenies are not congruent for strains within the clustered groups. Furthermore, analysis of the phyletic structure for rbcLX indicates recombinational events between the informative sites within this locus. Thus, our results are best explained by a model involving both intergenic and intragenic recombinations. This evolutionary model explains the DNA sequence clustering for the modern species as a result of sequence homogenization (concerted evolution) caused by exchange of genetic material for neutrally evolving genes. The morphological clustering, on the other hand, is explained by structural and functional stability of these characters. We also suggest that exchange of genetic material for neutrally evolving genes may explain the apparent stability of cyanobacterial morphological characters, perhaps over billions of years. PMID:9642201

  1. Maintenance of picobirnavirus (PBV) infection in an adult orangutan (Pongo pygmaeus) and genetic diversity of excreted viral strains during a three-year period.

    PubMed

    Masachessi, Gisela; Ganesh, Balasubramanian; Martinez, Laura C; Giordano, Miguel O; Barril, Patricia A; Isa, Maria B; Paván, Giorgio V; Mateos, Carlos A; Nates, Silvia V

    2015-01-01

    The present work provide data about the maintenance of picobirnavirus (PBV) infection during adulthood in a mammalian host. For this purpose PBV infection was studied in an adult orangutan (Pongo pygmaeus) by PAGE/SS, RT-PCR and nucleotide sequencing. PBV infection in the animal was asymptomatic and was characterized by interspaced silent and high/ low active viral excretion periods. The PBV strains excreted by the studied individual were identified as genogroup I and revealed a nucleotide identity among them of 64-81%. The results obtained allowed to arrive to a deeper understanding of the natural history of PBV infection, which seems to be characterized by new-born, juvenile and adult asymptomatic hosts which persistently excrete closely related strains in their feces. Consequently, picobirnaviruses could be considered frequent inhabitants of the gastrointestinal tract, leaving the question open about the molecular mechanisms governing persistent and asymptomatic coexistence within the host and the potential host suitability to maintain this relationship. PMID:25435283

  2. Autistic disorder and viral infections.

    PubMed

    Libbey, Jane E; Sweeten, Thayne L; McMahon, William M; Fujinami, Robert S

    2005-02-01

    Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism. PMID:15804954

  3. Viral Vectors for Gene Delivery to the Central Nervous System

    PubMed Central

    Lentz, Thomas B.; Gray, Steven J.; Samulski, R. Jude

    2011-01-01

    The potential benefits of gene therapy for neurological diseases such as Parkinson’s, Amyotrophic Lateral Sclerosis (ALS), Epilepsy, and Alzheimer’s are enormous. Even a delay in the onset of severe symptoms would be invaluable to patients suffering from these and other diseases. Significant effort has been placed in developing vectors capable of delivering therapeutic genes to the CNS in order to treat neurological disorders. At the forefront of potential vectors, viral systems have evolved to efficiently deliver their genetic material to a cell. The biology of different viruses offers unique solutions to the challenges of gene therapy, such as cell targeting, transgene expression and vector production. It is important to consider the natural biology of a vector when deciding whether it will be the most effective for a specific therapeutic function. In this review, we outline desired features of the ideal vector for gene delivery to the CNS and discuss how well available viral vectors compare to this model. Adeno-associated virus, retrovirus, adenovirus and herpesvirus vectors are covered. Focus is placed on features of the natural biology that have made these viruses effective tools for gene delivery with emphasis on their application in the CNS. Our goal is to provide insight into features of the optimal vector and which viral vectors can provide these features. PMID:22001604

  4. Genetic analysis of a hydrophobic domain of coxsackie B3 virus protein 2B: a moderate degree of hydrophobicity is required for a cis-acting function in viral RNA synthesis.

    PubMed Central

    van Kuppeveld, F J; Galama, J M; Zoll, J; Melchers, W J

    1995-01-01

    Coxsackie B virus protein 2B contains near its C terminus a hydrophobic domain with an amino acid composition that is characteristic for transmembrane regions. A molecular genetic approach was followed to define the role of this domain in virus reproduction and to study the structural and hydrophobic requirements of the domain. Nine substitution mutations were introduced in an infectious cDNA clone of coxsackie B3 virus. The effects of the mutations were studied in vivo by transfection of Buffalo green monkey cells with copy RNA transcripts. The results reported here suggest that a critical degree of hydrophobicity of the domain is essential for virus growth. The mutations S77M, C75M, I64S, and V66S, which caused either a small increase or decrease in mean hydrophobicity, yielded viable viruses. The double mutations S77M/C75M and I64S/V6-6S, which caused a more pronounced increase or decrease in hydrophobicity, were nonviable. Negatively charged residues (mutations A71E, I73E, and A71E/I73E) abolished virus growth. The mutations had no effect on the synthesis and processing of the viral polyprotein. Replication and complementation were studied by using a subgenomic coxsackievirus replicon containing the luciferase gene in place of the capsid coding region. Analysis of luciferase accumulation demonstrated that the mutations cause primary defects in viral RNA synthesis that cannot be complemented by wild-type protein 2B provided in trans. The hydrophobic domain is predicted by computer analysis to form a multimeric transmembrane helix. The proposed interaction with the membrane and the implications of the mutations on this interaction are discussed. PMID:7494289

  5. Genetics

    NSDL National Science Digital Library

    Jennifer Doherty

    This activity helps students to understand basic principles of genetics, including relationships of genotype to phenotype, concepts of recessive and dominant alleles, and how understanding meiosis and fertilization provides the basis for understanding inheritance, as summarized in Punnett squares. The Student Handout includes an analysis of the inheritance of albinism that teaches all of these concepts, a Coin Toss Genetics activity that helps students understand the probabilistic nature of Punnett square predictions, and an analysis of the inheritance of sickle cell anemia that reinforces the basic concepts and introduces some of the complexities of genetics. The Genetics Supplement includes two additional activities, an analysis of student data on the sex makeup of sibships and pedigree analyses of recessive and dominant alleles with challenge questions that introduce the role of mutations and an evaluation of Punnett squares and pedigrees as models of inheritance.

  6. Genetic change in the open reading frame of bovine viral diarrhea virus is introduced more rapidly during the establishment of a single persistent infection than by multiple acute infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea viruses (BVDV) are ubiquitous viral pathogens of cattle. There is a high degree of sequence diversity between strains circulating in livestock herds. The driving force behind change in sequence is not known but the inaccurate replication of the genomic RNA by a viral RNA polyme...

  7. Systemic Agrobacterium tumefaciens–mediated transfection of viral replicons for efficient transient expression in plants

    Microsoft Academic Search

    Sylvestre Marillonnet; Carola Thoeringer; Romy Kandzia; Victor Klimyuk; Yuri Gleba

    2005-01-01

    Plant biotechnology relies on two approaches for delivery and expression of heterologous genes in plants: stable genetic transformation and transient expression using viral vectors. Although much faster, the transient route is limited by low infectivity of viral vectors carrying average-sized or large genes. We have developed constructs for the efficient delivery of RNA viral vectors as DNA precursors and show

  8. Genetics

    NSDL National Science Digital Library

    National Science Teachers Association (NSTA)

    2005-04-01

    What affects how physical characteristics are transmitted from parent to offspring? This is a question that can be answered at many levels. Molecular biologists examine the pattern of nucleotides in deoxyribonucleic acid (DNA) and the effect of mutations on the proteins produced. Classical geneticists explore the patterns by which traits are transmitted through families. Medical geneticists attempt to describe and develop treatments for diseases that have a genetic component. Genetic engineers analyze how traits can be altered in organisms through modern technology. These are only a few of the strategies that scientists employ to explain the nature of heredity. Explore historical perspectives on the study of genetics and investigate how cutting-edge technology is being used to expand our understanding of heredity.

  9. A Novel, Real-Valued Genetic Algorithm for Optimizing Radar Absorbing Materials

    NASA Technical Reports Server (NTRS)

    Hall, John Michael

    2004-01-01

    A novel, real-valued Genetic Algorithm (GA) was designed and implemented to minimize the reflectivity and/or transmissivity of an arbitrary number of homogeneous, lossy dielectric or magnetic layers of arbitrary thickness positioned at either the center of an infinitely long rectangular waveguide, or adjacent to the perfectly conducting backplate of a semi-infinite, shorted-out rectangular waveguide. Evolutionary processes extract the optimal physioelectric constants falling within specified constraints which minimize reflection and/or transmission over the frequency band of interest. This GA extracted the unphysical dielectric and magnetic constants of three layers of fictitious material placed adjacent to the conducting backplate of a shorted-out waveguide such that the reflectivity of the configuration was 55 dB or less over the entire X-band. Examples of the optimization of realistic multi-layer absorbers are also presented. Although typical Genetic Algorithms require populations of many thousands in order to function properly and obtain correct results, verified correct results were obtained for all test cases using this GA with a population of only four.

  10. A Genetic Toolbox for Creating Reversible Ca2+-Sensitive Materials Shana Topp,, V. Prasad, Gianguido C. Cianci, Eric R. Weeks, and Justin P. Gallivan*,,

    E-print Network

    Weeks, Eric R.

    A Genetic Toolbox for Creating Reversible Ca2+-Sensitive Materials Shana Topp,,§ V. Prasad Here, we describe a genetic toolbox of natural and engineered protein modules that can be rationally anticipated that a fully genetic approach would provide several important advantages to creating

  11. Viral Disease Networks?

    NASA Astrophysics Data System (ADS)

    Gulbahce, Natali; Yan, Han; Vidal, Marc; Barabasi, Albert-Laszlo

    2010-03-01

    Viral infections induce multiple perturbations that spread along the links of the biological networks of the host cells. Understanding the impact of these cascading perturbations requires an exhaustive knowledge of the cellular machinery as well as a systems biology approach that reveals how individual components of the cellular system function together. Here we describe an integrative method that provides a new approach to studying virus-human interactions and its correlations with diseases. Our method involves the combined utilization of protein - protein interactions, protein -- DNA interactions, metabolomics and gene - disease associations to build a ``viraldiseasome''. By solely using high-throughput data, we map well-known viral associated diseases and predict new candidate viral diseases. We use microarray data of virus-infected tissues and patient medical history data to further test the implications of the viral diseasome. We apply this method to Epstein-Barr virus and Human Papillomavirus and shed light into molecular development of viral diseases and disease pathways.

  12. Best Pract Res Clin Gastroenterol . Author manuscript Diagnosis and management of chronic viral hepatitis: antigens, antibodies

    E-print Network

    Paris-Sud XI, Université de

    of chronic viral hepatitis: antigens, antibodies and viral genomes St phane Chevaliezé 1 2 , Jean ; Hepatitis B Antibodies ; blood ; Hepatitis B Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; diagnosis ; drug therapy ; genetics ; Hepatitis C Antibodies ; blood ; Hepatitis C

  13. [Viral safety of biological medicinal products].

    PubMed

    Stühler, A; Blümel, J

    2014-10-01

    Viral safety of blood donations, plasma products, viral vaccines and gene therapy medicinal products, biotechnical-derived products and tissue and cell therapy products is a particular challenge. These products are manufactured using a variety of human or animal-derived starting materials and reagents; therefore, extensive testing of donors and of cell banks established for production is required. Furthermore, the viral safety of reagents, such as bovine sera, porcine trypsin and human transferrin or albumin needs to be considered. Whenever possible, manufacturing steps for inactivation or removal of viruses should be introduced; however, sometimes it is not possible to introduce such steps for tissues or cell-based medicinal products as the activity and viability of cells will be compromised. It might be possible to implement steps for inactivation or removal of potential contaminating enveloped viruses only for production of small and stable non-enveloped viral gene vectors. PMID:25123140

  14. HUMAN VIRAL ONCOGENESIS: A CANCER HALLMARKS ANALYSIS

    PubMed Central

    Mesri, Enrique A.; Feitelson, Mark; Munger, Karl

    2014-01-01

    Approximately twelve percent of all human cancers are caused by oncoviruses. Human viral oncogenesis is complex and only a small percentage of the infected individuals develop cancer and often many years to decades after initial infection. This reflects the multistep nature of viral oncogenesis, host genetic variability and the fact that viruses contribute to only a portion of the oncogenic events. In this review, the Hallmarks of Cancer framework of Hanahan & Weinberg (2000 and 2011) is used to dissect the viral, host and environmental co-factors that contribute to the biology of multistep oncogenesis mediated by established human oncoviruses. The viruses discussed include Epstein Barr Virus (EBV), high-risk Human Papillomaviruses (HPV16/18), Hepatitis B and C viruses (HBV, HCV respectively), Human T-cell lymphotropic virus-1 (HTLV-1) and Kaposi’s sarcoma herpesvirus (KSHV). PMID:24629334

  15. Genetics

    NSDL National Science Digital Library

    The Tech Museum of Innovation

    2004-01-01

    This online tutorial from the TheTech Museum of Innovation focuses on genetics. The interactive topics will initially introduce the user to the DNA, chromosomes, and the make up of human genes. Further topics will examine forensic science, the history of forensics, fingerprinting, and cloning background research and community response to cloning. Finally, the resource provides connections to gallery exhibits, science labs, and a design challenge that engages the learner to write a persuasive letter to a group or organization responsible for cloning or DNA decision making. Copyright 2005 International Technology Education Association

  16. Viruses and viral proteins

    PubMed Central

    Verdaguer, Nuria; Ferrero, Diego; Murthy, Mathur R. N.

    2014-01-01

    For more than 30 years X-ray crystallography has been by far the most powerful approach for determining the structures of viruses and viral proteins at atomic resolution. The information provided by these structures, which covers many important aspects of the viral life cycle such as cell-receptor recognition, viral entry, nucleic acid transfer and genome replication, has extensively enriched our vision of the virus world. Many of the structures available correspond to potential targets for antiviral drugs against important human pathogens. This article provides an overview of the current knowledge of different structural aspects of the above-mentioned processes. PMID:25485129

  17. Viral infections during pregnancy.

    PubMed

    Silasi, Michelle; Cardenas, Ingrid; Kwon, Ja-Young; Racicot, Karen; Aldo, Paula; Mor, Gil

    2015-03-01

    Viral infections during pregnancy have long been considered benign conditions with a few notable exceptions, such as herpes virus. The recent Ebola outbreak and other viral epidemics and pandemics show how pregnant women suffer worse outcomes (such as preterm labor and adverse fetal outcomes) than the general population and non-pregnant women. New knowledge about the ways the maternal-fetal interface and placenta interact with the maternal immune system may explain these findings. Once thought to be 'immunosuppressed', the pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus. When this protection is breached, as in a viral infection, this security is weakened and infection with other microorganisms can then propagate and lead to outcomes, such as preterm labor. In this manuscript, we review the major viral infections relevant to pregnancy and offer potential mechanisms for the associated adverse pregnancy outcomes. PMID:25582523

  18. Haemorrhagic Fevers, Viral

    MedlinePLUS

    ... haemorrhagic fevers), Filoviridae (Ebola and Marburg) and Flaviviridae (yellow fever, dengue, Omsk haemorrhagic fever, Kyasanur forest disease). Ebola ... topics Dengue Disease outbreaks Infectious diseases Tropical diseases Yellow fever You are here: Health topics Haemorrhagic fevers, Viral ...

  19. Common childhood viral infections.

    PubMed

    Alter, Sherman J; Bennett, Jeffrey S; Koranyi, Katylin; Kreppel, Andrew; Simon, Ryan

    2015-02-01

    Infections caused by viruses are universal during childhood and adolescence. Clinicians will regularly care for children and adolescents who present with infections caused by a wide number of viral pathogens. These infections have varied presentations. Many infections may have clinical presentations that are specific to the infecting virus but present differently, based on the age and immunocompetence of the patient. Some children are directly impacted early in their lives when maternal disease results in an in utero infection (cytomegalovirus, rubella virus, or parvovirus B19). Other viruses may infect children in a predictable pattern as they grow older (rhinovirus or influenza virus). Fortunately, many viral infections frequently encountered in the past are no longer extant due to widespread immunization efforts. Recognition of these vaccine-preventable infections is important because outbreaks of some of these diseases (mumps or measles) continue to occur in the United States. Vigilance in vaccine programs against these viral agents can prevent their re-emergence. In addition, an increasing number of viral infections (herpes simplex virus, influenza virus, varicella zoster virus, or cytomegalovirus) can now be successfully treated with antiviral medications. Most viral infections in children result in self-limited illness and are treated symptomatically and infected children experience full recovery. This review will address the epidemiology, clinical presentation, diagnosis, treatment, and prevention of viral infections commonly encountered by the clinician. PMID:25703483

  20. Immigration and viral hepatitis.

    PubMed

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500million, with an annual mortality rate of up to 1.3million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants. PMID:25962882

  1. Viral and nonviral delivery systems for gene delivery

    PubMed Central

    Nayerossadat, Nouri; Maedeh, Talebi; Ali, Palizban Abas

    2012-01-01

    Gene therapy is the process of introducing foreign genomic materials into host cells to elicit a therapeutic benefit. Although initially the main focus of gene therapy was on special genetic disorders, now diverse diseases with different patterns of inheritance and acquired diseases are targets of gene therapy. There are 2 major categories of gene therapy, including germline gene therapy and somatic gene therapy. Although germline gene therapy may have great potential, because it is currently ethically forbidden, it cannot be used; however, to date human gene therapy has been limited to somatic cells. Although numerous viral and nonviral gene delivery systems have been developed in the last 3 decades, no delivery system has been designed that can be applied in gene therapy of all kinds of cell types in vitro and in vivo with no limitation and side effects. In this review we explain about the history of gene therapy, all types of gene delivery systems for germline (nuclei, egg cells, embryonic stem cells, pronuclear, microinjection, sperm cells) and somatic cells by viral [retroviral, adenoviral, adeno association, helper-dependent adenoviral systems, hybrid adenoviral systems, herpes simplex, pox virus, lentivirus, Epstein–Barr virus)] and nonviral systems (physical: Naked DNA, DNA bombardant, electroporation, hydrodynamic, ultrasound, magnetofection) and (chemical: Cationic lipids, different cationic polymers, lipid polymers). In addition to the above-mentioned, advantages, disadvantages, and practical use of each system are discussed. PMID:23210086

  2. Viral metagenomic analysis of feces of wild small carnivores

    PubMed Central

    2014-01-01

    Background Recent studies have clearly demonstrated the enormous virus diversity that exists among wild animals. This exemplifies the required expansion of our knowledge of the virus diversity present in wildlife, as well as the potential transmission of these viruses to domestic animals or humans. Methods In the present study we evaluated the viral diversity of fecal samples (n?=?42) collected from 10 different species of wild small carnivores inhabiting the northern part of Spain using random PCR in combination with next-generation sequencing. Samples were collected from American mink (Neovison vison), European mink (Mustela lutreola), European polecat (Mustela putorius), European pine marten (Martes martes), stone marten (Martes foina), Eurasian otter (Lutra lutra) and Eurasian badger (Meles meles) of the family of Mustelidae; common genet (Genetta genetta) of the family of Viverridae; red fox (Vulpes vulpes) of the family of Canidae and European wild cat (Felis silvestris) of the family of Felidae. Results A number of sequences of possible novel viruses or virus variants were detected, including a theilovirus, phleboviruses, an amdovirus, a kobuvirus and picobirnaviruses. Conclusions Using random PCR in combination with next generation sequencing, sequences of various novel viruses or virus variants were detected in fecal samples collected from Spanish carnivores. Detected novel viruses highlight the viral diversity that is present in fecal material of wild carnivores. PMID:24886057

  3. High Heritability Is Compatible with the Broad Distribution of Set Point Viral Load in HIV Carriers

    PubMed Central

    Bonhoeffer, Sebastian; Fraser, Christophe; Leventhal, Gabriel E.

    2015-01-01

    Set point viral load in HIV patients ranges over several orders of magnitude and is a key determinant of disease progression in HIV. A number of recent studies have reported high heritability of set point viral load implying that viral genetic factors contribute substantially to the overall variation in viral load. The high heritability is surprising given the diversity of host factors associated with controlling viral infection. Here we develop an analytical model that describes the temporal changes of the distribution of set point viral load as a function of heritability. This model shows that high heritability is the most parsimonious explanation for the observed variance of set point viral load. Our results thus not only reinforce the credibility of previous estimates of heritability but also shed new light onto mechanisms of viral pathogenesis. PMID:25658741

  4. Evaluation of terrestrial microcosms for detection, fate, and survival analysis of genetically engineered microorganisms and their recombinant genetic material

    SciTech Connect

    Fredrickson, J.K.; Seidler, R.J.

    1989-02-01

    The research included in this document represents the current scientific information available regarding the applicability of terrestrial microcosms and related methodologies for evaluating detection methods and the fate and survival of microorganisms in the environment. The three terrestrial microcosms described in this document were used to evaluate the survival and fate of recombinant bacteria in soils and in association with plant surfaces and insects and their transport through soil with percolating water and root systems, and to test new methods and procedures to improve detection and enumeration of bacteria in soil. Simple (potting soil composed of peat mix and perlite, lacking environmental control and monitoring) and complex microcosms (agricultural soil with partial control and monitoring of environmental conditions) were demonstrated to be useful tools for preliminary assessments of microbial viability in terrestrial ecosystems. These studies evaluated the survival patterns of Enterobacter cloacae (pBR322) in soil and on plant surfaces and the ingestion of this same microorganism by cutworms and survival in the foregut and frass. The Versacore microcosm design was used to monitor the fate and competitiveness of genetically engineered bacteria in soil. Both selective media and gene probes were used successfully to follow the fate of two recombinant Pseudomonas sp. introduced into Versacore microcosms. Intact soil-core microcosms were employed to evaluate the fate and transport of genetically altered Azospirillum sp. and Pseudomonas sp. in soil and the plant rhizosphere. The usefulness of these various microcosms as a tool for risk assessment is underscored by the ease in obtaining soil from a proposed field release site to evaluate subsequent GEM fate and survival.

  5. The use of wheat-alien and Aegilops-rye amphiploids for introgression of genetic material to wheat

    Microsoft Academic Search

    V. K. Simonenko; I. I. Motsny; A. L. Sechnyak; M. P. Kulbida

    1998-01-01

    An introduction of genetic material from rye, Aegilops and Elymus into durum and common wheat by crossing the wheat species\\u000a with different amphiploids, has been attempted. Meiotic studies of the hybrids demonstrated that the wheat Elymus sibiricus\\u000a amphiploid contained several (two or three) genes suppressing the activity of the wheat homoeologous pairing control system.\\u000a Somatic chromosome studies of the hybrids

  6. Occult Viral Hepatitis and Noncirrhotic Hepatocellular Carcinoma

    Microsoft Academic Search

    Stuart C. Gordon

    2005-01-01

    The achievement of a sustained virologic response to hepatitis C antiviral therapy represents a milestone occurrence that many tout as a cure. Recent studies, however, have found trace HCV viral material both among sustained responders and in patients with chronic liver disease who are HCV RNA negative, suggesting the entity of occult hepatitis C. As a body of literature emerges

  7. Viral apoptotic mimicry.

    PubMed

    Amara, Ali; Mercer, Jason

    2015-08-01

    As opportunistic pathogens, viruses have evolved many elegant strategies to manipulate host cells for infectious entry and replication. Viral apoptotic mimicry, defined by the exposure of phosphatidylserine - a marker for apoptosis - on the pathogen surface, is emerging as a common theme used by enveloped viruses to promote infection. Focusing on the four best described examples (vaccinia virus, dengue virus, Ebola virus and pseudotyped lentivirus), we summarize our current understanding of apoptotic mimicry as a mechanism for virus entry, binding and immune evasion. We also describe recent examples of non-enveloped viruses that use this mimicry strategy, and discuss future directions and how viral apoptotic mimicry could be targeted therapeutically. PMID:26052667

  8. Failure of Viral Shells

    NASA Astrophysics Data System (ADS)

    Klug, William S.; Bruinsma, Robijn F.; Michel, Jean-Philippe; Knobler, Charles M.; Ivanovska, Irena L.; Schmidt, Christoph F.; Wuite, Gijs J. L.

    2006-12-01

    We report a combined theoretical and experimental study of the structural failure of viral shells under mechanical stress. We find that discontinuities in the force-indentation curve associated with failure should appear when the so-called Föppl von Kármán (FvK) number exceeds a critical value. A nanoindentation study of a viral shell subject to a soft-mode instability, where the stiffness of the shell decreases with increasing pH, confirms the predicted onset of failure as a function of the FvK number.

  9. Viral Factors in Non-Progression

    PubMed Central

    Wang, Bin

    2013-01-01

    Research has undergone considerable development in understanding a small subset of human immunodeficiency virus type 1 (HIV-1)-infected, therapy-naive individuals who maintain a favorable course of infection surviving for longer periods of time. Although, viral, host genetic, and immunological factors have been analyzed in many previous studies in order to delineate mechanisms that contribute to non-progressive HIV disease, there appears to be a no clear cut winner and the non-progressive HIV disease in <1% of HIV-infected individuals appears to be a complex interplay between viral and host factors. Therefore, it is important to review them separately to signify their potential contribution to non-progressive HIV disease. With respect to virological features, genomic sequencing of HIV-1 strains derived from long-term non-progressors has shown that some individuals are infected with attenuated strains of HIV-1 and harbor mutations from single nucleotide polymorphisms to large deletions in HIV-1 structure, regulatory, and accessory genes. The elucidation of functional attributes of defective/attenuated HIV strains may provide better understanding of viral pathogenesis and the discovery of new therapeutic strategies against HIV. This review mainly focuses on the defects in viral genes that possibly guide non-progressive HIV disease. PMID:24400003

  10. Controlling viral capsid assembly with templating

    NASA Astrophysics Data System (ADS)

    Hagan, Michael F.

    2008-05-01

    We develop coarse-grained models that describe the dynamic encapsidation of functionalized nanoparticles by viral capsid proteins. We find that some forms of cooperative interactions between protein subunits and nanoparticles can dramatically enhance rates and robustness of assembly, as compared to the spontaneous assembly of subunits into empty capsids. For large core-subunit interactions, subunits adsorb onto core surfaces en masse in a disordered manner, and then undergo a cooperative rearrangement into an ordered capsid structure. These assembly pathways are unlike any identified for empty capsid formation. Our models can be directly applied to recent experiments in which viral capsid proteins assemble around functionalized inorganic nanoparticles [Sun , Proc. Natl. Acad. Sci. U.S.A. 104, 1354 (2007)]. In addition, we discuss broader implications for understanding the dynamic encapsidation of single-stranded genomic molecules during viral replication and for developing multicomponent nanostructured materials.

  11. BOVINE VIRAL DIARRHEA VIRUSES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. BVDV viruses are further subclassified as cytopathic and noncytopathic based on their activity in cultured epithelial cells. Noncytopathic BVDV p...

  12. BIOMARKERS OF VIRAL EXPOSURE

    EPA Science Inventory

    Viral and protozoan pathogens associated with raw sludge can cause encephalitis, gastroenteritis, hepatitis, myocarditis, and a number of other diseases. Raw sludge that has been treated to reduce these pathogens can be used for land application according to the regulations spec...

  13. Viral encephalitis in travellers.

    PubMed

    Aryee, Anna; Thwaites, Guy

    2015-02-01

    Viral infections are the commonest cause of encephalitis, and the purpose of this article is to inform UK clinicians of the presentation, diagnosis and management of viral encephalitis in travellers returning to the UK. The classical presentation is as a triad of fever, headache and altered mental state. There may be other findings either on examination or on imaging which, together with a travel history, may give clues as to the aetiology. It is important to note that in high- and middle-income countries the commonest cause of viral encephalitis is herpes simplex. This, coupled with the fact that untreated herpes simplex encephalitis (HSE) has a mortality of over 70%, means that aciclovir should always be included in the treatment of patients with suspected encephalitis, regardless of their history of travel. In the UK, the Rare and Imported Pathogens Laboratory (RIPL) at Public Health England can perform specific polymerase chain reaction (PCR) analyses on blood and CSF samples for many imported causes of viral encephalitis. PMID:25650207

  14. Chronic viral diseases.

    PubMed Central

    Berris, B

    1986-01-01

    Until 20 years ago the only chronic viral diseases known were those considered to be confined to the nervous system. As a result of recent advances in epidemiology, molecular biology and immunology, new viral diseases have been recognized and their clinical features and pathogenesis elucidated. Chronic disease may result from infection with the hepatitis B and D viruses and whatever agent or agents cause hepatitis non-A, non-B, the herpesviruses, Epstein-Barr virus, cytomegalovirus and human T-lymphotropic virus type III. These diseases have common features, including long-term or even lifetime asymptomatic carriage, viremia, with virus free in the plasma or attached to circulating mononuclear cells, presence of virus in body secretions, irreversible tissue injury in target organs and oncogenic potential. New information on these diseases is reviewed. Other chronic diseases for which the cause is currently unknown may eventually prove to be due to viral infection. In addition, vaccines may be developed for prophylaxis of some chronic viral diseases and associated malignant diseases. PMID:3022903

  15. Leafhopper viral pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four newly discovered viral pathogens in leafhopper vectors of Pierce’s disease of grapes, have been shown to replicate in sharpshooter leafhoppers; the glassy-winged sharpshooter, GWSS, Homalodisca vitripennis, and Oncometopia nigricans (Hemiptera: Cicadellidae). The viruses were classified as memb...

  16. FastStats: Viral Hepatitis

    MedlinePLUS

    ... States, 2014, table 37 [PDF - 9.8 MB] Mortality Number of deaths: 8,157 Deaths per 100, ... in Health Data Interactive Viral Hepatitis Related Links Mortality data Centers for Disease Control and Prevention: Viral ...

  17. Design of multilayer antireflection coatings made from co-sputtered and low-refractive-index materials by genetic algorithm.

    PubMed

    Schubert, Martin F; Mont, Frank W; Chhajed, Sameer; Poxson, David J; Kim, Jong Kyu; Schubert, E Fred

    2008-04-14

    Designs of multilayer antireflection coatings made from co-sputtered and low-refractive-index materials are optimized using a genetic algorithm. Co-sputtered and low-refractive-index materials allow the fine-tuning of refractive index, which is required to achieve optimum anti-reflection characteristics. The algorithm minimizes reflection over a wide range of wavelengths and incident angles, and includes material dispersion. Designs of antireflection coatings for silicon-based image sensors and solar cells, as well as triple-junction GaInP/GaAs/Ge solar cells are presented, and are shown to have significant performance advantages over conventional coatings. Nano-porous low-refractive-index layers are found to comprise generally half of the layers in an optimized antireflection coating, which underscores the importance of nano-porous layers for high-performance broadband and omnidirectional antireflection coatings. PMID:18542630

  18. Optogenetic Control of Cardiomyocytes via Viral Delivery

    PubMed Central

    Ambrosi, Christina M.; Entcheva, Emilia

    2014-01-01

    Optogenetics is an emerging technology for the manipulation and control of excitable tissues, such as the brain and heart. As this technique requires the genetic modification of cells in order to inscribe light sensitivity, for cardiac applications, here we describe the process through which neonatal rat ventricular myocytes are virally infected in vitro with channelrhodopsin-2 (ChR2). We also describe in detail the procedure for quantitatively determining the optimal viral dosage, including instructions for patterning gene expression in multicellular cardiomyocyte preparations (cardiac syncytia) to simulate potential in vivo transgene distributions. Finally, we address optical actuation of ChR2-transduced cells and means to measure their functional response to light. PMID:25070340

  19. HIV-1 Dynamics: A Reappraisal of Host and Viral Factors, as well as Methodological Issues

    PubMed Central

    Prentice, Heather A.; Tang, Jianming

    2012-01-01

    The dynamics of HIV-1 viremia is a complex and evolving landscape with clinical and epidemiological (public health) implications. Most studies have relied on the use of set-point viral load (VL) as a readily available proxy of viral dynamics to assess host and viral correlates. This review highlights recent findings from population-based studies of set-point VL, focusing primarily on robust data related to host genetics. A comprehensive understanding of viral dynamics will clearly need to consider both host and viral characteristics, with close attention to (i) the timing of VL measurements, (ii) the biology of viral evolution, (iii) compartments of active viral replication, (iv) the transmission source partner as the immediate past microenvironment, and (v) proper application of statistical models. PMID:23202454

  20. Genetic Algorithms, a Nature-Inspired Tool: Survey of Applications in Materials Science and Related Fields

    Microsoft Academic Search

    Wojciech Paszkowicz

    2009-01-01

    Genetic algorithms (GAs) are a tool used to solve high-complexity computational problems. Apart from modelling the phenomena occurring in Nature, they help in optimization, simulation, modelling, design and prediction purposes in science, medicine, technology, and everyday life. They can be adapted to the given task, be joined with other ones (this leads to combined or hybrid methods), and can work

  1. Viral infections of the newborn.

    PubMed

    Strodtbeck, F

    1995-09-01

    Viral infections of the newborn result in significant morbidity and mortality each year. The fetus and newborn are particularly vulnerable to viral infection. The range of expression may vary from no clinical disease to devastating illness and infection occurring before, during, or after birth. Nursing management is determined by the specific viral infection, the severity of the illness, and the unique conditions of the newborn and his/her family. Promising new therapies are on the horizon that may lessen the severity of viral disease. Until such time, the major thrusts of management of neonatal viral disease are prevention of infection and supportive care for the acutely ill newborn. PMID:7500196

  2. Viral RNA extraction for in-the-field analysis

    PubMed Central

    Zhong, Jiang F.; Weiner, Leslie P.; Burke, Kathy; Taylor, Clive R.

    2012-01-01

    Retroviruses encode their genetic information with RNA molecules, and have a high genomic recombination rate which allows them to mutate more rapidly, thereby posting a higher risk to humans. One important way to help combat a pandemic of viral infectious diseases is early detection before large scale outbreaks occur. The polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) have been used to identify precisely different strains of some very closely related pathogens. However, isolation and detection of viral RNA in the field are difficult due to the unstable nature of viral RNA molecules. Consequently, performing in-the-field nucleic acid analysis to monitor the spread of viruses is financially and technologically challenging in remote and underdeveloped regions that are high-risk areas for outbreaks. A simplified rapid viral RNA extraction method is reported to meet the requirements for in-the-field viral RNA extraction and detection. The ability of this device to perform viral RNA extraction with subsequent RT-PCR detection of retrovirus is demonstrated. This inexpensive device has the potential to be distributed on a large scale to underdeveloped regions for early detection of retrovirus, with the possibility of reducing viral pandemic events. PMID:17548117

  3. Journal of Hepatology Host-targeting agents for prevention and treatment of viral hepatitis C-

    E-print Network

    Boyer, Edmond

    1 Journal of Hepatology Host-targeting agents for prevention and treatment of viral hepatitis C viral hepatitis since they have (i) a high genetic barrier to resistance (ii) a pan- genotypic antiviral.Baumert@unistra.fr Abbreviations: DAA: direct-acting antiviral; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human

  4. Viral haemorrhagic fever.

    PubMed

    Fhogartaigh, Caoimhe Nic; Aarons, Emma

    2015-02-01

    Viral haemorrhagic fevers (VHF) are a range of viral infections with potential to cause life-threatening illness in humans. Apart from Crimean-Congo haemorrhagic fever (CCHF), they are largely confined to Africa, distribution being dependent on the ecology of reservoir hosts. At present, the largest ever epidemic of Ebola virus disease (EVD or Ebola) is occurring in West Africa, raising the possibility that cases could be imported into non-endemic countries. Diagnosis and management is challenging due to the non-specificity of early symptoms, limited laboratory facilities in endemic areas, severity of disease, lack of effective therapy, strict infection control requirements and propensity to cause epidemics with secondary cases in healthcare workers. PMID:25650201

  5. Viral Hepatitis D

    Microsoft Academic Search

    John M. Taylor

    \\u000a Viral hepatitis D, also known as hepatitis delta virus (HDV), was first discovered by Mario Rizzetto in 1977, in a study of\\u000a Italian patients infected with hepatitis B virus (HBV), who seemed to have a more damaging liver disease. For more information\\u000a on HBV, please see Chap. 37. In liver biopsies from such patients, a serum antibody detected a novel

  6. Viral inactivation in hemotherapy: systematic review on inactivators with action on nucleic acids

    PubMed Central

    Sobral, Patricia Marial; Barros, Artur Emilio de Lima; Gomes, Ayla Maritcha Alves Silva; do Bonfim, Cristine Vieira

    2012-01-01

    The aim of this study was to conduct a systematic review on the photoinactivators used in hemotherapy, with action on viral genomes. The SciELO, Science Direct, PubMed and Lilacs databases were searched for articles. The inclusion criterion was that these should be articles on inactivators with action on genetic material that had been published between 2000 and 2010. The key words used in identifying such articles were "hemovigilance", "viral inactivation", "photodynamics", "chemoprevention" and "transfusion safety". Twenty-four articles on viral photoinactivation were found with the main photoinactivators covered being: methylene blue, amotosalen HCl, S-303 frangible anchor linker effector (FRALE), riboflavin and inactin. The results showed that methylene blue has currently been studied least, because it diminishes coagulation factors and fibrinogen. Riboflavin has been studied most because it is a photoinactivator of endogenous origin and has few collateral effects. Amotosalen HCl is effective for platelets and is also used on plasma, but may cause changes both to plasma and to platelets, although these are not significant for hemostasis. S-303 FRALE may lead to neoantigens in erythrocytes and is less indicated for red-cell treatment; in such cases, PEN 110 is recommended. Thus, none of the methods for pathogen reduction is effective for all classes of agents and for all blood components, but despite the high cost, these photoinactivators may diminish the risk of blood-transmitted diseases. PMID:23049426

  7. Worming into the cell: Viral reproduction in Caenorhabditis elegans

    E-print Network

    Shaham, Shai

    mature viral particles, and exit the cell to initiate a subsequent round of infection. At all, genetic analysis has proven to be a powerful tool for studying virus (phage)­host interactions in bacte- ria. Mutants of both phage and their host bacteria have allowed detailed under- standing

  8. Neural Networks and Genetic Algorithms in Materials Science and Engineering, 2006 January 1113, 2006, Tata McGrawHill Publishing Company Ltd., India

    E-print Network

    Cambridge, University of

    Neural Networks and Genetic Algorithms in Materials Science and Engineering, 2006 January 11, Shibpur, Howrah, India Neural Networks in Materials Science: The Importance of Uncertainty H. K. D. H rela- tionships and structure within vast arrays of ill­understood data. The neural network method

  9. Broadening our expectations for viral safety risk mitigation.

    PubMed

    Kljavin, Ivar J

    2011-01-01

    CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) The production of biotechnology products using mammalian cell lines offers an inherent risk of viral contamination because of the scale of the process and the complexity of the materials employed. The testing of production cell lines, raw materials, and test execution at appropriate stages of production all combined with viral inactivation or removal strategies ensures that an infectious agent is absent from the purified final product. Perhaps because of these efforts, biotechnology products have not been linked to a negative clinical consequence. However, manufacturing viral contaminations still do occur and may have a great potential negative impact to our patients by disrupting the drug product supply chain. In this paper, additional end-to-end complementary viral safety program considerations are suggested beyond the traditional viral testing and inactivation/removal strategies. These additional points of consideration should be thought of as augmenting the above approaches to further provide a reasonable measure of mitigating the risk of viral contaminations within the biopharmaceutical manufacturing facility. The scope of this paper is on biologics produced in mammalian cells with an emphasis on viral contaminations involving Chinese hamster ovary cell production, although for the examples given as lessons learned with previous industry contaminations, vaccine production issues have been included as a general reference. PMID:22294591

  10. Estimation of the minimum uncertainty of DNA concentration in a genetically modified maize sample candidate certified reference material.

    PubMed

    Prokisch, J; Zeleny, R; Trapmann, S; Le Guern, L; Schimmel, H; Kramer, G N; Pauwels, J

    2001-08-01

    Homogeneity testing and the determination of minimum sample mass are an important part of the certification of reference materials. The smallest theoretically achievable uncertainty of certified concentration values is limited by the concentration distribution of analyte in the different particle size fractions of powdered biological samples. This might be of special importance if the reference material is prepared by dry mixing, a dilution technique which is used for the production of the new and third generation of genetically modified (GMO) plant certified reference materials. For the production of dry mixed PMON 810 maize reference material a computer program was developed to calculate the theoretically smallest uncertainty for a selected sample intake. This model was used to compare three differently milled maize samples, and the effect of dilution on the uncertainty of the DNA content of GMO maize was estimated as well. In the case of a 50-mg sample mass the lowest achievable standard deviation was 2% for the sample containing 0.1% GMO and the minimum deviation was less than 0.5% for the sample containing 5% GMO. PMID:11569879

  11. Hybrid viral vectors for vaccine and antibody production in plants.

    PubMed

    Yusibov, Vidadi; Streatfield, Stephen J; Kushnir, Natasha; Roy, Gourgopal; Padmanaban, Annamalai

    2013-01-01

    Plants have a demonstrated potential for large-scale, rapid production of recombinant proteins for diverse product applications, including subunit vaccines and monoclonal antibodies. In this field, the accent has recently shifted from the engineering of "edible" vaccines based on stable expression of target protein in transgenic or transplastomic plants to the development of purified formulated vaccines that are delivered via injection. The injectable vaccines are commonly produced using transient expression of target gene delivered into genetically unmodified plant host via viral or bacterial vectors. Most viral vectors are based on plant RNA viruses, where nonessential sequences are replaced with the gene of interest. Utilization of viral hybrids that consist of genes and regulatory elements of different virus species, or transcomplementation systems (vector/transgene) had a substantial impact on the level of target protein expression. Development and introduction of agroviral hybrid vectors that combine genetic elements of bacterial binary plasmids and plant viral vectors, and agroinfiltration as a tool of the vector delivery have resulted in significant progress in large-scale production of recombinant vaccines and monoclonal antibodies in plants. This article presents an overview of plant hybrid viral vector expression systems developed so far. PMID:23394571

  12. Viral noncoding RNAs: more surprises.

    PubMed

    Tycowski, Kazimierz T; Guo, Yang Eric; Lee, Nara; Moss, Walter N; Vallery, Tenaya K; Xie, Mingyi; Steitz, Joan A

    2015-03-15

    Eukaryotic cells produce several classes of long and small noncoding RNA (ncRNA). Many DNA and RNA viruses synthesize their own ncRNAs. Like their host counterparts, viral ncRNAs associate with proteins that are essential for their stability, function, or both. Diverse biological roles--including the regulation of viral replication, viral persistence, host immune evasion, and cellular transformation--have been ascribed to viral ncRNAs. In this review, we focus on the multitude of functions played by ncRNAs produced by animal viruses. We also discuss their biogenesis and mechanisms of action. PMID:25792595

  13. Viral hepatitis in Bucharest.

    PubMed Central

    Paquet, C.; Babes, V. T.; Drucker, J.; Sénémaud, B.; Dobrescu, A.

    1993-01-01

    A seroprevalence survey of viral hepatitis was conducted in Bucharest, Romania, between April and July 1990 on a systematic sample of 1355 persons drawn from the general population and groups at higher risk of infection. Sera were tested for hepatitis A, B, and C (HAV, HBV and HCV, resp.) markers using an enzyme-linked immunosorbent assay (ELISA) method. The prevalences of HAV and HBV markers were high in all groups. A total of 47% of the adults from the general population and 39.8% of the children aged 0-16 years had at least one HBV marker. Of the pregnant women 7.8% were positive for hepatitis B surface antigen. Among infants (0-3 years of age) living in orphanages, the prevalence of at least one HBV marker was 54.6%. The findings also confirmed that HCV was circulating in Romania. The results are consistent with national surveillance data and confirm that viral hepatitis is a major public health problem in Romania. Preventive measures will have to include HBV immunization of infants, with an appropriately targeted immunization strategy being determined through further epidemiological studies. PMID:8313496

  14. Viral veterinary vaccines.

    PubMed

    Pastoret, P P; Falize, F

    1999-01-01

    The value of animal models for assessing the quality of veterinary viral vaccines is not to be despised, particularly since one has access to target animal models which are often more relevant than those in the laboratory, especially for challenge/protection studies. Immune protection involves complex immunological phenomena and processes. It is particularly true whenever cellular immunity plays a crucial role because it is still easier to measure antibody responses than cellular ones in vitro. Nevertheless the trend is to replace animal models by in vitro system whenever possible. The problem of the replacement of in vivo by in vitro models is further impeded in Europe by the necessity to comply with Pharmacopoeia monographs where the use of laboratory and/or target animals is often requested. Recent advances have been made with several inactivated viral vaccines such as equine influenza, where strain variability poses a special problem, or rabies, for which the use of inactivated instead of attenuated vaccines for vaccination of animals became compulsory in many countries. PMID:10566778

  15. Viral meningitis and encephalitis: Traditional and emerging viral agents

    Microsoft Academic Search

    José R. Romero; Jason G. Newland

    2003-01-01

    In the United States, the annual number of central nervous system (CNS) infections that occur as a result of viral agents far exceeds that of infections caused by bacteria, yeast, molds, and protozoa combined. The recent incursion of West Nile virus (WNV) into North America has led to a dramatic change in the incidence and epidemiology of summer-associated viral CNS

  16. Evaluation and molecular characterization of human adenovirus in drinking water supplies: viral integrity and viability assays

    PubMed Central

    2013-01-01

    Background Human adenoviruses (HAdVs) are the second-leading cause of childhood gastroenteritis worldwide. This virus is commonly found in environmental waters and is very resistant to water disinfection and environmental stressors, especially UV light inactivation. Molecular techniques, such as PCR-based methods (Polymerase Chain Reaction), are commonly used to detect and identify viral contamination in water, although PCR alone does not allow the discrimination between infectious and non-infectious viral particles. A combination of cell culture and PCR has allowed detection of infectious viruses that grow slowly or fail to produce cytopathic effects (CPE) in cell culture. This study aimed to assess the integrity and viability of human adenovirus (HAdV) in environmental water and evaluate circulating strains by molecular characterization in three sites of the water supply in Florianópolis, Santa Catarina Island, Brazil: Peri Lagoon water, spring source water, and water from the public water supply system. Methods Water samples were collected, concentrated and HAdV quantified by real-time PCR. Viral integrity was evaluated by enzymatic assay (DNase I) and infectivity by plaque assay (PA) and integrated cell culture using transcribed mRNA (ICC-RT-qPCR). Samples containing particles of infectious HAdV were selected for sequencing and molecular characterization. Results The analyzed sites contained 83, 66 and 58% undamaged HAdV particles (defined as those in which the genetic material is protected by the viral capsid) at Peri Lagoon, spring source water and public supply system water, respectively. Of these, 66% of the particles (by PA) and 75% (by ICC-RT-qPCR) HAdV were shown to be infectious, due to being undamaged in Peri Lagoon, 33% (by PA) and 58% (by ICC-RT-qPCR) in spring source water and 8% (by PA) and 25% (by ICC-RT-qPCR) in the public water supply system. ICC-RT-qPCR, a very sensitive and rapid technique, was able to detect as low as 1?×?102 HAdV genome copies per milliliter of infectious viral particles in the environmental water samples. The molecular characterization studies indicated that HAdV-2 was the prevalent serotype. Conclusions These results indicate a lack of proper public health measures. We suggest that HAdV can be efficiently used as a marker of environmental and drinking water contamination and ICC-RT-qPCR demonstrated greater sensitivity and speed of detection of infectious viral particles compared to PA. PMID:23714224

  17. Viral meningitis and encephalitis: traditional and emerging viral agents.

    PubMed

    Romero, José R; Newland, Jason G

    2003-04-01

    In the United States, the annual number of central nervous system (CNS) infections that occur as a result of viral agents far exceeds that of infections caused by bacteria, yeast, molds, and protozoa combined. The recent incursion of West Nile virus (WNV) into North America has led to a dramatic change in the incidence and epidemiology of summer-associated viral CNS disease. As a result of increased testing for WNV, lesser known viral causes of CNS infection have been identified. Even the epidemiology of such traditional viral neuropathogens as rabies has changed in recent years. This review provides an overview of viruses traditionally associated with meningitis and encephalitis (enteroviruses, La Crosse virus, St. Louis encephalitis virus, eastern and western equine viruses, varicella-zoster virus), as well as several of the less common (Powassan virus, lymphocytic choriomeningitis virus, Colorado tick fever virus, rabies virus, influenza viruses, etc.) and emerging (West Nile virus) viral pathogens. PMID:12881794

  18. Influence of Dendritic Cells on Viral Pathogenicity

    Microsoft Academic Search

    Giulia Freer; Donatella Matteucci

    2009-01-01

    Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs) are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses.

