Letteratura scientifica selezionata sul tema "Virus de poisson"

The Weibull-Poisson distribution represents a continuous distribution type applicable to various forms of hazard, including monotone up, monotone down, and upside-down bathtub shapes that ascend. The distribution characterizes lifetimes and can effectively model failures within a series of systems, which evolves from the Exponential-Poisson distribution. This distribution emerges through the compounding of the Weibull Distribution and Zero Truncated Poisson Distribution. The compounding itself integrates several mathematical properties, such as statistical order and Taylor’s number expansion, to reach its final form. Alongside the formulation of the Weibull-Poisson distribution, this paper includes the probability density function, distribution function, rth moment, rth central moment, mean, and variance. For illustration, the Weibull-Poisson distribution is applied to guinea pig survival data after being infected with Turblece virus Bacilli.

This review describes the development of the bioassay as a means of quantifying plant viruses, with particular attention to tobamovirus. It delves into various models used to establish a correlation between virus particle concentration and the number of induced local lesions (the infectivity dilution curve), including the Poisson, Furumoto and Mickey, Kleczkowski, Growth curve, and modified Poisson models. The parameters of each model are described, and their application or performance in the context of the tobacco mosaic virus is explored. This overview highlights the enduring value of the infectivity dilution curve in tobamovirus quantification, providing valuable insights for researchers or practitioners of bioassays and theoreticians of modeling.

It is known that Bartoszyński’s model for the growth of rabies virus in an infected host is a continuous branching process. We show by explicit construction that any such process is a randomly time-transformed compound Poisson process having a negative linear drift.This connection is exploited to obtain limit theorems for the population size and for the jump times in the rabies model. Some of these results are obtained in a more general context wherein the compound Poisson process is replaced by a subordinator.

It is known that Bartoszyński’s model for the growth of rabies virus in an infected host is a continuous branching process. We show by explicit construction that any such process is a randomly time-transformed compound Poisson process having a negative linear drift. This connection is exploited to obtain limit theorems for the population size and for the jump times in the rabies model. Some of these results are obtained in a more general context wherein the compound Poisson process is replaced by a subordinator.