  19. The Impact of Viral Genotype on Pathogenesis and Disease Severity: Respiratory Syncytial Virus and Human Rhinoviruses

    PubMed Central

    Moore, Martin L.; Stokes, Kate L.; Hartert, Tina V.

    2013-01-01

    Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRI) and viral death in infants. RSV disease in infants is characterized by epithelial desquamation, neutrophilic bronchiolitis and pneumonia, and obstructive pulmonary mucus. Human rhinoviruses (HRV) are by far the most common cause of symptomatic upper respiratory tract infection (URI) in people and are more recently appreciated as a significant cause of LRI. RSV and HRV are also implicated in asthma pathogenesis. Within both RSV and HRV, viral genetic differences play a role in disease severity and/or prevalence in patient populations, and viral genetic differences affect pathogenesis. Here, we review data on how viral genetic differences impact disease using RSV and HRV as examples, including effects on the host immune response. Virus genotype-phenotype relationships can be exploited in the laboratory to gain insight into mechanisms by which respiratory viruses modulate host immune responses and cause disease. PMID:24455766

  20. Virally mediated gene manipulation in the adult CNS

    PubMed Central

    Edry, Efrat; Lamprecht, Raphael; Wagner, Shlomo; Rosenblum, Kobi

    2011-01-01

    Understanding how the CNS functions poses one of the greatest challenges in modern life science and medicine. Studying the brain is especially challenging because of its complexity, the heterogeneity of its cellular composition, and the substantial changes it undergoes throughout its life-span. The complexity of adult brain neural networks results also from the diversity of properties and functions of neuronal cells, governed, inter alia, by temporally and spatially differential expression of proteins in mammalian brain cell populations. Hence, research into the biology of CNS activity and its implications to human and animal behavior must use novel scientific tools. One source of such tools is the field of molecular genetics—recently utilized more and more frequently in neuroscience research. Transgenic approaches in general, and gene targeting in rodents have become fundamental tools for elucidating gene function in the CNS. Although spectacular progress has been achieved over recent decades by using these approaches, it is important to note that they face a number of restrictions. One of the main challenges is presented by the temporal and spatial regulation of introduced genetic manipulations. Viral vectors provide an alternative approach to temporally regulated, localized delivery of genetic modifications into neurons. In this review we describe available technologies for gene transfer into the adult mammalian CNS that use both viral and non-viral tools. We discuss viral vectors frequently used in neuroscience, with emphasis on lentiviral vector (LV) systems. We consider adverse effects of LVs, and the use of LVs for temporally and spatially controllable manipulations. Especially, we highlight the significance of viral vector-mediated genetic manipulations in studying learning and memory processes, and how they may be effectively used to separate out the various phases of learning: acquisition, consolidation, retrieval, and maintenance. PMID:22207836

  1. Complex genetic control of host susceptibility to coxsackievirus B3-induced myocarditis

    Microsoft Academic Search

    M Aly; S Wiltshire; G Chahrour; J-C Loredo Osti; S M Vidal

    2007-01-01

    The pathogenesis of viral myocarditis is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a model of infection with coxsackievirus B3 (CVB3) to characterize the contribution of host genetics to viral myocarditis in mice of different genetic backgrounds but with a common H2 haplotype: A\\/J and B10.A-H2a. Here we have

  2. Oral Manifestations of Viral Diseases

    Microsoft Academic Search

    Denis P. Lynch

    other chapters dealing with specific viruses. Second, the clinical oral manifestations of such infections are described, with an emphasis on the differential diagnosis of specific oral viral lesions. Third, the methods used in the diagno- sis of oral viral lesions are presented. Fourth, a summary of current therapeutic management strategies is presented, along with their relation- ship to long-term prognosis.

  3. 4 Viral serology and detection

    Microsoft Academic Search

    Shaun Greer; Graeme J. M. Alexander

    1995-01-01

    Viral detection is an important part of clinical hepatology. For many years practical clinical tests have been serological but recently newer molecular techniques have become available for virus detection, although these have yet to become routine and some, such as PCR of viral nucleic acid in blood or tissue are not yet consistently reliable. Serology remains the mainstay at present

  4. Dengue viral infections

    PubMed Central

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing this disease. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. This review outlines aspects of the epidemiology of dengue infections, the dengue virus and its mosquito vector, clinical features and pathogenesis of dengue infections, and the management and control of these infections. PMID:15466994

  5. DNA Extraction from Paraffin Embedded Material for Genetic and Epigenetic Analyses

    PubMed Central

    Cameron, Heryet; Lam, Wan L.

    2011-01-01

    Disease development and progression are characterized by frequent genetic and epigenetic aberrations including chromosomal rearrangements, copy number gains and losses and DNA methylation. Advances in high-throughput, genome-wide profiling technologies, such as microarrays, have significantly improved our ability to identify and detect these specific alterations. However as technology continues to improve, a limiting factor remains sample quality and availability. Furthermore, follow-up clinical information and disease outcome are often collected years after the initial specimen collection. Specimens, typically formalin-fixed and paraffin embedded (FFPE), are stored in hospital archives for years to decades. DNA can be efficiently and effectively recovered from paraffin-embedded specimens if the appropriate method of extraction is applied. High quality DNA extracted from properly preserved and stored specimens can support quantitative assays for comparisons of normal and diseased tissues and generation of genetic and epigenetic signatures 1. To extract DNA from paraffin-embedded samples, tissue cores or microdissected tissue are subjected to xylene treatment, which dissolves the paraffin from the tissue, and then rehydrated using a series of ethanol washes. Proteins and harmful enzymes such as nucleases are subsequently digested by proteinase K. The addition of lysis buffer, which contains denaturing agents such as sodium dodecyl sulfate (SDS), facilitates digestion 2. Nucleic acids are purified from the tissue lysate using buffer-saturated phenol and high speed centrifugation which generates a biphasic solution. DNA and RNA remain in the upper aqueous phase, while proteins, lipids and polysaccharides are sequestered in the inter- and organic-phases respectively. Retention of the aqueous phase and repeated phenol extractions generates a clean sample. Following phenol extractions, RNase A is added to eliminate contaminating RNA. Additional phenol extractions following incubation with RNase A are used to remove any remaining enzyme. The addition of sodium acetate and isopropanol precipitates DNA, and high speed centrifugation is used to pellet the DNA and facilitate isopropanol removal. Excess salts carried over from precipitation can interfere with subsequent enzymatic assays, but can be removed from the DNA by washing with 70% ethanol, followed by centrifugation to re-pellet the DNA 3. DNA is re-suspended in distilled water or the buffer of choice, quantified and stored at -20°C. Purified DNA can subsequently be used in downstream applications which include, but are not limited to, PCR, array comparative genomic hybridization 4 (array CGH), methylated DNA Immunoprecipitation (MeDIP) and sequencing, allowing for an integrative analysis of tissue/tumor samples. PMID:21490570

  6. Vaccination and the population structure of antigenically diverse pathogens that exchange genetic material.

    PubMed Central

    Gupta, S; Ferguson, N M; Anderson, R M

    1997-01-01

    Populations of antigenically diverse pathogens undergoing genetic exchange may be categorized into strains on the basis of a set of principal protective antigens. The extent to which polyvalent vaccines based on these protective antigens can alter the population structure of the pathogen is determined by the degree of cross-protection between strains. In the case where there is no cross-protection, vaccinating against a particular strain will have no effect on the others. As cross-protection increases, the strains containing the antigenic variants included in the vaccine will be diminished in prevalence, and those that do not will increase in prevalence. The rise in prevalence of the latter will become more and more exaggerated as cross-protection increases. However, beyond a critical level of cross-protection, in the absence of vaccination, the steady state of the system is asymmetric in that a certain subset of strains (with non-overlapping repertoires of antigenic variants) will dominate over the others in terms of prevalence. Under these circumstances, a vaccine consisting of the most immunogenic combinations of antigenic variants can cause a dramatic increase in frequency of a subset of rare strains. PMID:9364784

  7. A viral deubiquitylating enzyme targets viral RNA-dependent RNA polymerase and affects viral infectivity

    PubMed Central

    Chenon, Mélanie; Camborde, Laurent; Cheminant, Soizic; Jupin, Isabelle

    2012-01-01

    Selective protein degradation via the ubiquitin-proteasome system (UPS) plays an essential role in many major cellular processes, including host–pathogen interactions. We previously reported that the tightly regulated viral RNA-dependent RNA polymerase (RdRp) of the positive-strand RNA virus Turnip yellow mosaic virus (TYMV) is degraded by the UPS in infected cells, a process that affects viral infectivity. Here, we show that the TYMV 98K replication protein can counteract this degradation process thanks to its proteinase domain. In-vitro assays revealed that the recombinant proteinase domain is a functional ovarian tumour (OTU)-like deubiquitylating enzyme (DUB), as is the 98K produced during viral infection. We also demonstrate that 98K mediates in-vivo deubiquitylation of TYMV RdRp protein—its binding partner within replication complexes—leading to its stabilization. Finally, we show that this DUB activity contributes to viral infectivity in plant cells. The identification of viral RdRp as a specific substrate of the viral DUB enzyme thus reveals the intricate interplay between ubiquitylation, deubiquitylation and the interaction between viral proteins in controlling levels of RdRp and viral infectivity. PMID:22117220

  8. From the Cover: Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation

    Microsoft Academic Search

    Michael Anishchenko; Richard A. Bowen; Slobodan Paessler; Laura Austgen; Ivorlyne P. Greene; Scott C. Weaver

    2006-01-01

    RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood.

  9. Genetic variability and evolutionary dynamics of viruses of the family Closteroviridae

    PubMed Central

    Rubio, Luis; Guerri, José; Moreno, Pedro

    2013-01-01

    RNA viruses have a great potential for genetic variation, rapid evolution and adaptation. Characterization of the genetic variation of viral populations provides relevant information on the processes involved in virus evolution and epidemiology and it is crucial for designing reliable diagnostic tools and developing efficient and durable disease control strategies. Here we performed an updated analysis of sequences available in Genbank and reviewed present knowledge on the genetic variability and evolutionary processes of viruses of the family Closteroviridae. Several factors have shaped the genetic structure and diversity of closteroviruses. (I) A strong negative selection seems to be responsible for the high genetic stability in space and time for some viruses. (2) Long distance migration, probably by human transport of infected propagative plant material, have caused that genetically similar virus isolates are found in distant geographical regions. (3) Recombination between divergent sequence variants have generated new genotypes and plays an important role for the evolution of some viruses of the family Closteroviridae. (4) Interaction between virus strains or between different viruses in mixed infections may alter accumulation of certain strains. (5) Host change or virus transmission by insect vectors induced changes in the viral population structure due to positive selection of sequence variants with higher fitness for host-virus or vector-virus interaction (adaptation) or by genetic drift due to random selection of sequence variants during the population bottleneck associated to the transmission process. PMID:23805130

  10. Sphingolipids in viral infection.

    PubMed

    Schneider-Schaulies, Jürgen; Schneider-Schaulies, Sibylle

    2015-06-01

    Viruses exploit membranes and their components such as sphingolipids in all steps of their life cycle including attachment and membrane fusion, intracellular transport, replication, protein sorting and budding. Examples for sphingolipid-dependent virus entry are found for: human immunodeficiency virus (HIV), which besides its protein receptors also interacts with glycosphingolipids (GSLs); rhinovirus, which promotes the formation of ceramide-enriched platforms and endocytosis; or measles virus (MV), which induces the surface expression of its own receptor CD150 via activation of sphingomyelinases (SMases). While SMase activation was implicated in Ebola virus (EBOV) attachment, the virus utilizes the cholesterol transporter Niemann-Pick C protein 1 (NPC1) as 'intracellular' entry receptor after uptake into endosomes. Differential activities of SMases also affect the intracellular milieu required for virus replication. Sindbis virus (SINV), for example, replicates better in cells lacking acid SMase (ASMase). Defined lipid compositions of viral assembly and budding sites influence virus release and infectivity, as found for hepatitis C virus (HCV) or HIV. And finally, viruses manipulate cellular signaling and the sphingolipid metabolism to their advantage, as for example influenza A virus (IAV), which activates sphingosine kinase 1 and the transcription factor NF-?B. PMID:25525752

  11. Viral infection of engrafted human islets leads to diabetes.

    PubMed

    Gallagher, Glen R; Brehm, Michael A; Finberg, Robert W; Barton, Bruce A; Shultz, Leonard D; Greiner, Dale L; Bortell, Rita; Wang, Jennifer P

    2015-04-01

    Type 1 diabetes (T1D) is characterized by the destruction of the insulin-producing ?-cells of pancreatic islets. Genetic and environmental factors both contribute to T1D development. Viral infection with enteroviruses is a suspected trigger for T1D, but a causal role remains unproven and controversial. Studies in animals are problematic because of species-specific differences in host cell susceptibility and immune responses to candidate viral pathogens such as coxsackievirus B (CVB). In order to resolve the controversial role of viruses in human T1D, we developed a viral infection model in immunodeficient mice bearing human islet grafts. Hyperglycemia was induced in mice by specific ablation of native ?-cells. Human islets, which are naturally susceptible to CVB infection, were transplanted to restore normoglycemia. Transplanted mice were infected with CVB4 and monitored for hyperglycemia. Forty-seven percent of CVB4-infected mice developed hyperglycemia. Human islet grafts from infected mice contained viral RNA, expressed viral protein, and had reduced insulin levels compared with grafts from uninfected mice. Human-specific gene expression profiles in grafts from infected mice revealed the induction of multiple interferon-stimulated genes. Thus, human islets can become severely dysfunctional with diminished insulin production after CVB infection of ?-cells, resulting in diabetes. PMID:25392246

  12. Statistical Mechanics of Viral Entry

    NASA Astrophysics Data System (ADS)

    Zhang, Yaojun; Dudko, Olga K.

    2015-01-01

    Viruses that have lipid-membrane envelopes infect cells by fusing with the cell membrane to release viral genes. Membrane fusion is known to be hindered by high kinetic barriers associated with drastic structural rearrangements—yet viral infection, which occurs by fusion, proceeds on remarkably short time scales. Here, we present a quantitative framework that captures the principles behind the invasion strategy shared by all enveloped viruses. The key to this strategy—ligand-triggered conformational changes in the viral proteins that pull the membranes together—is treated as a set of concurrent, bias field-induced activated rate processes. The framework results in analytical solutions for experimentally measurable characteristics of virus-cell fusion and enables us to express the efficiency of the viral strategy in quantitative terms. The predictive value of the theory is validated through simulations and illustrated through recent experimental data on influenza virus infection.

  13. Ultrafast rotary PCR system for multiple influenza viral RNA detection.

    PubMed

    Jung, Jae Hwan; Choi, Seok Jin; Park, Byung Hyun; Choi, Young Ki; Seo, Tae Seok

    2012-05-01

    We presented a novel platform for an ultrafast PCR system, called the Rotary PCR Genetic Analyzer, which incorporates a thermal block and resistive temperature detector (RTD) for thermal cycling control, a disposable PCR microchip, and a stepper motor. The influenza viral RNAs from H3N2, H5N1, and H1N1 were simultaneously identified with high sensitivity and speed. PMID:22437437

  14. Immunologic features and HLA associations in chronic viral hepatitis

    Microsoft Academic Search

    Albert J. Czaja; Herschel A. Carpenter; Paula J. Santrach; S. Breanndan Moore

    1995-01-01

    Background\\/Aims: Chronic viral hepatitis may have immunologic manifestations, and such features may reflect genetic predispositions. The aim of this study was to assess associations between immune manifestations and HLA-DR antigens. Methods: Ninety-five patients were evaluated prospectively for immunologic features. A microlymphocytotoxicity technique was used to determine DR3, DR4, and A1-B8-DR3 phenotypes. DR antigens were also determined by restriction fragment length

  15. Nonlytic viral spread enhanced by autophagy components

    PubMed Central

    Bird, Sara Whitney; Maynard, Nathaniel D.; Covert, Markus W.; Kirkegaard, Karla

    2014-01-01

    The cell-to-cell spread of cytoplasmic constituents such as nonenveloped viruses and aggregated proteins is usually thought to require cell lysis. However, mechanisms of unconventional secretion have been described that bypass the secretory pathway for the extracellular delivery of cytoplasmic molecules. Components of the autophagy pathway, an intracellular recycling process, have been shown to play a role in the unconventional secretion of cytoplasmic signaling proteins. Poliovirus is a lytic virus, although a few examples of apparently nonlytic spread have been documented. Real demonstration of nonlytic spread for poliovirus or any other cytoplasmic constituent thought to exit cells via unconventional secretion requires demonstration that a small amount of cell lysis in the cellular population is not responsible for the release of cytosolic material. Here, we use quantitative time-lapse microscopy to show the spread of infectious cytoplasmic material between cells in the absence of lysis. siRNA-mediated depletion of autophagy protein LC3 reduced nonlytic intercellular viral transfer. Conversely, pharmacological stimulation of the autophagy pathway caused more rapid viral spread in tissue culture and greater pathogenicity in mice. Thus, the unconventional secretion of infectious material in the absence of cell lysis is enabled by components of the autophagy pathway. It is likely that other nonenveloped viruses also use this pathway for nonlytic intercellular spread to affect pathogenesis in infected hosts. PMID:25157142

  16. Transfer of genetic material between the chloroplast and nucleus: how is it related to stress in plants?

    PubMed Central

    Cullis, C. A.; Vorster, B. J.; Van Der Vyver, C.; Kunert, K. J.

    2009-01-01

    Background The presence of chloroplast-related DNA sequences in the nuclear genome is generally regarded as a relic of the process by which genes have been transferred from the chloroplast to the nucleus. The remaining chloroplast encoded genes are not identical across the plant kingdom indicating an ongoing transfer of genes from the organelle to the nucleus. Scope This review focuses on the active processes by which the nuclear genome might be acquiring or removing DNA sequences from the chloroplast genome. Present knowledge of the contribution to the nuclear genome of DNA originating from the chloroplast will be reviewed. In particular, the possible effects of stressful environments on the transfer of genetic material between the chloroplast and nucleus will be considered. The significance of this research and suggestions for the future research directions to identify drivers, such as stress, of the nuclear incorporation of plastid sequences are discussed. Conclusions The transfer to the nuclear genome of most of the protein-encoding functions for chloroplast-located proteins facilitates the control of gene expression. The continual transfer of fragments, including complete functional genes, from the chloroplast to the nucleus has been observed. However, the mechanisms by which the loss of functions and physical DNA elimination from the chloroplast genome following the transfer of those functions to the nucleus remains obscure. The frequency of polymorphism across chloroplast-related DNA fragments within a species will indicate the rate at which these DNA fragments are incorporated and removed from the chromosomes. PMID:18801916

  17. Current Status of Gene Delivery and Gene Therapy in Lacrimal Gland using Viral Vectors

    PubMed Central

    Selvam, Shivaram; Thomas, Padmaja B.; Hamm-Alvarez, Sarah F.; Schechter, Joel E.; Stevenson, Douglas; Mircheff, Austin K.; Trousdale*, Melvin D.

    2006-01-01

    Gene delivery is one of the biggest challenges in the field of gene therapy. It involves the efficient transfer of transgenes into somatic cells for therapeutic purposes. A few major drawbacks in gene delivery include inefficient gene transfer and lack of sustained transgene expression. However, the classical method of using viral vectors for gene transfer has circumvented some of these issues. Several kinds of viruses, including retrovirus, adenovirus, adeno-associated virus, and herpes simplex virus, have been manipulated for use in gene transfer and gene therapy applications. The transfer of genetic material into lacrimal epithelial cells and tissues, both in vitro and in vivo, has been critical for the study of tear secretory mechanisms and autoimmunity of the lacrimal gland. These studies will help in the development of therapeutic interventions for autoimmune disorders such as Sjögren’s syndrome and dry eye syndromes which are associated with lacrimal dysfunction. These studies are also critical for future endeavors which utilize the lacrimal gland as a reservoir for the production of therapeutic factors which can be released in tears, providing treatment for diseases of the cornea and posterior segment. This review will discuss the developments related to gene delivery and gene therapy in the lacrimal gland using several viral vector systems. PMID:17056149

  18. RNA Virus Reverse Genetics and Vaccine Design

    PubMed Central

    Stobart, Christopher C.; Moore, Martin L.

    2014-01-01

    RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines. PMID:24967693

  19. Noncoding RNPs of Viral Origin

    PubMed Central

    Steitz, Joan; Borah, Sumit; Cazalla, Demian; Fok, Victor; Lytle, Robin; Mitton-Fry, Rachel; Riley, Kasandra; Samji, Tasleem

    2011-01-01

    SUMMARY Like their host cells, many viruses produce noncoding (nc)RNAs. These show diversity with respect to time of expression during viral infection, length and structure, protein-binding partners and relative abundance compared with their host-cell counterparts. Viruses, with their limited genomic capacity, presumably evolve or acquire ncRNAs only if they selectively enhance the viral life cycle or assist the virus in combating the host’s response to infection. Despite much effort, identifying the functions of viral ncRNAs has been extremely challenging. Recent technical advances and enhanced understanding of host-cell ncRNAs promise accelerated insights into the RNA warfare mounted by this fascinating class of RNPs. PMID:20719877

  20. Escaping High Viral Load Exhaustion

    PubMed Central

    Reignat, Stephanie; Webster, George J.M.; Brown, David; Ogg, Graham S.; King, Abigail; Seneviratne, Suranjith L.; Dusheiko, Geoff; Williams, Roger; Maini, Mala K.; Bertoletti, Antonio

    2002-01-01

    Deletion, anergy, and a spectrum of functional impairments can affect virus-specific CD8 cells in chronic viral infections. Here we characterize a low frequency population of CD8 cells present in chronic hepatitis B virus (HBV) infection which survive in the face of a high quantity of viral antigen. Although they do not appear to exert immunological pressure in vivo, these CD8 cells are not classically “tolerant” since they proliferate, lyse, and produce antiviral cytokines in vitro. They are characterized by altered HLA/peptide tetramer reactivity, which is not explained by TCR down-regulation or reduced functional avidity and which can be reversed with repetitive stimulation. CD8 cells with altered tetramer binding appear to have a specificity restricted to envelope antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens. PMID:11994415

  1. Cutaneous manifestations of viral hepatitis.

    PubMed

    Akhter, Ahmed; Said, Adnan

    2015-02-01

    There are several extrahepatic cutaneous manifestations associated with hepatitis B and hepatitis C virus infection. Serum sickness and polyarteritis nodosa are predominantly associated with hepatitis B infection, whereas mixed cryoglobulinemia associated vasculitis and porphyria cutanea tarda are more frequently seen in hepatitis C infection. The clinico-pathogenic associations of these skin conditions are not completely defined but appear to involve activation of the host immune system including the complement system. Management of the aforementioned cutaneous manifestations of viral hepatitis is often similar to that done in cases without viral hepatitis, with control of immune activation being a key strategy. In cases associated with hepatitis B and C, control of viral replication with specific antiviral therapy is also important and associated with improvement in most of the associated clinical manifestations. PMID:25809574

  2. Deoxyribonucleic acid Genetic material

    E-print Network

    Rose, Michael R.

    into beaker. Mix by rocking bag slowly. Place bag on ice for 1 minute. Crush fruit for 5 minutes. Squeeze out minute. Crush fruit for ____ minutes. Squeeze out air and close bag. Add fruit to zip-lock bag. #12;

  3. Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation

    PubMed Central

    Anishchenko, Michael; Bowen, Richard A.; Paessler, Slobodan; Austgen, Laura; Greene, Ivorlyne P.; Weaver, Scott C.

    2006-01-01

    RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992–1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses. PMID:16549790

  4. Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation.

    PubMed

    Anishchenko, Michael; Bowen, Richard A; Paessler, Slobodan; Austgen, Laura; Greene, Ivorlyne P; Weaver, Scott C

    2006-03-28

    RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992-1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses. PMID:16549790

  5. Symptomatic improvement, increased life-span and sustained cell homing in amyotrophic lateral sclerosis after transplantation of human umbilical cord blood cells genetically modified with adeno-viral vectors expressing a neuro-protective factor and a neural cell adhesion molecule.

    PubMed

    Islamov, Rustem Robertovich; Rizvanov, Albert Anatolyevich; Mukhamedyarov, Marat Alexandrovich; Salafutdinov, Ilnur Ildusovich; Garanina, Ekaterina Evgenevna; Fedotova, Valeria Yuryevna; Solovyeva, Valeria Vladimirovna; Mukhamedshina, Yana Olegovna; Safiullov, Zufar Zufarovich; Izmailov, Andrey Alexandrovich; Guseva, Daria Sergeevna; Zefirov, Andrey Lvovich; Kiyasov, Andrey Pavlovich; Palotas, Andras

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is an incurable, chronic, fatal neuro-degenerative disease characterized by progressive loss of moto-neurons and paralysis of skeletal muscles. Reactivating dysfunctional areas is under earnest investigation utilizing various approaches. Here we present an innovative gene-cell construct aimed at reviving inert structure and function. Human umbilical cord blood cells (hUCBCs) transduced with adeno-viral vectors encoding human VEGF, GDNF and/or NCAM genes were transplanted into transgenic ALS mice models. Significant improvement in behavioral performance (open-field and grip-strength tests), as well as increased life-span was observed in rodents treated with NCAM-VEGF or NCAM-GDNF co-transfected cells. Active trans-gene expression was found in the spinal cord of ALS mice 10 weeks after delivering genetically modified hUCBCs, and cells were detectable even 5 months following transplantation. Our gene-cell therapy model yielded prominent symptomatic control and prolonged life-time in ALS. Incredible survivability of xeno-transpanted cells was also observed without any immune-suppression. These results suggest that engineered hUCBCs may offer effective gene-cell therapy in ALS. PMID:25619885

  6. Chapter VIII. Contributions of propagation techniques and genetic modification to breeding - genetic engineering for disease resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic engineering offers an opportunity to develop flower bulb crops with resistance to fungal, viral, and bacterial pathogens. Several of the flower bulb crops, Lilium spp., Gladiolus, Zantedeschia, Muscari, Hyacinthus, Narcissus, Ornithogalum, Iris, and Alstroemeria, have been transformed with t...

  7. 6 Immunopathogenesis of viral hepatitis

    Microsoft Academic Search

    Barbara Rehermann

    1996-01-01

    More than 500 million people world-wide suffer from viral hepatitis which can be caused by a variety of distinct infectious agents. The spectrum of disease, which ranges from acute self-limited hepatitis to liver cirrhosis, not only reflects the different biological properties and pathogenicity of the hepatitis viruses, but is also the result of the specific interaction between each virus and

  8. Viral hepatitis in the Arctic

    Microsoft Academic Search

    Brian J McMahon

    Objectives. Summarize research on viral hepatitis in indigenous populations in the Arctic. Study De- sign. Literature review. Methods. Medline search from 1966-2003. Results. High prevalence rates of total hepatitis A antibody of > 50% and of hepatitis B of between 22% in Alaska and 42% in Greenland for total infection and between 3% in Canada and 12% in Siberia for

  9. Viral Subversion of Nucleocytoplasmic Trafficking

    PubMed Central

    Yarbrough, Melanie L.; Mata, Miguel A.; Sakthivel, Ramanavelan; Fontoura, Beatriz M. A.

    2014-01-01

    Trafficking of proteins and RNA into and out of the nucleus occurs through the nuclear pore complex (NPC). Due to its critical function in many cellular processes, the NPC and transport factors are common targets of several viruses that disrupt key constituents of the machinery to facilitate viral replication. Many viruses such as poliovirus and severe acute respiratory syndrome (SARS) virus inhibit protein import into the nucleus, while viruses such as influenza A virus target and disrupt host mRNA nuclear export. Current evidence indicates that these viruses may employ such strategies to avert the host immune response. Conversely, many viruses co-opt nucleocytoplasmic trafficking to facilitate transport of viral RNAs. Since viral proteins interact with key regulators of the host nuclear transport machinery, viruses have served as invaluable tools of discovery that led to the identification of novel constituents of nuclear transport pathways. In addition, this review explores the importance of nucleocytoplasmic trafficking to viral pathogenesis as these studies revealed new antiviral therapeutic strategies and exposed previously unknown cellular mechanisms. Further understanding of nuclear transport pathways will determine whether such therapeutics will be useful treatments for important human pathogens. PMID:24289861

  10. Viral subversion of nucleocytoplasmic trafficking.

    PubMed

    Yarbrough, Melanie L; Mata, Miguel A; Sakthivel, Ramanavelan; Fontoura, Beatriz M A

    2014-02-01

    Trafficking of proteins and RNA into and out of the nucleus occurs through the nuclear pore complex (NPC). Because of its critical function in many cellular processes, the NPC and transport factors are common targets of several viruses that disrupt key constituents of the machinery to facilitate viral replication. Many viruses such as poliovirus and severe acute respiratory syndrome (SARS) virus inhibit protein import into the nucleus, whereas viruses such as influenza A virus target and disrupt host mRNA nuclear export. Current evidence indicates that these viruses may employ such strategies to avert the host immune response. Conversely, many viruses co-opt nucleocytoplasmic trafficking to facilitate transport of viral RNAs. As viral proteins interact with key regulators of the host nuclear transport machinery, viruses have served as invaluable tools of discovery that led to the identification of novel constituents of nuclear transport pathways. This review explores the importance of nucleocytoplasmic trafficking to viral pathogenesis as these studies revealed new antiviral therapeutic strategies and exposed previously unknown cellular mechanisms. Further understanding of nuclear transport pathways will determine whether such therapeutics will be useful treatments for important human pathogens. PMID:24289861

  11. VIRAL EVOLUTION Genomic surveillance elucidates

    E-print Network

    Napp, Nils

    VIRAL EVOLUTION Genomic surveillance elucidates Ebola virus origin and transmission during the 2014,12,13 § Robert F. Garry,8 § S. Humarr Khan,3 § Pardis C. Sabeti1,2 § In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78

  12. Treatment of acute viral croup

    Microsoft Academic Search

    W Lenney; A D Milner

    1978-01-01

    Total respiratory resistance (RT) was measured before and after nebulised alpha-adrenergic stimulant therapy in 8 children aged 4 to 18 months who had the clinical symptoms of acute viral croup. In 7 children there was a mean fall in RT of 30% after treatment, associated with an improvement in their clinical condition. This improvement was shortlived, the resistance returning to

  13. Mapping of a quantitative trait locus controlling susceptibility to Coxsackievirus B3-induced viral hepatitis.

    PubMed

    Wiltshire, S A; Marton, J; Leiva-Torres, G A; Vidal, S M

    2015-06-01

    The pathogenesis of coxsackieviral infection is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a mouse model of Coxsackievirus B3 infection to characterize the contribution of host genetics to infection survival and to viral hepatitis. Twenty-five AcB/BcA recombinant congenic mouse strains were screened. One, BcA86, was found to be particularly susceptible to early mortality; 100% of BcA86 mice died by day 6 compared with 0% of B6 mice (P=0.0012). This increased mortality was accompanied by an increased hepatic necrosis as measured by serum alanine aminotransferase (ALT) levels (19547±10556 vs 769±109, P=0.0055). This occurred despite a predominantly resistant (C57BL/6) genetic background. Linkage analysis in a cohort (n=210) of (BcA86x C56Bl/10)F2 animals revealed a new locus on chromosome 13 (peak linkage 101.2?Mbp, lod 4.50 and P=0.003). This locus controlled serum ALT levels as early as 48?h following the infection, and led to an elevated expression of type I interferon. Another locus on chromosome 17 (peak linkage 57.2?Mbp) was significantly linked to heart viral titer (lod 3.4 and P=0.046). These results provide new evidence for the presence of genetic loci contributing to the susceptibility of mice to viral hepatitis. PMID:25790079

  14. HIV1 subtype and viral tropism determination for evaluating antiretroviral therapy options: an analysis of archived Kenyan blood samples

    Microsoft Academic Search

    Raphael W Lihana; Samoel A Khamadi; Raphael M Lwembe; Joyceline G Kinyua; Joseph K Muriuki; Nancy J Lagat; Fredrick A Okoth; Ernest P Makokha; Elijah M Songok

    2009-01-01

    BACKGROUND: Infection with HIV-1 is characterized by genetic diversity such that specific viral subtypes are predominant in specific geographical areas. The genetic variation in HIV-1 pol and env genes is responsible for rapid development of resistance to current drugs. This variation has influenced disease progression among the infected and necessitated the search for alternative drugs with novel targets. Though successfully

  15. Do viral proteins possess unique biophysical features?

    Microsoft Academic Search

    Nobuhiko Tokuriki; Christopher J. Oldfield; Vladimir N. Uversky; Igor N. Berezovsky; Dan S. Tawfik

    2008-01-01

    Natural selection shapes the sequence, structure and biophysical properties of proteins to fit their environ- ment. We hypothesize that highly thermostable proteins and viral proteins represent two opposing adaptation strategies. Thermostable proteins are highly compact and possess well-packed hydrophobic cores and inten- sely charged surfaces. By contrast, viral proteins, and RNA viral proteins in particular, display a high occur- rence

  16. Influence of host resistance on viral adaptation: hepatitis C virus as a case study

    PubMed Central

    Plauzolles, Anne; Lucas, Michaela; Gaudieri, Silvana

    2015-01-01

    Genetic and cellular studies have shown that the host’s innate and adaptive immune responses are an important correlate of viral infection outcome. The features of the host’s immune response (host resistance) reflect the coevolution between hosts and pathogens that has occurred over millennia, and that has also resulted in a number of strategies developed by viruses to improve fitness and survival within the host (viral adaptation). In this review, we discuss viral adaptation to host immune pressure via protein–protein interactions and sequence-specific mutations. Specifically, we will present the “state of play” on viral escape mutations to host T-cell responses in the context of the hepatitis C virus, and their influence on infection outcome. PMID:25897250

  17. Bio-functional inorganic materials: an attractive branch of gene-based nano-medicine delivery for 21st century.

    PubMed

    Chowdhury, Ezharul H; Akaike, Toshihiro

    2005-12-01

    Treatment of a physiological disorder in the genetic level (gene therapy) and induction of a specific immunity by means of a genetic material (genetic vaccination), are considered two revolutionary approaches for clinical medicine. The implementation strategies for these basic concepts demand a vehicle for nucleic acid delivery. Viral delivery systems, although highly efficient, possess severe limitations in terms of life safety and thus non-viral synthetic systems have become increasingly desirable. Intensive efforts for the last 3 decades enabled the development of a lot of synthetic devices, most of which belong to cationic lipids, peptides and other polymers, but comparatively little attention was paid to inorganic materials. This is the first article aimed at reviewing the dramatic progress of non-viral gene delivery research focusing on the functional inorganic materials. Both biodegradable and non-biodegradable inorganic particles have been fabricated in the nano-scale with the attributes of binding DNA, internalizing across the plasma membrane and finally releasing it in the cytoplasm for final expression of a protein. Some in vivo trials also brought highly satisfactory results demonstrating their potential applications in the clinical medicine. PMID:16457655

  18. Fall 2010 SCI 1210: Principles of Modern Biology (with Laboratory): Course Materials: Laboratory: Detection of Genetically Modified Foods

    Microsoft Academic Search

    Jean J. Huang

    2010-01-01

    This course introduces students to the fundamental aspects of biological science including biochemistry, molecular biology, human molecular genetics, and cellular communication. Students gain experience with contemporary research methods and scientific reasoning through laboratory experiments. The relevance of biology to the environment and health is emphasized.

  19. Crop Registration: The Pathway to Public Access of Plant Genetic Materials to Build Crops for the Future

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starting as Crop Science Registrations in the American Journal of the Society of Agronomy in 1926, and continuing 80+ years later in the Journal of Plant Registrations, 11,241 plant cultivars, germplasm, parental lines, genetic stocks and mapping populations have been registered as of December 31, 2...

  20. Piston actuated nastic materials

    E-print Network

    Shah, Viral

    2009-05-15

    PISTON ACTUATED NASTIC MATERIALS A Thesis by VIRAL SHAH Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE December 2008... Major Subject: Mechanical Engineering PISTON ACTUATED NASTIC MATERIALS A Thesis by VIRAL SHAH Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER...

  1. Bovine viral diarrhea virus (BVDV) infections in pigs.

    PubMed

    Tao, Jie; Liao, Jinhu; Wang, Yin; Zhang, Xinjun; Wang, Jianye; Zhu, Guoqiang

    2013-08-30

    Cattle are the natural hosts of bovine viral diarrhea virus (BVDV), which causes mucosal disease, respiratory and gastrointestinal tract infections, and reproductive problems in cattle. However, BVDV can also infect goats, sheep, deer, and pigs. The prevalence of BVDV infection in pig herds has substantially increased in the last several years, causing increased economic losses to the global pig breeding industry. This article is a summary of BVDV infections in pigs, including a historical overview, clinical signs, pathology, source of infection, genetic characteristics, impacts of porcine BVDV infection for diagnosis of classical swine fever virus (CSFV), differentiation of infection with CSFV and BVDV, and future prospects of porcine BVDV infection. PMID:23587625

  2. Viral proteases as targets for drug design.

    PubMed

    Skore?ski, Marcin; Sie?czyk, Marcin

    2013-01-01

    In order to productively infect a host, viruses must enter the cell and force host cell replication mechanisms to produce new infectious virus particles. The success of this process unfortunately results in disease progression and, in the case of infection with many viral species, may cause mortality. The discoveries of Louis Pasteur and Edward Jenner led to one of the greatest advances in modern medicine - the development of vaccines that generate long-lasting memory immune responses to combat viral infection. Widespread use of vaccines has reduced mortality and morbidity associated with viral infection and, in some cases, has completely eradicated virus from the human population. Unfortunately, several viral species maintain a significant ability to mutate and "escape" vaccine-induced immune responses. Thus, novel anti-viral agents are required for treatment and prevention of viral disease. Targeting proteases that are crucial in the viral life cycle has proven to be an effective method to control viral infection, and this avenue of investigation continues to generate anti-viral treatments. Herein, we provide the reader with a brief history as well as a comprehensive review of the most recent advances in the design and synthesis of viral protease inhibitors. PMID:23016690

  3. Introductory molecular genetics

    SciTech Connect

    Edwards-Moulds, J.

    1986-01-01

    This book begins with an overview of the current principles of genetics and molecular genetics. Over this foundation, it adds detailed and specialized information: a description of the translation, transcription, expression and regulation of DNA and RNA; a description of the manipulation of genetic material via promoters, enhancers, and gene splicing; and a description of cloning techniques, especially those for blood group genes. The last chapter looks to the impact of molecular genetics on transfusion medicine.

  4. Efficient Non-Viral Reprogramming of Myoblasts to Stemness with a Single Small Molecule to Generate Cardiac Progenitor Cells

    Microsoft Academic Search

    Zeeshan Pasha; Husnain Kh Haider; Muhammad Ashraf

    2011-01-01

    The current protocols for generation of induced pluripotent stem (iPS) cells involve genome integrating viral vectors which may induce tumorgenesis. The aim of this study was to develop and optimize a non-viral method without genetic manipulation for reprogramming of skeletal myoblasts (SMs) using small molecules.Methods and ResultsSMs from young male Oct3\\/4-GFP+ transgenic mouse were treated with DNA methyltransferase (DNMT) inhibitor,

  5. Using The Interfaces In Self-Assembled Protein Cage Architectures For Materials Synthesis

    NASA Astrophysics Data System (ADS)

    Douglas, Trevor

    2007-03-01

    The self-assembled architectures of viral capsids have been used as models for understanding processes of encapsulation of both hard and soft materials. We have explored modifications to the exterior and interior interfaces of viral (and other protein cage architectures) while maintaining the assembly of stable icosahedral capsid particles. This has allowed us to utilize the high symmetry of the viral capsid to engineer unique functionality for highly ordered multivalent presentation for controlled nucleation of hard inorganic materials and packaging of soft organic materials. Of particular interest is the nature of the hard-soft interface in these systems. Through the incorporation of peptides derived from phage display we can direct the nucleation and growth of specific inorganic phases, constrained within the protein cage architecture. The coupled synthesis of cage-constrained ferrimagnetic and antiferromagnetic nanoparticles results in formation of stable composites that exhibit unique exchange bias magnetic coupling. To understand the role of the protein in directing inorganic materials synthesis, we have probed the protein-mineral interface using genetic and chemical modifications, spatially controlled inorganic synthesis, high-resolution transmission electron microscopy, and cryo-electron microscopy and image reconstruction. The role of protein interfaces in these assembled protein cage architectures has been explored to understand and exploit packaging of a wide range of materials as diverse as nucleic acids, drugs, and inorganic nano-materials.

  6. Viral vector-based models of Parkinson's disease.

    PubMed

    Van der Perren, Anke; Van den Haute, Chris; Baekelandt, Veerle

    2015-01-01

    In order to study the molecular pathways of Parkinson's disease (PD) and to develop novel therapeutic strategies, scientific investigators rely on animal models. The identification of PD-associated genes has led to the development of genetic PD models as an alternative to toxin-based models. Viral vector-mediated loco-regional gene delivery provides an attractive way to express transgenes in the central nervous system. Several vector systems based on various viruses have been developed. In this chapter, we give an overview of the different viral vector systems used for targeting the CNS. Further, we describe the different viral vector-based PD models currently available based on overexpression strategies for autosomal dominant genes such as ?-synuclein and LRRK2, and knockout or knockdown strategies for autosomal recessive genes, such as parkin, DJ-1, and PINK1. Models based on overexpression of ?-synuclein are the most prevalent and extensively studied, and therefore the main focus of this chapter. Many efforts have been made to increase the expression levels of ?-synuclein in the dopaminergic neurons. The best ?-synuclein models currently available have been developed from a combined approach using newer AAV serotypes and optimized vector constructs, production, and purification methods. These third-generation ?-synuclein models show improved face and predictive validity, and therefore offer the possibility to reliably test novel therapeutics. PMID:24839101

  7. Viral oncogenesis and cell differentiation

    SciTech Connect

    Diamond, L.; Wolman, S.R.

    1989-01-01

    This book covers the following topics: Retroviruses, Human lymphotropic viruses, Oncogenes, Hematopoiesis: Normal and Abnormal, Growth and differentiation of normal and malignant cells, Molecular and genetic control of cell proliferation.

  8. Viral Infection in Renal Transplant Recipients

    PubMed Central

    Cukuranovic, Jovana; Ugrenovic, Sladjana; Jovanovic, Ivan; Visnjic, Milan; Stefanovic, Vladisav

    2012-01-01

    Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens. PMID:22654630

  9. Live Cell Imaging of Viral Entry

    PubMed Central

    Sun, Eileen; He, Jiang; Zhuang, Xiaowei

    2013-01-01

    Viral entry encompasses the initial steps of infection starting from virion host cell attachment to viral genome release. Given the dynamic interactions between the virus and the host, many questions related to viral entry can be directly addressed by live cell imaging. Recent advances in fluorescent labeling of viral and cellular components, fluorescence microscopy with high sensitivity and spatiotemporal resolution, and image analysis enabled studies of a broad spectrum across many viral entry steps, including virus-receptor interactions, internalization, intracellular transport, genomic release, nuclear transport, and cell-to-cell transmission. Collectively, these live cell imaging studies have not only enriched our understandings of the viral entry mechanisms, but also provided novel insights into basic cellular biology processes. PMID:23395264

  10. Human Cytomegalovirus: Bacterial Artificial Chromosome (BAC) Cloning and Genetic Manipulation

    PubMed Central

    Paredes, Anne M.; Yu, Dong

    2011-01-01

    Our understanding of human cytomegalovirus (HCMV) biology was long hindered by the inability to perform efficient viral genetic analysis. This hurdle was recently overcome when the genomes of multiple HCMV strains were cloned as infectious bacterial artificial chromosomes (BACs). The BAC system takes advantage of the single-copy F plasmid of E. coli that can stably carry large pieces of foreign DNA. In this system, a recombinant HCMV virus carrying a modified F plasmid is first generated in eukaryotic cells. Recombinant viral genomes are then isolated and recovered in E. coli as BAC clones. BAC-captured viral genomes can be manipulated using prokaryotic genetics, and recombinant virus can be reconstituted from BAC transfection in eukaryotic cells. The BAC reverse genetic system provides a reliable and efficient method to introduce genetic alterations into the viral genome in E.coli and subsequently analyze their effects on virus biology in eukaryotic cells. PMID:22307551

  11. Detection of Viral Hemorrhagic Septicemia Virus by Quantitative Reverse Transcription Polymerase Chain Reaction from Two Fish Species at Two Sites in Lake Superior

    USGS Publications Warehouse

    Cornwell, Emily R.; Eckerlin, Geofrey E.; Getchell, Rodman G.; Groocock, Geoffrey H.; Thompson, Tarin M.; Batts, William N.; Casey, Rufina N.; Kurath, Gael; Winton, James R.; Bowser, Paul R.; Bain, Mark B.; Casey, James W.

    2011-01-01

    Viral hemorrhagic septicemia virus (VHSV) was first detected in the Laurentian Great Lakes in 2005 during a mortality event in the Bay of Quinte, Lake Ontario. Subsequent analysis of archived samples determined that the first known isolation of VHSV in the Laurentian Great Lakes was from a muskellunge Esox masquinongy collected in Lake St. Clair in 2003. By the end of 2008, mortality events and viral isolations had occurred in all of the Laurentian Great Lakes except Lake Superior. In 2009, a focused disease surveillance program was designed to determine whether VHSV was also present in Lake Superior. In this survey, 874 fish from 7 sites along the U.S. shoreline of Lake Superior were collected during June 2009. Collections were focused on nearshore species known to be susceptible to VHSV. All fish were dissected individually by using aseptic techniques and were tested for the presence of VHSV genetic material by use of a quantitative reverse transcription (qRT) polymerase chain reaction (PCR) targeting the viral nucleoprotein gene. Seventeen fish from two host species at two different sites tested positive at low levels for VHSV. All attempts to isolate virus in cell culture were unsuccessful. However, the presence of viral RNA was confirmed independently in five fish by using a nested PCR that targeted the glycoprotein (G) gene. Partial G gene sequences obtained from three fish were identical to the corresponding sequence from the original 2003 VHSV isolate (MI03) from muskellunge. These detections represent the earliest evidence for the presence of VHSV in Lake Superior and illustrate the utility of the highly sensitive qRT-PCR assay for disease surveillance in aquatic animals.

  12. The effects of immunosuppression on the pathogenicity of viral arthritis virus of chickens 

    E-print Network

    Pugh, Roberta Ann

    1979-01-01

    with tendon material from VAV-IBDV treated chickens. . . . . . . . . . . . . . . . . . . . . . . 42 INTRODUCTION Viral arthritis (VA) is a widespread reovirus infection of chickens characterized by the involvement of synovial membranes, tendon sheaths... characterized the West Virginia isolate of viral arthrit1s virus (VAV) as a reovirus. Other workers have confirmed their character1zat1on of the virus (38, 59). Reoviruses have been isolated from the respiratory and diges- t1ve tracts of chickens and turkeys...

  13. Gene therapy in HIV-infected cells to decrease viral impact by using an alternative delivery method.

    PubMed

    Gonzalo, Teresa; Clemente, Maria Isabel; Chonco, Louis; Weber, Nick D; Díaz, Laura; Serramía, María Jesús; Gras, Rafael; Ortega, Paula; de la Mata, F Javier; Gómez, Rafael; Lopez-Fernández, Luis A; Muñoz-Fernández, Maria Angeles; Jiménez, José Luís

    2010-06-01

    The ability of dendrimer 2G-[Si{O(CH(2))(2)N(Me)(2) (+)(CH(2))(2)NMe(3) (+)(I(-))(2)}](8) (NN16) to transfect a wide range of cell types, as well as the possible biomedical application in direct or indirect inhibition of HIV replication, was investigated. Cells implicated in HIV infection such as primary peripheral blood mononuclear cells (PBMC) and immortalized suspension cells (lymphocytes), primary macrophages and dendritic cells, and immortalized adherent cells (astrocytes and trophoblasts) were analyzed. Dendrimer toxicity was evaluated by mitochondrial activity, cell membrane rupture, release of lactate dehydrogenase, erythrocyte hemolysis, and the effect on global gene expression profiles using whole-genome human microarrays. Cellular uptake of genetic material was determined using flow cytometry and confocal microscopy. Transfection efficiency and gene knockdown was investigated using dendrimer-delivered antisense oligonucleotides and small interfering RNA (siRNA). Very little cytotoxicity was detected in a variety of cells relevant to HIV infection and erythrocytes after NN16 dendrimer treatment. Imaging of cellular uptake showed high transfection efficiency of genetic material in all cells tested. Interestingly, NN16 further enhanced the reduction of HIV protein 24 antigen release by antisense oligonucleotides due to improved transfection efficiency. Finally, the dendrimer complexed with siRNA exhibited therapeutic potential by specifically inhibiting cyclooxygenase-2 gene expression in HIV-infected nervous system cells. NN16 dendrimers demonstrated the ability to transfect genetic material into a vast array of cells relevant to HIV pathology, combining high efficacy with low toxicity. These results suggest that NN16 dendrimers have the potential to be used as a versatile non-viral vector for gene therapy against HIV infection. PMID:20414916

  14. Manipulating gene expression in projection-specific neuronal populations using combinatorial viral approaches

    PubMed Central

    Gore, Bryan B.; Soden, Marta E.; Zweifel, Larry S.

    2013-01-01

    The mammalian brain contains tremendous structural and genetic complexity that is vital for its function. The elucidation of gene expression profiles in the brain, coupled with the development of large-scale connectivity maps and emerging viral vector-based approaches for target-selective gene manipulation, now allow for detailed dissection of gene-circuit interfaces. This protocol details how to perform combinatorial viral injections to manipulate gene expression in subsets of neurons interconnecting two brain regions. This method utilizes stereotaxic injection of a retrograde transducing CAV2-Cre virus into one brain region, combined with injection of a locally transducing Cre-dependent AAV virus into another brain region. This technique is widely applicable to the genetic dissection of neural circuitry, as it enables selective expression of candidate genes, dominant-negatives, fluorescent reporters, or genetic tools within heterogeneous populations of neurons based upon their projection targets. PMID:25429312

  15. Sequencing Needs for Viral Diagnostics

    SciTech Connect

    Gardner, S N; Lam, M; Mulakken, N J; Torres, C L; Smith, J R; Slezak, T

    2004-01-26

    We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (''near neighbors'') that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. SARS and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near neighbor sequences are urgently needed. Our results also indicate that double stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.

  16. Biological roles and functional mechanisms of arenavirus Z protein in viral replication.

    PubMed

    Wang, Jialong; Danzy, Shamika; Kumar, Naveen; Ly, Hinh; Liang, Yuying

    2012-09-01

    Arenaviruses can cause severe hemorrhagic fever diseases in humans, with limited prophylactic or therapeutic measures. A small RING-domain viral protein Z has been shown to mediate the formation of virus-like particles and to inhibit viral RNA synthesis, although its biological roles in an infectious viral life cycle have not been directly addressed. By taking advantage of the available reverse genetics system for a model arenavirus, Pichinde virus (PICV), we provide the direct evidence for the essential biological roles of the Z protein's conserved residues, including the G2 myristylation site, the conserved C and H residues of RING domain, and the poorly characterized C-terminal L79 and P80 residues. Dicodon substitutions within the late (L) domain (PSAPPYEP) of the PICV Z protein, although producing viable mutant viruses, have significantly reduced virus growth, a finding suggestive of an important role for the intact L domain in viral replication. Further structure-function analyses of both PICV and Lassa fever virus Z proteins suggest that arenavirus Z proteins have similar molecular mechanisms in mediating their multiple functions, with some interesting variations, such as the role of the G2 residue in blocking viral RNA synthesis. In summary, our studies have characterized the biological roles of the Z protein in an infectious arenavirus system and have shed important light on the distinct functions of its domains in virus budding and viral RNA regulation, the knowledge of which may lead to the development of novel antiviral drugs. PMID:22761375

  17. Risk mitigation strategies for viral contamination of biotechnology products: consideration of best practices.

    PubMed

    Rosenberg, Amy S; Cherney, Barry; Brorson, Kurt; Clouse, Kathleen; Kozlowski, Steven; Hughes, Patricia; Friedman, Rick

    2011-01-01

    CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Viral contamination of biotech product facilities is a potentially devastating manufacturing risk and, unfortunately, is more common than is generally reported or previously appreciated. Although viral contaminants of biotech products are thought to originate principally from biological raw materials, all potential process risks merit evaluation. Limitations to existing methods for virus detection are becoming evident as emerging viruses have contaminated facilities and disrupted supplies of critical products. New technologies, such as broad-based polymerase chain reaction screens for multiple virus types, are increasingly becoming available to detect adventitious viral contamination and thus, mitigate risks to biotech products and processes. Further, the industry embrace of quality risk management that promotes improvements in testing stratagems, enhanced viral inactivation methods for raw materials, implementation and standardization of robust viral clearance procedures, and efforts to learn from both epidemiologic screening of raw material sources and from the experience of other manufacturers with regard to this problem will serve to enhance the safety of biotech products available to patients. Based on this evolving landscape, we propose a set of principles for manufacturers of biotech products: Pillars of Risk Mitigation for Viral Contamination of Biotech Products. PMID:22294578

  18. Estimation of the minimum uncertainty of DNA concentration in a genetically modified maize sample candidate certified reference material

    Microsoft Academic Search

    J. Prokisch; R. Zeleny; S. Trapmann; L. Le Guern; H. Schimmel; G. N. Kramer; J. Pauwels

    2001-01-01

    Homogeneity testing and the determination of minimum sample mass are an important part of the certification of reference\\u000a materials. The smallest theoretically achievable uncertainty of certified concentration values is limited by the concentration\\u000a distribution of analyte in the different particle size fractions of powdered biological samples. This might be of special\\u000a importance if the reference material is prepared by dry

  19. Current challenges in viral safety and extraneous agent testing.

    PubMed

    Mackay, David; Kriz, Nikolaus

    2010-05-01

    There are three principal elements related to viral safety in the context of immunological veterinary medicinal products: the presence of extraneous agents in either raw material used for production or in the finished product, residual pathogenicity of live viruses used as active ingredients, and incomplete inactivation of inactivated viruses used as active ingredients. Although the approach to controlling these areas of risk has not substantially changed in the recent past, a number of events, combined with advances in science and changes in the regulatory approach, make it timely to review the requirements in this area. This article reviews the major areas of change and progress with respect to the viral safety of immunological veterinary medicinal products and identifies current challenges from the perspectives of both industry and regulators. PMID:20338787

  20. Molecular biology of bovine viral diarrhea virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea viruses (BVDV) are arguably the most important viral pathogen of ruminants worldwide and can cause severe economic loss. Clinical symptoms of the disease caused by BVDV range from subclinical to severe acute hemorrhagic syndrome, with the severity of disease being strain depend...

  1. Viral diagnosis by antigen detection techniques

    Microsoft Academic Search

    Monica Grandien

    1996-01-01

    Background: Diagnosis of viral infections can be obtained in the early stages of a disease by detection of viral antigens directly in the clinical specimen. This has become an important tool for rapid virus diagnosis.Methods: Antigens produced during virus infections can be detected either in cells collected from the site of infection by immunohistological investigation or in secretions and blood

  2. Illuminating viral infections in the nervous system

    Microsoft Academic Search

    Silvia S. Kang; Dorian B. McGavern

    2011-01-01

    Viral infections are a major cause of human disease. Although most viruses replicate in peripheral tissues, some have developed unique strategies to move into the nervous system, where they establish acute or persistent infections. Viral infections in the central nervous system (CNS) can alter homeostasis, induce neurological dysfunction and result in serious, potentially life-threatening inflammatory diseases. This Review focuses on

  3. Molecular Engineering of Viral Gene Delivery Vehicles

    E-print Network

    Schaffer, David V.

    The Annual Review of Biomedical Engineering is online at bioeng.annualreviews.org This article's doi: 10 with novel gene delivery capabilities. Rational design of viral vectors has yielded successful advances-based design promise to aid the translation of engineered viral vectors toward the clinic. 169 Annu

  4. Viral ancestors of antiviral systems.

    PubMed

    Villarreal, Luis P

    2011-10-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the 'Big Bang' theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features. PMID:22069523

  5. Viral Ancestors of Antiviral Systems

    PubMed Central

    Villarreal, Luis P.

    2011-01-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features. PMID:22069523

  6. Itchy fish and viral dermatopathies: sampling, diagnosis, and management of common viral diseases.

    PubMed

    Weber, E P Scott

    2013-09-01

    Viral dermatopathies of fish bear clinical signs similar to those of dermatopathies from other causes. This article offers an overview to approaching dermatologic presentations in fish, with an emphasis on sampling, diagnosis, and management of viral dermatopathies, building on previous publications. It is vital to recognize clinical signs associated with viral dermatopathies because there are currently no treatments available. Avoidance and prevention is the key to controlling viral diseases in fish. Optimizing husbandry practices and providing appropriate quarantine procedures can help prevent viral disease outbreaks in collection and aquaculture stocks. PMID:24018032

  7. Accumulated lipids rather than the rigid cell walls impede the extraction of genetic materials for effective colony PCRs in Chlorella vulgaris

    PubMed Central

    2013-01-01

    Background Failure of colony PCRs in green microalga Chlorella vulgaris is typically attributed to the difficulty in disrupting its notoriously rigid cell walls for releasing the genetic materials and therefore the development of an effective colony PCR procedure in C. vulgaris presents a challenge. Results Here we identified that colony PCR results were significantly affected by the accumulated lipids rather than the rigid cell walls of C. vulgaris. The higher lipids accumulated in C. vulgaris negatively affects the effective amplification by DNA polymerase. Based on these findings, we established a simple and extremely effective colony PCR procedure in C. vulgaris. By simply pipetting/votexing the pellets of C. vulgaris in 10 ul of either TE (10 mM Tris/1 mM EDTA) or 0.2% SDS buffer at room temperature, followed by the addition of 10 ul of either hexane or Phenol:Chloroform:Isoamyl Alcohol in the same PCR tube for extraction. The resulting aqueous phase was readily PCR-amplified as genomic DNA templates as demonstrated by successful amplification of the nuclear 18S rRNA and the chloroplast rbcL gene. This colony PCR protocol is effective and robust in C. vulgaris and also demonstrates its effectiveness in other Chlorella species. Conclusions The accumulated lipids rather than the rigid cell walls of C. vulgaris significantly impede the extraction of genetic materials and subsequently the effective colony PCRs. The finding has the potential to aid the isolation of high-quality total RNAs and mRNAs for transcriptomic studies in addition to the genomic DNA isolation in Chlorella. PMID:24219401

  8. Use of Neural Network and Genetic Algorithm to Model Scanning Electron Microscopy for Enhanced Image of Material Surfaces

    Microsoft Academic Search

    Byungwhan Kim; Daehyun Kim; Sung Wook Baik; Sang Bum Lee; Dong Hwan Kim

    2011-01-01

    Scanning electron microscope (SEM) is a typical means to take an image of material surfaces. Enhancing the resolution of surface images is complicated by the presence of complex SEM components. SEM characteristics are studied as a function of its component by means of a statistical factor analysis as well as by constructing a neural network prediction model. A face-centered Box

  9. Finding and identifying the viral needle in the metagenomic haystack: trends and challenges

    PubMed Central

    Soueidan, Hayssam; Schmitt, Louise-Amélie; Candresse, Thierry; Nikolski, Macha

    2015-01-01

    Collectively, viruses have the greatest genetic diversity on Earth, occupy extremely varied niches and are likely able to infect all living organisms. Viral infections are an important issue for human health and cause considerable economic losses when agriculturally important crops or husbandry animals are infected. The advent of metagenomics has provided a precious tool to study viruses by sampling them in natural environments and identifying the genomic composition of a sample. However, reaching a clear recognition and taxonomic assignment of the identified viruses has been hampered by the computational difficulty of these problems. In this perspective paper we examine the trends in current research for the identification of viral sequences in a metagenomic sample, pinpoint the intrinsic computational difficulties for the identification of novel viral sequences within metagenomic samples, and suggest possible avenues to overcome them. PMID:25610431

  10. Assembly of viral genomes from metagenomes

    PubMed Central

    Smits, Saskia L.; Bodewes, Rogier; Ruiz-Gonzalez, Aritz; Baumgärtner, Wolfgang; Koopmans, Marion P.; Osterhaus, Albert D. M. E.; Schürch, Anita C.

    2014-01-01

    Viral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow rapid phylogenetic characterization of these new viruses. Often, however, complete viral genomes are not recovered, but rather several distinct contigs derived from a single entity are, some of which have no sequence homology to any known proteins. De novo assembly of single viruses from a metagenome is challenging, not only because of the lack of a reference genome, but also because of intrapopulation variation and uneven or insufficient coverage. Here we explored different assembly algorithms, remote homology searches, genome-specific sequence motifs, k-mer frequency ranking, and coverage profile binning to detect and obtain viral target genomes from metagenomes. All methods were tested on 454-generated sequencing datasets containing three recently described RNA viruses with a relatively large genome which were divergent to previously known viruses from the viral families Rhabdoviridae and Coronaviridae. Depending on specific characteristics of the target virus and the metagenomic community, different assembly and in silico gap closure strategies were successful in obtaining near complete viral genomes. PMID:25566226

  11. Viral infections of the folds (intertriginous areas).

    PubMed

    Ad??en, Esra; Önder, Meltem

    2015-01-01

    Viruses are considered intracellular obligates with a nucleic acid, either RNA or DNA. They have the ability to encode proteins involved in viral replication and production of the protective coat within the host cells but require host cell ribosomes and mitochondria for translation. The members of the families Herpesviridae, Poxviridae, Papovaviridae, and Picornaviridae are the most commonly known agents for the cutaneous viral diseases, but other virus families, such as Adenoviridae, Togaviridae, Parvoviridae, Paramyxoviridae, Flaviviridae, and Hepadnaviridae, can also infect the skin. Though the cutaneous manifestations of viral infections are closely related to the type and the transmission route of the virus, viral skin diseases may occur in almost any part of the body. In addition to friction caused by skin-to-skin touch, skin folds are warm and moist areas of the skin that have limited air circulation. These features provide a fertile breeding ground for many kinds of microorganisms, including bacteria and fungi. In contrast to specific bacterial and fungal agents that have an affinity for the skin folds, except for viral diseases of the anogenital area, which have well-known presentations, viral skin infections that have a special affinity to the skin folds are not known. Many viral exanthems may affect the skin folds during the course of the infection, but here we focus only on the ones that usually affect the fold areas and also on the less well-known conditions or recently described associations. PMID:26051057

  12. BOVINE VIRAL DIARRHEA VIRUS PERSISTENTLY INFECTED AND ACUTELY INFECTED CALVES: ASSAYS FOR VIRAL INFECTIVITY, POLYMERASE CHAIN REACTION ANALYSIS, AND ANTIGEN DETECTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are numerous assays for bovine viral diarrhea virus (BVDV) detecting infectious virus, nucleic material, and antigen. Persistently infected (PI) and acutely/transiently infected calves with BVDV represent two different manifestations. Diagnostic test results impact on differentiation of PI o...

  13. New Metrics for Evaluating Viral Respiratory Pathogenesis

    PubMed Central

    Menachery, Vineet D.; Gralinski, Lisa E.; Baric, Ralph S.; Ferris, Martin T.

    2015-01-01

    Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis. PMID:26115403

  14. Endosomal vesicles as vehicles for viral genomes.

    PubMed

    Nour, Adel M; Modis, Yorgo

    2014-08-01

    The endocytic pathway is the principal cell entry pathway for large cargos and pathogens. Among the wide variety of specialized lipid structures within endosomes, the intraluminal vesicles (ILVs) formed in early endosomes (EEs) and transferred to late endosomal compartments are emerging as critical effectors of viral infection and immune recognition. Various viruses deliver their genomes into these ILVs, which serve as vehicles to transport the genome to the nuclear periphery for replication. When secreted as exosomes, ILVs containing viral genomes can infect permissive cells or activate immune responses in myeloid cells. We therefore propose that endosomal ILVs and exosomes are key effectors of viral pathogenesis. PMID:24746011

  15. Dendritic cells in viral infections.

    PubMed

    Belz, Gabrielle; Mount, Adele; Masson, Frederick

    2009-01-01

    Antigen presenting cells (APCs) are recognized as key initiators of adaptive immunity, particularly to pathogens, by eliciting a rapid and potent immune attack on infected cells. Amongst APCs, dendritic cells (DCs) are specially equipped to initiate and regulate immune responses in a manner that depends on signals they receive from microbes and their cellular environment. To achieve this, they are equipped with highly efficient mechanisms that allow them to detect pathogens, to capture, process and present antigens, and to activate and guide the differentiation of T cells into effector and memory cells. DCs can no longer be considered as a homogeneous cell type performing a single function, but are heterogeneous both in phenotype, function and dependence on inflammatory stimuli for their formation and responsiveness. Recent studies of DC subtypes have highlighted the contrasting roles of different professional APCs in activating divergent arms of the immune response towards pathogens. In this review, we discuss the progress that has been made in dissecting the attributes of different DC subsets that migrate into, or reside permanently, within lymphoid tissues and their putative roles in the induction of the anti-viral immune response. PMID:19031021

  16. A Rapid Method for Viral Particle Detection in Viral-Induced Gastroenteritis: A TEM Study

    NASA Astrophysics Data System (ADS)

    Hicks, M. John; Barrish, James P.; Hayes, Elizabeth S.; Leer, Laurie C.; Estes, Mary K.; Cubitt, W. D.

    1995-10-01

    Infectious gastroenteritis is a common cause of hospitalization in the pediatric population. The most frequent cause of gastroenteritis is viral in origin. The purpose of this study was to compare a rapid modified negative-staining TEM method with the conventional pseudoreplica technique in detection of viral particles in fecal samples from children with viral gastroenteritis. The modified negative-staining method resulted in a significantly higher (2.5 ± 0.5, p = 0.02) viral rating score than that for the conventional pseudoreplica technique (1.7 ± 0.4). In addition, the preparation time for the negative-staining method was approximately one fifth that for the conventional pseudoreplica technique. Rapid diagnosis of viral gastroenteritis may be made by ultrastructural detection of viral particles in fecal samples using the negative staining technique.

  17. The role of viral evolution in rabies host shifts and emergence

    PubMed Central

    Mollentze, Nardus; Biek, Roman; Streicker, Daniel G

    2014-01-01

    Despite its ability to infect all mammals, Rabies virus persists in numerous species-specific cycles that rarely sustain transmission in alternative species. The determinants of these species-associations and the adaptive significance of genetic divergence between host-associated viruses are poorly understood. One explanation is that epidemiological separation between reservoirs causes neutral genetic differentiation. Indeed, recent studies attributed host shifts to ecological factors and selection of ‘preadapted’ viral variants from the existing viral community. However, phenotypic differences between isolates and broad scale comparative and molecular evolutionary analyses indicate multiple barriers that Rabies virus must overcome through adaptation. This review assesses various lines of evidence and proposes a synthetic hypothesis for the respective roles of ecology and evolution in Rabies virus host shifts. PMID:25064563

  18. History and Current Status of Development and Use of Viral Insecticides in China

    PubMed Central

    Sun, Xiulian

    2015-01-01

    The use of insect viruses as biological control agents started in the early 1960s in China. To date, more than 32 viruses have been used to control insect pests in agriculture, forestry, pastures, and domestic gardens in China. In 2014, 57 products from 11 viruses were authorized as commercial viral insecticides by the Ministry of Agriculture of China. Approximately 1600 tons of viral insecticidal formulations have been produced annually in recent years, accounting for about 0.2% of the total insecticide output of China. The development and use of Helicoverpa armigera nucleopolyhedrovirus, Mamestra brassicae nucleopolyhedrovirus, Spodoptera litura nucleopolyhedrovirus, and Periplaneta fuliginosa densovirus are discussed as case studies. Additionally, some baculoviruses have been genetically modified to improve their killing rate, infectivity, and ultraviolet resistance. In this context, the biosafety assessment of a genetically modified Helicoverpa armigera nucleopolyhedrovirus is discussed. PMID:25609304

  19. History and current status of development and use of viral insecticides in China.

    PubMed

    Sun, Xiulian

    2015-01-01

    The use of insect viruses as biological control agents started in the early 1960s in China. To date, more than 32 viruses have been used to control insect pests in agriculture, forestry, pastures, and domestic gardens in China. In 2014, 57 products from 11 viruses were authorized as commercial viral insecticides by the Ministry of Agriculture of China. Approximately 1600 tons of viral insecticidal formulations have been produced annually in recent years, accounting for about 0.2% of the total insecticide output of China. The development and use of Helicoverpa armigera nucleopolyhedrovirus, Mamestra brassicae nucleopolyhedrovirus, Spodoptera litura nucleopolyhedrovirus, and Periplaneta fuliginosa densovirus are discussed as case studies. Additionally, some baculoviruses have been genetically modified to improve their killing rate, infectivity, and ultraviolet resistance. In this context, the biosafety assessment of a genetically modified Helicoverpa armigera nucleopolyhedrovirus is discussed. PMID:25609304

  20. An update on canine coronaviruses: viral evolution and pathobiology.

    PubMed

    Decaro, Nicola; Buonavoglia, Canio

    2008-12-10

    The emergence of human severe acute respiratory syndrome incited renewed interest in animal coronaviruses (CoVs) as potential agents of direct and indirect zoonoses. The reinforced epidemiological surveillance on CoVs has led to the identification of new viruses, genotypes, pathotypes and host variants in animals and humans. In dogs, a CoV associated with mild enteritis, canine coronavirus (CCoV), has been known since 1970s. CoV strains with different biological and genetic properties with respect to classical CCoV strains have been identified in dogs in the last few years, leading to a full reconsideration of the CoV-induced canine diseases. The genetic evolution of dog CoVs is paradigmatic of how CoVs evolve through accumulation of point mutations, insertions or deletions in the viral genome, that led to the emergence of new genotypes (CCoV type I), biotypes (pantropic CCoV) and host variants (canine respiratory coronavirus). This paper is a review of the current literature on the recent genetic evolution of CCoV and emergence of new CoVs in the dog. The significances of the newly acquired information for the canine health status and prophylaxis programmes are also discussed. PMID:18635322

  1. Genetic Counseling

    MedlinePLUS

    ... this page It's been added to your dashboard . Genetic counseling Genetic counseling is a service to help ... child care and genetic testing. Who should get genetic counseling? Anyone who has unanswered questions about origins ...

  2. IFITM Proteins Restrict Viral Membrane Hemifusion

    E-print Network

    2013-01-01

    an intermediate of fusion, referred to as a cold arrestedcold arrested state (CAS), PLOS Pathogens | www.plospathogens.org January 2013 | Volume 9 | Issue 1 | e1003124 Restriction of Viral Membrane Fusion

  3. Viral fitness: definitions, measurement, and current insights

    USGS Publications Warehouse

    Wargo, Andrew R.; Kurath, Gael

    2012-01-01

    Viral fitness is an active area of research, with recent work involving an expanded number of human, non-human vertebrate, invertebrate, plant, and bacterial viruses. Many publications deal with RNA viruses associated with major disease emergence events, such as HIV-1, influenza virus, and Dengue virus. Study topics include drug resistance, immune escape, viral emergence, host jumps, mutation effects, quasispecies diversity, and mathematical models of viral fitness. Important recent trends include increasing use of in vivo systems to assess vertebrate virus fitness, and a broadening of research beyond replicative fitness to also investigate transmission fitness and epidemiologic fitness. This is essential for a more integrated understanding of overall viral fitness, with implications for disease management in the future.

  4. Theory of conformational transitions of viral shells

    NASA Astrophysics Data System (ADS)

    Guérin, Thomas; Bruinsma, Robijn

    2007-12-01

    We propose a continuum theory for the conformational transitions of viral shells. Conformational transitions of viral shells, as encountered during viral maturation, are associated with a soft mode instability of the capsid proteins [F. Tama and C. L. Brooks, J. Mol. Biol. 345(2), 299 (2005)]. The continuum theory presented here is an adaptation of the Ginzburg-Landau theory of soft-mode structural phase transitions of solids to viral shells. The theory predicts that the conformational transitions are characterized by a pronounced softening of the shell elasticity in the critical region. We demonstrate that the thermodynamics of the conformational transition can be probed quantitatively by a micromechanical atomic force microscope study. The external force can drive a capsid into a state of phase coexistence characterized by a highly nonlinear force deformation curve.

  5. Surveillance for Viral Hepatitis - United States, 2012

    MedlinePLUS

    ... Home Page Share Compartir Surveillance for Viral Hepatitis – United States, 2012 Entire report in a printable format [PDF - ... Reported cases of acute hepatitis A, by state ? United States, 2008–2012 Table 2.2 Clinical characteristics of ...

  6. Emerging viral infections of the nervous system

    Microsoft Academic Search

    Richard T. Johnson

    2003-01-01

    New viral infections of the nervous system have been appearing with great regularity. Some result from the evolution of new\\u000a agents and others from the entry of viruses into new hosts or environments. The emergence of neurovirulent enteroviruses causing\\u000a a paralytic poliomyelitis syndrome and rhomboencephalitis represent the evolution of new human viruses. Most emerging viral\\u000a infections represent movement of an

  7. Intra-host viral variability in children clinically infected with H1N1 (2009) pandemic influenza.

    PubMed

    Bourret, Vincent; Croville, Guillaume; Mansuy, Jean-Michel; Mengelle, Catherine; Mariette, Jérôme; Klopp, Christophe; Genthon, Clémence; Izopet, Jacques; Guérin, Jean-Luc

    2015-07-01

    Recent in-depth genetic analyses of influenza A virus samples have revealed patterns of intra-host viral genetic variability in a variety of relevant systems. These have included laboratory infected poultry, horses, pigs, chicken eggs and swine respiratory cells, as well as naturally infected poultry and horses. In humans, next generation sequencing techniques have enabled the study of genetic variability at specific positions of the viral genome. The present study investigated how 454 pyrosequencing could help unravel intra-host genetic diversity patterns on the full-length viral hæmagglutinin and neuraminidase genes from human H1N1 (2009) pandemic influenza clinical cases. This approach revealed unexpected patterns of co-infection in a 3-week old toddler, arising from rapid and complex reassortment phenomena on a local epidemiological scale. It also suggested the possible existence of very low frequency mutants resistant to neuraminidase inhibitors in two untreated patients. As well as revealing patterns of intra-host viral variability, this report highlights technical challenges in the appraisal of scientifically and medically relevant topics such as the natural occurrence of homologous recombination or very low frequency drug-resistant variants in influenza virus populations. PMID:25891282

  8. Vaccines 85: Molecular and chemical basis of resistance to parasitic, bacterial, and viral diseases

    SciTech Connect

    Lerner, R.A.; Chanock, R.M.; Brown, F.

    1985-01-01

    This book contains 70 selections. Some of the selection titles are: Structure of the Gene Encoding of Immunodominant Surface Antigen on the Sprozoite of the Human Malaria Parasite Plasmodium falciparum; Cloning and Expression in Bacteria of the Genes for Merozite-specific Antigens from the Malaria Parasite Plasmodium falciparum; A Major Surface Antigen of Plasmodium falciparum in Merozoites: Studies on the Protein and its Gene; Genetic Construction of Cholera Vaccine Prototypes; and Viral Genes, Cytotoxic T Lymphocytes and Immunity.

  9. Enhancement of Innate Immunity to Control Viral Infections in Livestock Species 

    E-print Network

    Ramirez Carvajal, Lisbeth

    2014-07-08

    for oncolytic viral therapy because it can selectively infect and kill malignant cells. VSV ability as oncolytic virus has demonstrated success in preclinical studies against a variety of malignancies, including prostate, breast cancer, melanoma, colorectal...-I-like receptors [RLRs: retinoic acid- inducible gene I (RIG-I); melanoma differentiation-associated gene 5 (MDA5); and laboratory of genetics and physiology 2 (LGP2)] and nucleotide-binding oligomerization domain (NOD) like receptors (NLRs) (76, 80, 81). A...

  10. Distribution pattern of bovine viral diarrhoea virus strains in intensive cattle herds in Italy

    Microsoft Academic Search

    C. Luzzago; C. Bandi; V. Bronzo; G. Ruffo; A. Zecconi

    2001-01-01

    The genetic variation of bovine viral diarrhoea virus (BVDV) was studied by comparative nucleotide sequence analysis of 26 Italian field strains collected during the period 1995–2000 in 18 cattle herds. A fragment within the 5?-untranslated region (UTR) was sequenced directly from gel-purified products obtained by reverse transcription polymerase chain reaction. BVDV-1b (n=14), -1c (n=1), -1d (n=1) and BVDV-2 (n=2) strains

  11. Detection, characterization, and control of bovine viral diarrhea virus infection in a large commercial dairy herd

    PubMed Central

    Schefers, Jeremy M.; Collins, James E.; Goyal, Sagar M.; Ames, Trevor R.

    2009-01-01

    Detection, genetic characterization, and control of bovine viral diarrhea virus (BVDV) disease in a large commercial dairy herd is reported. Precolostral BVDV serum antibody was detected in 5.3% (12/226) of newborn calves before the test and removal of persistently infected (PI) animals and in 0.4% (2/450) of newborn calves after the removal of PI heifers. PMID:20046608

  12. Involvement of a Bovine Viral Diarrhea Virus NS5B Locus in Virion Assembly

    Microsoft Academic Search

    Israrul H. Ansari; Li-Mei Chen; Delin Liang; Laura H. Gil; Weidong Zhong; Ruben O. Donis

    2004-01-01

    A novel mutant of bovine viral diarrhea virus (BVDV) was found with a virion assembly phenotype attrib- utable to an insertion into the NS5B polymerase locus. This mutant, termed 5B-741, was engineered by reverse genetics to express NS5B with a C-terminal peptide tag of 22 amino acids. Electroporation of bovine cells with genomic RNA from this mutant showed levels RNA

  13. Effects of chemical carcinogens on hemopoiesis, immunopoiesis and viral oncogenesis

    SciTech Connect

    OKunewick, J.P.; Raikow, R.B.; Buffo, M.J.; Kociban, D.L.; Meredith, R.F.

    1983-06-01

    Studies were undertaken to evaluate the effects of various selected carcinogenic hydrocarbon derivatives on the hematopoietic stem cell, on the immune response, and on viral induced leukemogenesis. The hydrocarbons chosen were recognized by-products of fossil fuel production and usage and all had been shown to induce cancer in animals given multiple exposure to them. This study concentrated on the effects of a single exposure to these agents. Significant effects were found in all aspects of the study. Depression of hematopoietic activity was seen with every chemical. Immune response was depressed by some, but not all, of the chemicals. A single exposure to most (but not all) of these chemicals also resulted in an increased incidence of leukemia in mice later given a leukemia causing virus. However, the amount of enhancement of leukemogenesis that was seen was dependent upon several factors, which included: (A) the natural genetically determined sensitivity of the test mouse to virus; (B) the action of the chemical itself; and (C) the time between chemical and virus exposure. In a particularly notable instance, one of the hydrocarbons actually had a protective effect against development of the viral leukemia, delaying it and reducing the incidence.

  14. Synthetic DNA vaccine strategies against persistent viral infections

    PubMed Central

    Villarreal, Daniel O; Talbott, Kendra T; Choo, Daniel K; Shedlock, Devon J; Weiner, David B

    2015-01-01

    The human body has developed an elaborate defense system against microbial pathogens and foreign antigens. However, particular microbes have evolved sophisticated mechanisms to evade immune surveillance, allowing persistence within the human host. In an effort to combat such infections, intensive research has focused on the development of effective prophylactic and therapeutic countermeasures to suppress or clear persistent viral infections. To date, popular therapeutic strategies have included the use of live-attenuated microbes, viral vectors and dendritic-cell vaccines aiming to help suppress or clear infection. In recent years, improved DNA vaccines have now re-emerged as a promising candidate for therapeutic intervention due to the development of advanced optimization and delivery technologies. For instance, genetic optimization of synthetic plasmid constructs and their encoded antigens, in vivo electroporation-mediated vaccine delivery, as well as codelivery with molecular adjuvants have collectively enhanced both transgene expression and the elicitation of vaccine-induced immunity. In addition, the development of potent heterologous prime–boost regimens has also provided significant contributions to DNA vaccine immunogenicity. Herein, the authors will focus on these recent improvements to this synthetic platform in relation to their application in combating persistent virus infection. PMID:23659301

  15. Pediatric knowledge about acute viral hepatitis.

    PubMed

    Franca, Rita; Silva, Luciana; Melo, Maria Clotildes; Cavalcante, Suzy; Lima, Bruno; Rocha, Anita; Gomes, Cristiana; Franca, Mônica

    2004-06-01

    Knowledge about hepatotropic viruses is crucial for pediatricians because of the high prevalence of viral hepatitis during childhood. The multiplicity of hepatotropic viruses, the spectrum of acute and chronic infections, and the sequels of viral hepatitis result in a need for physicians to better understand the clinical and epidemiological context of patients with viral hepatitis, as well as the importance of prevention measures for hepatitis. A descriptive cross-sectional study was made of pediatrician's knowledge about viral hepatitis, through questionnaires to 574 pediatricians, with no obligation of identification. The pediatricians were recruited among those who attended a national Congress of Pediatrics in Brasília, Brazil. Among these pediatricians, 50.1% frequently treated cases of hepatitis, and 74.7% indicated that they had knowledge of the existence of five hepatotropic viruses; 14.5% knew about at least four types of hepatitis complications, while only 7.7% and 4.3% were able to correctly diagnose viral hepatitis A and B, respectively. Many (28.4%) did not know how to treat the patients adequately. Only 37.5% had already recommended vaccination against hepatitis B. Only 50.2% of the pediatricians had been vaccinated against hepatitis B. We concluded that it is crucial to make pediatricians more knowledgeable about viral hepatitis, through continued education programs, especially emphasizing prevention procedures. PMID:15476061

  16. Viral Metagenomics: MetaView Software

    SciTech Connect

    Zhou, C; Smith, J

    2007-10-22

    The purpose of this report is to design and develop a tool for analysis of raw sequence read data from viral metagenomics experiments. The tool should compare read sequences of known viral nucleic acid sequence data and enable a user to attempt to determine, with some degree of confidence, what virus groups may be present in the sample. This project was conducted in two phases. In phase 1 we surveyed the literature and examined existing metagenomics tools to educate ourselves and to more precisely define the problem of analyzing raw read data from viral metagenomic experiments. In phase 2 we devised an approach and built a prototype code and database. This code takes viral metagenomic read data in fasta format as input and accesses all complete viral genomes from Kpath for sequence comparison. The system executes at the UNIX command line, producing output that is stored in an Oracle relational database. We provide here a description of the approach we came up with for handling un-assembled, short read data sets from viral metagenomics experiments. We include a discussion of the current MetaView code capabilities and additional functionality that we believe should be added, should additional funding be acquired to continue the work.

  17. Genetic Science Learning Center

    MedlinePLUS

    ... 2015 News Our Team What We Do Educational Materials Teacher Professional Development Research and Evaluation Community Collaboration Conferences Current Projects Publications Contact The Genetic Science Learning Center at The University of Utah is ...

  18. Medical genetics

    SciTech Connect

    Nora, J.J.; Fraser, F.C.

    1989-01-01

    This book presents a discussion of medical genetics for the practitioner treating or counseling patients with genetic disease. It includes a discussion of the relationship of heredity and diseases, the chromosomal basis for heredity, gene frequencies, and genetics of development and maldevelopment. The authors also focus on teratology, somatic cell genetics, genetics and cancer, genetics of behavior.

  19. Edinburgh Research Explorer The genetics of hostvirus coevolution in invertebrates

    E-print Network

    Millar, Andrew J.

    Edinburgh Research Explorer The genetics of host­virus coevolution in invertebrates Citation for published version: Obbard, DJ & Dudas, G 2014, 'The genetics of host­virus coevolution in invertebrates­virus coevolution in invertebrates Darren J Obbard1,2 and Gytis Dudas1 Although viral infection and antiviral

  20. What can we predict about viral evolution and emergence?

    PubMed Central

    Holmes, Edward C.

    2013-01-01

    Predicting the emergence of infectious diseases has been touted as one of the most important goals of biomedical science, with an array of funding schemes and research projects. However, evolutionary biology generally has a dim view of prediction, and there is a danger that erroneous predictions will mean a misuse of resources and undermine public confidence. Herein, I outline what can be realistically predicted about viral evolution and emergence, argue that any success in predicting what may emerge is likely to be limited, but that forecasting how viruses might evolve and spread following emergence is more tractable. I also emphasize that a properly grounded research program in disease prediction must involve a synthesis of ecological and genetic perspectives. PMID:23273851

  1. Detection of viral pathogens in high grade gliomas from unmapped next-generation sequencing data.

    PubMed

    Cimino, Patrick J; Zhao, Guoyan; Wang, David; Sehn, Jennifer K; Lewis, James S; Duncavage, Eric J

    2014-06-01

    Viral pathogens have been implicated in the development of certain cancers including human papillomavirus (HPV) in squamous cell carcinoma and Epstein-Barr virus (EBV) in Burkitt's lymphoma. The significance of viral pathogens in brain tumors is controversial, and human cytomegalovirus (HCMV) has been associated with glioblastoma (GBM) in some but not all studies, making the role of HCMV unclear. In this study we sought to determine if viral pathogen sequences could be identified in an unbiased manner from previously discarded, unmapped, non-human, next-generation sequencing (NGS) reads obtained from targeted oncology, panel-based sequencing of high grade gliomas (HGGs), including GBMs. Twenty one sequential HGG cases were analyzed by a targeted NGS clinical oncology panel containing 151 genes using DNA obtained from formalin-fixed, paraffin-embedded (FFPE) tissue. Sequencing reads that did not map to the human genome (average of 38,000 non-human reads/case (1.9%)) were filtered and low quality reads removed. Extracted high quality reads were then sequentially aligned to the National Center for Biotechnology Information (NCBI) non-redundant nucleotide (nt and nr) databases. Aligned reads were classified based on NCBI taxonomy database and all eukaryotic viral sequences were further classified into viral families. Two viral sequences (both herpesviruses), EBV and Roseolovirus were detected in 5/21 (24%) cases and in 1/21 (5%) cases, respectively. None of the cases had detectable HCMV. Of the five HGG cases with detectable EBV DNA, four had additional material for EBV in situ hybridization (ISH), all of which were negative for expressed viral sequence. Overall, a similar discovery approach using unmapped non-human NGS reads could be used to discover viral sequences in other cancer types. PMID:24704430

  2. Genetics Education Network

    NSDL National Science Digital Library

    Kenna Shaw (American Society of Human Genetics; )

    2006-05-31

    This is a searchable database of the state science standards reflective of genetics content for each grade in the US. Genetics content includes standards on heredity, DNA, evolution, population ecology, some disease and biotechnology. One half of the standards are currently linked to websites that cover the material and more are vetted and linked every day. Activities to help teach the material will also be added soon.

  3. Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak

    PubMed Central

    Romano, Camila Malta; Lauck, Michael; Salvador, Felipe S.; Lima, Célia Rodrigues; Villas-Boas, Lucy S.; Araújo, Evaldo Stanislau A.; Levi, José Eduardo; Pannuti, Claudio Sergio; O’Connor, David; Kallas, Esper Georges

    2013-01-01

    Background High genetic diversity at both inter- and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections. Methods and Principal Findings We deep sequenced the complete genome of ten DENV2 isolates from representative classical and severe cases sampled in a large outbreak in Brazil using two different approaches. Analysis of the consensus genomes confirmed the larger extent of the 2010 epidemic in comparison to a previous epidemic caused by the same viruses in another city two years before (genetic distance?=?0.002 and 0.0008 respectively). Analysis of viral populations within the host revealed a high level of conservation. After excluding homopolymer regions of 454/Roche generated sequences, we found 10 to 44 variable sites per genome population at a frequency of >1%, resulting in very low intra-host genetic diversity. While up to 60% of all variable sites at intra-host level were non-synonymous changes, only 10% of inter-host variability resulted from non-synonymous mutations, indicative of purifying selection at the population level. Conclusions and Significance Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability. PMID:23936406

  4. Exosomes from Hepatitis C Infected Patients Transmit HCV Infection and Contain Replication Competent Viral RNA in Complex with Ago2-miR122-HSP90

    PubMed Central

    Kodys, Karen; Bala, Shashi; Szabo, Gyongyi

    2014-01-01

    Antibodies targeting receptor-mediated entry of HCV into hepatocytes confer limited therapeutic benefits. Evidence suggests that exosomes can transfer genetic materials between cells; however, their role in HCV infection remains obscure. Here, we show that exosomes isolated from sera of chronic HCV infected patients or supernatants of J6/JFH1-HCV-infected Huh7.5 cells contained HCV RNA. These exosomes could mediate viral receptor-independent transmission of HCV to hepatocytes. Negative sense HCV RNA, indicative of replication competent viral RNA, was present in exosomes of all HCV infected treatment non-responders and some treatment-naïve individuals. Remarkably, HCV RNA was associated with Ago2, HSP90 and miR-122 in exosomes isolated from HCV-infected individuals or HCV-infected Huh7.5 cell supernatants. Exosome-loading with a miR-122 inhibitor, or inhibition of HSP90, vacuolar H+-ATPases, and proton pumps, significantly suppressed exosome-mediated HCV transmission to naïve cells. Our findings provide mechanistic evidence for HCV transmission by blood-derived exosomes and highlight potential therapeutic strategies. PMID:25275643

  5. The Aromatic Domain of the Coronavirus Class I Viral Fusion Protein Induces Membrane Permeabilization: Putative Role during Viral Entry

    E-print Network

    Wimley, William C.

    animal viruses requires fusion between the viral membrane and a cellular membrane, either the plasma) glycoprotein, a class I viral fusion protein. During viral and target cell membrane fusion, the heptad repeat to drive apposition and subsequent fusion of viral and target cell membranes; however, the exact mechanism

  6. Viral loads in clinical specimens and SARS manifestations.

    PubMed

    Hung, I F N; Lau, S K P; Woo, P C Y; Yuen, K Y

    2009-12-01

    1. A high viral load in nasopharyngeal aspirate (with or without a high viral load in serum) is a useful prognostic indicator of respiratory failure or mortality. The presence of viral RNA in multiple body sites is also indicative of poor prognosis. 2. Early treatment with an effective antiviral agent before day 10 may decrease the peak viral load, and thus ameliorate the clinical symptoms and mortality, and reduce viral shedding and the risk of transmission PMID:20393220

  7. Action mechanisms of petroleum hydrocarbons present in waters impacted by an oil spill on the genetic material of Allium cepa root cells.

    PubMed

    Leme, Daniela Morais; de Angelis, Dejanira de Franceschi; Marin-Morales, Maria Aparecida

    2008-07-30

    Chromosomal aberration (CA) assays have been widely used, not only to assess the genotoxic effects of chemical agents, but also to evaluate their action mechanisms on the genetic material of exposed organisms. This is of particular interest, since such analyses provide a better knowledge related to the action of these agents on DNA. Among test organisms, Allium cepa is an outstanding species due to its sensitivity and suitable chromosomal features, which are essential for studies on chromosomal damage or disturbances in cell cycle. The goal of the present study was to analyze the action mechanisms of chemical agents present in petroleum polluted waters. Therefore, CA assay was carried out in A. cepa meristematic cells exposed to the Guaecá river waters, located in the city of São Sebastião, SP, Brazil, which had its waters impacted by an oil pipeline leak. Analyses of the aberration types showed clastogenic and aneugenic effects for the roots exposed to the polluted waters from Guaecá river, besides the induction of cell death. Probably all the observed effects were induced by the petroleum hydrocarbons derived from the oil leakage. PMID:18556073

  8. DEVELOPMENT OF GENETICALLY ENHANCED BACULOVIRUS PESTICIDES

    EPA Science Inventory

    The assessment of potential environmental impacts of genetically improved viral pesticides will include an evaluation of the properties of the foreign gene product(s) as well as the biological properties of altered virus itself. It is anticipated that in the near future several t...

  9. Oncolytic Viral Therapy Using Reovirus.

    PubMed

    Thirukkumaran, Chandini; Morris, Don G

    2015-01-01

    Current mainstays in cancer treatment such as chemotherapy, radiation therapy, hormonal manipulation, and even targeted therapies such as Trastuzumab (herceptin) for breast cancer or Iressa (gefitinib) for non-small cell lung cancer among others are limited by lack of efficacy, cellular resistance, and toxicity. Dose escalation and combination therapies designed to overcome resistance and increase efficacy are limited by a narrow therapeutic index. Oncolytic viruses are one such group of new biological therapeutics that appears to have a wide spectrum of anticancer activity with minimal human toxicity.Since the malignant phenotype of tumors is the culmination of multiple mutations that occur in genes eventually leading to aberrant signaling pathways, oncolytic viruses either natural or engineered specifically target tumor cells taking advantage of this abnormal cellular signaling for their replication. Reovirus is one such naturally occurring double-stranded RNA virus that exploits altered signaling pathways (including Ras) in a myriad of cancers. The ability of reovirus to infect and lyse tumors under in vitro, in vivo, and ex vivo conditions has been well documented previously by us and others. The major mechanism of reovirus oncolysis of cancer cells has been shown to occur through apoptosis with autophagy taking place during this process in certain cancers. In addition, the synergistic antitumor effects of reovirus in combination with radiation or chemotherapy have also been demonstrated for reovirus resistant and moderately sensitive tumors. Recent progress in our understanding of viral immunology in the tumor microenvironment has diverted interest in exploring immunologic mechanisms to overcome resistance exhibited by chemotherapeutic drugs in cancer. Thus, currently several investigations are focusing on immune potentiating of reovirus for maximal tumor targeting. This chapter therefore has concentrated on immunologic cell death induction with reovirus as a novel approach to cancer therapy used under in vitro and in vivo conditions, as well as in a clinical setting. Reovirus phase I clinical trials have shown indications of efficacy, and several phase II/III trials are ongoing at present. Reovirus's extensive preclinical efficacy, replication competency, and low toxicity profile in humans have placed it as an attractive anticancer therapeutic for ongoing clinical testing that are highlighted in this chapter. PMID:26072409

  10. Dicer-2 Processes Diverse Viral RNA Species

    PubMed Central

    Sabin, Leah R.; Zheng, Qi; Thekkat, Pramod; Yang, Jamie; Hannon, Gregory J.; Gregory, Brian D.; Tudor, Matthew; Cherry, Sara

    2013-01-01

    RNA silencing pathways play critical roles in gene regulation, virus infection, and transposon control. RNA interference (RNAi) is mediated by small interfering RNAs (siRNAs), which are liberated from double-stranded (ds)RNA precursors by Dicer and guide the RNA-induced silencing complex (RISC) to targets. Although principles governing small RNA sorting into RISC have been uncovered, the spectrum of RNA species that can be targeted by Dicer proteins, particularly the viral RNAs present during an infection, are poorly understood. Dicer-2 potently restricts viral infection in insects by generating virus-derived siRNAs from viral RNA. To better characterize the substrates of Dicer-2, we examined the virus-derived siRNAs produced during the Drosophila antiviral RNAi response to four different viruses using high-throughput sequencing. We found that each virus was uniquely targeted by the RNAi pathway; dicing substrates included dsRNA replication intermediates and intramolecular RNA stem loops. For instance, a putative intergenic RNA hairpin encoded by Rift Valley Fever virus generates abundant small RNAs in both Drosophila and mosquito cells, while repetitive sequences within the genomic termini of Vaccinia virus, which give rise to abundant small RNAs in Drosophila, were found to be transcribed in both insect and mammalian cells. Moreover, we provide evidence that the RNA species targeted by Dicer-2 can be modulated by the presence of a viral suppressor of RNAi. This study uncovered several novel, heavily targeted features within viral genomes, offering insight into viral replication, viral immune evasion strategies, and the mechanism of antiviral RNAi. PMID:23424633

  11. Evaluation of the metabolic fate of munitions material (TNT & RDX) in plant systems and initial assessment of material interaction with plant genetic material (DNA). Initial assessment of plant DNA adducts as biomarkers

    SciTech Connect

    Harvey, S.D.; Clauss, T.W.; Fellows, R.J.; Cataldo, D.A.