Salah satu masalah kesehatan yang sering terjadi di Indonesia adalah gizi buruk. Seorang anak yang mengalami gizi buruk akan rentan terhadap berbagai penyakit karena sistem kekebalan tubuhnya mudah terinfeksi virus. Jumlah kasus anak gizi buruk merupakan data diskrit y­­ang dapat dimodelkan dengan regresi poisson. Penelitian ini bertujuan untuk menentukan model regresi poisson tergeneralisasi dalam mengatasi overdispersi pada model regresi poisson dari jumlah kasus gizi buruk dan menentukan faktor-faktor yang mempengaruhi jumlah kasus gizi buruk di Sulawesi Utara tahun 2018. Data yang digunakan berupa jumlah kasus gizi buruk sebagai variabel respon dan sejumlah variabel prediktor dengan unit pengamatannya adalah kota dan kabupaten di Sulawesi Utara. Hasil penelitian menunjukkan bahwa variabel yang mempengaruhi jumlah anak gizi buruk di Sulawesi Utara adalah persentase bayi dengan berat badan lahir rendah (BBLR) dan variabel yang tidak berpengaruh signifikan adalah jumlah posyandu, persentase keluarga yang memiliki sanitasi layak pakai, jumlah penduduk miskin, persentase bayi yang menggunakan ASI ekslusif dengan model regresi poisson tergeneralisasi.Kata kunci: Keluarga eksponensial; multikolinearitas; overdispersi; Sulawesi UtaraGeneralized Poisson Regression Model For Malnourished Children in North SulawesiABSTRACTOne of the health problems that often occurs in Indonesia is malnutrition. A child who is suffering from malnutrition will be vulnerable to various diseases because his immune system is easily infected by a virus. The number of cases of malnutrition children is discrete data that can be modeled by Poisson regression. This study aimed to determine the Generalized Poisson Regression (GPR) model for handling the overdispersion occurred in the Poisson regression model of the number of malnutrished children case and also to determine the factors that influence the number of malnutrished children case in North Sulawesi in 2018. This study utilizes the number of cases of malnutrition as a response variable and a number of predictor variables with the observation unit was cities and districts in North Sulawesi. The results of this study indicate that the variables that significantly affect the number of malnourished children in North Sulawesi include the percentage of child with low weight birth (LWB) and variables that have no significant effect are the number of posyandu, the percentage of families who have decent sanitation, the number of poor people, the percentage of babies who use exclusive breast milk with the generalized poisson regression model Keywords: Exponential family; multicolinearity; overdispersion; North SulawesiSalah satu masalah kesehatan yang sering terjadi di Indonesia adalah gizi buruk. Seorang anak yang mengalami gizi buruk akan rentan terhadap berbagai penyakit karena sistem kekebalan tubuhnya mudah terinfeksi virus. Jumlah kasus anak gizi buruk merupakan data diskrit y­­ang dapat dimodelkan dengan regresi poisson. Penelitian ini bertujuan untuk menentukan model regresi poisson tergeneralisasi dalam mengatasi overdispersi pada model regresi poisson dari jumlah kasus gizi buruk dan menentukan faktor-faktor yang mempengaruhi jumlah kasus gizi buruk di Sulawesi Utara tahun 2018. Data yang digunakan berupa jumlah kasus gizi buruk sebagai variabel respon dan sejumlah variabel prediktor dengan unit pengamatannya adalah kota dan kabupaten di Sulawesi Utara. Hasil penelitian menunjukkan bahwa variabel yang mempengaruhi jumlah anak gizi buruk di Sulawesi Utara adalah persentase bayi dengan berat badan lahir rendah (BBLR) dan variabel yang tidak berpengaruh signifikan adalah jumlah posyandu, persentase keluarga yang memiliki sanitasi layak pakai, jumlah penduduk miskin, persentase bayi yang menggunakan ASI ekslusif dengan model regresi poisson tergeneralisasi .Kata kunci: Keluarga eksponensial; multikolinearitas; overdispersi; Sulawesi UtaraGeneralized Poisson Regression Model For Malnourished Children in North Sulawesi ABSTRACTOne of the health problems that often occurs in Indonesia is malnutrition. A child who is suffering from malnutrition will be vulnerable to various diseases because his immune system is easily infected by a virus. The number of cases of malnutrition children is discrete data that can be modeled by Poisson regression. This study aimed to determine the Generalized Poisson Regression (GPR) model for handling the overdispersion occurred in the Poisson regression model of the number of malnutrished children case and also to determine the factors that influence the number of malnutrished children case in North Sulawesi in 2018. This study utilizes the number of cases of malnutrition as a response variable and a number of predictor variables with the observation unit was cities and districts in North Sulawesi. The results of this study indicate that the variables that significantly affect the number of malnourished children in North Sulawesi include the percentage of child with low weight birth (LWB) and variables that have no significant effect are the number of posyandu, the percentage of families who have decent sanitation, the number of poor people, the percentage of babies who use exclusive breast milk with the generalized poisson regression model Keywords: Exponential family; multicolinearity; overdispersion; North Sulawesi

Background and Objectives. In recent years, hepatitis C virus (HCV) infection represents a major public health problem. Evaluation of risk factors is one of the solutions which help protect people from the infection. This study aims to employ zero-inflated Poisson mixed models to evaluate prognostic factors of hepatitis C.Methods. The data was collected from a longitudinal study during 2005–2010. First, mixed Poisson regression (PR) model was fitted to the data. Then, a mixed zero-inflated Poisson model was fitted with compound Poisson random effects. For evaluating the performance of the proposed mixed model, standard errors of estimators were compared.Results. The results obtained from mixed PR showed that genotype 3 and treatment protocol were statistically significant. Results of zero-inflated Poisson mixed model showed that age, sex, genotypes 2 and 3, the treatment protocol, and having risk factors had significant effects on viral load of HCV patients. Of these two models, the estimators of zero-inflated Poisson mixed model had the minimum standard errors.Conclusions. The results showed that a mixed zero-inflated Poisson model was the almost best fit. The proposed model can capture serial dependence, additional overdispersion, and excess zeros in the longitudinal count data.