    1995-08-01

    Genetic damage to deoxyribonucleic acid (DNA) has long been suspected of being a fundamental event leading to cancer. A variety of causal factors can result in DNA damage including photodimerization of base pairs, ionizing radiation, specific reaction of DNA with environmental pollutants, and nonspecific oxidative damage caused by the action of highly reactive oxidizing agents produced by metabolism. Because organisms depend on an unadulterated DNA template for reproduction, DNA repair mechanisms are an important defense for maintaining genomic integrity. The objective of this exploratory project was to evaluate the potential for TNT to form DNA adducts in plants. These adducts, if they exist in sufficient quantities, could be potential biomarkers of munitions exposure. The ultimate goal is to develop a simple analytical assay for the determination of blomarkers that is indicative of munitions contamination. DNA repair exists in dynamic equilibrium with DNA damage. Repair mechanisms are capable of keeping DNA damage at remarkably low concentrations provided that the repair capacity is not overwhelmed.

  12. Use of Bovine Viral Diarrhoea Virus as an Internal Control for Amplification of Hepatitis C Virus

    Microsoft Academic Search

    A. Cleland; P. Nettleton; L. M. Jarvis; P. Simmonds

    1999-01-01

    Background and Objectives: Screening for hepatitis C virus (HCV) by polymerase chain reaction (PCR) will be mandatory for screening blood and plasma donors in Europe and elsewhere. This study describes an internally controlled, highly sensitive PCR method designed for screening blood donations in pools. Material and Methods: RNA extracted from bovine viral diarrhoea virus (BVDV) was used as an internal

  13. Lethal mutagenesis failure may augment viral adaptation.

    PubMed

    Paff, Matthew L; Stolte, Steven P; Bull, James J

    2014-01-01

    Lethal mutagenesis, the attempt to extinguish a population by elevating its mutation rate, has been endorsed in the virology literature as a promising approach for treating viral infections. In support of the concept, in vitro studies have forced viral extinction with high doses of mutagenic drugs. However, the one known mutagenic drug used on patients commonly fails to cure infections, and in vitro studies typically find a wide range of mutagenic conditions permissive for viral growth. A key question becomes how subsequent evolution is affected if the viral population is mutated but avoids extinction--Is viral adaptation augmented rather than suppressed? Here we consider the evolution of highly mutated populations surviving mutagenesis, using the DNA phage T7. In assays using inhibitory hosts, whenever resistance mutants were observed, the mutagenized populations exhibited higher frequencies, but some inhibitors blocked plaque formation by even the mutagenized stock. Second, outgrowth of previously mutagenized populations led to rapid and potentially complete fitness recovery but polymorphism was slow to decay, and mutations exhibited inconsistent patterns of change. Third, the combination of population bottlenecks with mutagenesis did cause fitness declines, revealing a vulnerability that was not apparent from mutagenesis of large populations. The results show that a population surviving high mutagenesis may exhibit enhanced adaptation in some environments and experience little negative fitness consequences in many others. PMID:24092771

  14. Lethal Mutagenesis Failure May Augment Viral Adaptation

    PubMed Central

    Paff, Matthew L.; Stolte, Steven P.; Bull, James J.

    2014-01-01

    Lethal mutagenesis, the attempt to extinguish a population by elevating its mutation rate, has been endorsed in the virology literature as a promising approach for treating viral infections. In support of the concept, in vitro studies have forced viral extinction with high doses of mutagenic drugs. However, the one known mutagenic drug used on patients commonly fails to cure infections, and in vitro studies typically find a wide range of mutagenic conditions permissive for viral growth. A key question becomes how subsequent evolution is affected if the viral population is mutated but avoids extinction—Is viral adaptation augmented rather than suppressed? Here we consider the evolution of highly mutated populations surviving mutagenesis, using the DNA phage T7. In assays using inhibitory hosts, whenever resistance mutants were observed, the mutagenized populations exhibited higher frequencies, but some inhibitors blocked plaque formation by even the mutagenized stock. Second, outgrowth of previously mutagenized populations led to rapid and potentially complete fitness recovery but polymorphism was slow to decay, and mutations exhibited inconsistent patterns of change. Third, the combination of population bottlenecks with mutagenesis did cause fitness declines, revealing a vulnerability that was not apparent from mutagenesis of large populations. The results show that a population surviving high mutagenesis may exhibit enhanced adaptation in some environments and experience little negative fitness consequences in many others. PMID:24092771

  15. Specific Anti Cross-Infection Measures may Help to Prevent Viral Contamination of Dental Unit Waterlines: a Pilot Study

    Microsoft Academic Search

    M. Artini; G. L. Scoarughi; R. Papa; G. Dolci; M. De Luca; G. Orsini; S. Pappalardo; J. W. Costerton; L. Selan

    2008-01-01

    Background: In recent years, several reports have suggested, but never definitely demonstrated that dental units (DU) could be potential sources of viral cross-infections sustained by viral agents including HBV, HCV and HIV. This work aims at assessing the risk of HCV cross-infection by dental unit water lines (DUWLs). Materials and Methods: Ten anti-HCV positive viremic patients were submitted to dental

  16. Medical genetics

    SciTech Connect

    Jorde, L.B.; Carey, J.C.; White, R.L.

    1995-10-01

    This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

  17. Genetic algorithms

    NASA Technical Reports Server (NTRS)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

  18. [Epidemiology of viral hepatitis in Mexico].

    PubMed

    Panduro, Arturo; Escobedo Meléndez, Griselda; Fierro, Nora A; Ruiz Madrigal, Bertha; Zepeda-Carrillo, Eloy Alfonso; Román, Sonia

    2011-01-01

    The main etiology of liver disease in Mexico is alcohol and viral hepatitis. The aim of the present study was to analyze the current epidemiology of viral hepatitis in Mexico. From 2000 to 2007 the Ministry of Health reported 192 588 cases of hepatitis, 79% HAV, 3.3% HBV, 6% HCV, and 12% without a specific etiologic factor. Due to high endemic areas for HBV infection in native Mexican population, limitations in the diagnostic sensitivity and specificity of the serological immunoassays used to date and presence of occult hepatitis B in the country, the real prevalence of HBV infection could be even higher than HCV in Mexico. Hepatitis E virus in cirrhotic patients and in porcine farms could at least partially explain the cases of hepatitis that are diagnosed without a specific etiologic agent. Specific strategies to establish control regulations against viral hepatitis infections in Mexico are proposed. PMID:21877071

  19. Molecular basis of viral and microbial pathogenesis

    SciTech Connect

    Rott, R.; Goebel, W.

    1988-01-01

    The contents of this book are: Correlation Between Viroid Structure and Pathogenicty; Antigenicity of the Influenza Haemagglutinia Membrane Glycoprotein; Viral Glycoproteins as Determinants of Pathogenicity; Virus Genes Involved in Host Range and Pathogenicity; Molecular Heterogenetiy of Pathogenic Herpus Viruses; Recombination of Foreign (Viral) DNA with Host Genome: Studies in Vivo and in a Cell-Free system; Disorders of Cellular Neuro-Functions by Persistent Viral Infection; Pathogenic Aspects of Measles Virus-Persistent Infections in Man; Analysis of the Dual Lineage Specificity of E26 Avian Leukemia Virus; Mx Gene Control of Influenza Virus Susceptibility; Shiga and Shika-Like Toxins: A Family of Related Cytokinons; and Molecular Mechanisms of Pathogenicity in Shigella Flexneri.

  20. Viral croup: diagnosis and a treatment algorithm.

    PubMed

    Petrocheilou, Argyri; Tanou, Kalliopi; Kalampouka, Efthimia; Malakasioti, Georgia; Giannios, Christos; Kaditis, Athanasios G

    2014-05-01

    Viral croup is a frequent disease in early childhood. Although it is usually self-limited, it may occasionally become life-threatening. Mild croup is characterized by the presence of stridor without intercostal retractions, whereas moderate-to-severe croup is accompanied by increased work of breathing. A single dose of orally administered dexamethasone (0.15-0.6?mg/kg) is the mainstay of treatment with addition of nebulized epinephrine only in cases of moderate-to-severe croup. Nebulized budesonide (2?mg) can be given alternatively to children who do not tolerate oral dexamethasone. Exposure to cold air or administration of cool mist are treatment interventions for viral croup that are not supported by published evidence, but breathing heliox can potentially reduce the work of breathing related to upper airway obstruction. In summary, corticosteroids may decrease the intensity of viral croup symptoms irrespective to their severity on presentation to the emergency department. PMID:24596395

  1. Association of PNPLA3 I148M Variant With Chronic Viral Hepatitis, Autoimmune Liver Diseases and Outcomes of Liver Transplantation

    PubMed Central

    Geng, Ning; Xin, Yong-Ning; Xia, Harry Hua-Xiang; Jiang, Man; Wang, Jian; Liu, Yang; Chen, Li-Zhen; Xuan, Shi-Ying

    2015-01-01

    Context: The PNPLA3 I148M variant has been recognized as a genetic determinant of liver fat content and a genetic risk factor of liver damage progression associated with steatohepatitis. The I148M variant is associated with many chronic liver diseases. However, its potential association with inflammatory and autoimmune liver diseases has not been established. Evidence Acquisition: We systemically reviewed the potential associations of I148M variant with chronic viral hepatitis, autoimmune liver diseases and the outcome of liver transplantation, explored the underlying molecular mechanisms and tried to translate them into more individualized decision-making and personalized medicine. Results: There were associations between I148M variant and chronic viral hepatitis and autoimmune liver diseases and differential associations of I148M variant in donors and recipients with post-liver transplant outcomes. I148M variant may activate the development of steatosis caused by host metabolic disorders in chronic viral hepatitis, but few researches were found to illustrate the mechanisms in autoimmune liver diseases. The peripherally mediated mechanism (via extrahepatic adipose tissue) may play a principal role in triglyceride accumulation regardless of adiponutrin activity in the graft liver. Conclusions: Evidences have shown the associations between I148M variant and mentioned diseases. I148M variant induced steatosis may be involved in the mechanism of chronic viral hepatitis and genetic considered personalized therapies, especially for PSC male patients. It is also crucial to pay attention to this parameter in donor selection and prognosis estimation in liver transplantation.

  2. IFITM Proteins Restrict Viral Membrane Hemifusion

    PubMed Central

    Golfetto, Ottavia; Bungart, Brittani; Li, Minghua; Ding, Shilei; He, Yuxian; Liang, Chen; Lee, James C.; Gratton, Enrico; Cohen, Fredric S.; Liu, Shan-Lu

    2013-01-01

    The interferon-inducible transmembrane (IFITM) protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. Here we provide evidence that IFITM proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. IFITM1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; IFITM2 and IFITM3 also strongly inhibited their fusion, with efficiency somewhat dependent on cell types. Furthermore, treatment of cells with IFN also markedly inhibited viral membrane fusion and entry. By using the Jaagsiekte sheep retrovirus envelope and influenza A virus hemagglutinin as models for study, we showed that IFITM-mediated restriction on membrane fusion is not at the steps of receptor- and/or low pH-mediated triggering; instead, the creation of hemifusion was essentially blocked by IFITMs. Chlorpromazine (CPZ), a chemical known to promote the transition from hemifusion to full fusion, was unable to rescue the IFITM-mediated restriction on fusion. In contrast, oleic acid (OA), a lipid analog that generates negative spontaneous curvature and thereby promotes hemifusion, virtually overcame the restriction. To explore the possible effect of IFITM proteins on membrane molecular order and fluidity, we performed fluorescence labeling with Laurdan, in conjunction with two-photon laser scanning and fluorescence-lifetime imaging microscopy (FLIM). We observed that the generalized polarizations (GPs) and fluorescence lifetimes of cell membranes expressing IFITM proteins were greatly enhanced, indicating higher molecularly ordered and less fluidized membranes. Collectively, our data demonstrated that IFITM proteins suppress viral membrane fusion before the creation of hemifusion, and suggested that they may do so by reducing membrane fluidity and conferring a positive spontaneous curvature in the outer leaflets of cell membranes. Our study provides novel insight into the understanding of how IFITM protein family restricts viral membrane fusion and infection. PMID:23358889

  3. Metatranscriptomic analysis of extremely halophilic viral communities.

    PubMed

    Santos, Fernando; Moreno-Paz, Mercedes; Meseguer, Inmaculada; López, Cristina; Rosselló-Mora, Ramon; Parro, Víctor; Antón, Josefa

    2011-10-01

    Hypersaline environments harbour the highest number of viruses reported for aquatic environments. In crystallizer ponds from solar salterns, haloviruses coexist with extremely halophilic Archaea and Bacteria and present a high diversity although little is known about their activity. In this work, we analyzed the viral expression in one crystallizer using a metatranscriptomic approach in which clones from a metaviromic library were immobilized in a microarray and used as probes against total mRNA extracted from the hypersaline community. This approach has two advantages: (i) it overcomes the fact that there is no straightforward, unambiguous way to extract viral mRNA from bulk mRNAs and (ii) it makes the sequencing of all mRNAs unnecessary. Transcriptomic data indicated that the halovirus assemblage was highly active at the time of sampling and the viral groups with the highest expression levels were those related to high GC content haloarchaea and Salinibacter representatives, which are minor components in the environment. Moreover, the changes in the viral expression pattern and in the numbers of free viral particles were analyzed after submitting the samples to two stress conditions: ultraviolet-radiation and dilution. Results showed that Archaea were more sensitive than Bacteria to these stress conditions. The overexpression in the predicted archaeal virus fraction raised and the total numbers of free viruses increased. Furthermore, we identified some very closely related viral clones, displaying single-nucleotide polymorphisms, which were expressed only under certain conditions. These clones could be part of very closely related virus genomes for which we propose the term 'ecoviriotypes'. PMID:21490689

  4. Multiple NF-?B Sites in HIV-1 Subtype C Long Terminal Repeat Confer Superior Magnitude of Transcription and Thereby the Enhanced Viral Predominance*

    PubMed Central

    Bachu, Mahesh; Yalla, Swarupa; Asokan, Mangaiarkarasi; Verma, Anjali; Neogi, Ujjwal; Sharma, Shilpee; Murali, Rajesh V.; Mukthey, Anil Babu; Bhatt, Raghavendra; Chatterjee, Snehajyoti; Rajan, Roshan Elizabeth; Cheedarla, Narayana; Yadavalli, Venkat S.; Mahadevan, Anita; Shankar, Susarla K.; Rajagopalan, Nirmala; Shet, Anita; Saravanan, Shanmugam; Balakrishnan, Pachamuthu; Solomon, Suniti; Vajpayee, Madhu; Satish, Kadappa Shivappa; Kundu, Tapas K.; Jeang, Kuan-Teh; Ranga, Udaykumar

    2012-01-01

    We demonstrate that at least three different promoter variant strains of HIV-1 subtype C have been gradually expanding and replacing the standard subtype C viruses in India, and possibly in South Africa and other global regions, over the past decade. The new viral strains contain an additional NF-?B, NF-?B-like, or RBEIII site in the viral promoter. Although the acquisition of an additional RBEIII site is a property shared by all the HIV-1 subtypes, acquiring an additional NF-?B site remains an exclusive property of subtype C. The acquired ?B site is genetically distinct, binds the p50-p65 heterodimer, and strengthens the viral promoter at the levels of transcription initiation and elongation. The 4-?B viruses dominate the 3-?B “isogenic” viral strains in pairwise competition assays in T-cell lines, primary cells, and the ecotropic human immunodeficiency virus mouse model. The dominance of the 4-?B viral strains is also evident in the natural context when the subjects are coinfected with ?B-variant viral strains. The mean plasma viral loads, but not CD4 counts, are significantly different in 4-?B infection suggesting that these newly emerging strains are probably more infectious. It is possible that higher plasma viral loads underlie selective transmission of the 4-?B viral strains. Several publications previously reported duplication or deletion of diverse transcription factor-binding sites in the viral promoter. Unlike previous reports, our study provides experimental evidence that the new viral strains gained a potential selective advantage as a consequence of the acquired transcription factor-binding sites and importantly that these strains have been expanding at the population level. PMID:23132857

  5. Viral Serine/Threonine Protein Kinases ?

    PubMed Central

    Jacob, Thary; Van den Broeke, Céline; Favoreel, Herman W.

    2011-01-01

    Phosphorylation represents one the most abundant and important posttranslational modifications of proteins, including viral proteins. Virus-encoded serine/threonine protein kinases appear to be a feature that is unique to large DNA viruses. Although the importance of these kinases for virus replication in cell culture is variable, they invariably play important roles in virus virulence. The current review provides an overview of the different viral serine/threonine protein kinases of several large DNA viruses and discusses their function, importance, and potential as antiviral drug targets. PMID:21084474

  6. A proteomics perspective on viral DNA sensors in host defense and viral immune evasion mechanisms.

    PubMed

    Crow, Marni S; Javitt, Aaron; Cristea, Ileana M

    2015-06-01

    The sensing of viral DNA is an essential step of cellular immune response to infections with DNA viruses. These human pathogens are spread worldwide, triggering a wide range of virus-induced diseases, and are associated with high levels of morbidity and mortality. Despite similarities between DNA molecules, mammalian cells have the remarkable ability to distinguish viral DNA from their own DNA. This detection is carried out by specialized antiviral proteins, called DNA sensors. These sensors bind to foreign DNA to activate downstream immune signaling pathways and alert neighboring cells by eliciting the expression of antiviral cytokines. The sensing of viral DNA was shown to occur both in the cytoplasm and in the nucleus of infected cells, disproving the notion that sensing occurred by simple spatial separation of viral and host DNA. A number of omic approaches, in particular, mass-spectrometry-based proteomic methods, have significantly contributed to the constantly evolving field of viral DNA sensing. Here, we review the impact of omic methods on the identification of viral DNA sensors, as well as on the characterization of mechanisms involved in host defense or viral immune evasion. PMID:25728651

  7. Genetic Algorithms

    Microsoft Academic Search

    Kumara Sastry; David Goldberg; Graham Kendall

    Genetic algorithms (GAs) are search methods based on principles of natural selection and genetics (Fraser, 1957;Bremermann, 1958;Holland, 1975). We start with a brief introduction to simple genetic algorithms and associated terminology.

  8. Genetic Counseling

    MedlinePLUS

    Genetic counseling provides information and support to people who have, or may be at risk for, genetic disorders. A ... meets with you to discuss genetic risks. The counseling may be for yourself or a family member. ...

  9. Distinct macrophage subpopulations regulate viral encephalitis but not viral clearance in the CNS.

    PubMed

    Steel, Christina D; Kim, Woong-Ki; Sanford, Larry D; Wellman, Laurie L; Burnett, Sandra; Van Rooijen, Nico; Ciavarra, Richard P

    2010-09-14

    Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair VSV encephalitis or viral clearance from the brain, whereas, depletion of splenic marginal dendritic cells impaired this response and enhanced morbidity/mortality. Selective depletion of brain perivascular macrophages also suppressed this response without altering viral clearance. Thus, two anatomically distinct phagocytic populations regulate VSV encephalitis in a non-redundant fashion although neither population is essential for viral clearance in the CNS. PMID:20599280

  10. A Family of Plasmodesmal Proteins with Receptor-Like Properties for Plant Viral Movement Proteins

    PubMed Central

    Schmitt-Keichinger, Corinne; Fernandez-Calvino, Lourdes; Didier, Pascal; Lerich, Alexander; Mutterer, Jérome; Thomas, Carole L.; Heinlein, Manfred; Mély, Yves; Maule, Andrew J.; Ritzenthaler, Christophe

    2010-01-01

    Plasmodesmata (PD) are essential but poorly understood structures in plant cell walls that provide symplastic continuity and intercellular communication pathways between adjacent cells and thus play fundamental roles in development and pathogenesis. Viruses encode movement proteins (MPs) that modify these tightly regulated pores to facilitate their spread from cell to cell. The most striking of these modifications is observed for groups of viruses whose MPs form tubules that assemble in PDs and through which virions are transported to neighbouring cells. The nature of the molecular interactions between viral MPs and PD components and their role in viral movement has remained essentially unknown. Here, we show that the family of PD-located proteins (PDLPs) promotes the movement of viruses that use tubule-guided movement by interacting redundantly with tubule-forming MPs within PDs. Genetic disruption of this interaction leads to reduced tubule formation, delayed infection and attenuated symptoms. Our results implicate PDLPs as PD proteins with receptor-like properties involved the assembly of viral MPs into tubules to promote viral movement. PMID:20886105

  11. Respiratory viral infections in children with asthma: do they matter and can we prevent them?

    PubMed Central

    2012-01-01

    Background Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. Discussion While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use. Summary Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children. PMID:22974166

  12. Correlation Study Between HCV Genotypes Distribution Pattern and Viral Load in a Tertiary Care Hospital in Kolkata, India

    PubMed Central

    Mukherjee, Kheya; Chakroborti, Goutam; Ghosh, Ranadeep; Mandal, Nabarun; Bose, Mohua

    2015-01-01

    Background Hepatitis C virus infection is a leading cause for chronic liver disease. It has wide population specific genotype variability. Genotype knowledge and viral load assessment are equally important for designing therapeutic strategies and as predictors of treatment outcome among hepatitis C (HCV) infected patients. Materials and Methods Between June 2012 and 2013 an observational study was conducted among 350 chronic hepatitis patients visiting Calcutta National Medical College, Kolkata, India. Among them, 110 anti-HCV antibody positive cases were diagnosed and subjected to viral RNA extraction, viral genotyping and viral load quantification using polymerase chain reaction (PCR) based techniques. Statistical Analysis Statistical analysis was done with IBM SPSS Statistics software, version 20. p-value <0.05 was regarded as statically significant. Results Among 66 HCV RNA positive cases, genotypes 1a, 3a and 3b were observed among 18 (27%), 44(67%) and 4(6%) cases respectively. Genotype 3a had higher viral load than patients infected with genotypes 1and 3b. However, no statistical significance was observed for viral load among the various HCV RNA genotypes. Conclusion Genotype 3a accounted for the highest number of cases with positive HCV RNA. However, no statistically significant difference existed for viral load among the various HCV RNA genotypes in this study.

  13. Viral pathogens of Glassy-winged sharpshooters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A newly discovered viral pathogen to the glassy-winged sharpshooter, GWSS, Homalodisca vitripennis, (Hemiptera: Cicadellidae) was characterized. The virus genome was sequenced, and the path of infection into the leafhopper was determined to be through the midgut tissues. The virus occurs naturally i...

  14. Bovine Viral Diarrhea Virus: Global Status

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite the success of regional bovine viral diarrhea viruses (BVDV) eradication programs, infections with this diverse group of viruses remain a source of economic loss for producers worldwide. There is a wide range of variation among BVDV results in differences in genotype (BVDV1 and BVDV2), biot...

  15. 65 FR 56807 - Equine Viral Arteritis

    Federal Register 2010, 2011, 2012, 2013, 2014

    2000-09-20

    ...viral disease characterized by fever, edema, conjunctivitis...principal means of the spread of infection among horses that are closely...significant role in maintaining EVA infection in horse populations. When...vaccination against the disease or infection with the EVA virus, can...

  16. STUDIES OF WATERBORNE AGENTS OF VIRAL GASTROENTERITIS

    EPA Science Inventory

    The etiologic agent of a large outbreak of waterborne viral gastroenteritis was detected employing immune electron microscopy (IEM) and a newly developed solid phase radioimmunoassay (RIA). This agent, referred to as the Snow Mountain Agent (SMA), is 27-32 nm. in diameter, has cu...

  17. New viral vaccines for dermatologic disease

    Microsoft Academic Search

    Christine Orlova Urman; Alice B. Gottlieb

    Two new viral vaccines have recently been approved by the Food and Drug Administration. Human papillomavirus (HPV) vaccine is intended to reduce infection with the most common HPV types that cause anogenital disease, including cervical cancer and genital warts. Herpes zoster (HZ) vaccine is intended to prevent shingles and its complications. The use of these two vaccines will immediately begin

  18. Viral genome sequencing bt random priming methods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most emerging health threats are of zoonotic origin. For the overwhelming majority, their causative agents are viruses which include but are not limited to HIV, Influenza, SARS, Ebola, Dengue, and Hantavirus. Of increasing importance therefore is an understanding of the viral diversity to enable b...

  19. A calcium fortified viral matrix protein

    PubMed Central

    Amarasinghe, Gaya K.; Dutch, Rebecca Ellis

    2014-01-01

    Summary In this issue of Structure, Leyrat and colleagues provide the first structural analysis of the HMPV matrix protein, a key regulator of viral assembly. Though structurally similar to other matrix proteins, two calcium binding sites suggest intriguing differences in regulation. PMID:24411575

  20. Edinburgh Research Explorer Viral Etiologies of Hospitalized Acute Lower Respiratory

    E-print Network

    Edinburgh, University of

    Edinburgh Research Explorer Viral Etiologies of Hospitalized Acute Lower Respiratory Infection, Feikin, D, Yu, H & Yang, W 2014, 'Viral Etiologies of Hospitalized Acute Lower Respiratory Infection, Georgia, United States of America Abstract Background: Acute lower respiratory infections (ALRIs

  1. Disparities in HIV/AIDS, Viral Hepatitis, STDs, and TB

    MedlinePLUS

    ... this page: About CDC.gov . Disparities in HIV/AIDS, Viral Hepatitis, STDs, and TB Health Disparities Social ... Islanders LGBT Populations/MSM MMWR Publications HIV and AIDS Viral Hepatitis STDs Tuberculosis Training and Networking Resources ...

  2. Suspected viral erythrocytic necrosis (VEN) in a juvenile blackbar triggerfish,

    E-print Network

    Grutter, Alexandra "Lexa"

    Suspected viral erythrocytic necrosis (VEN) in a juvenile blackbar triggerfish, Rhinecanthus Suspected viral erythrocytic necrosis (VEN) was detected in blood films from an immature blackbar erythrocytes affected by the VEN-like condition, but accompanying erythroblasts appeared free from infection

  3. Genetics Home Reference: Genetic Consultation

    MedlinePLUS

    ... Mutations and Health Inheritance Traits Consultation Testing Therapy Human Genome Project Genomic Research Precision Medicine Next Handbook > Genetic Consultation Finding and visiting a genetic counselor or ...

  4. Bovine viral diarrhea virus contamination of nutrient serum, cell cultures and viral vaccines.

    PubMed

    Levings, R L; Wessman, S J

    1991-01-01

    Bovine viral diarrhea virus (BVDV) infection is common in the bovine population. Infection in utero leads to virus and antibody contamination of the fetal bovine serum used in cell cultures. These contaminants can interfere with diagnosis of viral infection. The high frequency of virus and antibody detection in individual animal or small pool samples suggests that any large pool of unscreened sera will be contaminated. Infection of cell cultures with BVDV can lead to interference with the growth of other viruses. Vaccine produced on contaminated cells may in turn be contaminated, leading to seroconversion or disease in the vaccine. The safety, purity, and efficacy of viral vaccines require BVDV testing of ingredients, cell substrates and final product. Methods for detection of BVDV in nutrient serum, cell cultures, seed viruses, and viral vaccines, and the frequency of their detection at the National Veterinary Services Laboratories are discussed. PMID:1665461

  5. Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer-Deficient Neonates

    PubMed Central

    Ostermann, Eleonore; Macquin, Cécile; Krezel, Wojciech; Bahram, Seiamak; Georgel, Philippe

    2015-01-01

    Among Herpesviruses, Human Cytomegalovirus (HCMV or HHV-5) represents a major threat during congenital or neonatal infections, which may lead to encephalitis with serious neurological consequences. However, as opposed to other less prevalent pathogens, the mechanisms and genetic susceptibility factors for CMV encephalitis are poorly understood. This lack of information considerably reduces the prognostic and/or therapeutic possibilities. To easily monitor the effects of genetic defects on brain dissemination following CMV infection we used a recently developed in vivo mouse model based on the neonatal inoculation of a MCMV genetically engineered to express Luciferase. Here, we further validate this protocol for live imaging, and demonstrate increased lethality associated with viral infection and encephalitis in mutant mice lacking Dicer activity. Our data indicate that miRNAs are important players in the control of MCMV pathogenesis and suggest that miRNA-based endothelial functions and integrity are crucial for CMV encephalitis. PMID:25955106

  6. Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer-Deficient Neonates.

    PubMed

    Ostermann, Eleonore; Macquin, Cécile; Krezel, Wojciech; Bahram, Seiamak; Georgel, Philippe

    2015-05-01

    Among Herpesviruses, Human Cytomegalovirus (HCMV or HHV-5) represents a major threat during congenital or neonatal infections, which may lead to encephalitis with serious neurological consequences. However, as opposed to other less prevalent pathogens, the mechanisms and genetic susceptibility factors for CMV encephalitis are poorly understood. This lack of information considerably reduces the prognostic and/or therapeutic possibilities. To easily monitor the effects of genetic defects on brain dissemination following CMV infection we used a recently developed in vivo mouse model based on the neonatal inoculation of a MCMV genetically engineered to express Luciferase. Here, we further validate this protocol for live imaging, and demonstrate increased lethality associated with viral infection and encephalitis in mutant mice lacking Dicer activity. Our data indicate that miRNAs are important players in the control of MCMV pathogenesis and suggest that miRNA-based endothelial functions and integrity are crucial for CMV encephalitis. PMID:25955106

  7. RNAi and miRNA in viral infections and cancers.

    PubMed

    Mollaie, Hamid Reza; Monavari, Seyed Hamid Reza; Arabzadeh, Seyed Ali Mohammad; Shamsi-Shahrabadi, Mahmoud; Fazlalipour, Mehdi; Afshar, Reza Malekpour

    2013-01-01

    Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed. PMID:24460249

  8. Kinetics of viral shedding provide insights into the epidemiology of viral hemorrhagic septicemia in Pacific herring

    USGS Publications Warehouse

    Hershberger, P.; Gregg, J.; Grady, C.; Collins, R.; Winton, J.

    2010-01-01

    Losses from infectious diseases are an important component of natural mortality among marine fish species, but factors controlling the ecology of these diseases and their potential responses to anthropogenic changes are poorly understood. We used viral hemorrhagic septicemia virus (VHSV) and a laboratory stock of Pacific herring Clupea pallasii to investigate the kinetics of viral shedding and its effect on disease transmission and host mortality. Outbreaks of acute disease, accompanied by mortality and viral shedding, were initiated after waterborne exposure of herring to concentrations of VHSV as low as 10 1 plaque-forming units (pfu) ml-1. Shed virus in flow-through tanks was first detected 4 to 5 d post-exposure, peaked after 6 to 10 d, and was no longer detected after 16 d. Shedding rates, calculated from density, flow and waterborne virus titer reached 1.8 to 5.0 ?? ?10 8 pfu fish-1 d-1. Onset of viral shedding was dose-dependent and preceded initial mortality by 2 d. At 21 d, cumulative mortality in treatment groups ranged from 81 to 100% and was dependent not on challenge dose, but on the kinetics and level of viral shedding by infected fish in the tank. Possible consequences of the viral shedding and disease kinetics are discussed in the context of epizootic initiation and perpetuation among populations of wild Pacific herring. ?? Inter-Research 2010.

  9. Kinetics of viral shedding provide insights into the epidemiology of viral hemorrhagic septicemia in Pacific herring

    USGS Publications Warehouse

    Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Courtney; Collins, Rachael

    2010-01-01

    Losses from infectious diseases are an important component of natural mortality among marine fish species, but factors controlling the ecology of these diseases and their potential responses to anthropogenic changes are poorly understood. We used viral hemorrhagic septicemia virus (VHSV) and a laboratory stock of Pacific herring Clupea pallasii to investigate the kinetics of viral shedding and its effect on disease transmission and host mortality. Outbreaks of acute disease, accompanied by mortality and viral shedding, were initiated after waterborne exposure of herring to concentrations of VHSV as low as 101 plaque-forming units (pfu) ml–1. Shed virus in flow-through tanks was first detected 4 to 5 d post-exposure, peaked after 6 to 10 d, and was no longer detected after 16 d. Shedding rates, calculated from density, flow and waterborne virus titer reached 1.8 to 5.0 × 108 pfu fish–1 d–1. Onset of viral shedding was dose-dependent and preceded initial mortality by 2 d. At 21 d, cumulative mortality in treatment groups ranged from 81 to 100% and was dependent not on challenge dose, but on the kinetics and level of viral shedding by infected fish in the tank. Possible consequences of the viral shedding and disease kinetics are discussed in the context of epizootic initiation and perpetuation among populations of wild Pacific herring.

  10. Adenoviral and adeno-associated viral vectors-mediated neuronal gene transfer to cardiovascular control regions of the rat brain.

    PubMed

    Zhang, Yanling; Gao, Yongxin; Speth, Robert C; Jiang, Nan; Mao, Yingying; Sumners, Colin; Li, Hongwei

    2013-01-01

    Viral vectors have been utilized extensively to introduce genetic material into the central nervous system. In order to investigate gene functions in cardiovascular control regions of rat brain, we applied WPRE (woodchuck hepatitis virus post-transcriptional regulatory element) enhanced-adenoviral (Ad) and adeno-assoicated virus (AAV) type 2 vectors to mediate neuronal gene delivery to the paraventricular nucleus of the hypothalamus, the nucleus tractus solitarius and the rostral ventrolateral medulla, three important cardiovascular control regions known to express renin-angiotensin system (RAS) genes. Ad or AAV2 harboring an enhanced green fluorescent protein (EGFP) reporter gene or the angiotensin type 2 receptor gene were microinjected into these brain regions in adult rats. Our results demonstrated that both AAV2 and Ad vectors elicited long-term neuronal transduction in these regions. Interestingly, we found that the WPRE caused expression of GFP driven by the synapsin1 promoter in pure glial cultures or co-cultures of neurons and glia derived from rat hypothalamus and brainstem. However, in rat paraventricular nucleus WPRE did not cause expression of GFP in glia. This demonstrates the potential use of these vectors in studies of physiological functions of certain genes in the cardiovascular control regions of the brain. PMID:23569423

  11. Primer on molecular genetics

    SciTech Connect

    Not Available

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  12. Role of HIV1 Gag domains in viral assembly

    Microsoft Academic Search

    Suzanne Scarlata; Carol Carter

    2003-01-01

    After entry of the human immunodeficiency virus type 1 (HIV-1) into T cells and the subsequent synthesis of viral products, viral proteins and RNA must somehow find each other in the host cells and assemble on the plasma membrane to form the budding viral particle. In this general review of HIV-1 assembly, we present a brief overview of the HIV

  13. T Lymphocyte Apoptosis and Memory in Viral Infection: A Dissertation

    Microsoft Academic Search

    Enal Shahid Razvi

    1994-01-01

    Acute viral infections in humans and mice induce T lymphocyte responses which mediate viral clearance and result in the establishment of immunological memory. The course of an immune response to acute viral infection is associated with an immune deficiency in the lymphocyte compartment. This is usually characterized by the inability of lymphocytes to productively respond to mitogen or recall antigen.

  14. Discovery of Cationic Polymers for Non-viral Gene Delivery using Combinatorial Approaches

    PubMed Central

    Barua, Sutapa; Ramos, James; Potta, Thrimoorthy; Taylor, David; Huang, Huang-Chiao; Montanez, Gabriela; Rege, Kaushal

    2015-01-01

    Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated transgene uptake, transport, transcription, and expression. This review summarizes and discusses recent advances in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery systems. PMID:21843141

  15. [An enhanced viral safety of blood preparations].

    PubMed

    Zhiburt, E B

    2004-01-01

    Inactivation or elimination of (possibly) contaminated viruses from a pool of prepared several hundreds or thousands of donor-blood samples are an obligatory stage in the donor-blood preparation process. Virus-inactivation is verified through contaminating the basic material with viruses. The quality control of blood preparations, according to the Russian compulsory regulations, must include the testing of ready blood-based drugs for a lack of antibodies to HIV, hepatitis C virus and hepatitis B virus by using the test systems, which could not be exactly designed for the above purpose. Therefore, the below tasks are vital for the Russian Blood Service: 1) cancellation of the norm (belonging to the regulations of the quality control of blood preparations) to test the blood preparations for a lack of antibodies to HIV, hepatitis C virus and to the surface antigen of hepatitis B virus because it is biologically inexpedient and has no analogues in the world practice; 2) introduction of the virus-inactivation methods into the practice of plasma processing; 3) establishment of a special center that would evaluate the efficiency of the virus-inactivation methods used by producers of blood-based preparations; and 4) introduction of the methods of genetic testing of HIV, hepatitis B and C viruses into monitoring the quality of donor-sera pools that are later used in preparations' manufacturing. PMID:15293512

  16. Integrating Bacterial and Viral Water Quality Assessment to Predict Swimming-Associated Illness at a Freshwater Beach: A Cohort Study

    PubMed Central

    Marion, Jason W.; Lee, Cheonghoon; Lee, Chang Soo; Wang, Qiuhong; Lemeshow, Stanley; Buckley, Timothy J.; Saif, Linda J.; Lee, Jiyoung

    2014-01-01

    Background & Objective Recreational waters impacted by fecal contamination have been linked to gastrointestinal illness in swimmer populations. To date, few epidemiologic studies examine the risk for swimming-related illnesses based upon simultaneous exposure to more than one microbial surrogate (e.g. culturable E. coli densities, genetic markers). We addressed this research gap by investigating the association between swimming-related illness frequency and water quality determined from multiple bacterial and viral genetic markers. Methods Viral and bacterial genetic marker densities were determined from beach water samples collected over 23 weekend days and were quantified using quantitative polymerase chain reaction (qPCR). These genetic marker data were paired with previously determined human exposure data gathered as part of a cohort study carried out among beach users at East Fork Lake in Ohio, USA in 2009. Using previously unavailable genetic marker data in logistic regression models, single- and multi-marker/multi-water quality indicator approaches for predicting swimming-related illness were evaluated for associations with swimming-associated gastrointestinal illness. Results Data pertaining to genetic marker exposure and 8- or 9-day health outcomes were available for a total of 600 healthy susceptible swimmers, and with this population we observed a significant positive association between human adenovirus (HAdV) exposure and diarrhea (odds ratio ?=?1.6; 95% confidence interval: 1.1–2.3) as well as gastrointestinal illness (OR ?=?1.5; 95% CI: 1.0–2.2) upon adjusting for culturable E. coli densities in multivariable models. No significant associations between bacterial genetic markers and swimming-associated illness were observed. Conclusions This study provides evidence that a combined measure of recreational water quality that simultaneously considers both bacterial and viral densities, particularly HAdV, may improve prediction of disease risk than a measure of a single agent in a beach environment likely influenced by nonpoint source human fecal contamination. PMID:25409012

  17. Genetic Algorithms Genetic Programming

    E-print Network

    ] F. H. Bennett III, J. R. Koza, D. Andre, and M. A. Keane, Evolution of a 60 Decibel OP Amp using) Configuration Bit Stream Bennett III #12;rossover mutation rossover Mutation crossover . crossover point transactions on evolutionary computation, vol3, no 3, pp. 220-235, september 1999. [2] Koza, J. R., Genetic

  18. Genome-Wide Patterns of Intrahuman Dengue Virus Diversity Reveal Associations with Viral Phylogenetic Clade and Interhost Diversity

    PubMed Central

    Parameswaran, Poornima; Charlebois, Patrick; Tellez, Yolanda; Nunez, Andrea; Ryan, Elizabeth M.; Malboeuf, Christine M.; Levin, Joshua Z.; Lennon, Niall J.; Balmaseda, Angel

    2012-01-01

    Analogous to observations in RNA viruses such as human immunodeficiency virus, genetic variation associated with intrahost dengue virus (DENV) populations has been postulated to influence viral fitness and disease pathogenesis. Previous attempts to investigate intrahost genetic variation in DENV characterized only a few viral genes or a limited number of full-length genomes. We developed a whole-genome amplification approach coupled with deep sequencing to capture intrahost diversity across the entire coding region of DENV-2. Using this approach, we sequenced DENV-2 genomes from the serum of 22 Nicaraguan individuals with secondary DENV infection and captured ?75% of the DENV genome in each sample (range, 40 to 98%). We identified and quantified variants using a highly sensitive and specific method and determined that the extent of diversity was considerably lower than previous estimates. Significant differences in intrahost diversity were detected between genes and also between antigenically distinct domains of the Envelope gene. Interestingly, a strong association was discerned between the extent of intrahost diversity in a few genes and viral clade identity. Additionally, the abundance of viral variants within a host, as well as the impact of viral mutations on amino acid encoding and predicted protein function, determined whether intrahost variants were observed at the interhost level in circulating Nicaraguan DENV-2 populations, strongly suggestive of purifying selection across transmission events. Our data illustrate the value of high-coverage genome-wide analysis of intrahost diversity for high-resolution mapping of the relationship between intrahost diversity and clinical, epidemiological, and virological parameters of viral infection. PMID:22647702

  19. NS Reassortment of an H7-Type Highly Pathogenic Avian Influenza Virus Affects Its Propagation by Altering the Regulation of Viral RNA Production and Antiviral Host Response? †

    PubMed Central

    Wang, Zhongfang; Robb, Nicole C.; Lenz, Eva; Wolff, Thorsten; Fodor, Ervin; Pleschka, Stephan

    2010-01-01

    Highly pathogenic avian influenza viruses (HPAIV) with reassorted NS segments from H5- and H7-type avian virus strains placed in the genetic background of the A/FPV/Rostock/34 HPAIV (FPV; H7N1) were generated by reverse genetics. Virological characterizations demonstrated that the growth kinetics of the reassortant viruses differed from that of wild-type (wt) FPV and depended on whether cells were of mammalian or avian origin. Surprisingly, molecular analysis revealed that the different reassortant NS segments were not only responsible for alterations in the antiviral host response but also affected viral genome replication and transcription as well as nuclear ribonucleoprotein (RNP) export. RNP reconstitution experiments demonstrated that the effects on accumulation levels of viral RNA species were dependent on the specific NS segment as well as on the genetic background of the RNA-dependent RNA polymerase (RdRp). Beta interferon (IFN-?) expression and the induction of apoptosis were found to be inversely correlated with the magnitude of viral growth, while the NS allele, virus subtype, and nonstructural protein NS1 expression levels showed no correlation. Thus, these results demonstrate that the origin of the NS segment can have a dramatic effect on the replication efficiency and host range of HPAIV. Overall, our data suggest that the propagation of NS reassortant influenza viruses is affected at multiple steps of the viral life cycle as a result of the different effects of the NS1 protein on multiple viral and host functions. PMID:20739516

  20. In vivo imaging of alphaherpesvirus infection reveals synchronized activity dependent on axonal sorting of viral proteins.

    PubMed

    Granstedt, Andrea E; Bosse, Jens B; Thiberge, Stephan Y; Enquist, Lynn W

    2013-09-10

    A clinical hallmark of human alphaherpesvirus infections is peripheral pain or itching. Pseudorabies virus (PRV), a broad host range alphaherpesvirus, causes violent pruritus in many different animals, but the mechanism is unknown. Previous in vitro studies have shown that infected, cultured peripheral nervous system (PNS) neurons exhibited aberrant electrical activity after PRV infection due to the action of viral membrane fusion proteins, yet it is unclear if such activity occurs in infected PNS ganglia in living animals and if it correlates with disease symptoms. Using two-photon microscopy, we imaged autonomic ganglia in living mice infected with PRV strains expressing GCaMP3, a genetically encoded calcium indicator, and used the changes in calcium flux to monitor the activity of many neurons simultaneously with single-cell resolution. Infection with virulent PRV caused these PNS neurons to fire synchronously and cyclically in highly correlated patterns among infected neurons. This activity persisted even when we severed the presynaptic axons, showing that infection-induced firing is independent of input from presynaptic brainstem neurons. This activity was not observed after infections with an attenuated PRV recombinant used for circuit tracing or with PRV mutants lacking either viral glycoprotein B, required for membrane fusion, or viral membrane protein Us9, required for sorting virions and viral glycoproteins into axons. We propose that the viral fusion proteins produced by virulent PRV infection induce electrical coupling in unmyelinated axons in vivo. This action would then give rise to the synchronous and cyclical activity in the ganglia and contribute to the characteristic peripheral neuropathy. PMID:23980169

  1. In vivo imaging of alphaherpesvirus infection reveals synchronized activity dependent on axonal sorting of viral proteins

    PubMed Central

    Granstedt, Andrea E.; Bosse, Jens B.; Thiberge, Stephan Y.; Enquist, Lynn W.

    2013-01-01

    A clinical hallmark of human alphaherpesvirus infections is peripheral pain or itching. Pseudorabies virus (PRV), a broad host range alphaherpesvirus, causes violent pruritus in many different animals, but the mechanism is unknown. Previous in vitro studies have shown that infected, cultured peripheral nervous system (PNS) neurons exhibited aberrant electrical activity after PRV infection due to the action of viral membrane fusion proteins, yet it is unclear if such activity occurs in infected PNS ganglia in living animals and if it correlates with disease symptoms. Using two-photon microscopy, we imaged autonomic ganglia in living mice infected with PRV strains expressing GCaMP3, a genetically encoded calcium indicator, and used the changes in calcium flux to monitor the activity of many neurons simultaneously with single-cell resolution. Infection with virulent PRV caused these PNS neurons to fire synchronously and cyclically in highly correlated patterns among infected neurons. This activity persisted even when we severed the presynaptic axons, showing that infection-induced firing is independent of input from presynaptic brainstem neurons. This activity was not observed after infections with an attenuated PRV recombinant used for circuit tracing or with PRV mutants lacking either viral glycoprotein B, required for membrane fusion, or viral membrane protein Us9, required for sorting virions and viral glycoproteins into axons. We propose that the viral fusion proteins produced by virulent PRV infection induce electrical coupling in unmyelinated axons in vivo. This action would then give rise to the synchronous and cyclical activity in the ganglia and contribute to the characteristic peripheral neuropathy. PMID:23980169

  2. Foodborne viral illness--status in Australia.

    PubMed

    Fleet, G H; Heiskanen, P; Reid, I; Buckle, K A

    2000-07-25

    Norwalk-like virus contamination of oysters and orange juice, and hepatitis A virus contamination of oysters have been responsible for large outbreaks of foodborne viral disease in Australia. Rotavirus, adenovirus, astrovirus, parvovirus and other enteroviruses also contribute to the incidence of gastroenteritis in this country but the role of foods and waters in transmitting these viruses is unclear. Protocols for the investigation, surveillance and reporting of foodborne viral illness require further development to enable a more accurate description of the problem. Few laboratories have the capability to analyse foods for viruses and specific training in this technology is needed. Management of food safety in Australia largely relies on the implementation of HACCP principles, but these need to be adapted to address the specific risks from viruses. PMID:10946844

  3. Broad-spectrum antivirals against viral fusion.

    PubMed

    Vigant, Frederic; Santos, Nuno C; Lee, Benhur

    2015-07-01

    Effective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This 'one bug-one drug' approach to antiviral drug development can be successful, but it may be inadequate for responding to an increasing diversity of viruses that cause significant diseases in humans. The majority of viral pathogens that cause emerging and re-emerging infectious diseases are membrane-enveloped viruses, which require the fusion of viral and cell membranes for virus entry. Therefore, antivirals that target the membrane fusion process represent new paradigms for broad-spectrum antiviral discovery. In this Review, we discuss the mechanisms responsible for the fusion between virus and cell membranes and explore how broad-spectrum antivirals target this process to prevent virus entry. PMID:26075364

  4. Multiplexing Short Primers for Viral Family PCR

    SciTech Connect

    Gardner, S N; Hiddessen, A L; Hara, C A; Williams, P L; Wagner, M; Colston, B W

    2008-06-26

    We describe a Multiplex Primer Prediction (MPP) algorithm to build multiplex compatible primer sets for large, diverse, and unalignable sets of target sequences. The MPP algorithm is scalable to larger target sets than other available software, and it does not require a multiple sequence alignment. We applied it to questions in viral detection, and demonstrated that there are no universally conserved priming sequences among viruses and that it could require an unfeasibly large number of primers ({approx}3700 18-mers or {approx}2000 10-mers) to generate amplicons from all sequenced viruses. We then designed primer sets separately for each viral family, and for several diverse species such as foot-and-mouth disease virus, hemagglutinin and neuraminidase segments of influenza A virus, Norwalk virus, and HIV-1.

  5. Evaluation of viral inactivation of pseudorabies virus, encephalomyocarditis virus, bovine viral diarrhea virus and porcine parvovirus in pancreatin of porcine origin.

    PubMed

    Caruso, C; Gobbi, E; Biosa, T; Andra', M; Cavallazzi, U; Masoero, L

    2014-11-01

    Pancreatin is a substance containing enzymes, principally amylase, lipase, and protease. It is obtained from bovine or porcine pancreas and used in the treatment of pancreatic endocrine insufficiency in humans. Regulations and safety concerns mandate viral clearance (virus removal or inactivation) in biopharmaceuticals such as pancreatin. A virus validation study was performed to evaluate virus clearance achieved in the final step of drying under vacuum by testing a panel of four animal viruses: Pseudorabies virus (PRV), Encephalomyocarditis virus (EMCV), Bovine viral diarrhea virus (BVDV), and Porcine parvovirus (PPV). Because of the product's virucidal effect and high cytotoxicity, the starting material was diluted to a ratio of 0.67 g of dried pancreatin resuspended in 13.5 mL of cell culture medium followed by a 50-fold dilution in cell culture medium before spiking. After heating at 60±1°C for 5 h, the samples were diluted about 5-fold in cell culture medium and titered by the plaque assay method. The virus reduction factor ranged from 5.59 (for PPV) to 7.07 (for EMCV) and no viral plaque was observed, indicating that the process step was effective in the reduction and removal of virus contamination. Though no virus contamination events in pancreatin have been reported to date, evaluation of the production process for its ability to inactivate and/or remove virus contamination, particularly from zoonotic viral agents such as hepatitis E virus and Norovirus considered emerging pathogens, is necessary to ensure the viral safety of animal-derived biopharmaceuticals. PMID:25110118

  6. RT-PCR–RFLP for genetic diversity analysis of Tunisian Grapevine fanleaf virus isolates in their natural host plants

    Microsoft Academic Search

    Sami Fattouch; Hajer Acheche; Sonia M’hirsi; Lotfi Mellouli; Samir Bejar; Mohamed Marrakchi; Najib Marzouki

    2005-01-01

    Genetic diversity was characterized in 20 isolates of Grapevine fanleaf virus (GFLV) recovered from naturally infected grapevine plants (Vitis vinifera) in the North of Tunisia. Viral RNAs were isolated by oligoprobe capture, and a 605bp fragment containing a part of the viral coat protein gene was amplified by RT-PCR. Sequence variation among isolates was characterized by restriction fragment length polymorphism

  7. A type I interferon transcriptional signature precedes autoimmunity in children genetically at-risk of type 1 diabetes

    E-print Network

    Ferreira, Ricardo C.; Guo, Hui; Coulson, Richard M. R.; Smyth, Deborah J.; Pekalski, Marcin L.; Burren, Oliver S.; Cutler, Antony J.; Doecke, James D.; Flint, Shaun; McKinney, Eoin F.; Lyons, Paul A.; Smith, Kenneth G. C.; Achenbach, Peter; Beyerlein, Andreas; Dunger, David B.; Clayton, David G.; Wicker, Linda S.; Todd, John A.; Bonifacio, Ezio; Wallace, Chris; Ziegler, Anette-G.

    2014-02-21

    and genetic data have associated viral infections and anti-viral type I interferon (IFN) immune response genes with T1D. Here, we first used DNA microarray analysis to identify IFN-? inducible genes in vitro and then used this set of genes to define an IFN...

  8. Inflammasomes and Anti-Viral Immunity

    Microsoft Academic Search

    Vijay A. K. Rathinam; Katherine A. Fitzgerald

    2010-01-01

    Type I Interferons are the hallmark cytokines deployed during infection to combat invading viruses. However, inflammatory\\u000a cytokines such as Interleukin (IL)-1? and IL-18 also play important roles in anti-viral defenses. The activity of IL-1? and\\u000a IL18 are regulated at the level of expression, processing, and secretion. Several classes of innate immune receptors control\\u000a the expression of these cytokines, which must

  9. The Role of Inflammasomes in Viral Infection

    Microsoft Academic Search

    Christopher R. Lupfer; Thirumala-Devi Kanneganti

    \\u000a There are three known receptors capable of inducing inflammasome formation in response to viral infections: NLRP3, AIM2, and\\u000a RIG-I. Here, we discuss the viruses and mechanisms of activation involved in inflammasome signaling. We also briefly discuss\\u000a some of the viruses known to activate caspase-1 and induce secretion of IL-1? or IL-18, but for which the upstream inflammasome\\u000a signaling pathway is

  10. The pathology of viral hepatitis in chimpanzees

    Microsoft Academic Search

    Hans Popper; Jules L. Dienstag; Stephen M. Feinstone; Harvey J. Alter; Robert H. Purcell

    1980-01-01

    Serial biopsy specimens (up to 21) of 39 chimpanzees who received inocula of defined infectivity containing hepatitis virus A (9 animals), B (7 animals), and non-A-non-B (24 animals) were evaluated under code for light-microscopic alterations. These studies demonstrated the basic pathologic features seen in human viral hepatitis, although to a lesser degree. These included besides hepatocytic degeneration and necrosis lobular

  11. West Nile Virus-Induced Activation of Mammalian Target of Rapamycin Complex 1 Supports Viral Growth and Viral Protein Expression

    PubMed Central

    Shives, Katherine D.; Beatman, Erica L.; Chamanian, Mastooreh; O'Brien, Caitlin; Hobson-Peters, Jody

    2014-01-01

    ABSTRACT Since its introduction in New York City, NY, in 1999, West Nile virus (WNV) has spread to all 48 contiguous states of the United States and is now the leading cause of epidemic encephalitis in North America. As a member of the family Flaviviridae, WNV is part of a group of clinically important human pathogens, including dengue virus and Japanese encephalitis virus. The members of this family of positive-sense, single-stranded RNA viruses have limited coding capacity and are therefore obligated to co-opt a significant amount of cellular factors to translate their genomes effectively. Our previous work has shown that WNV growth was independent of macroautophagy activation, but the role of the evolutionarily conserved mammalian target of rapamycin (mTOR) pathway during WNV infection was not well understood. mTOR is a serine/threonine kinase that acts as a central cellular censor of nutrient status and exercises control of vital anabolic and catabolic cellular responses such as protein synthesis and autophagy, respectively. We now show that WNV activates mTOR and cognate downstream activators of cap-dependent protein synthesis at early time points postinfection and that pharmacologic inhibition of mTOR (KU0063794) significantly reduced WNV growth. We used an inducible Raptor and Rictor knockout mouse embryonic fibroblast (MEF) system to further define the role of mTOR complexes 1 and 2 in WNV growth and viral protein synthesis. Following inducible genetic knockout of the major mTOR cofactors raptor (TOR complex 1 [TORC1]) and rictor (TORC2), we now show that TORC1 supports flavivirus protein synthesis via cap-dependent protein synthesis pathways and supports subsequent WNV growth. IMPORTANCE Since its introduction in New York City, NY, in 1999, West Nile virus (WNV) has spread to all 48 contiguous states in the United States and is now the leading cause of epidemic encephalitis in North America. Currently, the mechanism by which flaviviruses such as WNV translate their genomes in host cells is incompletely understood. Elucidation of the host mechanisms required to support WNV genome translation will provide broad understanding for the basic mechanisms required to translate capped viral RNAs. We now show that WNV activates mTOR and cognate downstream activators of cap-dependent protein synthesis at early time points postinfection. Following inducible genetic knockout of the major mTOR complex cofactors raptor (TORC1) and rictor (TORC2), we now show that TORC1 supports WNV growth and protein synthesis. This study demonstrates the requirement for TORC1 function in support of WNV RNA translation and provides insight into the mechanisms underlying flaviviral RNA translation in mammalian cells. PMID:24920798

  12. The post-viral syndrome: a review

    PubMed Central

    Archer, M.I.

    1987-01-01

    The post-viral syndrome is described and its aetiology is discussed. Many features of the syndrome point to hysteria and altered medical perception as causes but much evidence for organic disease is also presented. Current interest focuses on recent or persisting infection with Coxsackie viruses. A balanced view of the syndrome as a mixture of organic and psychiatric dysfunction is offered. Widely differing estimates of incidence are quoted, possibly owing to varying medical awareness of the syndrome. Many drug therapies have been tried without success and management of the post-viral syndrome is hampered by the reluctance of patients to accept psychiatric support once the diagnosis is known. Many names have been proposed for the syndrome, some implying a purely physical or purely psychogenic aetiology: post-viral syndrome is suggested as the most appropriate term. Increased awareness of the syndrome will lead to an increase in its diagnosis in general practice: the role of the Myalgic Encephalomyelitis Association in promoting a combined psychiatric and organic view of the disease among sufferers is emphasized. PMID:3320358

  13. Identification of alpha interferon-induced envelope mutations of hepatitis C virus in vitro associated with increased viral fitness and interferon resistance.

    PubMed

    Serre, Stéphanie B N; Krarup, Henrik B; Bukh, Jens; Gottwein, Judith M

    2013-12-01

    Alpha interferon (IFN-?) is an essential component of innate antiviral immunity and of treatment regimens for chronic hepatitis C virus (HCV) infection. Resistance to IFN might be important for HCV persistence and failure of IFN-based therapies. Evidence for HCV genetic correlates of IFN resistance is limited. Experimental studies were hampered by lack of HCV culture systems. Using genotype (strain) 1a(H77) and 3a(S52) Core-NS2 JFH1-based recombinants, we aimed at identifying viral correlates of IFN-? resistance in vitro. Long-term culture with IFN-?2b in Huh7.5 cells resulted in viral spread with acquisition of putative escape mutations in HCV structural and nonstructural proteins. Reverse genetic studies showed that primarily amino acid changes I348T in 1a(H77) E1 and F345V/V414A in 3a(S52) E1/E2 increased viral fitness. Single-cycle assays revealed that I348T and F345V/V414A enhanced viral entry and release, respectively. In assays allowing viral spread, these mutations conferred a level of IFN-? resistance exceeding the observed fitness effect. The identified mutations acted in a subtype-specific manner but were not found in genotype 1a and 3a patients, who failed IFN-? therapy. Studies with HCV recombinants with different degrees of culture adaptation confirmed the correlation between viral fitness and IFN-? resistance. In conclusion, in vitro escape experiments led to identification of HCV envelope mutations resulting in increased viral fitness and conferring IFN-? resistance. While we established a close link between viral fitness and IFN-? resistance, identified mutations acted via different mechanisms and appeared to be relatively specific to the infecting virus, possibly explaining difficulties in identifying signature mutations for IFN resistance. PMID:24049176

  14. who . . .GENETIC ASSOCIATION OF

    E-print Network

    Kay, Mark A.

    who . . .GENETIC ASSOCIATION OF COUNSELING DIRECTORS ROGRAMP are genetic counselors ? Genetic, medical genetics, epidemiological principles, and counseling theory with their skills in genetic risk and their families for a diverse set of genetic or genomic indications. Genetic counselors help people

  15. Bovine Viral Diarrhea Virus Variability and Prevalence of BVDV Subtypes in Persistently Infected Cattle Entering Feedlots: BVDV1b as Predominant Subtype

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aim: Bovine viral diarrhea viruses (BVDV) are a diverse group of viruses causing infections and disease in domestic and wild ruminants worldwide. BVDV biotypes are based on presence or absence of cytopathology in infected cultures: CP (cytopathic) or NCP (noncytopathic). BVDV are genetically diverse...

  16. Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons: A strategy to increase opioid antinociception

    Microsoft Academic Search

    Y. Xu; Y. Gu; G.-Y. Xu; P. Wu; G.-W. Li; L.-Y. M. Huang

    2003-01-01

    To develop a genetic approach for the treatment of pain, we introduced a recombinant adeno-associated viral (rAAV) vector containing the cDNA for the mu-opioid receptor (muOR) into primary afferent neurons in dorsal root ganglia (DRGs) of rats, which resulted in a long-lasting (>6 months) increase in muOR expression in DRG neurons. The increase greatly potentiated the antinociceptive effects of morphine

  17. Kaposi's Sarcoma-Associated Herpesvirus ORF45 Interacts with Kinesin2 Transporting Viral Capsid-Tegument Complexes along Microtubules

    Microsoft Academic Search

    Narayanan Sathish; Fan Xiu Zhu; Yan Yuan

    2009-01-01

    Open reading frame (ORF) 45 of Kaposi's sarcoma-associated herpesvirus (KSHV) is a tegument protein. A genetic analysis with a null mutant suggested a possible role for this protein in the events leading to viral egress. In this study, ORF45 was found to interact with KIF3A, a kinesin-2 motor protein that transports cargoes along microtubules to cell periphery in a yeast

  18. Peripheral challenge with a viral mimic upregulates expression of the complement genes in the hippocampus.

    PubMed

    Michalovicz, Lindsay T; Lally, Brent; Konat, Gregory W

    2015-08-15

    Peripheral challenge with a viral mimetic, polyinosinic-polycytidylic acid (PIC) induces hippocampal hyperexcitability in mice. Here, we characterized this hippocampal response through a whole genome transcriptome analysis. Intraperitoneal injection of PIC resulted in temporal dysregulation of 625 genes in the hippocampus, indicating an extensive genetic reprogramming. The bioinformatics analysis of these genes revealed the complement pathway to be the most significantly activated. The gene encoding complement factor B (CfB) exhibited the highest response, and its upregulation was commensurate with the development of hyperexcitability. Collectively, these results suggest that the induction of hippocampal hyperexcitability may be mediated by the alternative complement cascades. PMID:26198930

  19. RAPD-based Analysis of Genetic Diversity and Selection of Lingonberry ( Vaccinium vitis-idaea L.) Material for ex situ Conservation

    Microsoft Academic Search

    L. Garkava-Gustavsson; H. A. Persson; H. Nybom; K. Rumpunen; B. A. Gustavsson; I. V. Bartish

    2005-01-01

    Random amplified polymorphic DNA markers were used to assess relatedness and genetic diversity for 15 lingonberry (Vaccinium vitis-idaea) populations. Seven primers yielding 59 polymorphic bands were used to analyse 13 populations, representing ssp. vitis-idaea from Sweden, Finland, Norway, Estonia and Russia, and two populations, representing ssp. minus from Japan and Canada. A cluster analysis and a multidimensional scaling analysis (MDS)

  20. Single stem cell gene therapy for genetic skin disease.

    PubMed

    Larsimont, Jean-Christophe; Blanpain, Cédric

    2015-04-01

    Stem cell gene therapy followed by transplantation into damaged regions of the skin has been successfully used to treat genetic skin blistering disorder. Usually, many stem cells are virally transduced to obtain a sufficient number of genetically corrected cells required for successful transplantation, as genetic insertion in every stem cell cannot be precisely defined. In this issue of EMBO Molecular Medicine, Droz-Georget Lathion et al developed a new strategy for ex vivo single cell gene therapy that allows extensive genomic and functional characterization of the genetically repaired individual cells before they can be used in clinical settings. PMID:25724199

  1. Viral degradasome hijacks mitochondria to suppress innate immunity.

    PubMed

    Goswami, Ramansu; Majumdar, Tanmay; Dhar, Jayeeta; Chattopadhyay, Saurabh; Bandyopadhyay, Sudip K; Verbovetskaya, Valentina; Sen, Ganes C; Barik, Sailen

    2013-08-01

    The balance between the innate immunity of the host and the ability of a pathogen to evade it strongly influences pathogenesis and virulence. The two nonstructural (NS) proteins, NS1 and NS2, of respiratory syncytial virus (RSV) are critically required for RSV virulence. Together, they strongly suppress the type I interferon (IFN)-mediated innate immunity of the host cells by degrading or inhibiting multiple cellular factors required for either IFN induction or response pathways, including RIG-I, IRF3, IRF7, TBK1 and STAT2. Here, we provide evidence for the existence of a large and heterogeneous degradative complex assembled by the NS proteins, which we named "NS-degradasome" (NSD). The NSD is roughly ?300-750 kD in size, and its degradative activity was enhanced by the addition of purified mitochondria in vitro. Inside the cell, the majority of the NS proteins and the substrates of the NSD translocated to the mitochondria upon RSV infection. Genetic and pharmacological evidence shows that optimal suppression of innate immunity requires mitochondrial MAVS and mitochondrial motility. Together, we propose a novel paradigm in which the mitochondria, known to be important for the innate immune activation of the host, are also important for viral suppression of the innate immunity. PMID:23877405

  2. An Epistatic Relationship between the Viral Protein Kinase UL97 and the UL133-UL138 Latency Locus during the Human Cytomegalovirus Lytic Cycle

    PubMed Central

    Li, Gang; Rak, Michael; Nguyen, Christopher C.; Umashankar, Mahadevaiah; Goodrum, Felicia D.

    2014-01-01

    ABSTRACT We report that UL133-UL138 (UL133/8), a transcriptional unit within the ULb? region (ULb?) of the human cytomegalovirus (HCMV) genome, and UL97, a viral protein kinase encoded by HCMV, play epistatic roles in facilitating progression of the viral lytic cycle. In studies with HCMV strain TB40/E, pharmacological blockade or genetic ablation of UL97 significantly reduced the levels of mRNA and protein for IE2 and viral early and early-late genes during a second wave of viral gene expression that commenced at between 24 and 48 h postinfection. These effects were accompanied by significant defects in viral DNA synthesis and viral replication. Interestingly, deletion of UL133/8 likewise caused significant defects in viral DNA synthesis, viral gene expression, and viral replication, which were not exacerbated upon UL97 inhibition. When UL133/8 was restored to HCMV laboratory strain AD169, which otherwise lacks the locus, the resulting recombinant virus replicated similarly to the parental virus. However, during UL97 inhibitor treatment, the virus in which UL133/8 was restored showed significantly exacerbated defects in viral DNA synthesis, viral gene expression, and production of infectious progeny virus, thus recapitulating the differences between wild-type TB40/E and its UL133/8-null derivative. Phenotypic evaluation of mutants null for specific open reading frames within UL133/8 revealed a role for UL135 in promoting viral gene expression, viral DNA synthesis, and viral replication, which depended on UL97. Taken together, our findings suggest that UL97 and UL135 play interdependent roles in promoting the progression of a second phase of the viral lytic cycle and that these roles are crucial for efficient viral replication. IMPORTANCE A unique feature of the herpesviruses, such as human cytomegalovirus (HCMV), is that they can undergo latency, a state during which the virus silences its gene expression, which allows lifelong viral persistence in immunocompetent hosts. We have uncovered an unexpected link between a cluster of HCMV genes involved in latency, UL133-UL138, and a virally encoded protein kinase, UL97, which plays crucial roles in manipulating the cell cycle during HCMV lytic replication. Although viral immediate early (IE) gene expression is essential for HCMV lytic replication, the activation of IE gene expression in latently infected cells is not sufficient to result in production of infectious virus. Our findings here and in an accompanying study (M. Umashankar, M. Rak, F. Bughio, P. Zagallo, K. Caviness, and F. D. Goodrum, J. Virol. 88:5987–6002, 2014) show that proteins expressed from the UL133-UL138 latency locus and UL97 play interdependent roles in overcoming checkpoints that restrict the viral lytic replication cycle, findings which suggest intriguing implications for establishment of and reactivation from HCMV latency. PMID:24623439

  3. [Central nervous system viral infections--analysis of routine laboratory results].

    PubMed

    Siennicka, Joanna; Trzci?ska, Agnieszka

    2008-01-01

    The most of registered in Poland cases of encephalitis and meningitis have viral aetiology. Confirmation of viral central nervous system (CNS) infection and diagnosis of pathogenic agent is critical for therapeutic treatment, especially if antiviral chemotherapy is available. The aim of this work was analysis of routine laboratory results obtained in Laboratory of Department of Virology NIZP-PZH by examination of materials obtained from 82 medical canters in Poland in aim of CNS infection confirmation. Materials, cerebrospinal fluid (CSN) n=277, and CSN together with serum (n=452) were obtained from patients aged from 3 days to 83 years. Accordingly with the range of tests performed in Laboratory of Department of Virology NIZP-PZH, obtained samples were examinated for 11 viral infections: HSV, CMV, EBV, VZV, HHV-6, HHV-7, TBE, measles, mumps, rubella and enteroviruses. Confirmation of viral infection was obtained in 104 out of 729 tested patients (14.3%). The highest number of confirmations was obtained in case of TBE infection (18.4%) and HSV (9.2%). The methods gave the highest number of confirmations were testing of intrathecal IgG synthesis (14.4%) and presence of IgM in serum (10.3%). If test was conducted only with CSF, confirmation of viral infection was obtained in 13 cases (4.7%). In conclusions it was ascertained that testing CSF and serum samples together greatly increase possibility of etiological agent detection and a range of ordered tests (i.e. intrathecal synthesis versus PCR) should account dynamics of pathological process. PMID:19143179

  4. Modeling and simulation of the mechanical response from nanoindentation test of DNA-filled viral capsids.

    PubMed

    Ahadi, Aylin; Johansson, Dan; Evilevitch, Alex

    2013-03-01

    Viruses can be described as biological objects composed mainly of two parts: a stiff protein shell called a capsid, and a core inside the capsid containing the nucleic acid and liquid. In many double-stranded DNA bacterial viruses (aka phage), the volume ratio between the liquid and the encapsidated DNA is approximately 1:1. Due to the dominant DNA hydration force, water strongly mediates the interaction between the packaged DNA strands. Therefore, water that hydrates the DNA plays an important role in nanoindentation experiments of DNA-filled viral capsids. Nanoindentation measurements allow us to gain further insight into the nature of the hydration and electrostatic interactions between the DNA strands. With this motivation, a continuum-based numerical model for simulating the nanoindentation response of DNA-filled viral capsids is proposed here. The viral capsid is modeled as large- strain isotropic hyper-elastic material, whereas porous elasticity is adopted to capture the mechanical response of the filled viral capsid. The voids inside the viral capsid are assumed to be filled with liquid, which is modeled as a homogenous incompressible fluid. The motion of a fluid flowing through the porous medium upon capsid indentation is modeled using Darcy's law, describing the flow of fluid through a porous medium. The nanoindentation response is simulated using three-dimensional finite element analysis and the simulations are performed using the finite element code Abaqus. Force-indentation curves for empty, partially and completely DNA-filled capsids are directly compared to the experimental data for bacteriophage ?. Material parameters such as Young's modulus, shear modulus, and bulk modulus are determined by comparing computed force-indentation curves to the data from the atomic force microscopy (AFM) experiments. Predictions are made for pressure distribution inside the capsid, as well as the fluid volume ratio variation during the indentation test. PMID:23860868

  5. Viral exploitation of actin: force-generation and scaffolding functions in viral infection.

    PubMed

    Spear, Mark; Wu, Yuntao

    2014-06-01

    As a fundamental component of the host cellular cytoskeleton, actin is routinely engaged by infecting viruses. Furthermore, viruses from diverse groups, and infecting diverse hosts, have convergently evolved an array of mechanisms for manipulating the actin cytoskeleton for efficacious infection. An ongoing chorus of research now indicates that the actin cytoskeleton is critical for viral replication at many stages of the viral life cycle, including binding, entry, nuclear localization, genomic transcription and reverse transcription, assembly, and egress/dissemination. Specifically, viruses subvert the force-generating and macromolecular scaffolding properties of the actin cytoskeleton to propel viral surfing, internalization, and migration within the cell. Additionally, viruses utilize the actin cytoskeleton to support and organize assembly sites, and eject budding virions for cell-to-cell transmission. It is the purpose of this review to provide an overview of current research, focusing on the various mechanisms and themes of virus-mediated actin modulation described therein. PMID:24938714

  6. Underreporting of Viral Encephalitis and Viral Meningitis, Ireland, 2005–2008

    PubMed Central

    O’Lorcain, Piaras; Moran, Joanne; Garvey, Patricia; McKeown, Paul; Connell, Jeff; Cotter, Suzanne

    2013-01-01

    Viral encephalitis (VE) and viral meningitis (VM) have been notifiable infectious diseases under surveillance in the Republic of Ireland since 1981. Laboratories have reported confirmed cases by detection of viral nucleic acid in cerebrospinal fluid since 2004. To determine the prevalence of these diseases in Ireland during 2005–2008, we analyzed 3 data sources: Hospital In-patient Enquiry data (from hospitalized following patients discharge) accessed through Health Intelligence Ireland, laboratory confirmations from the National Virus Reference Laboratory, and events from the Computerised Infectious Disease Reporting surveillance system. We found that the national surveillance system underestimates the incidence of these diseases in Ireland with a 10-fold higher VE hospitalization rate and 3-fold higher VM hospitalization rate than the reporting rate. Herpesviruses were responsible for most specified VE and enteroviruses for most specified VM from all 3 sources. Recommendations from this study have been implemented to improve the surveillance of these diseases in Ireland. PMID:23965781

  7. SOYBEAN GENETICS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean genetics is a broad area encompassing all aspects, such as qualitative genetics, molecular genetics, etc. The objective of this book chapter, a revision of a 1998 book on soybean, was to include information that could be used for soybean improvement, and to summarize the current status of s...

  8. Effects of Oils and Essential Oils from Seeds of Zanthoxylum schinifolium against Foodborne Viral Surrogates

    PubMed Central

    Chung, Mi Sook

    2014-01-01

    Human noroviruses are the most frequent cause of foodborne viral disease and are responsible for the vast majority of nonbacterial gastroenteritis. However, no specific therapies are available for the efficient control or prevention of foodborne viral disease. Here, we determined the antiviral activities of oils from seeds of Zanthoxylum schinifolium (ZSO) against foodborne viral surrogates, feline calicivirus-F9 (FCV-F9), and murine norovirus-1 (MNV-1), using plaque assay. Time-of-addition experiments were designed to determine the antiviral mechanism of action of ZSO against the surrogates. Maximal antiviral effect was observed upon pretreatment of FCV-F9 or MNV-1 with ZSO, which comprised oleic acid, linoleic acid, palmitic acid, and linolenic acid as the major fatty acids. FCV-F9 was more sensitive to ZSO than MNV-1, and the 50% effective concentration of ZSO against pretreatment of FCV-F9 was 0.0007%. However, essential oils from Z. schinifolium (ZSE), which comprised 42% estragole, showed no inhibitory effects against FCV-F9 and MNV-1. These results suggest that the inhibitory activities of ZSO were exerted by direct interaction of FCV-F9 or MNV-1 virion with ZSO, which may be a food material candidate for control of foodborne viral disease. PMID:25587338

  9. Mobile elements and viral integrations prompt considerations for bacterial DNA integration as a novel carcinogen.

    PubMed

    Robinson, Kelly M; Dunning Hotopp, Julie C

    2014-10-01

    Insertional mutagenesis has been repeatedly demonstrated in cancer genomes and has a role in oncogenesis. Mobile genetic elements can induce cancer development by random insertion into cancer related genes or by inducing translocations. L1s are typically implicated in cancers of an epithelial cell origin, while Alu elements have been implicated in leukemia as well as epithelial cell cancers. Likewise, viral infections have a significant role in cancer development predominantly through integration into the human genome and mutating or deregulating cancer related genes. Human papilloma virus is the best-known example of viral integrations contributing to carcinogenesis. However, hepatitis B virus, Epstein-Barr virus, and Merkel cell polyomavirus also integrate into the human genome and disrupt cancer related genes. Thus far, the role of microbes in cancer has primarily been attributed to mutations induced through chronic inflammation or toxins, as is the case with Helicobacter pylori and enterotoxigenic Bacteroides fragilis. We hypothesize that like mobile elements and viral DNA, bacterial and parasitic DNA may also integrate into the human somatic genome and be oncogenic. Until recently it was believed that bacterial DNA could not integrate into the human genome, but new evidence demonstrates that bacterial insertional mutagenesis may occur in cancer cells. Although this work does not show causation between bacterial insertions and cancer, it prompts more research in this area. Promising new sequencing technologies may reduce the risk of artifactual chimeric sequences, thus diminishing some of the challenges of identifying novel insertions in the somatic human genome. PMID:24956175

  10. Hybrid nonviral/viral vector systems for improved piggyBac DNA transposon in vivo delivery.

    PubMed

    Cooney, Ashley L; Singh, Brajesh K; Sinn, Patrick L

    2015-04-01

    The DNA transposon piggyBac is a potential therapeutic agent for multiple genetic diseases such as cystic fibrosis (CF). Recombinant piggyBac transposon and transposase are typically codelivered by plasmid transfection; however, plasmid delivery is inefficient in somatic cells in vivo and is a barrier to the therapeutic application of transposon-based vector systems. Here, we investigate the potential for hybrid piggyBac/viral vectors to transduce cells and support transposase-mediated genomic integration of the transposon. We tested both adenovirus (Ad) and adeno-associated virus (AAV) as transposon delivery vehicles. An Ad vector expressing hyperactive insect piggyBac transposase (iPB7) was codelivered. We show transposase-dependent transposition activity and mapped integrations in mammalian cells in vitro and in vivo from each viral vector platform. We also demonstrate efficient and persistent transgene expression following nasal delivery of piggyBac/viral vectors to mice. Furthermore, using piggyBac/Ad expressing Cystic Fibrosis transmembrane Conductance Regulator (CFTR), we show persistent correction of chloride current in well-differentiated primary cultures of human airway epithelial cells derived from CF patients. Combining the emerging technologies of DNA transposon-based vectors with well-studied adenoviral and AAV delivery provides new tools for in vivo gene transfer and presents an exciting opportunity to increase the delivery efficiency for therapeutic genes such as CFTR. PMID:25557623

  11. Bovine viral diarrhoea: pathogenesis and diagnosis.

    PubMed

    Lanyon, Sasha R; Hill, Fraser I; Reichel, Michael P; Brownlie, Joe

    2014-02-01

    Bovine viral diarrhoea virus (BVDV) is the most prevalent infectious disease of cattle. It causes financial losses from a variety of clinical manifestations and is the subject of a number of mitigation and eradication schemes around the world. The pathogenesis of BVDV infection is complex, with infection pre- and post-gestation leading to different outcomes. Infection of the dam during gestation results in fetal infection, which may lead to embryonic death, teratogenic effects or the birth of persistently infected (PI) calves. PI animals shed BVDV in their excretions and secretions throughout life and are the primary route of transmission of the virus. These animals can usually be readily detected by virus or viral antigen detection assays (RT-PCR, ELISA), except in the immediate post-natal period where colostral antibodies may mask virus presence. PI calves in utero (the 'Trojan cow' scenario) currently defy detection with available diagnostic tests, although dams carrying PI calves have been shown to have higher antibody levels than seropositive cows carrying non-PI calves. Acute infection with BVDV results in transient viraemia prior to seroconversion and can lead to reproductive dysfunction and immunosuppression leading to an increased incidence of secondary disease. Antibody assays readily detect virus exposure at the individual level and can also be used in pooled samples (serum and milk) to determine herd exposure or immunity. Diagnostic tests can be used to diagnose clinical cases, establish disease prevalence in groups and detect apparently normal but persistently infected animals. This review outlines the pathogenesis and pathology of BVD viral infection and uses this knowledge to select the best diagnostic tests for clinical diagnosis, monitoring, control and eradication efforts. Test methods, types of samples and problems areas of BVDV diagnosis are discussed. PMID:24053990

  12. Integrated Genetic Analysis Microsystems

    Microsoft Academic Search

    E. T. Lagally; H. T. Soh

    2005-01-01

    The advent of integrated microsystems for genetic analysis allows the acquisition of information at unprecedented length and time scales. The convergence of molecular biology, chemistry, physics, and materials science is required for their design and construction. The utility of the microsystems originates from increased analysis speed, lower analysis cost, and higher parallelism leading to increased assay throughput. In addition, when

  13. Exploring Image Virality in Google Plus

    E-print Network

    Guerini, Marco; Albanese, Davide

    2013-01-01

    Reactions to posts in an online social network show different dynamics depending on several textual features of the corresponding content. Do similar dynamics exist when images are posted? Exploiting a novel dataset of posts, gathered from the most popular Google+ users, we try to give an answer to such a question. We describe several virality phenomena that emerge when taking into account visual characteristics of images (such as orientation, mean saturation, etc.). We also provide hypotheses and potential explanations for the dynamics behind them, and include cases for which common-sense expectations do not hold true in our experiments.

  14. Oncolytic Viral Therapy of Malignant Glioma

    PubMed Central

    Parker, Jacqueline Nuss; Bauer, David; Cody, James J.; Markert, James M.

    2014-01-01

    SUMMARY Novel approaches to treatment of malignant glioma, the most frequently occurring primary brain tumor, have included the use of a wide range of oncolytic viral vectors. These vectors, either naturally tumor-selective, or engineered as such, have shown promise in the handful of Phase I and Phase II clinical trials conducted in recent years. The strategies developed for each of the different viruses currently being studied, and the history of their development, are summarized here. Additionally, the results of clinical trials in patients, and their implication for future trials, are also discussed. PMID:19560745

  15. [Bovine viral diarrhea control in Russian Federation].

    PubMed

    Guliukin, M I; Iurov, K P; Glotov, A G; Donchenko, N A

    2013-01-01

    Bovine viral diarrhea (BVD) is one of the greatest challenges for breeding and commercial livestock. It is characterized by lesions of the respiratory and gastrointestinal tract, abortion, infertility, immune deficiency, and persistence of the pathogen. In this work, a set of measures for the rehabilitation and prevention of BVD in cattle is described. It includes the data of the literature, guidance documents for the diagnosis and control of BVD adopted by OIE, EU countries, USA, as well as the results of this research. PMID:24772640

  16. Exploiting viral natural history for vaccine development.

    PubMed

    Barry, Peter A

    2015-06-01

    The partial successes of the Phase 2 gB-based vaccine trials for HCMV highlight the very real likelihood that vaccine-mediated induction of antibodies that neutralize the fusion pathway of fibroblast infection is not sufficient as a singular strategy to confer protective efficacy against primary HCMV infection. Alternative strategies that serve as adjuncts to gB-based vaccines are likely required to target different aspects of the complex lifecycle of HCMV infection. There has been considerable recent interest in targeting the gH/gL/UL128/UL130/UL131 pentamer complex (gH/gL-PC) to neutralize the endocytic pathway of HCMV infection of epithelial and endothelial cells. Since both cell types are critical during primary mucosal infection, intrahost spread, and shedding of HCMV in an infected host, the gH/gL-PC represents a high-value target for vaccination to interrupt the HCMV lifecycle. The natural history of HCMV is exceedingly complex and incompletely resolved, and the protective efficacy generated by gH/gL-PC remains to be validated in clinical trials. Yet, there are salient aspects of its lifecycle that offer clues about how other novel vaccine strategies can be targeted to especially susceptible parts of the viral proteome to significantly disrupt HCMV's ability to infect susceptible hosts. In particular, the protracted evolution of Herpesvirales has endowed HCMV with two remarkable properties of its natural history: (1) lifelong persistence within immune hosts that develop extraordinarily large antiviral immune responses and (2) the ability to reinfect those with prior immunity. The latter phenotype strongly implies that, if HCMV can overcome prior immunity to initiate a new infection, it is likely irrelevant whether prior immunity derives from prior infection or prior vaccination. Both phenotypes are unified by the extensive devotion of the HCMV coding repertoire (~50 %) to viral proteins that modulate host cell signaling, trafficking, activation, antigen presentation, and resistance to apoptosis. Collectively, these viral proteins are the likely reason for the high barrier to success for the 4-decade effort to design an HCMV vaccine, and they represent the viral proteins that make HCMV be the virus that it is. James Hanshaw wrote in 1971 that, based on a 15-year retrospective of congenital HCMV cases, "… any thoughtful program designed at prevention or treatment deserves consideration". Drawing upon natural history data from the nonhuman primate model of HCMV persistence and pathogenesis, a "thoughtful program" is put forth that HCMV immune-modulating proteins should be considered as vaccine candidates. PMID:25794555

  17. APOBEC3 Interference during Replication of Viral Genomes

    PubMed Central

    Willems, Luc; Gillet, Nicolas Albert

    2015-01-01

    Co-evolution of viruses and their hosts has reached a fragile and dynamic equilibrium that allows viral persistence, replication and transmission. In response, infected hosts have developed strategies of defense that counteract the deleterious effects of viral infections. In particular, single-strand DNA editing by Apolipoprotein B Editing Catalytic subunits proteins 3 (APOBEC3s) is a well-conserved mechanism of mammalian innate immunity that mutates and inactivates viral genomes. In this review, we describe the mechanisms of APOBEC3 editing during viral replication, the viral strategies that prevent APOBEC3 activity and the consequences of APOBEC3 modulation on viral fitness and host genome integrity. Understanding the mechanisms involved reveals new prospects for therapeutic intervention. PMID:26110583

  18. Nonsense-mediated decay serves as a general viral restriction mechanism in plants.

    PubMed

    Garcia, Damien; Garcia, Shahinez; Voinnet, Olivier

    2014-09-10

    (+)strand RNA viruses have to overcome various points of restriction in the host to establish successful infection. In plants, this includes RNA silencing. To uncover additional bottlenecks to RNA virus infection, we genetically attenuated the impact of RNA silencing on transgenically expressed Potato virus X (PVX), a (+)strand RNA virus that replicates in Arabidopsis. A genetic screen in this sensitized background uncovered how nonsense-mediated decay (NMD), a host RNA quality control mechanism, recognizes and eliminates PVX RNAs with internal termination codons and long 3' UTRs. NMD also operates in natural infection contexts, and while some viruses have evolved genome expression strategies to overcome this process altogether, the virulence of NMD-activating viruses entails their ability to directly suppress NMD or to promote an NMD-unfavorable cellular state. These principles of induction, evasion, and suppression define NMD as a general viral restriction mechanism in plants that also likely operates in animals. PMID:25155460

  19. GENETICALLY MODIFIED FOODS: HEALTH AND SAFETY ISSUES

    Microsoft Academic Search

    Javed Akhter; Mohammed Qutub; Norman Burnham

    2001-01-01

    For thousands of years, humans have taken advantage of naturally occurring genetic variation within species to selectively breed organisms with desirable traits. Many of the characteristics of domestic animals and agricultural crops have been developed through selective breeding. What is revolutionary about genetic engineering is that it involves the transfer of genetic material between organisms that would never be able

  20. DEVELOPMENTAL GENETICS OF PLANTS BIOLOGY 244

    E-print Network

    Schläppi, Michael

    the addressed genetic and epigenetic concepts of plant development; students will have a theoretical1 DEVELOPMENTAL GENETICS OF PLANTS BIOLOGY 244 Fall 2007 Michael Schläppi MW 4:00 PM - 5:15 PM In this section of BIOL 244 we will discuss aspects of plant developmental genetics. All material is based

  1. Introducing High School Students to Human Genetics.

    ERIC Educational Resources Information Center

    Haddow, Paula K.; And Others

    1988-01-01

    Considers six key concepts in human genetics in a question-and-answer format designed to help guide students to an understanding of the concept. Lists eight workshops in human genetics for high school biology teachers and four curriculum material packages on human genetics. (CW)

  2. Localization of viral proteins in cells infected with bovine viral diarrhoea virus

    Microsoft Academic Search

    B. Grummer; M. Beer; E. Liebler-Tenorio; I. Greiser-Wilke

    Bovine viral diarrhoea virus (BVDV) is a member of the genus Pestivirus within the family Flaviviridae. In this report, protein localization studies were performed to assess the mechanism for the release of mature virus particles from infected cells. Since BVDV is an enveloped virus, budding from either intra- or extracellular membranes is feasible. A prerequisite for the latter mechanism is

  3. Congenital Anomalies and Viral Infections in Infants—The Etiologic Role of Maternal Viral Infections

    PubMed Central

    Wright, Harry T.

    1966-01-01

    Some viruses, such as rubella and human cytomegalovirus, are known to cross the placental barrier and infect the fetus. In other cases of maternal viral infections, such as herpes simplex, evidence for transplacental passage is less convincing and fetal damage or neonatal disease may be coincidental or associated with perinatal infection. Certain cases of fetal or neonatal disease following maternal viral infections may be associated with disease in the mother which affects her metabolic processes or the placenta in such a way as to interfere with development of the fetus and infant. The possible effects of transplacental viral infections are several. Fetal loss may occur by means of abortion or stillbirth. There may be infection of the fetus, with clinical manifestations such as rash, or without clinical manifestations. The infant may be born with congenital defects, including such deformities as cataracts, cardiac anomalies, mental retardation or cerebral palsy. Although a number of maternal viral diseases have been etiologically incriminated in congenital defects, only two—rubella and cytomegalovirus infection—are definitely proved to be associated with anomalies or mental retardation in infants. PMID:5957431

  4. Viral spreading of daily information in online social networks

    NASA Astrophysics Data System (ADS)

    Kawamoto, Tatsuro; Hatano, Naomichi

    2014-07-01

    We explain a possible mechanism of an information spreading on a network which spreads extremely far from a seed node, namely the viral spreading. On the basis of a model of the information spreading in an online social network, in which the dynamics is expressed as a random multiplicative process of the spreading rates, we will show that the correlation between the spreading rates enhances the chance of the viral spreading, shifting the tipping point at which the spreading goes viral.

  5. Structure, sequence and expression of the hepatitis delta (?) viral genome

    NASA Astrophysics Data System (ADS)

    Wang, Kang-Sheng; Choo, Qui-Lim; Weiner, Amy J.; Ou, Jing-Hsiung; Najarian, Richard C.; Thayer, Richard M.; Mullenbach, Guy T.; Denniston, Katherine J.; Gerin, John L.; Houghton, Michael

    1986-10-01

    Biochemical and electron microscopic data indicate that the human hepatitis ? viral agent contains a covalently closed circular and single-stranded RNA genome that has certain similarities with viroid-like agents from plants. The sequence of the viral genome (1,678 nucleotides) has been determined and an open reading frame within the complementary strand has been shown to encode an antigen that binds specifically to antisera from patients with chronic hepatitis ? viral infections.

  6. Gene expression associated with compatible viral diseases in grapevine cultivars

    Microsoft Academic Search

    C. Espinoza; A. Vega; C. Medina; K. Schlauch; G. Cramer; P. Arce-Johnson

    2007-01-01

    Viral diseases affect grapevine cultures without inducing any resistance response. Thus, these plants develop systemic diseases\\u000a and are chronically infected. Molecular events associated with viral compatible infections responsible for disease establishment\\u000a and symptoms development are poorly understood. In this study, we surveyed viral infection in grapevines at a transcriptional\\u000a level. Gene expression in the Vitis vinifera red wine cultivars Carmnre

  7. Effect of ultraviolet germicidal irradiation on viral aerosols.

    PubMed

    Walker, Christopher M; Ko, Gwangpyo

    2007-08-01

    Ultraviolet (UV) germicidal air disinfection is an engineering method used to control the airborne transmission of pathogenic microorganisms in high-risk settings. Despite the recent emergence of respiratory viral pathogens such as SARS and avian influenza viruses, UV disinfection of pathogenic viral aerosols has not been examined. Hence, we characterized the UV disinfection of viral aerosols using the bacteriophage MS2, adenovirus, and coronavirus. Our objectives were to characterize the effect of nebulization and air sampling on the survival of important viral pathogens, quantitatively characterize and estimate the UV susceptibility of pathogenic viral aerosols, and evaluate the effect of relative humidity (RH) on the susceptibility of viral aerosols, to 254 nm UV-C. The viruses were aerosolized into an experimental chamber using a six-jet Collison nebulizer, exposed to 254 nm UV, and sampled using an AGI-30 liquid impinger. Both the MS2 and adenovirus aerosols were very resistant to UV air disinfection, with a reduction of less than 1 logarithm in viable viral aerosols at a UV dose of 2608 microW s/cm2. The susceptibility of coronavirus aerosols was 7-10 times that of the MS2 and adenovirus aerosols. Unlike bacterial aerosols, there was no significant protective effect of high RH on UV susceptibility of the tested viral aerosols. We confirmed that the UV disinfection rate differs greatly between viral aerosols and viruses suspended in liquid. PMID:17822117

  8. [Hepatitis C viral infection and depression].

    PubMed

    Lengyel, Gabriella; Aszalós, Zsuzsa; Tulassay, Zsolt

    2007-01-01

    About 170 million individuals can be found with chronic hepatitis C viral infection all over the world. The occurrence of depression is more frequent among the persons than in the healthy population, this depression can be found in 58 per cent of patients with chronic hepatitis C. On the basis of the literature the authors review the aetiology of depression in liver diseases, examining the neuropathogenic effect of HCV. They demonstrate the scientific results which are evidences of hepatitis C viral infection for the alterations in the central nerve system. The depression is one of the side effects of the alpha-interferon treatment used in the therapy of HCV. The authors demonstrate the biological basis, development, consequences of depression produced by interferon and they give a review of the protocol in the diagnostic procedure of a patient with depression. They summarize the steps of psychiatric drug therapy in chronic liver diseases. That is also important whether the chronic HCV infected patient with depression can be treated with interferon. The loss of interferon treatment can lead to the fatal outcome of liver disease. In order to have the correct decision a collaboration between internist and psychiatric specialist is necessary. PMID:17344112

  9. Optimal viral strategies for bypassing RNA silencing

    PubMed Central

    Rodrigo, Guillermo; Carrera, Javier; Jaramillo, Alfonso; Elena, Santiago F.

    2011-01-01

    The RNA silencing pathway constitutes a defence mechanism highly conserved in eukaryotes, especially in plants, where the underlying working principle relies on the repressive action triggered by the intracellular presence of double-stranded RNAs. This immune system performs a post-transcriptional suppression of aberrant mRNAs or viral RNAs by small interfering RNAs (siRNAs) that are directed towards their target in a sequence-specific manner. However, viruses have evolved strategies to escape from silencing surveillance while promoting their own replication. Several viruses encode suppressor proteins that interact with different elements of the RNA silencing pathway and block it. The different suppressors are not phylogenetically nor structurally related and also differ in their mechanism of action. Here, we adopt a model-driven forward-engineering approach to understand the evolution of suppressor proteins and, in particular, why viral suppressors preferentially target some components of the silencing pathway. We analysed three strategies characterized by different design principles: replication in the absence of a suppressor, suppressors targeting the first protein component of the pathway and suppressors targeting the siRNAs. Our results shed light on the question of whether a virus must opt for devoting more time into transcription or into translation and on which would be the optimal step of the silencing pathway to be targeted by suppressors. In addition, we discussed the evolutionary implications of such designing principles. PMID:20573628

  10. Interleukin-1 production in acute viral hepatitis.

    PubMed Central

    Müller, C; Gödl, I; Ahmad, R; Wolf, H M; Mannhalter, J W; Eibl, M M

    1989-01-01

    The in vitro production of interleukin-1 in 15 children with acute hepatitis A and five children with acute hepatitis B was determined by measuring lymphocyte activating factor secreted by peripheral blood monocytes in a thymocyte proliferation assay. Aluminium hydroxide induced production of lymphocyte activating factor was significantly lower in patients with acute hepatitis A as well as patients with hepatitis B as compared with healthy control subjects. In both forms of acute viral hepatitis production of lymphocyte activating factor was severely depressed during the first week, increased gradually during the further course of the illness, but did not reach normal concentrations within the first three weeks after onset of the acute symptoms of the disease. No correlation could be found between in vitro production of lymphocyte activating factor and the severity of liver disease as estimated by the rise of serum concentrations of transaminases, bilirubin, or several parameters of acute phase reaction (alpha 1 antitrypsin, C reactive protein, erythrocyte sedimentation rate). The reduced production of interleukin-1, as assessed by determination of lymphocyte activating factor, could explain the only moderate acute phase reaction seen during acute viral hepatitis. PMID:2784656

  11. Next generation sequencing of viral RNA genomes

    PubMed Central

    2013-01-01

    Background With the advent of Next Generation Sequencing (NGS) technologies, the ability to generate large amounts of sequence data has revolutionized the genomics field. Most RNA viruses have relatively small genomes in comparison to other organisms and as such, would appear to be an obvious success story for the use of NGS technologies. However, due to the relatively low abundance of viral RNA in relation to host RNA, RNA viruses have proved relatively difficult to sequence using NGS technologies. Here we detail a simple, robust methodology, without the use of ultra-centrifugation, filtration or viral enrichment protocols, to prepare RNA from diagnostic clinical tissue samples, cell monolayers and tissue culture supernatant, for subsequent sequencing on the Roche 454 platform. Results As representative RNA viruses, full genome sequence was successfully obtained from known lyssaviruses belonging to recognized species and a novel lyssavirus species using these protocols and assembling the reads using de novo algorithms. Furthermore, genome sequences were generated from considerably less than 200 ng RNA, indicating that manufacturers’ minimum template guidance is conservative. In addition to obtaining genome consensus sequence, a high proportion of SNPs (Single Nucleotide Polymorphisms) were identified in the majority of samples analyzed. Conclusions The approaches reported clearly facilitate successful full genome lyssavirus sequencing and can be universally applied to discovering and obtaining consensus genome sequences of RNA viruses from a variety of sources. PMID:23822119

  12. Branching dynamics of viral information spreading.

    PubMed

    Iribarren, José Luis; Moro, Esteban

    2011-10-01

    Despite its importance for rumors or innovations propagation, peer-to-peer collaboration, social networking, or marketing, the dynamics of information spreading is not well understood. Since the diffusion depends on the heterogeneous patterns of human behavior and is driven by the participants' decisions, its propagation dynamics shows surprising properties not explained by traditional epidemic or contagion models. Here we present a detailed analysis of our study of real viral marketing campaigns where tracking the propagation of a controlled message allowed us to analyze the structure and dynamics of a diffusion graph involving over 31,000 individuals. We found that information spreading displays a non-Markovian branching dynamics that can be modeled by a two-step Bellman-Harris branching process that generalizes the static models known in the literature and incorporates the high variability of human behavior. It explains accurately all the features of information propagation under the "tipping point" and can be used for prediction and management of viral information spreading processes. PMID:22181236

  13. Development of a contemporary globally diverse HIV viral panel by the EQAPOL program.

    PubMed

    Sanchez, Ana M; DeMarco, C Todd; Hora, Bhavna; Keinonen, Sarah; Chen, Yue; Brinkley, Christie; Stone, Mars; Tobler, Leslie; Keating, Sheila; Schito, Marco; Busch, Michael P; Gao, Feng; Denny, Thomas N

    2014-07-01

    The significant diversity among HIV-1 variants poses serious challenges for vaccine development and for developing sensitive assays for screening, surveillance, diagnosis, and clinical management. Recognizing a need to develop a panel of HIV representing the current genetic and geographic diversity NIH/NIAID contracted the External Quality Assurance Program Oversight Laboratory (EQAPOL) to isolate, characterize and establish panels of HIV-1 strains representing global diverse subtypes and circulating recombinant forms (CRFs), and to make them available to the research community. HIV-positive plasma specimens and previously established isolates were collected through a variety of collaborations with a preference for samples from acutely/recently infected persons. Source specimens were cultured to high-titer/high-volume using well-characterized cryopreserved PBMCs from National y donors. Panel samples were stored as neat culture supernatant or diluted into defibrinated plasma. Characterization for the final expanded virus stocks included viral load, p24 antigen, infectivity (TCID), sterility, coreceptor usage, and near full-length genome sequencing. Viruses are made available to approved, interested laboratories using an online ordering application. The current EQAPOL Viral Diversity panel includes 100 viral specimens representing 6 subtypes (A, B, C, D, F, and G), 2 sub-subtypes (F1 and F2), 7 CRFs (01, 02, 04, 14, 22, 24, and 47), 19 URFs and 3 group O viruses from 22 countries. The EQAPOL Viral Diversity panel is an invaluable collection of well-characterized reagents that are available to the scientific community, including researchers, epidemiologists, and commercial manufacturers of diagnostics and pharmaceuticals to support HIV research, as well as diagnostic and vaccine development. PMID:24447533

  14. Three distinct suppressors of RNA silencing encoded by a 20-kb viral RNA genome

    NASA Astrophysics Data System (ADS)

    Lu, Rui; Folimonov, Alexey; Shintaku, Michael; Li, Wan-Xiang; Falk, Bryce W.; Dawson, William O.; Ding, Shou-Wei

    2004-11-01

    Viral infection in both plant and invertebrate hosts requires a virus-encoded function to block the RNA silencing antiviral defense. Here, we report the identification and characterization of three distinct suppressors of RNA silencing encoded by the 20-kb plus-strand RNA genome of citrus tristeza virus (CTV). When introduced by genetic crosses into plants carrying a silencing transgene, both p20 and p23, but not coat protein (CP), restored expression of the transgene. Although none of the CTV proteins prevented DNA methylation of the transgene, export of the silencing signal (capable of mediating intercellular silencing spread) was detected only from the F1 plants expressing p23 and not from the CP- or p20-expressing F1 plants, demonstrating suppression of intercellular silencing by CP and p20 but not by p23. Thus, intracellular and intercellular silencing are each targeted by a CTV protein, whereas the third, p20, inhibits silencing at both levels. Notably, CP suppresses intercellular silencing without interfering with intracellular silencing. The novel property of CP suggests a mechanism distinct to p20 and all of the other viral suppressors known to interfere with intercellular silencing and that this class of viral suppressors may not be consistently identified by Agrobacterium coinfiltration because it also induces RNA silencing against the infiltrated suppressor transgene. Our analyses reveal a sophisticated viral counter-defense strategy that targets the silencing antiviral pathway at multiple steps and may be essential for protecting CTV with such a large RNA genome from antiviral silencing in the perennial tree host. RNA interference | citrus tristeza virus | virus synergy | antiviral immunity

  15. A comprehensive collection of systems biology data characterizing the host response to viral infection

    PubMed Central

    Aevermann, Brian D.; Pickett, Brett E.; Kumar, Sanjeev; Klem, Edward B.; Agnihothram, Sudhakar; Askovich, Peter S.; Bankhead, Armand; Bolles, Meagen; Carter, Victoria; Chang, Jean; Clauss, Therese R.W.; Dash, Pradyot; Diercks, Alan H.; Eisfeld, Amie J.; Ellis, Amy; Fan, Shufang; Ferris, Martin T.; Gralinski, Lisa E.; Green, Richard R.; Gritsenko, Marina A.; Hatta, Masato; Heegel, Robert A.; Jacobs, Jon M.; Jeng, Sophia; Josset, Laurence; Kaiser, Shari M.; Kelly, Sara; Law, G. Lynn; Li, Chengjun; Li, Jiangning; Long, Casey; Luna, Maria L.; Matzke, Melissa; McDermott, Jason; Menachery, Vineet; Metz, Thomas O.; Mitchell, Hugh; Monroe, Matthew E.; Navarro, Garnet; Neumann, Gabriele; Podyminogin, Rebecca L.; Purvine, Samuel O.; Rosenberger, Carrie M.; Sanders, Catherine J.; Schepmoes, Athena A.; Shukla, Anil K.; Sims, Amy; Sova, Pavel; Tam, Vincent C.; Tchitchek, Nicolas; Thomas, Paul G.; Tilton, Susan C.; Totura, Allison; Wang, Jing; Webb-Robertson, Bobbie-Jo; Wen, Ji; Weiss, Jeffrey M.; Yang, Feng; Yount, Boyd; Zhang, Qibin; McWeeney, Shannon; Smith, Richard D.; Waters, Katrina M.; Kawaoka, Yoshihiro; Baric, Ralph; Aderem, Alan; Katze, Michael G.; Scheuermann, Richard H.

    2014-01-01

    The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection. PMID:25977790

  16. A comprehensive collection of systems biology data characterizing the host response to viral infection.

    PubMed

    Aevermann, Brian D; Pickett, Brett E; Kumar, Sanjeev; Klem, Edward B; Agnihothram, Sudhakar; Askovich, Peter S; Bankhead, Armand; Bolles, Meagen; Carter, Victoria; Chang, Jean; Clauss, Therese R W; Dash, Pradyot; Diercks, Alan H; Eisfeld, Amie J; Ellis, Amy; Fan, Shufang; Ferris, Martin T; Gralinski, Lisa E; Green, Richard R; Gritsenko, Marina A; Hatta, Masato; Heegel, Robert A; Jacobs, Jon M; Jeng, Sophia; Josset, Laurence; Kaiser, Shari M; Kelly, Sara; Law, G Lynn; Li, Chengjun; Li, Jiangning; Long, Casey; Luna, Maria L; Matzke, Melissa; McDermott, Jason; Menachery, Vineet; Metz, Thomas O; Mitchell, Hugh; Monroe, Matthew E; Navarro, Garnet; Neumann, Gabriele; Podyminogin, Rebecca L; Purvine, Samuel O; Rosenberger, Carrie M; Sanders, Catherine J; Schepmoes, Athena A; Shukla, Anil K; Sims, Amy; Sova, Pavel; Tam, Vincent C; Tchitchek, Nicolas; Thomas, Paul G; Tilton, Susan C; Totura, Allison; Wang, Jing; Webb-Robertson, Bobbie-Jo; Wen, Ji; Weiss, Jeffrey M; Yang, Feng; Yount, Boyd; Zhang, Qibin; McWeeney, Shannon; Smith, Richard D; Waters, Katrina M; Kawaoka, Yoshihiro; Baric, Ralph; Aderem, Alan; Katze, Michael G; Scheuermann, Richard H

    2014-01-01

    The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection. PMID:25977790

  17. HIV Viral Load Response to Antiretroviral Therapy According to the Baseline CD4 Cell Count and Viral Load

    Microsoft Academic Search

    Andrew N. Phillips; Schlomo Staszewski; Rainer Weber; Ole Kirk; Patrick Francioli; Veronica Miller; Pietro Vernazza; Jens D. Lundgren; Bruno Ledergerber

    \\/L or higher, after adjustment for several factors including baseline viral load. For baseline viral load, the RHs were 0.95 (95% CI, 0.84-1.07) and 0.65 (95% CI, 0.58- 0.74), for 10000 to 99999 and 100000 copies\\/mL or greater, respectively, compared with less than 10000 copies\\/mL, but the probability of viral load lower than 500 cop- ies\\/mL at week 32 was

  18. Cholesterol-conjugated peptide antivirals: a path to a rapid response to emerging viral diseases.

    PubMed

    Pessi, Antonello

    2015-05-01

    While it is now possible to identify and genetically fingerprint the causative agents of emerging viral diseases, often with extraordinary speed, suitable therapies cannot be developed with equivalent speed, because drug discovery requires information that goes beyond knowledge of the viral genome. Peptides, however, may represent a special opportunity. For all enveloped viruses, fusion between the viral and the target cell membrane is an obligatory step of the life cycle. Class I fusion proteins harbor regions with a repeating pattern of amino acids, the heptad repeats (HRs), that play a key role in fusion, and HR-derived peptides such as enfuvirtide, in clinical use for HIV, can block the process. Because of their characteristic sequence pattern, HRs are easily identified in the genome by means of computer programs, providing the sequence of candidate peptide inhibitors directly from genomic information. Moreover, a simple chemical modification, the attachment of a cholesterol group, can dramatically increase the antiviral potency of HR-derived inhibitors and simultaneously improve their pharmacokinetics. Further enhancement can be provided by dimerization of the cholesterol-conjugated peptide. The examples reported so far include inhibitors of retroviruses, paramyxoviruses, orthomyxoviruses, henipaviruses, coronaviruses, and filoviruses. For some of these viruses, in vivo efficacy has been demonstrated in suitable animal models. The combination of bioinformatic lead identification and potency/pharmacokinetics improvement provided by cholesterol conjugation may form the basis for a rapid response strategy, where development of an emergency cholesterol-conjugated therapeutic would immediately follow the availability of the genetic information of a new enveloped virus. PMID:25331523

  19. Associations between Single Nucleotide Polymorphisms in Cellular Viral Receptors and Attachment Factor-Related Genes and Humoral Immunity to Rubella Vaccination

    PubMed Central

    Haralambieva, Iana H.; Lambert, Nathaniel D.; Ovsyannikova, Inna G.; Kennedy, Richard B.; Larrabee, Beth R.; Pankratz, V. Shane; Poland, Gregory A.

    2014-01-01

    Background Viral attachment and cell entry host factors are important for viral replication, pathogenesis, and the generation and sustenance of immune responses after infection and/or vaccination, and are plausible genetic regulators of vaccine-induced immunity. Methods Using a tag-SNP approach in candidate gene study, we assessed the role of selected cell surface receptor genes, attachment factor-related genes, along with other immune genes in the genetic control of immune response variations after live rubella vaccination in two independent study cohorts. Results Our analysis revealed evidence for multiple associations between genetic variants in the PVR, PVRL2, CD209/DC-SIGN, RARB, MOG, IL6 and other immune function-related genes and rubella-specific neutralizing antibodies after vaccination (meta p-value <0.05). Conclusion Our results indicate that multiple SNPs from genes involved in cell adhesion, viral attachment, and viral entry, as well as others in genes involved in signaling and/or immune response regulation, play a role in modulating humoral immune responses following live rubella vaccination. PMID:24945853

  20. "What is this genetics, anyway?" Understandings of genetics, illness causality and inheritance among British Pakistani users of genetic services.

    PubMed

    Shaw, Alison; Hurst, Jane A

    2008-08-01

    Misconceptions about basic genetic concepts and inheritance patterns may be widespread in the general population. This paper investigates understandings of genetics, illness causality and inheritance among British Pakistanis referred to a UK genetics clinic. During participant observation of genetics clinic consultations and semi-structured interviews in Urdu or English in respondents' homes, we identified an array of environmental, behavioral and spiritual understandings of the causes of medical and intellectual problems. Misconceptions about the location of genetic information in the body and of genetic mechanisms of inheritance were common, reflected the range of everyday theories observed for White British patients and included the belief that a child receives more genetic material from the father than the mother. Despite some participants' conversational use of genetic terminology, some patients had assimilated genetic information in ways that conflict with genetic theory with potentially serious clinical consequences. Additionally, skepticism of genetic theories of illness reflected a rejection of a dominant discourse of genetic risk that stigmatizes cousin marriages. Patients referred to genetics clinics may not easily surrender their lay or personal theories about the causes of their own or their child's condition and their understandings of genetic risk. Genetic counselors may need to identify, work with and at times challenge patients' understandings of illness causality and inheritance. PMID:18607703

  1. Genetic counseling 

    E-print Network

    Stough, Laura

    2014-01-01

    be at increased risk for complications or disability, as well as women over 35 who are pregnant. Couples who already have a child with a genetic disability or who give birth to infants diagnosed with a genetic dis- ease by routine newborn screening may also seek...). Genetic counselors usually work as part of a health- care team, providing information and support to families who have members with birth defects or genetic disor- ders and to families who may be at risk for a variety of inherited conditions (National...

  2. CSF LPV concentrations and viral load in viral suppressed patients on LPV/r monotherapy given once daily

    PubMed Central

    Tiraboschi, Juan; Imaz, Arkaitz; Ferrer, Elena; Saumoy, Maria; Rozas, Nerea; Maso, Marga; Vila, Antonia; Niubo, Jordi; Podzamczer, Daniel

    2014-01-01

    Introduction Plasma trough concentrations of lopinavir (LPV) given as LPV/r 800/200 mg once daily (OD) are reduced in comparison with 400/100 mg twice daily (BID). While OD dosage of LPV/r is sufficient to achieve viral suppression in plasma, data about drug penetration and viral suppression in central nervous system (CNS) is needed, mainly if LPVr is used as maintenance monotherapy strategy in selected patients. The objective of this study was to evaluate CSF HIV-1 RNA and CSF LPV concentrations in patients receiving LPV/r monotherapy OD (LPVrMOD). Material and Methods This is a cross-sectional sub-study within a prospective, open-label pilot simplification study to evaluate the efficacy and safety of LPV/rMOD in virologically suppressed patients previously receiving a BID LPV/r monotherapy regimen (LPV/rMBID), the “Kmon study” (NCT01581853). To assess LPV concentrations and HIV-1 RNA in CSF, a lumbar puncture (LP) was performed in a subgroup of patients after at least one month of LPVrMOD treatment. Plasma-paired samples of all patients were also obtained. HIV-1 RNA was determined by real-time PCR (limit of detection 40 copies/mL). Liquid chromatography-tandem mass spectrometry (Tandem labs, NJ) was used to determine CSF and blood plasma LPV concentrations. Results Nine patients were included. Median (range) age was 48 (34–56) years, median CD4 cell count 672 (252–1,408) cells/mL, median nadir CD4 count 125 (35–537) cells/mL and 40% of subjects were HCV-positive. Before starting LPV/rMOD median time on a LPV/r-containing regimen and on LPV/rMBID were 9 (4–11) years and 15 (7–24) months respectively, median time with undetectable HIV viral load was 5 (3–12) years and 2 patients had a previous documented blip. LP was performed a median of 24 (8–36) weeks after starting LPV/rMOD and 24 (11–28) hours after the last LPV/rMOD dose CSF and plasma HIV RNA was 40 copies/mL in all patients. Median LPV CSF concentration was 9.78 (1.93–78.3) ng/mL, median LPV plasma concentration 1,103 (377–16,700) ng/mL and median LPV CSF/plasma ratio 0.3% (0.1–1.2). Conclusions No CSF viral escape was detected and LPV concentrations were above the IC50 for wtHIV-1 (1.9 ng/mL). However, as concentrations were close to IC50 in some patients, a careful clinical follow up of patients receiving this regimen would be advisable. Larger longitudinal studies will be helpful for a better understanding of the CNS antiviral activity of LPVr monotherapy. PMID:25394093

  3. HTLV-1 Yin and Yang: Rex and p30 master regulators of viral mRNA trafficking.

    PubMed

    Baydoun, Hicham H; Bellon, Marcia; Nicot, Christophe

    2008-01-01

    Human retroviruses are associated with a variety of malignancies including Kaposi's sarcoma and Epstein-Barr virus-associated lymphoma in HIV infection, T-cell leukemia/lymphoma and a neurologic disorder in human T-cell lymphotropic virus type 1 (HTLV-1) infection. Both HIV and human T-cell lymphotropic virus type 1 have evolved a complex genetic organization for optimal use of their limited genome and production of all necessary structural and regulatory proteins. Use of alternative splicing is essential for balanced expression of multiple viral regulators from one genomic polycistronic RNA. In addition, nuclear export of incompletely spliced RNA is required for production of structural and enzymatic proteins and virus particles. Decisions controlling these events are largely guarded by viral proteins. In human T-cell lymphotropic virus type 1, Rex and p30 are both nuclear/nucleolar RNA binding regulatory proteins. Rex interacts with a Rex-responsive element to stimulate nuclear export of incompletely spliced RNA and increase production of virus particles. In contrast, human T-cell lymphotropic virus type 1 p30 is involved in the nuclear retention of the tax/rex mRNA leading to inhibition of virus expression and establishment of viral latency. How these two proteins, with apparently opposite functions, orchestrate virus replication and ensure vigilant control of viral gene expression is discussed. PMID:19092975

  4. HTLV-1 Yin and Yang: Rex and p30 Master Regulators of Viral mRNA Trafficking

    PubMed Central

    Baydoun, Hicham H.; Bellon, Marcia; Nicot, Christophe

    2009-01-01

    Human retroviruses are associated with a variety of malignancies including Kaposi’s sarcoma and Epstein-Barr virus-associated lymphoma in HIV infection, T-cell leukemia/lymphoma and a neurologic disorder in human T-cell lymphotropic virus type 1 (HTLV-1) infection. Both HIV and human T-cell lymphotropic virus type 1 have evolved a complex genetic organization for optimal use of their limited genome and production of all necessary structural and regulatory proteins. Use of alternative splicing is essential for balanced expression of multiple viral regulators from one genomic polycistronic RNA. In addition, nuclear export of incompletely spliced RNA is required for production of structural and enzymatic proteins and virus particles. Decisions controlling these events are largely guarded by viral proteins. In human T-cell lymphotropic virus type 1, Rex and p30 are both nuclear/nucleolar RNA binding regulatory proteins. Rex interacts with a Rex-responsive element to stimulate nuclear export of incompletely spliced RNA and increase production of virus particles. In contrast, human T-cell lymphotropic virus type 1 p30 is involved in the nuclear retention of the tax/rex mRNA leading to inhibition of virus expression and establishment of viral latency. How these two proteins, with apparently opposite functions, orchestrate virus replication and ensure vigilant control of viral gene expression is discussed. PMID:19092975

  5. Performance assessment of the Illumina massively parallel sequencing platform for deep sequencing analysis of viral minority variants.

    PubMed

    Thys, Kim; Verhasselt, Peter; Reumers, Joke; Verbist, Bie M P; Maes, Bart; Aerssens, Jeroen

    2015-09-01

    Massively parallel sequencing (MPS) technology has opened new avenues to study viral dynamics and treatment-induced resistance mechanisms of infections such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Whereas the Roche/454 platform has been used widely for the detection of low-frequent drug resistant variants, more recently developed short-read MPS technologies have the advantage of delivering a higher sequencing depth at a lower cost per sequenced base. This study assesses the performance characteristics of Illumina MPS technology for the characterization of genetic variability in viral populations by deep sequencing. The reported results from MPS experiments comprising HIV and HCV plasmids demonstrate that a 0.5-1% lower limit of detection can be achieved readily with Illumina MPS while retaining good accuracy also at low frequencies. Deep sequencing of a set of clinical samples (12 HIV and 9 HCV patients), designed at a similar budget for both MPS platforms, reveals a comparable lower limit of detection for Illumina and Roche/454. Finally, this study shows the possibility to apply Illumina's paired-end sequencing as a strategy to assess linkage between different mutations identified in individual viral subspecies. These results support the use of Illumina as another MPS platform of choice for deep sequencing of viral minority species. PMID:25917877

  6. The ?6 Cystovirus Protein P7 Becomes Accessible to Antibodies in the Transcribing Nucleocapsid: A Probe for Viral Structural Elements

    PubMed Central

    Alimova, Alexandra; Wei, Hui; Katz, Al; Spatz, Linda; Gottlieb, Paul

    2015-01-01

    Protein P7 is a component of the cystovirus viral polymerase complex. In the unpackaged procapsid, the protein is situated in close proximity to the viral directed RNA polymerase, P2. Cryo-electron microscopy difference maps from the species ?6 procapsid have demonstrated that P7 and P2 likely interact prior to viral RNA packaging. The location of P7 in the post-packaged nucleocapsid (NC) remains unknown. P7 may translocate closer to the five-fold axis of a filled procapsid but this has not been directly visualized. We propose that monoclonal antibodies (Mabs) can be selected that serve as probe- reagents for viral assembly and structure. A set of Mabs have been isolated that recognize and bind to the ?6 P7. The antibody set contains five unique Mabs, four of which recognize a linear epitope and one which recognizes a conformational epitope. The four unique Mabs that recognize a linear epitope display restricted utilization of V? and VH genes. The restricted genetic range among 4 of the 5 antibodies implies that the antibody repertoire is limited. The limitation could be the consequence of a paucity of exposed antigenic sites on the ?6 P7 surface. It is further demonstrated that within ?6 nucleocapsids that are primed for early-phase transcription, P7 is partially accessible to the Mabs, indicating that the nucleocapsid shell (protein P8) has undergone partial disassembly exposing the protein’s antigenic sites. PMID:25799314

  7. Functional genomics approach for the identification of human host factors supporting dengue viral propagation

    PubMed Central

    Barrows, Nicholas J.; Jamison, Sharon F.; Bradrick, Shelton S.; Le Sommer, Caroline; Kim, So Young; Pearson, James; Garcia-Blanco, Mariano A.

    2014-01-01

    Dengue virus (DENV) is endemic throughout tropical regions around the world and there are no approved treatments or anti-transmission agents currently available. Consequently, there exists an enormous unmet need to treat the human diseases caused by DENV and block viral transmission by the mosquito vector. RNAi screening represents an efficient method to expand the pool of known host factors that could become viable targets for treatments or provide rationale to consider available drugs as anti-DENV treatments. We developed a high throughput siRNA-based screening protocol that can identify human DENV host factors. The protocol herein describes the materials and the procedures necessary to screen a human cell line in order to identify genes which are either necessary for or restrict DENV propagation at any stage in the viral life cycle. PMID:24696344

  8. Viral vectors, tools for gene transfer in the nervous system

    Microsoft Academic Search

    Wim T. J. M. C Hermens; Joost Verhaagen

    1998-01-01

    Viral vectors are becoming increasingly important tools to investigate the function of neural proteins and to explore the feasibility of gene therapy to treat diseases of the nervous system. This gene transfer technology is based on the use of a virus as a gene delivery vehicle. In contrast to functional analysis of gene products in transgenic mouse, viral vectors can

  9. Mechanisms of inhibition of viral replication in plants

    SciTech Connect

    Not Available

    1990-01-01

    We have made a number of interesting observations of importance to the fields of virology and plant molecular biology. Topics include the genome of cucumber mosaic virus (CMV), recombination of the CMV genome, transgenic plants and viral movement genes, mapping resistance breakage sequences in the tomato mosaic virus (TMV) genome, and mapping pathogeneticity domains and viral RNA heterogeneity. 1 fig., 1 tab.

  10. Review article Emerging viral diseases of fish and shrimp

    E-print Network

    Paris-Sud XI, Université de

    Review article Emerging viral diseases of fish and shrimp Peter J. WALKER 1*, James R. WINTON 2 1 and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular the challenges presented by climate change. disease emergence / shrimp / fish / virus Table of contents 1

  11. Latest development in viral vectors for gene therapy

    Microsoft Academic Search

    Kenneth Lundstrom

    2003-01-01

    Gene therapy includes the application of various viral vectors, which represent most types and families of viruses, suitable for infection of mammalian host cells. Both hereditary diseases and acquired illnesses, such as cancer, can be targeted. Because of the various properties of each viral vector, the definition of their application range depends on factors such as packaging capacity, host range,

  12. A Machine Learning Approach to Differentiating Bacterial From Viral Meningitis

    Microsoft Academic Search

    Kenneth Revett; Florin Gorunescu; Marius Ene

    2006-01-01

    Clinical reports indicate that differentiating bacterial from viral (aseptic) meningitis is still a difficult issue, compounded by factors such as age and time of presentation. Clinicians routinely rely on the results from blood and cerebrospinal fluid (CSF) to discriminate bacterial from viral meningitis. Tests such as the CSF Gram stain performed prior to broad-spectrum antibiotic treatment yield sensitivities between 60

  13. Adoptive immunotherapy for viral infections after allogeneic stem cell transplantation

    Microsoft Academic Search

    Maarten Laurens Zandvliet

    2011-01-01

    Het transplanteren van stamcellen van een gezonde donor, allogene stamceltransplantatie, is een potentieel genezende behandeling van hematologische maligniteiten en aangeboren hematopoïetische ziekten. In de periode na allogene stamceltransplantatie kunnen ernstige virale infecties optreden. Omdat het herstel van virus-specifieke T cellen gepaard gaat met bescherming tegen virale ziekte na stamceltransplantatie, is het overbrengen van virus-specifieke donor T cellen naar de ontvanger

  14. Molecular Clock of Viral Evolution, and the Neutral Theory

    Microsoft Academic Search

    Takashi Gojobori; En Moriyama; Motoo Kimura

    1990-01-01

    Evolution of viral genes is characterized by enormously high speed compared with that of nuclear genes of eukaryotic organisms. In this paper, the evolutionary rates and patterns of base substitutions are examined for retroviral oncogenes, human immunodeficiency viruses (HIV), hepatitis B viruses (HBV), and influenza A viruses. Our results show that the evolutionary process of these viral genes can readily

  15. Investigating a Mystery Disease: Tales from a Viral Detective

    PubMed Central

    2014-01-01

    Viral outbreak investigation is challenging logistically as well as scientifically. In the context of addressing a fictional emerging viral disease, I describe the process of discovery, from the initial report of a problem through discussions of intellectual property and sample management, study design, management, experimental execution, and reporting of results. PMID:25165103

  16. Viral Discovery and Sequence Recovery Using DNA Microarrays

    E-print Network

    Wang, David

    Viral Discovery and Sequence Recovery Using DNA Microarrays David Wang1 , Anatoly Urisman1 , Yu, there is a great demand for new technological methods for viral discovery. We describe herein a DNA microarray-based platform for novel virus identification and characterization. Central to this approach was a DNA microarray

  17. Viral Haemorrhagic Fevers LUCILLE BLUMBERG | DELIA ENRIA | DANIEL G. BAUSCH

    E-print Network

    Rambaut, Andrew

    171 Viral Haemorrhagic Fevers LUCILLE BLUMBERG | DELIA ENRIA | DANIEL G. BAUSCH 16 Overview INTRODUCTION Viral haemorrhagic fever (HF) is a term first coined by Russian physicians in the 1940s to describe a syndrome comprised of fever, a constellation of initially nonspecific signs and symp- toms

  18. Nucleic acid probes in diagnosis of viral diseases of man

    Microsoft Academic Search

    J. K. Kulski; Mary Norval

    1985-01-01

    Summary With the recent, rapid advances in recombinant DNA technology, it has become possible to consider the use of nucleic acid probes in diagnosis of human viral diseases. Several examples are discussed which employ techniques of dot blot hybridization, sandwich hybridization andin situ hybridization. Typing of viral strains using restriction endonuclease digestion as an epidemiological tool is considered. Finally, the

  19. Ménière’s Disease Is a Viral Neuropathy

    Microsoft Academic Search

    Richard R. Gacek

    2009-01-01

    Morphological and clinical evidence supports a viral neuropathy in Ménière’s disease (MD). Quantitative examination of 11 sectioned temporal bones (TBs) from 8 patients with a history of MD revealed a significant loss of vestibular ganglion cells in both the endolymph hydropic (EH) and non-EH ears. Transmission electron microscopy of vestibular ganglion cells excised from a patient with MD revealed viral

  20. Bovine viral diarrhea virus modulations of monocyte derived macrophages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is a single stranded, positive sense RNA virus and is the causative agent of bovine viral diarrhea (BVD). Disease can range from persistently infected (PI) animals displaying no clinical symptoms of disease to an acute, severe disease. Presently, limited studies ha...

  1. Development of viral nanoparticles for efficient intracellular delivery

    NASA Astrophysics Data System (ADS)

    Wu, Zhuojun; Chen, Kevin; Yildiz, Ibrahim; Dirksen, Anouk; Fischer, Rainer; Dawson, Philip E.; Steinmetz, Nicole F.

    2012-05-01

    Viral nanoparticles (VNPs) based on plant viruses such as Cowpea mosaic virus (CPMV) can be used for a broad range of biomedical applications because they present a robust scaffold that allows functionalization by chemical conjugation and genetic modification, thereby offering an efficient drug delivery platform that can target specific cells and tissues. VNPs such as CPMV show natural affinity to cells; however, cellular uptake is inefficient. Here we show that chemical modification of the CPMV surface with a highly reactive, specific and UV-traceable hydrazone linker allows bioconjugation of polyarginine (R5) cell penetrating peptides (CPPs), which can overcome these limitations. The resulting CPMV-R5 particles were taken up into a human cervical cancer cell line (HeLa) more efficiently than native particles. Uptake efficiency was dependent on the density of R5 peptides on the surface of the VNP; particles displaying 40 R5 peptides per CPMV (denoted as CPMV-R5H) interact strongly with the plasma membrane and are taken up into the cells via an energy-dependent mechanism whereas particles displaying 10 R5 peptides per CPMV (CPMV-R5L) are only slowly taken up. The fate of CPMV-R5 versus native CPMV particles within cells was evaluated in a co-localization time course study. It was indicated that the intracellular localization of CPMV-R5 and CPMV differs; CPMV remains trapped in Lamp-1 positive endolysosomes over long time frames; in contrast, 30-50% of the CPMV-R5 particles transitioned from the endosome into other cellular vesicles or compartments. Our data provide the groundwork for the development of efficient drug delivery formulations based on CPMV-R5.Viral nanoparticles (VNPs) based on plant viruses such as Cowpea mosaic virus (CPMV) can be used for a broad range of biomedical applications because they present a robust scaffold that allows functionalization by chemical conjugation and genetic modification, thereby offering an efficient drug delivery platform that can target specific cells and tissues. VNPs such as CPMV show natural affinity to cells; however, cellular uptake is inefficient. Here we show that chemical modification of the CPMV surface with a highly reactive, specific and UV-traceable hydrazone linker allows bioconjugation of polyarginine (R5) cell penetrating peptides (CPPs), which can overcome these limitations. The resulting CPMV-R5 particles were taken up into a human cervical cancer cell line (HeLa) more efficiently than native particles. Uptake efficiency was dependent on the density of R5 peptides on the surface of the VNP; particles displaying 40 R5 peptides per CPMV (denoted as CPMV-R5H) interact strongly with the plasma membrane and are taken up into the cells via an energy-dependent mechanism whereas particles displaying 10 R5 peptides per CPMV (CPMV-R5L) are only slowly taken up. The fate of CPMV-R5 versus native CPMV particles within cells was evaluated in a co-localization time course study. It was indicated that the intracellular localization of CPMV-R5 and CPMV differs; CPMV remains trapped in Lamp-1 positive endolysosomes over long time frames; in contrast, 30-50% of the CPMV-R5 particles transitioned from the endosome into other cellular vesicles or compartments. Our data provide the groundwork for the development of efficient drug delivery formulations based on CPMV-R5. Electronic supplementary information (ESI) available: Experimental details and additional supporting data. See DOI: 10.1039/c2nr30366c

  2. [Pregnancy and viral hepatitis B and C].

    PubMed

    Sogni, Philippe

    2015-06-01

    The screening for HBsAg is a medical obligation in France during pregnancy. A serovaccination with antiHBs immunoglobulins (100 IU) and a 1st dose of vaccine (10?g) has to be realized during the first 12hours of life when the mother is HBsAg+. The serovaccination failures are related to high maternal viral load (HBV-DNA>7 log IU/mL). In this case, a treatment with analogue (tenofovir) associated with serovaccination could be performed during the last trimester of pregnancy. The risk of mother-to-child transmission of virus C is around 3 to 5% in case of HCV-RNA positive without co-infection with HIV. The mode of delivery is unchanged in case of maternal HBV or HCV. Breast-feeding is not contra-indicated in case of maternal HBV or HCV infection. PMID:26033559

  3. Viral gastroenteritis: the USS THEODORE ROOSEVELT experience.

    PubMed

    Whittaker, David R; Campbell, Jerome T; McCarten, Michael D

    2004-09-01

    Although the spread of disease on board Navy ships is not a novel concept, the medical department of the USS THEODORE ROOSEVELT recently experienced a significant outbreak of viral gastroenteritis while at sea. The impact on the crew and medical department is reviewed in this case report. The use of the Navy Disease Non-Battle Injury tracking system was validated. Furthermore, we proposed the placement of waterless, isopropyl alcohol-based, hand-cleaning systems in strategic locations throughout the ship, to help prevent and minimize the spread of future disease. Finally, more stringent recommendations regarding sick in quarters status and careful utilization of consumable resources are necessary components of an effective outbreak management strategy. PMID:15495733

  4. Viral infections and bovine mastitis: a review.

    PubMed

    Wellenberg, G J; van der Poel, W H M; Van Oirschot, J T

    2002-08-01

    This review deals with the role of viruses in the aetiology of bovine mastitis. Bovine herpesvirus 1, bovine herpesvirus 4, foot-and-mouth disease virus, and parainfluenza 3 virus have been isolated from milk from cows with clinical mastitis. Intramammary inoculations of bovine herpesvirus 1 or parainfluenza 3 virus-induced clinical mastitis, while an intramammary inoculation of foot-and-mouth disease virus resulted in necrosis of the mammary gland. Subclinical mastitis has been induced after a simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4. Bovine leukaemia virus has been detected in mammary tissue of cows with subclinical mastitis, but whether this virus was able to induce bovine mastitis has not been reported. Bovine herpesvirus 2, vaccinia, cowpox, pseudocowpox, vesicular stomatitis, foot-and-mouth disease viruses, and bovine papillomaviruses can play an indirect role in the aetiology of bovine mastitis. These viruses can induce teat lesions, for instance in the ductus papillaris, which result in a reduction of the natural defence mechanisms of the udder and indirectly in bovine mastitis due to bacterial pathogens. Bovine herpesvirus 1, bovine viral diarrhoea virus, bovine immunodeficiency virus, and bovine leukaemia virus infections may play an indirect role in bovine mastitis, due to their immunosuppressive properties. But, more research is warranted to underline their indirect role in bovine mastitis. We conclude that viral infections can play a direct or indirect role in the aetiology of bovine mastitis; therefore, their importance in the aetiology of bovine mastitis and their economical impact needs further attention. PMID:12119136

  5. Pregnancy and sexually transmitted viral infections

    PubMed Central

    Singhal, P.; Naswa, S.; Marfatia, Y. S.

    2009-01-01

    Viral infections in pregnancy are a major cause of morbidity and mortality for both mother and fetus. Viral STIs occur as surface infection and then gradually infect immunologically protected sites. Therefore, these are asymptomatic, hidden and hence underdiagnosed, persistent and difficult to treat. HSV, HPV, HBV, HIV and CMV (cytomegalovirus) are the common ones. Most of these are transmitted during intrapartum period. Proper screening, identification and treatment offered during prenatal period may help in preventing their complications. Twenty five percent of women with a history of genital herpes have an outbreak at some point during the last month of pregnancy. Acyclovir is the accepted efficacious and safe therapy for HSV in pregnancy. Globally, HPV infection is the most common sexually transmitted infection. Neonatal transmission can occur in the absence of clinically evident lesions. HPV 6 or 11 may lead to Juvenile Onset Recurrent Respiratory Papillomatosis (JORRP). TCA, liquid nitrogen, laser ablation or electrocautery can be used to treat external genital HPV lesions at any time during pregnancy. Cesarean section is recommended only if the lesions are obstructing the birth canal. Mother to child transmission (MTCT) in HIV accounts for 15–30% during pregnancy and delivery, and a further 5–20% of transmission occurs through breastfeeding. HBV infection during pregnancy does not alter the natural course of the disease. In women who are seropositive for both HBsAg and HBeAg, vertical transmission is approximately 90%. Pregnancy is not a contraindication for HBV vaccination. Cytomegalovirus (CMV) is the most common intrauterine infection. Cytomegalic inclusion disease (CID) is the most severe form of congenital CMV infection. Treatment is supportive. PMID:21938124

  6. Superresolution imaging of viral protein trafficking.

    PubMed

    Colberg-Poley, Anamaris M; Patterson, George H; Salka, Kyle; Bhuvanendran, Shivaprasad; Yang, David; Jaiswal, Jyoti K

    2015-06-01

    The endoplasmic reticulum (ER) membrane is closely apposed to the outer mitochondrial membrane (OMM), which facilitates communication between these organelles. These contacts, known as mitochondria-associated membranes (MAM), facilitate calcium signaling, lipid transfer, as well as antiviral and stress responses. How cellular proteins traffic to the MAM, are distributed therein, and interact with ER and mitochondrial proteins are subject of great interest. The human cytomegalovirus UL37 exon 1 protein or viral mitochondria-localized inhibitor of apoptosis (vMIA) is crucial for viral growth. Upon synthesis at the ER, vMIA traffics to the MAM and OMM, where it reprograms the organization and function of these compartments. vMIA significantly changes the abundance of cellular proteins at the MAM and OMM, including proteins that regulate calcium homeostasis and cell death. Through the use of superresolution imaging, we have shown that vMIA is distributed at the OMM in nanometer scale clusters. This is similar to the clusters reported for the mitochondrial calcium channel, VDAC, as well as electron transport chain, translocase of the OMM complex, and mitochondrial inner membrane organizing system components. Thus, aside from addressing how vMIA targets the MAM and regulates survival of infected cells, biochemical studies and superresolution imaging of vMIA offer insights into the formation, organization, and functioning of MAM. Here, we discuss these insights into trafficking, function, and organization of vMIA at the MAM and OMM and discuss how the use of superresolution imaging is contributing to the study of the formation and trafficking of viruses. PMID:25724304

  7. Inhibition of viral transcription using designed zinc finger proteins.

    PubMed

    Hoeksema, Kimberley A; Tyrrell, D Lorne J

    2010-01-01

    Currently available therapeutics for hepatitis B virus (HBV) infection have limited effectiveness in patients and often do not clear HBV from the liver due to the persistence of the stable, double-stranded (ds) DNA genome of HBV. By designing zinc finger proteins (ZFPs) to bind the dsDNA genome of a model virus, duck HBV (DHBV), we were able to inhibit viral transcription, and subsequently, viral protein and progeny production. This inhibition is likely due to competition for DNA binding sites between the ZFPs and transcription factors, and interference with read-through transcription by RNA polymerase across the ZFP-binding region. Taking into account some design considerations, this method of inhibiting viral transcription can be applied to other viral infections where viral dsDNA occurs. PMID:20680830

  8. Isolation of RNA transcripts from the entire Sendai viral genome.

    PubMed Central

    Roux, L; Kolakofsky, D

    1975-01-01

    Three classes of viral transcripts (18S, 24S, and 33S) were isolated from viral ribonucleoproteins in Sendai virus-infected cells. Hybridization studies with virion minus strand genome RNA demonstrated that the 18S RNA contained transcripts from 60% of the viral genome while the 33S RNA contained transcripts from the entire viral genome. Brief heat of ME2SO treatment of the 33S RNA demonstrated that this RNA was composed of two classes: RNA which continued to sediment at 33S (33S RNA) and 18S RNA aggregates (18S RNA). The 33S RNA was determined to be a transcript from the 40% of the viral genome not protected by the 18S RNA. The aggregated 18S RNA does not appear to be an artifact of isolation. PMID:172654

  9. Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring

    USGS Publications Warehouse

    Lovy, Jan; Lewis, N.L.; Hershberger, P.K.; Bennett, W.; Meyers, T.R.; Garver, K.A.

    2012-01-01

    Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring.

  10. Genetically modified.

    PubMed

    Cheek, Dennis J; Brazeau, Dan

    2015-05-01

    SINCE THE 1990s, and certainly since the completion of the Human Genome Project in 2003, the need for nurses to understand genetic information has become increasingly evident. Knowledge of genetics, genomics, pharmacogenetics and pharmacogenomics, the study of heredity, gene function and how medication targets genes, continues to increase and is important in the nursing care of patients. PMID:26014775

  11. Landscape Genetics

    NSDL National Science Digital Library

    Rolf Holderegger (Swiss Federal Research Institute; )

    2008-03-01

    Landscape genetics is a rapidly evolving interdisciplinary field that integrates approaches from population genetics and landscape ecology. In the context of habitat fragmentation, the current focus of landscape genetics is on assessing the degree to which landscapes facilitate the movement of organisms (landscape connectivity) by relating gene-flow patterns to landscape structure. Neutral genetic variation among individuals or direct estimates of current gene flow are statistically related to landscape characteristics such as the presence of hypothesized barriers or the least-cost distance for an organism to move from one habitat patch to another, given the nature of the intervening matrix or habitat types. In the context of global change, a major challenge for landscape genetics is to address the spread of adaptive variation across landscapes. Genome scans combined with genetic sample collection along environmental gradients or in different habitat types attempt to identify molecular markers that are statistically related to specific environmental conditions, indicating adaptive genetic variation. The landscape genetics of adaptive variation may also help answer fundamental questions about the collective evolution of populations.

  12. genetic disease

    Microsoft Academic Search

    Gerhard Nahler

    \\u000a Disease linked to a genetic defect such as a mutated gene; there are about 4,000 to 5,000 genetic diseases known to medical\\u000a science such as cystic fibrosis, Down syndrome, sickle cell anemia, haemophilia, Gilles de la Tourette syndrome or Fabry’s\\u000a disease; ? see also gene therapy, orphan diseases.

  13. Social genetics

    Microsoft Academic Search

    J. P. Scott

    1977-01-01

    Most behavior is expressed within social systems, and the genetic analysis of its variance therefore presents theoretical and technical problems that have been sidestepped in most previous research. The dog presents obvious advantages for studying behavioral interactions between genotypes. Two sets of data are summarized that indicate that the magnitude of genetic differences is related to the differentiation of social

  14. A Comprehensive Functional Map of the Hepatitis C Virus Genome Provides a Resource for Probing Viral Proteins

    PubMed Central

    Remenyi, Roland; Qi, Hangfei; Su, Sheng-Yao; Chen, Zugen; Wu, Nicholas C.; Arumugaswami, Vaithilingaraja; Truong, Shawna; Chu, Virginia; Stokelman, Tamar; Lo, Hung-Hao; Olson, C. Anders; Wu, Ting-Ting; Chen, Shu-Hwa; Lin, Chung-Yen

    2014-01-01

    ABSTRACT Pairing high-throughput sequencing technologies with high-throughput mutagenesis enables genome-wide investigations of pathogenic organisms. Knowledge of the specific functions of protein domains encoded by the genome of the hepatitis C virus (HCV), a major human pathogen that contributes to liver disease worldwide, remains limited to insight from small-scale studies. To enhance the capabilities of HCV researchers, we have obtained a high-resolution functional map of the entire viral genome by combining transposon-based insertional mutagenesis with next-generation sequencing. We generated a library of 8,398 mutagenized HCV clones, each containing one 15-nucleotide sequence inserted at a unique genomic position. We passaged this library in hepatic cells, recovered virus pools, and simultaneously assayed the abundance of mutant viruses in each pool by next-generation sequencing. To illustrate the validity of the functional profile, we compared the genetic footprints of viral proteins with previously solved protein structures. Moreover, we show the utility of these genetic footprints in the identification of candidate regions for epitope tag insertion. In a second application, we screened the genetic footprints for phenotypes that reflected defects in later steps of the viral life cycle. We confirmed that viruses with insertions in a region of the nonstructural protein NS4B had a defect in infectivity while maintaining genome replication. Overall, our genome-wide HCV mutant library and the genetic footprints obtained by high-resolution profiling represent valuable new resources for the research community that can direct the attention of investigators toward unidentified roles of individual protein domains. PMID:25271282

  15. Integrated Evaluation of Latent Viral Reactivation During Spaceflight

    NASA Technical Reports Server (NTRS)

    Pierson, Duane L.; Paloski, W. H. (Technical Monitor)

    2000-01-01

    This application proposes a continuation of our current effort, which has provided the first demonstration of viral reactivation during space flight. We have used the herpesvirus EBV as a model for latent viral reactivation and have shown that increased amounts of EBV DNA were shed by astronauts during space flight. Analysis of the Antarctic space flight analog indicated that the frequency of viral shedding may also increase (along with the increased numbers of virus) during long periods of isolation. However, a number of critical questions remain before the findings may be considered a significant health risk during extended space flight. These include: Are other latent viruses (e.g., other herpesviruses and polyornaviruses) in addition to EBV also reactivated and shed more frequently and/or in higher numbers during space flight? Is the viral reactivation observed in space flight and ground-based analogs mediated through the hypothalamus-pituitary-adrenal (HPA) axis resulting in a decreased cell-mediated immune response? How does detection of viral DNA by PCR analysis correlate with infectious virus? How does the amount of virus found during flight compare with viral levels observed in acute/chronic viral illnesses and in control individuals? This expanded study will examine the phenomenon of viral reactivation from the initiating stress through the HPA axis with the accompanying suppression of the immune system resulting in viral reactivation. This information is essential to determine if latent viral reactivation among crewmembers represents a sufficient medical risk to space travel to require the development of suitable countermeasures.

  16. Viral metagenomics analysis demonstrates the diversity of viral flora in piglet diarrhoeic faeces in China.

    PubMed

    Zhang, Bin; Tang, Cheng; Yue, Hua; Ren, Yupeng; Song, Zhigang

    2014-07-01

    To investigate the diversity of viral flora, we used metagenomics to study the viral communities in a pooled faecal sample of 27 diarrhoeic piglets from intensive commercial farms in China. The 15 distinct mammalian viruses identified in the pooled diarrhoeic sample were, in order of abundance of nucleic acid sequence, Porcine epidemic diarrhea virus (PEDV), sapovirus, porcine bocavirus-4 (PBoV-4), sapelovirus, torovirus, coronavirus, PBoV-2, stool-associated single-stranded DNA virus (poSCV), astrovirus (AstV), kobuvirus, posavirus-1, porcine enterovirus-9 (PEV-9), porcine circovirus-like (po-circo-like) virus, picobirnavirus (PBV) and Torque teno sus virus 2 (TTSuV-2). The prevalence rate of each virus was verified from diarrhoeic and healthy piglets by PCR assay. A mean of 5.5 different viruses were shed in diarrhoeic piglets, and one piglet was in fact co-infected with 11 different viruses. By contrast, healthy piglets shed a mean of 3.2 different viruses. Compared with samples from healthy piglets, the co-infection of PEDV and PBoV had a high prevalence rate in diarrhoea samples, suggesting a correlation with the appearance of diarrhoea in piglets. Furthermore, we report here for the first time the presence of several recently described viruses in China, and the identification of novel genotypes. Therefore, our investigation results provide an unbiased survey of viral communities and prevalence in faecal samples of piglets. PMID:24718833

  17. 65 FR 31175 - Integration of Viral Hepatitis Prevention Services Into Existing Prevention Programs; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2000-05-16

    ...Announcement 00046] Integration of Viral Hepatitis Prevention Services Into Existing Prevention...agreement program for integration of viral hepatitis prevention services into existing prevention...guidance for integrating recommended viral hepatitis prevention and control services for...

  18. 68 FR 40961 - Viral Hepatitis Integration and Intervention Projects; Notice of Availability of Funds

    Federal Register 2010, 2011, 2012, 2013, 2014

    2003-07-09

    ...Program Announcement 04009] Viral Hepatitis Integration and Intervention Projects...cooperative agreement program for Viral Hepatitis Integration and Intervention Projects...improve the delivery of existing viral hepatitis prevention services in programs...

  19. 21 CFR 866.3980 - Respiratory viral panel multiplex nucleic acid assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...Respiratory viral panel multiplex nucleic acid assay. 866.3980 Section 866.3980...Respiratory viral panel multiplex nucleic acid assay. (a) Identification . A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro...

  20. 21 CFR 866.3980 - Respiratory viral panel multiplex nucleic acid assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...Respiratory viral panel multiplex nucleic acid assay. 866.3980 Section 866.3980...Respiratory viral panel multiplex nucleic acid assay. (a) Identification . A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro...

  1. Dissecting inhibitory brain circuits with genetically-targeted technologies

    PubMed Central

    Murphey, Dona K.; Herman, Alexander M.; Arenkiel, Benjamin R.

    2014-01-01

    The evolution of genetically targeted tools has begun to allow us to dissect anatomically and functionally heterogeneous interneurons, and to probe circuit function from synapses to behavior. Over the last decade, these tools have been used widely to visualize neurons in a cell type-specific manner, and engage them to activate and inactivate with exquisite precision. In this process, we have expanded our understanding of interneuron diversity, their functional connectivity, and how selective inhibitory circuits contribute to behavior. Here we discuss the relative assets of genetically encoded fluorescent proteins (FPs), viral tracing methods, optogenetics, chemical genetics, and biosensors in the study of inhibitory interneurons and their respective circuits. PMID:25368555

  2. Counseling customers: emerging roles for genetic counselors in the direct-to-consumer genetic testing market.

    PubMed

    Harris, Anna; Kelly, Susan E; Wyatt, Sally

    2013-04-01

    Individuals now have access to an increasing number of internet resources offering personal genomics services. As the direct-to-consumer genetic testing (DTC GT) industry expands, critics have called for pre- and post-test genetic counseling to be included with the product. Several genetic testing companies offer genetic counseling. There has been no examination to date of this service provision, whether it meets critics' concerns and implications it may have for the genetic counseling profession. Considering the increasing relevance of genetics in healthcare, the complexity of genetic information provided by DTC GT, the mediating role of the internet in counseling, and potential conflicts of interest, this is a topic which deserves further attention. In this paper we offer a discourse analysis of ways in which genetic counseling is represented on DTC GT websites, blogs and other online material. This analysis identified four types of genetic counseling represented on the websites: the integrated counseling product; discretionary counseling; independent counseling; and product advice. Genetic counselors are represented as having the following roles: genetics educator; mediator; lifestyle advisor; risk interpreter; and entrepreneur. We conclude that genetic counseling as represented on DTC GT websites demonstrates shifting professional roles and forms of expertise in genetic counseling. Genetic counselors are also playing an important part in how the genetic testing market is taking shape. Our analysis offers important and timely insights into recent developments in the genetic counseling profession, which have relevance for practitioners, researchers and policy makers concerned with the evolving field of personal genomics. PMID:23093333

  3. Additive effects of HLA alleles and innate immune genes determine viral outcome in HCV infection

    PubMed Central

    Fitzmaurice, Karen; Hurst, Jacob; Dring, Megan; Rauch, Andri; McLaren, Paul J; Günthard, Huldrych F; Gardiner, Clair; Klenerman, Paul

    2015-01-01

    Background Chronic HCV infection is a leading cause of liver-related morbidity globally. The innate and adaptive immune responses are thought to be important in determining viral outcomes. Polymorphisms associated with the IFNL3 (IL28B) gene are strongly associated with spontaneous clearance and treatment outcomes. Objective This study investigates the importance of HLA genes in the context of genetic variation associated with the innate immune genes IFNL3 and KIR2DS3. Design We assess the collective influence of HLA and innate immune genes on viral outcomes in an Irish cohort of women (n=319) who had been infected from a single source as well as a more heterogeneous cohort (Swiss Cohort, n=461). In the Irish cohort, a number of HLA alleles are associated with different outcomes, and the impact of IFNL3-linked polymorphisms is profound. Results Logistic regression was performed on data from the Irish cohort, and indicates that the HLA-A*03 (OR 0.36 (0.15 to 0.89), p=0.027) -B*27 (OR 0.12 (0.03 to 0.45), p=<0.001), -DRB1*01:01 (OR 0.2 (0.07 to 0.61), p=0.005), -DRB1*04:01 (OR 0.31 (0.12 to 0.85, p=0.02) and the CC IFNL3 rs12979860 genotypes (OR 0.1 (0.04 to 0.23), p<0.001) are significantly associated with viral clearance. Furthermore, DQB1*02:01 (OR 4.2 (2.04 to 8.66), p=0.008), KIR2DS3 (OR 4.36 (1.62 to 11.74), p=0.004) and the rs12979860 IFNL3 ‘T’ allele are associated with chronic infection. This study finds no interactive effect between IFNL3 and these Class I and II alleles in relation to viral clearance. There is a clear additive effect, however. Data from the Swiss cohort also confirms independent and additive effects of HLA Class I, II and IFNL3 genes in their prediction of viral outcome. Conclusions This data supports a critical role for the adaptive immune response in the control of HCV in concert with the innate immune response. PMID:24996883

  4. Metagenomic Analysis of the Viral Communities in Fermented Foods? †

    PubMed Central

    Park, Eun-Jin; Kim, Kyoung-Ho; Abell, Guy C. J.; Kim, Min-Soo; Roh, Seong Woon; Bae, Jin-Woo

    2011-01-01

    Viruses are recognized as the most abundant biological components on Earth, and they regulate the structure of microbial communities in many environments. In soil and marine environments, microorganism-infecting phages are the most common type of virus. Although several types of bacteriophage have been isolated from fermented foods, little is known about the overall viral assemblages (viromes) of these environments. In this study, metagenomic analyses were performed on the uncultivated viral communities from three fermented foods, fermented shrimp, kimchi, and sauerkraut. Using a high-throughput pyrosequencing technique, a total of 81,831, 70,591 and 69,464 viral sequences were obtained from fermented shrimp, kimchi and sauerkraut, respectively. Moreover, 37 to 50% of these sequences showed no significant hit against sequences in public databases. There were some discrepancies between the prediction of bacteriophages hosts via homology comparison and bacterial distribution, as determined from 16S rRNA gene sequencing. These discrepancies likely reflect the fact that the viral genomes of fermented foods are poorly represented in public databases. Double-stranded DNA viral communities were amplified from fermented foods by using a linker-amplified shotgun library. These communities were dominated by bacteriophages belonging to the viral order Caudovirales (i.e., Myoviridae, Podoviridae, and Siphoviridae). This study indicates that fermented foods contain less complex viral communities than many other environmental habitats, such as seawater, human feces, marine sediment, and soil. PMID:21183634

  5. Metagenomic analysis of the viral communities in fermented foods.

    PubMed

    Park, Eun-Jin; Kim, Kyoung-Ho; Abell, Guy C J; Kim, Min-Soo; Roh, Seong Woon; Bae, Jin-Woo

    2011-02-01

    Viruses are recognized as the most abundant biological components on Earth, and they regulate the structure of microbial communities in many environments. In soil and marine environments, microorganism-infecting phages are the most common type of virus. Although several types of bacteriophage have been isolated from fermented foods, little is known about the overall viral assemblages (viromes) of these environments. In this study, metagenomic analyses were performed on the uncultivated viral communities from three fermented foods, fermented shrimp, kimchi, and sauerkraut. Using a high-throughput pyrosequencing technique, a total of 81,831, 70,591 and 69,464 viral sequences were obtained from fermented shrimp, kimchi and sauerkraut, respectively. Moreover, 37 to 50% of these sequences showed no significant hit against sequences in public databases. There were some discrepancies between the prediction of bacteriophages hosts via homology comparison and bacterial distribution, as determined from 16S rRNA gene sequencing. These discrepancies likely reflect the fact that the viral genomes of fermented foods are poorly represented in public databases. Double-stranded DNA viral communities were amplified from fermented foods by using a linker-amplified shotgun library. These communities were dominated by bacteriophages belonging to the viral order Caudovirales (i.e., Myoviridae, Podoviridae, and Siphoviridae). This study indicates that fermented foods contain less complex viral communities than many other environmental habitats, such as seawater, human feces, marine sediment, and soil. PMID:21183634

  6. Genetic Counseling Training

    MedlinePLUS

    Genetic Counseling Training Find out the answers the questions you may have about becoming a genetic counselor with these Frequently Asked ... Graduate School Simulated Genetic Counseling Sessions Genetic Counseling Training Programs Applying Interviewing Acceptance Learn More about Genetic ...

  7. Reimbursement for Genetic Testing

    MedlinePLUS

    Reimbursement for Genetic Testing You are here Home Testing & Services Testing for genetic conditions Reimbursement for Genetic Testing Testing for genetic ... insurance coverage and reimbursement process. Twitter YouTube RSS Genetics and Health How Genes Work Genes, Lifestyle, & Environment ...

  8. Genetic Terminology

    PubMed Central

    Elston, Robert; Satagopan, Jaya; Sun, Shuying

    2015-01-01

    Summary Common terms used in genetics with multiple meanings are explained and the terminology used in subsequent chapters is defined. Statistical Human Genetics has existed as a discipline for over a century, and during that time the meanings of many of the terms used have evolved, largely driven by molecular discoveries, to the point that molecular and statistical geneticists often have difficulty understanding each other. It is therefore imperative, now that so much of molecular genetics is becoming an in silico and statistical science, that we have well-defined, common terminology. PMID:22307690

  9. "Genetically Engineered" Nanoelectronics

    NASA Technical Reports Server (NTRS)

    Klimeck, Gerhard; Salazar-Lazaro, Carlos H.; Stoica, Adrian; Cwik, Thomas

    2000-01-01

    The quantum mechanical functionality of nanoelectronic devices such as resonant tunneling diodes (RTDs), quantum well infrared-photodetectors (QWIPs), quantum well lasers, and heterostructure field effect transistors (HFETs) is enabled by material variations on an atomic scale. The design and optimization of such devices requires a fundamental understanding of electron transport in such dimensions. The Nanoelectronic Modeling Tool (NEMO) is a general-purpose quantum device design and analysis tool based on a fundamental non-equilibrium electron transport theory. NEW was combined with a parallelized genetic algorithm package (PGAPACK) to evolve structural and material parameters to match a desired set of experimental data. A numerical experiment that evolves structural variations such as layer widths and doping concentrations is performed to analyze an experimental current voltage characteristic. The genetic algorithm is found to drive the NEMO simulation parameters close to the experimentally prescribed layer thicknesses and doping profiles. With such a quantitative agreement between theory and experiment design synthesis can be performed.

  10. Silk-silica composites from genetically engineered chimeric proteins: materials properties correlate with silica condensation rate and colloidal stability of the proteins in aqueous solution.

    PubMed

    Belton, David J; Mieszawska, Aneta J; Currie, Heather A; Kaplan, David L; Perry, Carole C

    2012-03-01

    The aim of the study was to determine the extent and mechanism of influence on silica condensation that is presented by a range of known silicifying recombinant chimeras (R5: SSKKSGSYSGSKGSKRRIL; A1: SGSKGSKRRIL; and Si4-1: MSPHPHPRHHHT and repeats thereof) attached at the N-terminus end of a 15-mer repeat of the 32 amino acid consensus sequence of the major ampullate dragline Spindroin 1 (Masp1) Nephila clavipes spider silk sequence ([SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQG](15)X). The influence of the silk/chimera ratio was explored through the adjustment of the type and number of silicifying domains (denoted X above), and the results were compared with their non-chimeric counterparts and the silk from Bombyx mori. The effect of pH (3-9) on reactivity was also explored. Optimum conditions for rate and control of silica deposition were determined, and the solution properties of the silks were explored to determine their mode(s) of action. For the silica-silk-chimera materials formed there is a relationship between the solution properties of the chimeric proteins (ability to carry charge), the pH of reaction, and the solid state materials that are generated. The region of colloidal instability correlates with the pH range observed for morphological control and coincides with the pH range for the highest silica condensation rates. With this information it should be possible to predict how chimeric or chemically modified proteins will affect structure and morphology of materials produced under controlled conditions and extend the range of composite materials for a wide spectrum of uses in the biomedical and technology fields. PMID:22313382

  11. Silk-silica composites from genetically engineered chimeric proteins: materials properties correlate with silica condensation rate and colloidal stability of the proteins in aqueous solution

    PubMed Central

    Belton, David J.; Mieszawska, Aneta J.; Currie, Heather A.; Kaplan, David L.; Perry, Carole C.

    2012-01-01

    The aim of the study was to determine the extent and mechanism of influence on silica condensation that is presented by a range of known silicifying recombinant chimeras (R5- SSKKSGSYSGSKGSKRRIL; A1- SGSKGSKRRIL; and Si4-1- MSPHPHPRHHHT and repeats thereof) attached at the N-terminus end of a 15 mer repeat of the 32 amino acid consensus sequence of the major ampullate dragline Spindroin 1 (Masp1) Nephila clavipes spider silk sequence ([SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQG]15X). The influence of the silk/chimera ratio was explored through the adjustment of the type and number of silicifying domains, (denoted X above), and the results were compared with their non chimeric counterparts and the silk from Bombyx mori. The effect of pH (3–9) on reactivity was also explored. Optimum conditions for rate and control of silica deposition were determined and the solution properties of the silks were explored to determine their mode(s) of action. For the silica-silk-chimera materials formed there is a relationship between the solution properties of the chimeric proteins (ability to carry charge), the pH of reaction and the solid state materials that are generated. The region of colloidal instability correlates with the pH range observed for morphological control and coincides with the pH range for the highest silica condensation rates. With this information it should be possible to predict how chimeric or chemically modified proteins will affect structure and morphology of materials produced under controlled conditions and extend the range of composite materials for a wide spectrum of uses in the biomedical and technology fields. PMID:22313382

  12. Genetic/Genome Lesson Plans

    NSDL National Science Digital Library

    Since 1995, staff members at the University of Kansas's Medical Center have worked to provide access to a wide range of educational resources for teachers seeking materials on genetics and the human genome. The site is organized in a series of lists, and it starts out with a set of resources created at the Genetics Education Center at the University of Kansas. There are six different resources in this particular area, and they include genetic lesson plans, a curricula list, and genetics standards for different grade levels. Moving on, visitors can look over the "Genetic Programs/Centers/Lesson Plans" area, which contains over 60 teaching activities, interactive websites, and lesson plans from places such as the Howard Hughes Medical Institute and the University of Wisconsin-Madison.

  13. Improved material properties of solution-cast starch films: Effect of varying amylopectin structure and amylose content of starch from genetically modified potatoes.

    PubMed

    Menzel, Carolin; Andersson, Mariette; Andersson, Roger; Vázquez-Gutiérrez, José L; Daniel, Geoffrey; Langton, Maud; Gällstedt, Mikael; Koch, Kristine

    2015-10-01

    High-amylose potato starches were produced through genetic modification resulting in changed granule morphology and composition, with higher amylose content and increased chain length of amylopectin. The increased amylose content and structural changes in amylopectin enhanced film-forming behavior and improved barrier and tensile properties in starch films. The molecular structure in these starches was related to film-forming properties. Solution-cast films of high-amylose starch revealed a homogeneous structure with increasing surface roughness at higher amylose content, possibly due to amylose aggregation. Films exhibited significantly higher stress and strain at break compared with films of wild-type starch, which could be attributable to the longer chains of amylopectin being involved in the interconnected network and more interaction between chains, as shown using transmission electron microscopy. The oxygen permeability of high-amylose starch films was significantly decreased compared with wild-type starch. The nature of the modified starches makes them an interesting candidate for replacement of non-renewable oxygen and grease barrier polymers used today. PMID:26076640

  14. Genetic Testing

    MedlinePLUS

    ... on to their children Screening embryos for disease Testing for genetic diseases in adults before they cause ... provide information about the pros and cons of testing. NIH: National Human Genome Research Institute

  15. [Human immunodeficiency virus infection and viral hepatitis].

    PubMed

    Soriano, Vicente; Martin-Carbonero, Luz; Vispo, Eugenia; Labarga, Pablo; Barreiro, Pablo

    2011-11-01

    Hepatic complications currently represent one of the leading reasons for medical consultations, hospitalisation, and death in the HIV-infected population. This is due to a large extent to viral hepatitis, given its disproportionate frequency in this population. Chronic hepatitis B affects 5-10% of the HIV-infected population. Vaccination has reduced the incidence of liver disease related to hepatitis-B virus (HBV), and the availability of tenofovir has dramatically improved the prognosis of HIV/HBV carriers. Delta hepatitis affects around 15% of HIV-infected individuals in Europe harbouring positive HBsAg. It has the worst prognosis, given its accelerated course to cirrhosis and the absence of successful therapy. Lastly, chronic hepatitis C is the major cause of liver disease in the HIV population. Although classically linked to persons infected parenterally (i.e., intravenous drug users), outbreaks of acute hepatitis C among homosexual men have been reported over the last decade. Treatment with pegylated interferon plus ribavirin provides a cure in less than 40% of patients. However, the introduction of new direct acting antivirals against hepatitis- C virus (HCV) (telaprevir, boceprevir) has revolutionised the field, as HAART did in 1996 in the HIV field, improving the prognosis of co-infected patients. However, interactions between these drugs and antiretroviral agents and the risk of selective resistance pose huge threats in this population. PMID:21978797

  16. Animal models of viral hemorrhagic fever.

    PubMed

    Smith, Darci R; Holbrook, Michael R; Gowen, Brian B

    2014-12-01

    The term "viral hemorrhagic fever" (VHF) designates a syndrome of acute febrile illness, increased vascular permeability and coagulation defects which often progresses to bleeding and shock and may be fatal in a significant percentage of cases. The causative agents are some 20 different RNA viruses in the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae, which are maintained in a variety of animal species and are transferred to humans through direct or indirect contact or by an arthropod vector. Except for dengue, which is transmitted among humans by mosquitoes, the geographic distribution of each type of VHF is determined by the range of its animal reservoir. Treatments are available for Argentine HF and Lassa fever, but no approved countermeasures have been developed against other types of VHF. The development of effective interventions is hindered by the sporadic nature of most infections and their occurrence in geographic regions with limited medical resources. Laboratory animal models that faithfully reproduce human disease are therefore essential for the evaluation of potential vaccines and therapeutics. The goal of this review is to highlight the current status of animal models that can be used to study the pathogenesis of VHF and test new countermeasures. PMID:25448088

  17. Bacterial and viral superantigens: roles in autoimmunity?

    PubMed Central

    Acha-Orbea, H

    1993-01-01

    Superantigens are bacterial, viral, or retroviral proteins which can activate specifically a large proportion of T cells. In contrast with classical peptide antigen recognition, superantigens do not require processing to small peptides but act as complete or partially processed proteins. They can bind to major histocompatibility complex class II molecules and stimulate T cells expressing particular T cell receptor V beta chains. The other polymorphic parts of the T cell receptor, which are crucial for classical antigen recognition, are not important for this interaction. When this strategy is used a large proportion of the host immune system can be activated shortly after infection. The activated cells have a wide variety of antigen specificities. The ability to stimulate polyclonal B (IgG) as well as T cell responses raises possibilities of a role for superantigens in the induction of autoimmune diseases. Superantigens have been a great tool in the hands of immunologists in unravelling some of the basic mechanisms of tolerance and immunity. PMID:8481060

  18. Filovirus Tropism: Cellular Molecules for Viral Entry

    PubMed Central

    Takada, Ayato

    2012-01-01

    In human and non-human primates, filoviruses (Ebola and Marburg viruses) cause severe hemorrhagic fever. Recently, other animals such as pigs and some species of fruit bats have also been shown to be susceptible to these viruses. While having a preference for some cell types such as hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages, filoviruses are known to be pantropic in infection of primates. The envelope glycoprotein (GP) is responsible for both receptor binding and fusion of the virus envelope with the host cell membrane. It has been demonstrated that filovirus GP interacts with multiple molecules for entry into host cells, whereas none of the cellular molecules so far identified as a receptor/co-receptor fully explains filovirus tissue tropism and host range. Available data suggest that the mucin-like region (MLR) on GP plays an important role in attachment to the preferred target cells, whose infection is likely involved in filovirus pathogenesis, whereas the MLR is not essential for the fundamental function of the GP in viral entry into cells in vitro. Further studies elucidating the mechanisms of cellular entry of filoviruses may shed light on the development of strategies for prophylaxis and treatment of Ebola and Marburg hemorrhagic fevers. PMID:22363323

  19. Air pollution and respiratory viral infection.

    PubMed

    Ciencewicki, Jonathan; Jaspers, Ilona

    2007-11-01

    Despite current regulations, which limit the levels of certain air pollutants, there are still a number of adverse health effects that result from exposure to these agents. Numerous epidemiological studies have noted an association between the levels of air pollution and hospital admissions for a variety of different health reasons, including a number of respiratory diseases, as well as increased morbidity and mortality associated with various respiratory conditions and diseases. Because of the large impact respiratory virus infections have on morbidity and even mortality, it is important to understand whether and how exposure to common air pollutants could exacerbate the susceptibility to and severity of respiratory virus infections. This review focuses on current epidemiological and experimental studies, which have examined the association between and effect of air pollutants and respiratory viral infections, as well as potential mechanisms associated with these effects. Examined in this review are U.S. Environmental Protection Agency (EPA) "criteria" pollutants nitrogen dioxide (NO(2)), ozone (O(3)), and particulate matter (PM), as well as indoor pollutants such as environmental tobacco smoke (ETS) and combustion products of biomass fuels. Although a number of studies indicate associations between exposure to air pollutants and increased risk for respiratory virus infections, potential mechanisms mediating these effects are largely unexplored. Therefore, additional studies, both epidemiologic and mechanistic, are necessary to increase our understanding of how exposure to air pollutants could affect respiratory virus infections, especially in populations already at risk of developing significant morbidity/mortality after infections with respiratory viruses. PMID:17987465

  20. Waterborne viral infections and their prevention

    PubMed Central

    Chang, Shih L.

    1968-01-01

    Unless special measures are taken, community water supplies are likely to contain enteric viruses which may lead to sporadic cases, or even epidemics, of such diseases as infectious hepatitis or poliomyelitis. After a general discussion of waterborne viral infections, in which it is pointed out that subclinical infections may considerably outnumber clinical cases, the author proposes a method for the concentration and detection of enteric viruses in water by means of membrane filtration and growth on monkey-kidney-cell or other tissue cultures. The various methods of disinfection of water which can reduce the virus concentration to an acceptable level are discussed, and it is concluded that flocculation and filtration followed by chlorination, or ozonation followed by chlorination, are adequate methods where large volumes of water are to be treated. In developing countries where relatively small volumes of water have to be treated, iodination appears to offer certain advantages, allowing the construction of a simple water-treatment plant requiring little supervision. However, until the long-term effects of iodine, in particular on pregnant women and young children, are known iodination plants should be used only on an experimental basis. PMID:5302332

  1. Emerging viral diseases of fish and shrimp

    USGS Publications Warehouse

    Winton, James R.; Walker, Peter J.

    2010-01-01

    The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change.

  2. Viral Determinants of HIV-1 Macrophage Tropism

    PubMed Central

    Duncan, Christopher J. A.; Sattentau, Quentin J.

    2011-01-01

    Macrophages are important target cells for HIV-1 infection that play significant roles in the maintenance of viral reservoirs and other aspects of pathogenesis. Understanding the determinants of HIV-1 tropism for macrophages will inform HIV-1 control and eradication strategies. Tropism for macrophages is both qualitative (infection or not) and quantitative (replication capacity). For example many R5 HIV-1 isolates cannot infect macrophages, but for those that can the macrophage replication capacity can vary by up to 1000-fold. Some X4 viruses are also capable of replication in macrophages, indicating that cellular tropism is partially independent of co-receptor preference. Preliminary data obtained with a small number of transmitted/founder viruses indicate inefficient macrophage infection, whereas isolates from later in disease are more frequently tropic for macrophages. Thus tropism may evolve over time, and more macrophage tropic viruses may be implicated in the pathogenesis of advanced HIV-1 infection. Compartmentalization of macrophage-tropic brain-derived envelope glycoproteins (Envs), and non-macrophage tropic non-neural tissue-derived Envs points to adaptation of HIV-1 quasi-species in distinct tissue microenvironments. Mutations within and adjacent to the Env-CD4 binding site have been identified that determine macrophage tropism at the entry level, but post-entry molecular determinants of macrophage replication capacity involving HIV-1 accessory proteins need further definition. PMID:22163344

  3. IRGM in autophagy and viral infections

    PubMed Central

    Petkova, Denitsa S.; Viret, Christophe; Faure, Mathias

    2013-01-01

    Autophagy is a cell autonomous process allowing each individual cell to fight intracellular pathogens. Autophagy can destroy pathogens within the cytosol, and can elicit innate and adaptive immune responses against microorganisms. Nevertheless, numerous pathogens have developed molecular strategies enabling them to avoid or even exploit autophagy for their own benefit. IRGM (immunity-related GTPase family M) is a human protein recently highlighted for its contribution to autophagy upon infections. The physical association of IRGM with mitochondria and different autophagy-regulating proteins, ATG5, ATG10, SH3GLB1, and LC3, contribute to explain how IRGM could regulate autophagy. Whereas IRGM is involved in autophagy-mediated immunity against bacteria, certain viruses seem to have developed strategies to manipulate autophagy through the selective targeting of this protein. Furthermore, irgm variants are linked to infection-associated human pathologies such as the inflammatory Crohn’s disease. Here, we discuss how IRGM might contribute to human autophagy upon viral infection, and why its targeting might be beneficial to virus replication. PMID:23335927

  4. Coarse-grained mechanics of viral shells

    NASA Astrophysics Data System (ADS)

    Klug, William S.; Gibbons, Melissa M.

    2008-03-01

    We present an approach for creating three-dimensional finite element models of viral capsids from atomic-level structural data (X-ray or cryo-EM). The models capture heterogeneous geometric features and are used in conjunction with three-dimensional nonlinear continuum elasticity to simulate nanoindentation experiments as performed using atomic force microscopy. The method is extremely flexible; able to capture varying levels of detail in the three-dimensional structure. Nanoindentation simulations are presented for several viruses: Hepatitis B, CCMV, HK97, and ?29. In addition to purely continuum elastic models a multiscale technique is developed that combines finite-element kinematics with MD energetics such that large-scale deformations are facilitated by a reduction in degrees of freedom. Simulations of these capsid deformation experiments provide a testing ground for the techniques, as well as insight into the strength-determining mechanisms of capsid deformation. These methods can be extended as a framework for modeling other proteins and macromolecular structures in cell biology.

  5. Assessment of viral community functional potential from viral metagenomes may be hampered by contamination with cellular sequences

    PubMed Central

    Roux, Simon; Krupovic, Mart; Debroas, Didier; Forterre, Patrick; Enault, François

    2013-01-01

    Although the importance of viruses in natural ecosystems is widely acknowledged, the functional potential of viral communities is yet to be determined. Viral genomes are traditionally believed to carry only those genes that are directly pertinent to the viral life cycle, though this view was challenged by the discovery of metabolism genes in several phage genomes. Metagenomic approaches extended these analyses to a community scale, and several studies concluded that microbial and viral communities encompass similar functional potentials. However, these conclusions could originate from the presence of cellular DNA within viral metagenomes. We developed a computational method to estimate the proportion and origin of cellular sequences in a set of 67 published viromes. A quarter of the datasets were found to contain a substantial amount of sequences originating from cellular genomes. When considering only viromes with no cellular DNA detected, the functional potential of viral and microbial communities was found to be fundamentally different—a conclusion more consistent with the actual picture drawn from known viruses. Yet a significant number of cellular metabolism genes was still retrieved in these viromes, suggesting that the presence of auxiliary genes involved in various metabolic pathways within viral genomes is a general trend in the virosphere. PMID:24335607

  6. Genetic Algorithms

    Microsoft Academic Search

    Enrique Alba; Francisco Chicano

    In this chapter we describe the basics of Genetic Algorithms and how they can be used to train Artificial Neural Networks.\\u000a Supervised training of Multilayer Perceptrons for classification problems is considered. We also explain how the Genetic Algorithm\\u000a can be hybridized with other algorithms and present two hybrids between it and two classical algorithms for the neural network\\u000a training: Backpropagation

  7. Genetic counseling

    E-print Network

    Stough, Laura

    2014-01-01

    syndrome or spina bifida, while postnatal testing may reveal phenylke- tonuria or hypothyroidism. Most disorders occur when one or both of the parents pass on their genes. Couples who are carriers may choose to have their DNA tested before conception... and susceptibility genes brought forth by the sequencing of the human genome has brought challenges to the field of genetic counseling. The traditional role of genetic counseling has significantly widened to address a diversity of developing needs, ranging from...

  8. Low-Replicating Viruses and Strong Anti-Viral Immune Response Associated with Prolonged Disease Control in a Superinfected HIV-1 LTNP Elite Controller

    PubMed Central

    Pernas, María; Casado, Concepción; Arcones, Carolina; Llano, Anuska; Sánchez-Merino, Víctor; Mothe, Beatriz; Vicario, José L.; Grau, Eulalia; Ruiz, Lidia; Sánchez, Jorge; Telenti, Amalio; Yuste, Eloísa; Brander, Christian; Galíndez, Cecilio López-

    2012-01-01

    Objective To study the causes for the lack of clinical progression in a superinfected HIV-1 LTNP elite controller patient. Methodology and Principal Findings We studied host genetic, virological and immunological factors associated with viral control in a SI long term non progressor elite controller (LTNP-EC). The individual contained both viruses and maintained undetectable viral loads for >20 years and he did not express any of the described host genetic polymorphisms associated with viral control. None of four full-length gp160 recombinants derived from the LTNP-EC replicated in heterologous peripheral blood mononuclear cells. CTL responses after SI were maintained in two samples separated by 9 years and they were higher in breadth and magnitude than responses seen in most of 250 treatment naïve patients and also 25 controller subjects. The LTNP-EC showed a neutralization response, against 4 of the 6 viruses analyzed, superior to other ECs. Conclusions The study demonstrated that a strong and sustained cellular and humoral immune response and low replicating viruses are associated with viral control in the superinfected LTNP-EC. PMID:22384103

  9. What's in a name; Genetic structure in Solanum section Petota studied using population-genetic tools

    Microsoft Academic Search

    Mirjam MJ Jacobs; Marinus JM Smulders; Ronald G van den Berg; Ben Vosman

    2011-01-01

    BACKGROUND: The taxonomy and systematic relationships among species of Solanum section Petota are complicated and the section seems overclassified. Many of the presumed (sub)species from South America are very similar and they are able to exchange genetic material. We applied a population genetic approach to evaluate support for subgroups within this material, using AFLP data. Our approach is based on

  10. Metagenomic Characterization of Airborne Viral DNA Diversity in the Near-Surface Atmosphere

    PubMed Central

    Whon, Tae Woong; Kim, Min-Soo; Roh, Seong Woon; Shin, Na-Ri; Lee, Hae-Won

    2012-01-01

    Airborne viruses are expected to be ubiquitous in the atmosphere but they still remain poorly understood. This study investigated the temporal and spatial dynamics of airborne viruses and their genotypic characteristics in air samples collected from three distinct land use types (a residential district [RD], a forest [FR], and an industrial complex [IC]) and from rainwater samples freshly precipitated at the RD site (RD-rain). Viral abundance exhibited a seasonal fluctuation in the range between 1.7 × 106 and 4.0 × 107 viruses m?3, which increased from autumn to winter and decreased toward spring, but no significant spatial differences were observed. Temporal variations in viral abundance were inversely correlated with seasonal changes in temperature and absolute humidity. Metagenomic analysis of air viromes amplified by rolling-circle phi29 polymerase-based random hexamer priming indicated the dominance of plant-associated single-stranded DNA (ssDNA) geminivirus-related viruses, followed by animal-infecting circovirus-related sequences, with low numbers of nanoviruses and microphages-related genomes. Particularly, the majority of the geminivirus-related viruses were closely related to ssDNA mycoviruses that infect plant-pathogenic fungi. Phylogenetic analysis based on the replication initiator protein sequence indicated that the airborne ssDNA viruses were distantly related to known ssDNA viruses, suggesting that a high diversity of viruses were newly discovered. This research is the first to report the seasonality of airborne viruses and their genetic diversity, which enhances our understanding of viral ecology in temperate regions. PMID:22623790

  11. Synthesis and characterization of different immunogenic viral nanoconstructs from rotavirus VP6 inner capsid protein.

    PubMed

    Bugli, Francesca; Caprettini, Valeria; Cacaci, Margherita; Martini, Cecilia; Paroni Sterbini, Francesco; Torelli, Riccardo; Della Longa, Stefano; Papi, Massimiliano; Palmieri, Valentina; Giardina, Bruno; Posteraro, Brunella; Sanguinetti, Maurizio; Arcovito, Alessandro

    2014-01-01

    In order to deliver low-cost viral capsomeres from a large amount of soluble viral VP6 protein from human rotavirus, we developed and optimized a biotechnological platform in Escherichia coli. Specifically, three different expression protocols were compared, differing in their genetic constructs, ie, a simple native histidine-tagged VP6 sequence, VP6 fused to thioredoxin, and VP6 obtained with the newly described small ubiquitin-like modifier (SUMO) fusion system. Our results demonstrate that the histidine-tagged protein does not escape the accumulation in the inclusion bodies, and that SUMO is largely superior to the thioredoxin-fusion tag in enhancing the expression and solubility of VP6 protein. Moreover, the VP6 protein produced according to the SUMO fusion tag displays well-known assembly properties, as observed in both transmission electron microscopy and atomic force microscopy images, giving rise to either VP6 trimers, 60 nm spherical virus-like particles, or nanotubes a few microns long. This different quaternary organization of VP6 shows a higher level of immunogenicity for the elongated structures with respect to the spheres or the protein trimers. Therefore, the expression and purification strategy presented here - providing a large amount of the viral capsid protein in the native form with relatively simple, rapid, and economical procedures - opens a new route toward large-scale production of a more efficient antigenic compound to be used as a vaccination tool or as an adjuvant, and also represents a top-quality biomaterial to be further modified for biotechnological purposes. PMID:24936129

  12. Vitamin D and the anti-viral state

    PubMed Central

    Beard, Jeremy A.; Bearden, Allison; Striker, Rob

    2012-01-01

    Vitamin D has long been recognized as essential to the skeletal system. Newer evidence suggests that it also plays a major role regulating the immune system, perhaps including immune responses to viral infection. Interventional and observational epidemiological studies provide evidence that vitamin D deficiency may confer increased risk of influenza and respiratory tract infection. Vitamin D deficiency is also prevalent among patients with HIV infection. Cell culture experiments support the thesis that vitamin D has direct anti-viral effects particularly against enveloped viruses. Though vitamin D’s anti-viral mechanism has not been fully established, it may be linked to vitamin D’s ability to up-regulate the anti-microbial peptides LL-37 and human beta defensin 2. Additional studies are necessary to fully elucidate the efficacy and mechanism of vitamin D as an anti-viral agent. PMID:21242105

  13. Demographics of lytic viral infection of coastal ocean vibrio

    E-print Network

    Kauffman, Anne Kathryn Marie

    2014-01-01

    Viral predation on bacteria in the ocean liberates carbon from the particulate fraction, where it is accessible to higher trophic levels, and redirects it to the dissolved fraction, where it supports microbial growth. ...

  14. Expanding the histological findings in postvaccinial non-viral folliculitis

    PubMed Central

    Bunick, Christopher G.; Mariwalla, Kavita; Ibrahim, Omer; Modi, Badri; Imaeda, Suguru; McNiff, Jennifer

    2014-01-01

    Postvaccinial non-viral folliculitis has been recognized in the past decade as a new adverse cutaneous reaction to the smallpox vaccination. Contrary to more serious smallpox vaccine reactions, postvaccinial non-viral folliculitis has a benign course resolving spontaneously within approximately seven days. We describe additional histopathological findings associated with postvaccinial non-viral folliculitis, which has only been described once previously. New findings include the presence of neutrophilic or lymphohistiocytic infiltrates that concentrate around the hair follicles. We compare our findings to the follicular nature of varicella and herpes zoster infections, generating the hypothesis of deposition of vaccinia protein within folliculosebaceous units as a potential pathophysiologic mechanism behind postvaccinial non-viral folliculitis. PMID:23278890

  15. The Complex Role of STAT3 in Viral Infections

    PubMed Central

    Kuchipudi, Suresh V.

    2015-01-01

    Signal transducer and activators of transcription-3 (STAT3) regulates diverse biological functions including cell growth, differentiation, and apoptosis. In addition, STAT3 plays a key role in regulating host immune and inflammatory responses and in the pathogenesis of many cancers. Several studies reported differential regulation of STAT3 in a range of viral infections. Interestingly, STAT3 appears to direct seemingly contradictory responses and both pro- and antiviral roles of STAT3 have been described. This review summarized the currently known functions of STAT3 in the regulation of viral replication and pathogenesis of viral infections. Some of the key unanswered questions and the gap in our current understanding of the role of STAT3 in viral pathogenesis are discussed. PMID:26199948

  16. Non Viral Vectors in Gene Therapy- An Overview

    PubMed Central

    Narvekar, Aparna

    2015-01-01

    Non-viral vectors are simple in theory but complex in practice. Apart from intra cellular and extracellular barriers, number of other challenges also needs to be overcome in order to increase the effectiveness of non-viral gene transfer. These barriers are categorized as production, formulation and storage. No one-size-fits-all solution to gene delivery, which is why in spite of various developments in liposome, polymer formulation and optimization, new compounds are constantly being proposed and investigated. In this review, we will see in detail about various types of non-viral vectors highlighting promising development and recent advances that had improved the non-viral gene transfer efficiency of translating from “Bench to bedside”. PMID:25738007

  17. Viral spread with or without emotions in online community

    E-print Network

    Jarynowski, Andrzej; Zbieg, Anita

    2013-01-01

    Diffusion of information and viral content, social contagion and influence are still topics of broad evaluation. We have studied the information epidemic in a social networking platform in order compare different campaign setups. The goal of this work is to present the new knowledge obtained from studying two artificial (experimental) and one natural (where people act emotionally) viral spread that took place in a closed virtual world. We propose an approach to modeling the behavior of online community exposed on external impulses as an epidemic process. The presented results base on online multilayer system observation, and show characteristic difference between setups, moreover, some important aspects of branching processes are presented. We run experiments, where we introduced viral to system and agents were able to propagate it. There were two modes of experiment: with or without award. Dynamic of spreading both of virals were described by epidemiological model and diffusion. Results of experiments were c...

  18. Chromosome Structure Viral and Bacterial Genomes are__________ than Eukaryotes

    E-print Network

    Cutler, Chris

    Chromosome Structure Viral and Bacterial Genomes are__________ than Eukaryotes They Usually Consist as the ___________________________, was Proposed by Margulis The Idea is that Mitochondria and Chloroplasts were Originally Independent Bacteria ________________________ Chloroplasts Chloroplasts Also have their ____________________ __________________ (cpDNA) is Generally Much

  19. Snapshot of Viral Infections in Wild Carnivores Reveals Ubiquity of Parvovirus and Susceptibility of Egyptian Mongoose to Feline Panleukopenia Virus

    PubMed Central

    Duarte, Margarida D.; Henriques, Ana Margarida; Barros, Sílvia Carla; Fagulha, Teresa; Mendonça, Paula; Carvalho, Paulo; Monteiro, Madalena; Fevereiro, Miguel; Basto, Mafalda P.; Rosalino, Luís Miguel; Barros, Tânia; Bandeira, Victor; Fonseca, Carlos; Cunha, Mónica V.

    2013-01-01

    The exposure of wild carnivores to viral pathogens, with emphasis on parvovirus (CPV/FPLV), was assessed based on the molecular screening of tissue samples from 128 hunted or accidentally road-killed animals collected in Portugal from 2008 to 2011, including Egyptian mongoose (Herpestes ichneumon, n?=?99), red fox (Vulpes vulpes, n?=?19), stone marten (Martes foina, n?=?3), common genet (Genetta genetta, n?=?3) and Eurasian badger (Meles meles, n?=?4). A high prevalence of parvovirus DNA (63%) was detected among all surveyed species, particularly in mongooses (58%) and red foxes (79%), along with the presence of CPV/FPLV circulating antibodies that were identified in 90% of a subset of parvovirus-DNA positive samples. Most specimens were extensively autolysed, restricting macro and microscopic investigations for lesion evaluation. Whenever possible to examine, signs of active disease were not present, supporting the hypothesis that the parvovirus vp2 gene fragments detected by real-time PCR possibly correspond to viral DNA reminiscent from previous infections. The molecular characterization of viruses, based on the analysis of the complete or partial sequence of the vp2 gene, allowed typifying three viral strains of mongoose and four red fox’s as feline panleukopenia virus (FPLV) and one stone marten’s as newCPV-2b type. The genetic similarity found between the FPLV viruses from free-ranging and captive wild species originated in Portugal and publicly available comparable sequences, suggests a closer genetic relatedness among FPLV circulating in Portugal. Although the clinical and epidemiological significance of infection could not be established, this study evidences that exposure of sympatric wild carnivores to parvovirus is common and geographically widespread, potentially carrying a risk to susceptible populations at the wildlife-domestic interface and to threatened species, such as the wildcat (Felis silvestris) and the critically endangered Iberian lynx (Lynx pardinus). PMID:23527182

  20. Viral infections as controlling factors for the deep biosphere? (Invited)

    NASA Astrophysics Data System (ADS)

    Engelen, B.; Engelhardt, T.; Sahlberg, M.; Cypionka, H.

    2009-12-01

    The marine deep biosphere represents the largest biotope on Earth. Throughout the last years, we have obtained interesting insights into its microbial community composition. However, one component that was completely overlooked so far is the viral inventory of deep-subsurface sediments. While viral infections were identified to have a major impact on the benthic microflora of deep-sea surface sediments (Danavaro et al. 2008), no studies were performed on deep-biosphere samples, so far. As grazers probably play only a minor role in anoxic and highly compressed deep sediments, viruses might be the main “predators” for indigenous microorganisms. Furthermore, the release of cell components, called “the viral shunt”, could have a major impact on the deep biosphere in providing labile organic compounds to non-infected microorganisms in these generally nutrient depleted sediments. However, direct counting of viruses in sediments is highly challenging due to the small size of viruses and the high background of small particles. Even molecular surveys using “universal” PCR primers that target phage-specific genes fail due to the vast phage diversity. One solution for this problem is the lysogenic viral life cycle as many bacteriophages integrate their DNA into the host genome. It is estimated that up to 70% of cultivated bacteria contain prophages within their genome. Therefore, culture collections (Batzke et al. 2007) represent an archive of the viral composition within the respective habitat. These prophages can be induced to become free phage particles in stimulation experiments in which the host cells are set under certain stress situations such as a treatment with UV exposure or DNA-damaging antibiotics. The study of the viral component within the deep biosphere offers to answer the following questions: To which extent are deep-biosphere populations controlled by viral infections? What is the inter- and intra-specific diversity and the host-specific viral biogeography? Can viral infections tell us something about the physiological state of indigenous microorganisms? Finally, we will obtain estimates for the viral shunt as an important factor for sustaining the deep biosphere. References: Batzke A, Engelen B, Sass H, Cypionka H (2007) Phylogenetic and physiological diversity of cultured deep-biosphere bacteria from Equatorial Pacific Ocean and Peru Margin sediments. Geomicrobiology J 24:261-273 Danovaro R, Dell'Anno A, Corinaldesi C, Magagnini M, Noble R, Tamburini C, Weinbauer M (2008) Major viral impact on the functioning of benthic deep-sea ecosystems. Nature 454: 1084-U1027.

  1. Multiwalled carbon nanotube filter: improving viral removal at low pressure.

    PubMed

    Brady-Estévez, Anna S; Schnoor, Mary H; Vecitis, Chad D; Saleh, Navid B; Elimelech, Menachem

    2010-09-21

    The effective removal of viruses by a multiwalled carbon nanotube (MWNT) filter is demonstrated over a range of solution chemistries. MS2 bacteriophage viral removal by the MWNT filter was between 1.5 and 3 log higher than that observed with a recently reported single-walled carbon nanotube (SWNT) filter when examined under similar loadings (0.3 mg/cm(2)) of carbon nanotubes (CNTs). The greater removal of viruses by the MWNT filter is attributed to a more uniform CNT-filter matrix that allows effective removal of viruses by physicochemical (depth) filtration. Viral removal by the MWNT filter was examined under a broad range of water compositions (ionic strength, monovalent and divalent salts, solution pH, natural organic matter, alginate, phosphate, and bicarbonate) and filter approach velocities (0.0016, 0.0044, and 0.0072 cm/s). Log viral removal increased as the fluid approach velocity decreased, exhibiting a dependence on approach velocity in agreement with colloid filtration theory for Brownian particles. Viral removal improved with increasing ionic strength (NaCl), from 5.06 log removal at 1 mM NaCl to greater than 6.56 log removal at 100 mM NaCl. Addition of calcium ions also enhanced viral removal, but the presence of magnesium ions resulted in a decrease in viral removal. Solution pH also played an important role in viral removal, with log removals of 8.13, 5.38, and 4.00 being documented at solution pH values of 3.0, 5.5, and 9.0, respectively. Dissolved natural organic matter (NOM) had a negligible effect on viral removal at low concentration (1 mg/L), but higher concentrations of NOM significantly reduced the viral removal by the MWNT filter, likely due to steric repulsion. Addition of alginate (model polysaccharide) also caused a marked decrease in viral removal by the MWNT filter. This highly scalable MWNT-filter technology at gravity-driven pressures presents new, cost-effective options for point-of-use filters for viral removal. PMID:20795662

  2. Property rights in genetic information.

    PubMed

    Spinello, Richard A

    2004-01-01

    The primary theme of this paper is the normative case against ownership of one's genetic information along with the source of that information (usually human tissues samples). The argument presented here against such "upstream" property rights is based primarily on utilitarian grounds. This issue has new salience thanks to the Human Genome Project and "bio-prospecting" initiatives based on the aggregation of genetic information, such as the one being managed by deCODE Genetics in Iceland. The rationale for ownership is twofold: ownership will protect the basic human rights of privacy and autonomy and it will enable the data subjects to share in the tangible benefits of the genetic research. Proponents of this viewpoint often cite the principle of genetic exceptionalism, which asserts that genetic information needs a higher level of protection than other kinds of personal information such as financial data. We argue, however, that the recognition of such ownership rights would lead to inefficiency along with the disutility of genetic discoveries. Biomedical research will be hampered if property rights in genes and genetic material are too extensive. We contend that other mechanisms such as informed consent and strict confidentiality rules can accomplish the same result as a property right without the liabilities of an exclusive entitlement. PMID:16969959

  3. Staphylococcus aureus ?-toxin modulates skin host response to viral infection

    PubMed Central

    Bin, Lianghua; Kim, Byung Eui; Brauweiler, Anne; Goleva, Elena; Streib, Joanne; Ji, Yinduo; Schlievert, Patrick M.; Leung, Donald Y. M.

    2012-01-01

    Background Patients with atopic dermatitis (AD) with a history of eczema herpeticum have increased staphylococcal colonization and infections. However, whether Staphylococcus aureus alters the outcome of skin viral infection has not been determined. Objective We investigated whether S aureus toxins modulated host response to herpes simplex virus (HSV) 1 and vaccinia virus (VV) infections in normal human keratinocytes (NHKs) and in murine infection models. Methods NHKs were treated with S aureus toxins before incubation of viruses. BALB/c mice were inoculated with S aureus 2 days before VV scarification. Viral loads of HSV-1 and VV were evaluated by using real-time PCR, a viral plaque-forming assay, and immunofluorescence staining. Small interfering RNA duplexes were used to knockdown the gene expression of the cellular receptor of ?-toxin, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 protein and ?-toxin heptamers were detected by using Western blot assays. Results We demonstrate that sublytic staphylococcal ?-toxin increases viral loads of HSV-1 and VV in NHKs. Furthermore, we demonstrate in vivo that the VV load is significantly greater (P < .05) in murine skin inoculated with an ?-toxin–producing S aureus strain compared with murine skin inoculated with the isogenic ?-toxin–deleted strain. The viral enhancing effect of ?-toxin is mediated by ADAM10 and is associated with its poreforming property. Moreover, we demonstrate that ?-toxin promotes viral entry in NHKs. Conclusion The current study introduces the novel concept that staphylococcal ?-toxin promotes viral skin infection and provides a mechanism by which S aureus infection might predispose the host toward disseminated viral infections. PMID:22840852

  4. Viral Gastroenteritis Outbreaks in Europe, 1995-2000

    Microsoft Academic Search

    Ben A. Lopman; Mark H. Reacher; Yvonne van Duijnhoven; François-Xavier Hanon; David Brown; Marion Koopmans

    2003-01-01

    To gain understanding of surveillance and epidemiology of viral gastroenteritis outbreaks in Europe, we compiled data from 10 surveillance systems in the Foodborne Viruses in Europe network. Established surveillance systems found Norovirus to be responsible for >85% (N=3,714) of all nonbac- terial outbreaks of gastroenteritis reported from 1995 to 2000. However, the absolute number and population-based rates of viral gastroenteritis

  5. Specific sequence amplification of bovine viral diarrhoea virus nucleic acid

    Microsoft Academic Search

    B. A. Schroeder; T. C. Balassu-Chan

    1990-01-01

    Summary Bovine viral diarrhoea virus (BVDV) causes infection of cattle worldwide and is a common contaminant of cell cultures in the laboratory. Methods of diagnosis for BVDV are time-consuming and inconsistent. We describe the development of an in vitro test based on enzymatic DNA amplification withThermus aquaticus DNA polymerase of sequences of BVDV cDNA reverse transcribed from viral RNA. Specific

  6. In vitro neutralization against HoBi-like viruses by antiobodies in serum of cattle immunized with inactivated or modified live vaccines of bovine viral diarrhea virus 1 and 2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    HoBi-like viruses are an emerging species of pestiviruses with genetic and antigenic similarities to bovine viral diarrhea viruses 1 and 2 (BVDV1 and BVDV2). These viruses have been detected associated with respiratory and/or reproductive disease in cattle in Italy and Brazil. Vaccines for HoBi-like...

  7. Interchange of L polymerase protein between two strains of viral hemorrhagic septicemia virus (VHSV) genotype IV alters temperature sensitivities in vitro.

    PubMed

    Kim, Sung-Hyun; Yusuff, Shamila; Vakharia, Vikram N; Evensen, Øystein

    2015-01-01

    Viral hemorrhagic septicemia virus (VHSV) has four genotypes (I-IV) and sub-lineages within genotype I and IV. Using a reverse genetics approach, we explored the importance of the L gene for growth characteristics at different temperatures following interchange of the L gene within genotype IV (IVa and IVb) strains. VHSV strains harboring heterologous L gene were recovered and we show that the L gene determines growth characteristics at different temperatures in permissive cell lines. PMID:25456404

  8. The role of cytidine deaminases on innate immune responses against human viral infections.

    PubMed

    Vieira, Valdimara C; Soares, Marcelo A

    2013-01-01

    The APOBEC family of proteins comprises deaminase enzymes that edit DNA and/or RNA sequences. The APOBEC3 subgroup plays an important role on the innate immune system, acting on host defense against exogenous viruses and endogenous retroelements. The role of APOBEC3 proteins in the inhibition of viral infection was firstly described for HIV-1. However, in the past few years many studies have also shown evidence of APOBEC3 action on other viruses associated with human diseases, including HTLV, HCV, HBV, HPV, HSV-1, and EBV. APOBEC3 inhibits these viruses through a series of editing-dependent and independent mechanisms. Many viruses have evolved mechanisms to counteract APOBEC effects, and strategies that enhance APOBEC3 activity constitute a new approach for antiviral drug development. On the other hand, novel evidence that editing by APOBEC3 constitutes a source for viral genetic diversification and evolution has emerged. Furthermore, a possible role in cancer development has been shown for these host enzymes. Therefore, understanding the role of deaminases on the immune response against infectious agents, as well as their role in human disease, has become pivotal. This review summarizes the state-of-the-art knowledge of the impact of APOBEC enzymes on human viruses of distinct families and harboring disparate replication strategies. PMID:23865062

  9. Trade practices are main factors involved in the transmission of viral haemorrhagic septicaemia.

    PubMed

    Reichert, M; Matras, M; Skall, H F; Olesen, N J; Kahns, S

    2013-02-01

    Viral haemorrhagic septicaemia (VHS), caused by the novirhabdovirus viral haemorrhagic septicaemia virus (VHSV), causes significant economic problems to European rainbow trout, Oncorhynchus mykiss (Walbaum), production. The virus isolates can be divided into four distinct genotypes with additional subgroups. The main source of outbreaks in European rainbow trout farming is sublineage Ia isolates. Recently, this group of isolates has been further subdivided in to two subclades of which the Ia-2 consists of isolates occurring mainly in Continental Europe outside of Denmark. In this study, we sequenced the full-length G-gene sequences of 24 VHSV isolates that caused VHS outbreaks in Polish trout farms between 2005 and 2009. All these isolates were identified as genotype Ia-2; they divided however into two genetically distinct subgroups, that we name Pol I and Pol II. The Pol I isolates mainly caused outbreaks in the southern part of Poland, while Pol II isolates predominantly were sampled in the north of Poland, although it seems that they have been transmitted to other parts of the country. Molecular epidemiology was used for characterization of transmission pathways. This study shows that a main cause of virus transmission appears to be movement of fish. At least in Polish circumstances trading practices appear to have significant impact on spreading of VHSV infection. PMID:23020691

  10. Detection of Viral Hemorrhagic Septicemia virus (VHSV) from the leech Myzobdella lugubris Leidy, 1851

    PubMed Central

    Faisal, Mohamed; Schulz, Carolyn A

    2009-01-01

    The leech Myzobdella lugubris is widespread in the Lake Erie Watershed, especially Lake St. Clair. However, its role in pathogen transmission is not fully understood. In this same watershed, several widespread fish mortalities associated with the Viral Hemorrhagic Septicemia virus (VHSV) were recorded. Viral Hemorrhagic Septicemia is an emerging disease in the Great Lakes Basin that is deadly to the fish population, yet little is known about its mode of transmission. To assess the potential role of M. lugubris in VHSV transmission, leeches were collected from Lake St. Clair and Lake Erie and pooled into samples of five. Cell culture and reverse transcriptase polymerase chain reaction (RT-PCR) were used to determine the presence of the virus and its identity. Results showed that 57 of the 91 pooled leech samples were positive by cell culture for VHSV and 66 of the 91 pooled leech samples were positive by RT-PCR for the VHSV. Two representative virus isolates were sequenced for further genetic confirmation and genotype classification. VHSV detected within M. lugubris was homologous to the Great Lakes strain of VHSV genotype IVb. This is the first record of the VHSV being detected from within a leech, specifically M. lugubris, and suggests the potential of M. lugubris being involved in VHSV transmission. PMID:19785752

  11. Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus.

    PubMed

    Hansen, Thomas R; Smirnova, Natalia P; Webb, Brett T; Bielefeldt-Ohmann, Helle; Sacco, Randy E; Van Campen, Hana

    2015-06-01

    Infection of pregnant cows with noncytopathic (ncp) bovine viral diarrhea virus (BVDV) induces rapid innate and adaptive immune responses, resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent infection with ncpBVDV in the fetus has been attributed to the inability to mount an immune response before 90-150 days of gestational age. The result is 'immune tolerance', persistent viral replication and shedding of ncpBVDV. In contrast, we describe the chronic upregulation of fetal Type I interferon (IFN) pathway genes and the induction of IFN-? pathways in fetuses of cows infected on day 75 of gestation. Persistently infected (PI) fetal IFN-? concentrations also increased at day 97 at the peak of fetal viremia and IFN-? mRNA was significantly elevated in fetal thymus, liver and spleen 14-22 days post maternal inoculation. PI fetuses respond to ncpBVDV infection through induction of Type I IFN and IFN-? activated genes leading to a reduction in ncpBVDV titer. We hypothesize that fetal infection with BVDV persists because of impaired induction of IFN-? in the face of activated Type I IFN responses. Clarification of the mechanisms involved in the IFN-associated pathways during BVDV fetal infection may lead to better detection methods, antiviral compounds and selection of genetically resistant breeding animals. PMID:26050568

  12. Circulating virus load determines the size of bottlenecks in viral populations progressing within a host.

    PubMed

    Gutiérrez, Serafín; Yvon, Michel; Pirolles, Elodie; Garzo, Eliza; Fereres, Alberto; Michalakis, Yannis; Blanc, Stéphane

    2012-01-01

    For any organism, population size, and fluctuations thereof, are of primary importance in determining the forces driving its evolution. This is particularly true for viruses--rapidly evolving entities that form populations with transient and explosive expansions alternating with phases of migration, resulting in strong population bottlenecks and associated founder effects that increase genetic drift. A typical illustration of this pattern is the progression of viral disease within a eukaryotic host, where such demographic fluctuations are a key factor in the emergence of new variants with altered virulence. Viruses initiate replication in one or only a few infection foci, then move through the vasculature to seed secondary infection sites and so invade distant organs and tissues. Founder effects during this within-host colonization might depend on the concentration of infectious units accumulating and circulating in the vasculature, as this represents the infection dose reaching new organs or "territories". Surprisingly, whether or not the easily measurable circulating (plasma) virus load directly drives the size of population bottlenecks during host colonization has not been documented in animal viruses, while in plants the virus load within the sap has never been estimated. Here, we address this important question by monitoring both the virus concentration flowing in host plant sap, and the number of viral genomes founding the population in each successive new leaf. Our results clearly indicate that the concentration of circulating viruses directly determines the size of bottlenecks, which hence controls founder effects and effective population size during disease progression within a host. PMID:23133389

  13. Molecular investigation of bovine viral diarrhea virus infection in yaks (Bos gruniens) from Qinghai, China

    PubMed Central

    2014-01-01

    Background Bovine viral diarrhea virus (BVDV) is a pestivirus which infects both domestic animals and wildlife species worldwide. In China, cattle are often infected with BVDV of different genotypes, but there is very limited knowledge regarding BVDV infection in Chinese yaks and the genetic diversity of the virus. The objectives of this study were to detect viral infection in yaks in Qinghai, China and to determine the genotypes of BVDV based on analysis of the 5?untranslated region (5?UTR) and N-terminal protease (Npro) region. Results Between 2010 and 2012, 407 blood samples were collected from yaks with or without clinical signs in six counties of Qinghai Province. Ninety-eight samples (24%) were found to be positive by reverse transcription polymerase chain reaction (RT-PCR) targeting a conserved region of BVDV-1 and BVDV-2. The nucleotide sequences of the 5?UTR and complete Npro region were determined for 16 positive samples. Phylogenetic reconstructions demonstrated that all 16 samples belong to subgenotypes BVDV-1b, BVDV-1d and BVDV-1q. Conclusions This study provides, for the first time, molecular evidence for BVDV infection in yaks in Qinghai involving multiple subgenotypes of BVDV-1. This may have occurred under three possible scenarios: interspecies transmission, natural infection, and the use of vaccines contaminated with BVDV. The results have important implications for yak production and management in China, and specifically indicate that unscientific vaccination practices should be stopped and bio-security increased. PMID:24524442

  14. The Role of Cytidine Deaminases on Innate Immune Responses against Human Viral Infections

    PubMed Central

    Vieira, Valdimara C.; Soares, Marcelo A.

    2013-01-01

    The APOBEC family of proteins comprises deaminase enzymes that edit DNA and/or RNA sequences. The APOBEC3 subgroup plays an important role on the innate immune system, acting on host defense against exogenous viruses and endogenous retroelements. The role of APOBEC3 proteins in the inhibition of viral infection was firstly described for HIV-1. However, in the past few years many studies have also shown evidence of APOBEC3 action on other viruses associated with human diseases, including HTLV, HCV, HBV, HPV, HSV-1, and EBV. APOBEC3 inhibits these viruses through a series of editing-dependent and independent mechanisms. Many viruses have evolved mechanisms to counteract APOBEC effects, and strategies that enhance APOBEC3 activity constitute a new approach for antiviral drug development. On the other hand, novel evidence that editing by APOBEC3 constitutes a source for viral genetic diversification and evolution has emerged. Furthermore, a possible role in cancer development has been shown for these host enzymes. Therefore, understanding the role of deaminases on the immune response against infectious agents, as well as their role in human disease, has become pivotal. This review summarizes the state-of-the-art knowledge of the impact of APOBEC enzymes on human viruses of distinct families and harboring disparate replication strategies. PMID:23865062

  15. Competition–colonization trade-off promotes coexistence of low-virulence viral strains

    PubMed Central

    Ojosnegros, Samuel; Delgado-Eckert, Edgar; Beerenwinkel, Niko

    2012-01-01

    RNA viruses exist as genetically diverse populations displaying a range of virulence degrees. The evolution of virulence in viral populations is, however, poorly understood. On the basis of the experimental observation of an RNA virus clone in cell culture diversifying into two subpopulations of different virulence, we study the dynamics of mutating virus populations with varying virulence. We introduce a competition–colonization trade-off into standard mathematical models of intra-host viral infection. Colonizers are fast-spreading virulent strains, whereas the competitors are less-virulent variants but more successful within co-infected cells. We observe a two-step dynamics of the population. Early in the infection, the population is dominated by colonizers, which later are outcompeted by competitors. Our simulations suggest the existence of steady state in which all virulence classes coexist but are dominated by the most competitive ones. This equilibrium implies collective virulence attenuation in the population, in contrast to previous models predicting evolution of the population towards increased virulence. PMID:22513722

  16. Novel Gene Therapy Viral Vector Using Non-Oncogenic Lymphotropic Herpesvirus

    PubMed Central

    Shimizu, Akihiro; Kobayashi, Nobuyuki; Shimada, Kazuya; Oura, Kuniaki; Tanaka, Tadao; Okamoto, Aikou; Kondo, Kazuhiro

    2013-01-01

    Despite the use of retroviral vectors, efficiently introducing target genes into immunocytes such as T cells is difficult. In addition, retroviral vectors carry risks associated with the oncogenicity of the native virus and the potential for introducing malignancy in recipients due to genetic carryover from immortalized cells used during vector production. To address these issues, we have established a new virus vector that is based on human herpesvirus 6 (HHV-6), a non-oncogenic lymphotropic herpesvirus that infects CD4+ T cells, macrophages, and dendritic cells. In the present study, we have altered the cell specificity of the resulting recombinant HHV-6 by knocking out the U2–U8 genes. The resulting virus proliferated only in activated cord blood cells and not in peripheral blood cells. Umbilical cord blood cells produced replication-defective recombinant virus in sufficiently high titer to omit the use of immortalized cells during vector production. HHV-6 vectors led to high rates (>90%) of gene transduction in both CD4+ and CD8+ T cells. These viruses showed low-level replication of viral DNA that supported greater expression of the induced genes than that of other methods but that was insufficient to support the production of replication-competent virus. Furthermore, HHV-6 vectors containing short hairpin RNAs against CD4 and HIV Gag remarkably inhibited the production of these proteins and HIV particles. Here we demonstrate the utility of HHV-6 as a new non-carcinogenic viral vector for immunologic diseases and immunotherapy. PMID:23409116

  17. Nanotip analysis for dielectrophoretic concentration of nanosized viral particles

    NASA Astrophysics Data System (ADS)

    Yeo, Woon-Hong; Lee, Hyun-Boo; Kim, Jong-Hoon; Lee, Kyong-Hoon; Chung, Jae-Hyun

    2013-05-01

    Rapid and sensitive detection of low-abundance viral particles is strongly demanded in health care, environmental control, military defense, and homeland security. Current detection methods, however, lack either assay speed or sensitivity, mainly due to the nanosized viral particles. In this paper, we compare a dendritic, multi-terminal nanotip (‘dendritic nanotip’) with a single terminal nanotip (‘single nanotip’) for dielectrophoretic (DEP) concentration of viral particles. The numerical computation studies the concentration efficiency of viral particles ranging from 25 to 100 nm in radius for both nanotips. With DEP and Brownian motion considered, when the particle radius decreases by two times, the concentration time for both nanotips increases by 4-5 times. In the computational study, a dendritic nanotip shows about 1.5 times faster concentration than a single nanotip for the viral particles because the dendritic structure increases the DEP-effective area to overcome the Brownian motion. For the qualitative support of the numerical results, the comparison experiment of a dendritic nanotip and a single nanotip is conducted. Under 1 min of concentration time, a dendritic nanotip shows a higher sensitivity than a single nanotip. When the concentration time is 5 min, the sensitivity of a dendritic nanotip for T7 phage is 104 particles ml-1. The dendritic nanotip-based concentrator has the potential for rapid identification of viral particles.

  18. Viral DNA in horses infected with equine infectious anemia virus.

    PubMed Central

    Rice, N R; Lequarre, A S; Casey, J W; Lahn, S; Stephens, R M; Edwards, J

    1989-01-01

    The amount and distribution of viral DNA were established in a horse acutely infected with the Wyoming strain of equine infectious anemia virus (EIAV). The highest concentration of viral DNA were found in the liver, lymph nodes, bone marrow, and spleen. The kidney, choroid plexus, and peripheral blood leukocytes also contained viral DNA, but at a lower level. It is estimated that at day 16 postinoculation, almost all of the viral DNA was located in the tissues, with the liver alone containing about 90 times more EIAV DNA than the peripheral blood leukocytes did. Assuming a monocyte-macrophage target, each infected cell contained multiple copies of viral DNA (between 6 and 60 copies in liver Kupffer cells). At day 16 postinoculation, most of the EIAV DNA was not integrated into host DNA, but existed in both linear and circular unintegrated forms. In contrast to acute infection, viral DNA was not detectable in tissues from asymptomatic horses with circulating antibody to EIAV. Images PMID:2555550

  19. Strategies for viral cross protection in plants.

    PubMed

    Zhou, Changyong; Zhou, Yan

    2012-01-01

    Viral cross protection in plants is known as an acquired immunity phenomenon, where a mild virus isolate/strain can protect plants against economic damage caused by a severe challenge strain/isolate of the same virus. Mild strain cross protection (MSCP) has been used extensively to control losses caused by a few major virus diseases in some parts of the world. So far, none of the many proposed mechanisms can fully explain the intact process of MSCP. In fact, it may be that different mechanisms are involved in MSCP against different viruses, even when different research approaches are used for the same virus, different mechanisms could be proposed. The molecular detail of MSCP still remains unclear, although several lines of evidence imply that the resistance is protein and/or RNA mediated. Some data to date have shown that a minimum time (a few days to less than a month) is required for the mild virus strain to establish MSCP. To investigate interference among virus strains and the plant host at an early stage of MSCP at a subcellular level, we developed a rapid micro-extraction method for the preparation of total nucleic acid (TNA), combined with other molecular methods, to monitor the interaction of virus strains at short time intervals in young plants. This method was initially developed to further study the mechanism of MSCP against Citrus tristeza virus, but has potentially widespread application to other viruses after having been efficiently used to extract over 50,000 TNA samples of citrus viruses, viroids, and bacteria. PMID:22678573

  20. The genetics of host–virus coevolution in invertebrates

    PubMed Central

    Obbard, Darren J; Dudas, Gytis

    2014-01-01

    Although viral infection and antiviral defence are ubiquitous, genetic data are currently unavailable from the vast majority of animal phyla — potentially biasing our overall perspective of the coevolutionary process. Rapid adaptive evolution is seen in some insect antiviral genes, consistent with invertebrate-virus ‘arms-race’ coevolution, but equivalent signatures of selection are hard to detect in viruses. We find that, despite the large differences in vertebrate, invertebrate, and plant immune responses, comparison of viral evolution fails to identify any difference among these hosts in the impact of positive selection. The best evidence for invertebrate-virus coevolution is currently provided by large-effect polymorphisms for host resistance and/or viral evasion, as these often appear to have arisen and spread recently, and can be favoured by virus-mediated selection. PMID:25063907

  1. Noise Cancellation: Viral Fine Tuning of the Cellular Environment for Its Own Genome Replication

    Microsoft Academic Search

    Yoshitaka Sato; Tatsuya Tsurumi

    2010-01-01

    Productive replication of DNA viruses elicits host cell DNA damage responses, which cause both beneficial and detrimental effects on viral replication. In response to the viral productive replication, host cells attempt to attenuate the S-phase cyclin-dependent kinase (CDK) activities to inhibit viral replication. However, accumulating evidence regarding interactions between viral factors and cellular signaling molecules indicate that viruses utilize them

  2. Viral nanoparticles as platforms for next-generation therapeutics and imaging devices

    PubMed Central

    Steinmetz, Nicole F.

    2010-01-01

    Nanomaterials have been developed for potential applications in biomedicine, such as tissue-specific imaging and drug delivery. There are many different platforms under development, each with advantages and disadvantages, but viral nanoparticles (VNPs) are particularly attractive because they are naturally occurring nanomaterials, and as such they are both biocompatible and biodegradable. VNPs can be designed and engineered using both genetic and chemical protocols. The use of VNPs has evolved rapidly since their introduction 20 years ago, encompassing numerous chemistries and modification strategies that allow the functionalization of VNPs with imaging reagents, targeting ligands and therapeutic molecules. This review discusses recent advances in the design of “smart” targeted VNPs for therapeutic and imaging applications. PMID:20433947

  3. Genetics Home Reference: Hypochondroplasia

    MedlinePLUS

    ... for hypochondroplasia? HCH Hypochondrodysplasia For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes ...

  4. Genetics Home Reference: Hypercholesterolemia

    MedlinePLUS

    ... for hypercholesterolemia? Elevated cholesterol For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes ...

  5. Viruses Roll the Dice: The Stochastic Behavior of Viral Genome Molecules Accelerates Viral Adaptation at the Cell and Tissue Levels

    PubMed Central

    Miyashita, Shuhei; Ishibashi, Kazuhiro; Kishino, Hirohisa; Ishikawa, Masayuki

    2015-01-01

    Recent studies on evolutionarily distant viral groups have shown that the number of viral genomes that establish cell infection after cell-to-cell transmission is unexpectedly small (1–20 genomes). This aspect of viral infection appears to be important for the adaptation and survival of viruses. To clarify how the number of viral genomes that establish cell infection is determined, we developed a simulation model of cell infection for tomato mosaic virus (ToMV), a positive-strand RNA virus. The model showed that stochastic processes that govern the replication or degradation of individual genomes result in the infection by a small number of genomes, while a large number of infectious genomes are introduced in the cell. It also predicted two interesting characteristics regarding cell infection patterns: stochastic variation among cells in the number of viral genomes that establish infection and stochastic inequality in the accumulation of their progenies in each cell. Both characteristics were validated experimentally by inoculating tobacco cells with a library of nucleotide sequence–tagged ToMV and analyzing the viral genomes that accumulated in each cell using a high-throughput sequencer. An additional simulation model revealed that these two characteristics enhance selection during tissue infection. The cell infection model also predicted a mechanism that enhances selection at the cellular level: a small difference in the replication abilities of coinfected variants results in a large difference in individual accumulation via the multiple-round formation of the replication complex (i.e., the replication machinery). Importantly, this predicted effect was observed in vivo. The cell infection model was robust to changes in the parameter values, suggesting that other viruses could adopt similar adaptation mechanisms. Taken together, these data reveal a comprehensive picture of viral infection processes including replication, cell-to-cell transmission, and evolution, which are based on the stochastic behavior of the viral genome molecules in each cell. PMID:25781391

  6. Linkage and retention in care and the time to HIV viral suppression and viral rebound - New York City.

    PubMed

    Robertson, McKaylee; Laraque, Fabienne; Mavronicolas, Heather; Braunstein, Sarah; Torian, Lucia

    2015-01-01

    The success of antiretroviral therapy (ART) as treatment for the individual patient and as prevention requires the achievment and maintenance of human immunodeficiency virus (HIV) viral suppression. Linkage to and retention in care are required for access to ART. We describe the impact of care on viral suppression using routinely reported surveillance data. We included New York City residents ?13 years of age, diagnosed with HIV/AIDS from 1 July 2005 to 30 June 2009 with a viral load (VL) or CD4 reported within six months of diagnosis and ?1 VL reported from 1 July 2005 to 30 June 2011. To examine viral rebound, we restricted the analysis to those who achieved viral suppression and had a subsequent VL measure reported by 30 June 2011. Cox proportional hazards models were used to evaluate factors associated with time to viral suppression (VL ? 400 copies/mL) and rebound (VL > 1000 copies/mL). Initiation of care within three months of diagnosis (CD4/VL report within three months of diagnosis), female sex, and an initial CD4 < 350 (cells/mm(3)) at diagnosis significantly increased the likelihood of viral suppression. Irregular care (no CD4/VL reported every six months), younger age, non-white race/ethnicity, having an initial CD4 ? 350 at diagnosis, and AIDS diagnosis by 2010 increased the likelihood of rebound. These findings lend support to interventions for improving linkage to and maintenance in regular care as a way to achieve and maintain suppression. Surveillance data represent an ideal means for monitoring engagement in care and viral suppression at the population level. PMID:25244545

  7. Defining the Chemokine Basis for Leukocyte Recruitment during Viral Encephalitis

    PubMed Central

    Michlmayr, Daniela; Pingen, Marieke; Haxton, Ben; Mansfield, Karen; Johnson, Nicholas; Fooks, Anthony R.

    2014-01-01

    ABSTRACT The encephalitic response to viral infection requires local chemokine production and the ensuing recruitment of immune and inflammatory leukocytes. Accordingly, chemokine receptors present themselves as plausible therapeutic targets for drugs aimed at limiting encephalitic responses. However, it remains unclear which chemokines are central to this process and whether leukocyte recruitment is important for limiting viral proliferation and survival in the brain or whether it is predominantly a driver of coincident inflammatory pathogenesis. Here we examine chemokine expression and leukocyte recruitment in the context of avirulent and virulent Semliki Forest virus (SFV) as well as West Nile virus infection and demonstrate rapid and robust expression of a variety of inflammatory CC and CXC chemokines in all models. On this basis, we define a chemokine axis involved in leukocyte recruitment to the encephalitic brain during SFV infection. CXCR3 is the most active; CCR2 is also active but less so, and CCR5 plays only a modest role in leukocyte recruitment. Importantly, inhibition of each of these receptors individually and the resulting suppression of leukocyte recruitment to the infected brain have no effect on viral titer or survival following infection with a virulent SFV strain. In contrast, simultaneous blockade of CXCR3 and CCR2 results in significantly reduced mortality in response to virulent SFV infection. In summary, therefore, our data provide an unprecedented level of insight into chemokine orchestration of leukocyte recruitment in viral encephalitis. Our data also highlight CXCR3 and CCR2 as possible therapeutic targets for limiting inflammatory damage in response to viral infection of the brain. IMPORTANCE Brain inflammation (encephalitis) in response to viral infection can lead to severe illness and even death. This therefore represents an important clinical problem and one that requires the development of new therapeutic approaches. Central to the pathogenesis of encephalitis is the recruitment of inflammatory leukocytes to the infected brain, a process driven by members of the chemokine family. Here we provide an in-depth analysis of the chemokines involved in leukocyte recruitment to the virally infected brain and demonstrate that simultaneous blockade of two of these receptors, namely, CXCR3 and CCR2, does not alter viral titers within the brain but markedly reduces inflammatory leukocyte recruitment and enhances survival in a murine model of lethal viral encephalitis. Our results therefore highlight chemokine receptors as plausible therapeutic targets in treating viral encephalitis. PMID:24899190

  8. VirSorter: mining viral signal from microbial genomic data

    PubMed Central

    Roux, Simon; Enault, Francois; Hurwitz, Bonnie L.

    2015-01-01

    Viruses of microbes impact all ecosystems where microbes drive key energy and substrate transformations including the oceans, humans and industrial fermenters. However, despite this recognized importance, our understanding of viral diversity and impacts remains limited by too few model systems and reference genomes. One way to fill these gaps in our knowledge of viral diversity is through the detection of viral signal in microbial genomic data. While multiple approaches have been developed and applied for the detection of prophages (viral genomes integrated in a microbial genome), new types of microbial genomic data are emerging that are more fragmented and larger scale, such as Single-cell Amplified Genomes (SAGs) of uncultivated organisms or genomic fragments assembled from metagenomic sequencing. Here, we present VirSorter, a tool designed to detect viral signal in these different types of microbial sequence data in both a reference-dependent and reference-independent manner, leveraging probabilistic models and extensive virome data to maximize detection of novel viruses. Performance testing shows that VirSorter’s prophage prediction capability compares to that of available prophage predictors for complete genomes, but is superior in predicting viral sequences outside of a host genome (i.e., from extrachromosomal prophages, lytic infections, or partially assembled prophages). Furthermore, VirSorter outperforms existing tools for fragmented genomic and metagenomic datasets, and can identify viral signal in assembled sequence (contigs) as short as 3kb, while providing near-perfect identification (>95% Recall and 100% Precision) on contigs of at least 10kb. Because VirSorter scales to large datasets, it can also be used in “reverse” to more confidently identify viral sequence in viral metagenomes by sorting away cellular DNA whether derived from gene transfer agents, generalized transduction or contamination. Finally, VirSorter is made available through the iPlant Cyberinfrastructure that provides a web-based user interface interconnected with the required computing resources. VirSorter thus complements existing prophage prediction softwares to better leverage fragmented, SAG and metagenomic datasets in a way that will scale to modern sequencing. Given these features, VirSorter should enable the discovery of new viruses in microbial datasets, and further our understanding of uncultivated viral communities across diverse ecosystems. PMID:26038737

  9. The Pacific Ocean virome (POV): a marine viral metagenomic dataset and associated protein clusters for quantitative viral ecology.

    PubMed

    Hurwitz, Bonnie L; Sullivan, Matthew B

    2013-01-01

    Bacteria and their viruses (phage) are fundamental drivers of many ecosystem processes including global biogeochemistry and horizontal gene transfer. While databases and resources for studying function in uncultured bacterial communities are relatively advanced, many fewer exist for their viral counterparts. The issue is largely technical in that the majority (often 90%) of viral sequences are functionally 'unknown' making viruses a virtually untapped resource of functional and physiological information. Here, we provide a community resource that organizes this unknown sequence space into 27 K high confidence protein clusters using 32 viral metagenomes from four biogeographic regions in the Pacific Ocean that vary by season, depth, and proximity to land, and include some of the first deep pelagic ocean viral metagenomes. These protein clusters more than double currently available viral protein clusters, including those from environmental datasets. Further, a protein cluster guided analysis of functional diversity revealed that richness decreased (i) from deep to surface waters, (ii) from winter to summer, (iii) and with distance from shore in surface waters only. These data provide a framework from which to draw on for future metadata-enabled functional inquiries of the vast viral unknown. PMID:23468974

  10. Adoptive transfer of lymphocytes isolated from simian immunodeficiency virus SIVmac239?nef-vaccinated macaques does not affect acute-phase viral loads but may reduce chronic-phase viral loads in major histocompatibility complex-matched recipients.

    PubMed

    Greene, Justin M; Lhost, Jennifer J; Hines, Paul J; Scarlotta, Matthew; Harris, Max; Burwitz, Benjamin J; Budde, Melisa L; Dudley, Dawn M; Pham, Ngoc; Cain, Brian; Mac Nair, Caitlin E; Weiker, Madelyn K; O'Connor, Shelby L; Friedrich, Thomas C; O'Connor, David H

    2013-07-01

    The live attenuated simian immunodeficiency virus (SIV) SIVmac239?nef is the most effective SIV/human immunodeficiency virus (HIV) vaccine in preclinical testing. An understanding of the mechanisms responsible for protection may provide important insights for the development of HIV vaccines. Leveraging the uniquely restricted genetic diversity of Mauritian cynomolgus macaques, we performed adoptive transfers between major histocompatibility complex (MHC)-matched animals to assess the role of cellular immunity in SIVmac239?nef protection. We vaccinated and mock vaccinated donor macaques and then harvested between 1.25 × 10(9) and 3.0 × 10(9) mononuclear cells from multiple tissues for transfer into 12 naive recipients, followed by challenge with pathogenic SIVmac239. Fluorescently labeled donor cells were detectable for at least 7 days posttransfer and trafficked to multiple tissues, including lung, lymph nodes, and other mucosal tissues. There was no difference between recipient macaques' peak or postpeak plasma viral loads. A very modest difference in viral loads during the chronic phase between vaccinated animal cell recipients and mock-vaccinated animal cell recipients did not reach significance (P = 0.12). Interestingly, the SIVmac239 challenge virus accumulated escape mutations more rapidly in animals that received cells from vaccinated donors. These results may suggest that adoptive transfers influenced the course of infection despite the lack of significant differences in the viral loads among animals that received cells from vaccinated and mock-vaccinated donor animals. PMID:23616658

  11. Molecular genetic medicine. Vol. 2

    SciTech Connect

    Friedmann, T. (ed.)

    1992-01-01

    Theodore Friedmann has put together an interesting spectrum of articles for volume 2 of Molecular Genetic Medicine. Perhaps related to his own interest in the X chromosome, three articles deal with X-chromosomal topics, while two deal with autosomal disorders and two treat viral disorders. The fragile-X syndrome is thoroughly covered by Brown and Jenkins with an article that is heavily weighted to clinical aspects and now out-of-date RFLP approaches. The timeliness of the volume is insured by the coverage (albeit brief) that they give to the cloning of FMR-1. Gartler et al. present a balanced review of X inactivation - the oft-surveyed subject was comprehensively covered in a manner that provided new perspectives. Lambert et al. provide an exhaustive review of natural and induced mutation of hypoxanthine phosphoribosyltransferase. For autosomal disorders, an excellent review of the molecular genetics of hemoglobin syntheses and their alterations in disease is provided by Berg and Schecter. The level of detail presented seemed just right to this reviewer. A concise review of recent advances in the study of Down syndrome and its animal model, trisomy 16 mice, is provided by Holtzman and Epstein. With regard to viral topics, Chisari thoughtfully reviews hepatitis B virus structure and function and the possible pathogenic mechanisms involved in its induction of hepatocellular carcinoma. Wong-Staal and Haseltine's up-to-date review of the increasingly complex regulatory genes of HIV is marred by a mix-up in figure legends - an exception to an otherwise well-proofread book. In summary, this is a good volume of its type and is recommended for those who might benefit from reading such review articles.

  12. On Gene Concepts and Teaching Genetics: Episodes from Classical Genetics

    NASA Astrophysics Data System (ADS)

    Burian, Richard M.

    2013-02-01

    This paper addresses the teaching of advanced high school courses or undergraduate courses for non-biology majors about genetics or history of genetics. It will probably be difficult to take the approach described here in a high school science course, although the general approach could help improve such courses. It would be ideal for a college course in history of genetics or a course designed to teach non-science majors how science works or the rudiments of the genetics in a way that will help them as citizens. The approach aims to teach the processes of discovery, correction, and validation by utilizing illustrative episodes from the history of genetics. The episodes are treated in way that should foster understanding of basic questions about genes, the sorts of techniques used to answer questions about the constitution and structure of genes, how they function, and what they determine, and some of the major biological disagreements that arose in dealing with these questions. The material covered here could be connected to social and political issues raised by genetics, but these connections are not surveyed here. As it is, to cover this much territory, the article is limited to four major episodes from Mendel's paper to the beginning of World War II. A sequel will deal with the molecularization of genetics and with molecular gene concepts through the Human Genome Project.

  13. Mouse Oocytes and Embryos Cryotop-vitrification Using Low Concentrated Solutions: Effects on Meiotic Spindle, Genetic Material Array and Developmental Ability

    PubMed Central

    Almasi turk, Sahar; Roozbehi, Amrollah

    2013-01-01

    Objective(s): The examination of the possibility of applying lower CPA- concentrations and obtaining the similar results to those using higher concentrations; as it is shown, the toxicity of the CPAs used in vitrification approach will diminish. Materials and Methods: Following vitrification/warming, oocytes were subjected to PZD/ICSI. SRs, FRs, and DRs were recorded. SRs and DRs of the embryos were monitored after vitrification/warming. IHC studies were done. Data were analyzed in comparison to the data of Exp. (experimental groups) applying 1.5 M CPA- concentrations (largely-used concentration). Results: The data of oocytes exposed to 1.25 M concentrated CPAs were in consistency with those exposed to 1.5 M and fresh oocytes in terms of SRs, FRs and DRs. Normal spindle and chromatin configuration is in consistence between the two experimental groups, but lower in comparison with control group. The lower the concentrations were, the less SRs, FRs, DRs were. Also, spindle organizations were more normal in comparison with the experimental groups as the concentrations decreased. The results of DRs for embryos which were exposed to 1.25 and 1.0 M concentrated CPAs were close to those vitrified with 1.5 M and fresh embryos but IHC observations in the three Exp. were significantly lower than those of fresh embryos. The results of 7.5 M concentrated CPAs solutions were significantly lower than those of the control group 1.5, 1.25 and 1.0 M treated. Conclusions: Vitrification by cryotop technology using minimal volume approach increases both cooling and warming rates, therefore, the CPAs limited reduction to 1.25 and 1.0 M instead of using 1.5 M for oocytes and embryos cryotop-vitrification procedure, may be a slight adjustment. PMID:24250935

  14. Mouse Oocytes and Embryos Cryotop-vitrification Using Low Concentrated Solutions: Effects on Meiotic Spindle, Genetic Material Array and Developmental Ability

    PubMed Central

    Almasi turk, Sahar; Roozbehi, Amrollah

    2013-01-01

    Objective(s): The examination of the possibility of applying lower CPA- concentrations and obtaining the similar results to those using higher concentrations; as it is shown, the toxicity of the CPAs used in vitrification approach will diminish. Materials and Methods: Following vitrification/warming, oocytes were subjected to PZD/ICSI. SRs, FRs, and DRs were recorded. SRs and DRs of the embryos were monitored after vitrification/warming. IHC studies were done. Data were analyzed in comparison to the data of Exp. (experimental groups) applying 1.5 M CPA- concentrations (largely-used concentration). Results: The data of oocytes exposed to 1.25 M concentrated CPAs were in consistency with those exposed to 1.5 M and fresh oocytes in terms of SRs, FRs and DRs. Normal spindle and chromatin configuration is in consistence between the two experimental groups, but lower in comparison with control group. The lower the concentrations were, the less SRs, FRs, DRs were. Also, spindle organizations were more normal in comparison with the experimental groups as the concentrations decreased. The results of DRs for embryos which were exposed to 1.25 and 1.0 M concentrated CPAs were close to those vitrified with 1.5 M and fresh embryos but IHC observations in the three Exp. were significantly lower than those of fresh embryos. The results of 7.5 M concentrated CPAs solutions were significantly lower than those of the control group 1.5, 1.25 and 1.0 M treated. Conclusions: Vitrification by cryotop technology using minimal volume approach increases both cooling and warming rates, therefore, the CPAs limited reduction to 1.25 and 1.0 M instead of using 1.5 M for oocytes and embryos cryotop-vitrification procedure, may be a slight adjustment. PMID:24250933

  15. West Nile virus population genetics and evolution

    PubMed Central

    Pesko, Kendra N.; Ebel, Gregory D.

    2015-01-01

    West Nile virus (WNV) (Flaviviridae: Flavivirus) is transmitted from mosquitoes to birds, but can cause fatal encephalitis in infected humans. Since its introduction into North America in New York in 1999, it has spread throughout the western hemisphere. Multiple outbreaks have also occurred in Europe over the last 20 years. This review highlights recent efforts to understand how host pressures impact viral population genetics, genotypic and phenotypic changes which have occurred in the WNV genome as it adapts to this novel environment, and molecular epidemiology of WNV worldwide. Future research directions are also discussed. PMID:22226703

  16. Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals

    PubMed Central

    Baker, Steven F.; Nogales, Aitor; Finch, Courtney; Tuffy, Kevin M.; Domm, William; Perez, Daniel R.; Topham, David J.

    2014-01-01

    ABSTRACT Influenza A and B viruses cocirculate in humans and together cause disease and seasonal epidemics. These two types of influenza viruses are evolutionarily divergent, and exchange of genetic segments inside coinfected cells occurs frequently within types but never between influenza A and B viruses. Possible mechanisms inhibiting the intertypic reassortment of genetic segments could be due to incompatible protein functions of segment homologs, a lack of processing of heterotypic segments by influenza virus RNA-dependent RNA polymerase, an inhibitory effect of viral proteins on heterotypic virus function, or an inability to specifically incorporate heterotypic segments into budding virions. Here, we demonstrate that the full-length hemagglutinin (HA) of prototype influenza B viruses can complement the function of multiple influenza A viruses. We show that viral noncoding regions were sufficient to drive gene expression for either type A or B influenza virus with its cognate or heterotypic polymerase. The native influenza B virus HA segment could not be incorporated into influenza A virus virions. However, by adding the influenza A virus packaging signals to full-length influenza B virus glycoproteins, we rescued influenza A viruses that possessed HA, NA, or both HA and NA of influenza B virus. Furthermore, we show that, similar to single-cycle infectious influenza A virus, influenza B virus cannot incorporate heterotypic transgenes due to packaging signal incompatibilities. Altogether, these results demonstrate that the lack of influenza A and B virus reassortants can be attributed at least in part to incompatibilities in the virus-specific packaging signals required for effective segment incorporation into nascent virions. IMPORTANCE Reassortment of influenza A or B viruses provides an evolutionary strategy leading to unique genotypes, which can spawn influenza A viruses with pandemic potential. However, the mechanism preventing intertypic reassortment or gene exchange between influenza A and B viruses is not well understood. Nucleotides comprising the coding termini of each influenza A virus gene segment are required for specific segment incorporation during budding. Whether influenza B virus shares a similar selective packaging strategy or if packaging signals prevent intertypic reassortment remains unknown. Here, we provide evidence suggesting a similar mechanism of influenza B virus genome packaging. Furthermore, by appending influenza A virus packaging signals onto influenza B virus segments, we rescued recombinant influenza A/B viruses that could reassort in vitro with another influenza A virus. These findings suggest that the divergent evolution of packaging signals aids with the speciation of influenza A and B viruses and is in part responsible for the lack of intertypic viral reassortment. PMID:25008914

  17. Cancer Genetics Professionals

    Cancer.gov

    The information below is from the NCI Cancer Genetics Services Directory.  This directory lists professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, and others). Professionals

  18. Non-viral gene delivery strategies for cancer therapy, tissue engineering and regenerative medicine

    NASA Astrophysics Data System (ADS)

    Bhise, Nupura S.

    Gene therapy involves the delivery of deoxyribonucleic acid (DNA) into cells to override or replace a malfunctioning gene for treating debilitating genetic diseases, including cancer and neurodegenerative diseases. In addition to its use as a therapeutic, it can also serve as a technology to enable regenerative medicine strategies. The central challenge of the gene therapy research arena is developing a safe and effective delivery agent. Since viral vectors have critical immunogenic and tumorogenic safety issues that limit their clinical use, recent efforts have focused on developing non-viral biomaterial based delivery vectors. Cationic polymers are an attractive class of gene delivery vectors due to their structural versatility, ease of synthesis, biodegradability, ability to self-complex into nanoparticles with negatively charged DNA, capacity to carry large cargo, cellular uptake and endosomal escape capacity. In this thesis, we hypothesized that developing a biomaterial library of poly(betaamino esters) (PBAE), a newer class of cationic polymers consisting of biodegradable ester groups, would allow investigating vector design parameters and formulating effective non-viral gene delivery strategies for cancer drug delivery, tissue engineering and stem cell engineering. Consequently, a high-throughput transfection assay was developed to screen the PBAE-based nanoparticles in hard to transfect fibroblast cell lines. To gain mechanistic insights into the nanoparticle formulation process, biophysical properties of the vectors were characterized in terms of molecular weight (MW), nanoparticle size, zeta potential and plasmid per particle count. We report a novel assay developed for quantifying the plasmid per nanoparticle count and studying its implications for co-delivery of multiple genes. The MW of the polymers ranged from 10 kDa to 100 kDa, nanoparticle size was about 150 run, zeta potential was about 30 mV in sodium acetate buffer (25 mM, pH 5) and 30 to 100 plasmids were associated with a single polymeric nanoparticle. To develop PBAE vectors for application in cancer drug delivery and 3-D tissue engineered cultures, the gene delivery efficacy of PBAE nanoparticles was evaluated in mammary epithelial cells used as a model for studying normal development of mammary gland as well as the events that lead to development of breast cancer. We investigated how small molecular changes to the end-capping terminal group of the polymer and changes to the polymer MW affect gene delivery in 2-D mammary cell culture compared to 3-D primary organotypic cultured mouse mammary tissue. We reported that the polymers synthesized here are more effective for gene delivery than FuGENERTM HD, one of the leading commercially available reagents for non-viral gene delivery. We also highlighted that transfection of the 3-D organotypic cultures is more difficult than transfection of 2-D cultures, but likely models some of the key challenges for in vivo gene therapy more closely than 2-D cultures. Finally, we evaluated the use of PBAE nanotechnology for genetic manipulation of stem cell fate for regenerative medicine applications. We developed a PBAE nanoparticle based non-viral protocol and compared it with an electroporation based approach to deliver episomal plasmids encoding reprogramming factors for derivation of human induced pluripotent stem cells (hiPSC). The hiPSCs generated using these approaches can be differentiated into specific cell types for in vitro disease modeling and drug screening, specifically to study retinal degeneration.

  19. AN UPDATE: GENETIC STOCKS - ORYZA COLLECTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic stocks help preserve materials that otherwise might be lost as researchers retire and/or grants terminate. The GSOR was established at the DB NRRC in 2003 to fulfil this function for the US. To date the GSOR is small with 20 genetic stocks and a 353-line mapping population of a japonica/in...

  20. Genetic Recombination

    ERIC Educational Resources Information Center

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)