In this study, the Poisson (PD) distribution was compounded with a continuous distribution to produce the Poisson XLindley distribution (PXLD). Its raw moments and central moments are acquired as a result of a general expression for its rth factorial moment concerning origin being derived. Additionally, the expressions for its coefficient of variation, skewness, kurtosis and index of dispersion have been provided. For the estimate of its parameters, in particular, the methods of maximum likelihood and moments have been addressed. The applicability of the proposed distribution in modeling real data sets on Nipah virus infection, number of Hemocytometer yeast cell count data, and epileptic seizure counts data is examined by analyzing two real-world data sets.

In this paper, a size-biased Poisson-Gamma Lindley distribution (SBPGLD) has been obtained by size-biasing the Poisson-Gamma Lindley distribution (PGLD) introduced recently by Nedjar and Zeghdoudi (2020). Some of its statistical properties have been discussed. The method of maximum likelihood and the method of moments for the estimation of its parameters have been discussed. Also, an application on the real data of survival times of (56) Indian state of Kerala individus infected with Nipah virus is given.

Considering the availability of serological and molecular biological methods, the bioassay has been paled into insignificance, although it is the only experimental method that can be used to demonstrate the infectivity of a virus. We compared goodness-of-fit and predictability power of five models for the quantification of tomato brown rugose fruit virus (ToBRFV) based on local lesion assays: the Kleczkowski model, Furumoto and Mickey models I and II, the Gokhale and Bald model (growth curve model), and the modified Poisson model. For this purpose, mechanical inoculations onto Nicotiana tabacum L. cv. Xanthi nc and N. glutionosa L. with defined virus concentrations were first performed with half-leaf randomization in a Latin square design. Subsequently, models were implemented using Python software and fitted to the number of local lesions. All models could fit to the data for quantifying ToBRFV based on local lesions, among which the modified Poisson model had the best prediction of virus concentration in spike samples based on local lesions, although data of individual indicator plants showed variations. More accurate modeling was obtained from the test plant N. glutinosa than from N. tabacum cv. Xanthi nc. The position of the half-leaves on the test plants had no significant effect on the number of local lesions.

Demam Berdarah Dengue (DBD) adalah penyakit infeksi yang disebabkan oleh virus Dengue melalui gigitan nyamuk Aedes. Penelitian ini bertujuan untuk memperoleh model dengan metode regresi Poisson untuk jumlah kasus DBD yang meninggal di Kota Padang dan mengetahui faktor apa saja yang mempengaruhinya. Regresi Poisson ini digunakan untuk kejadian yang relatif jarang terjadi. Faktor yang diduga mempengaruhi DBD tersebut adalah faktor lingkungan, diantaranya persentase rumah sehat, persentase sarana air bersih yang memenuhi syarat, persentase rumah ber-Prilaku Hidup Bersih Sehat (ber-PHBS), persentase pengelolaan sampah yang memenuhi syarat dan persentase jamban yang memenuhi syarat. Kriteria pemilihan model terbaik yang digunakan adalah AIC dan BIC. Faktor yang berpengaruh terhadap jumlah kasus DBD yang meninggal adalah Persentase rumah sehat dan persentase rumah ber-Prilaku Hidup Bersih Sehat (ber-PHBS).Kata Kunci: Regresi Poisson, Demam Berdarah Dengue (DBD), Maximum Likelihood Estimator(MLE)

The electrostatic properties of a molecule are often essential in determining its behavior; as such, the ability to approximate these electrostatic potentials computationally is often essential to obtaining a full understanding of how these molecules function. An approximate, analytical solution to the (linearized) Poisson-Boltzmann equation is proposed that is suitable for realistic biomolecules of virtually any size. A comparison with accepted numerical approaches on a large test set of biomolecular structures shows that the proposed method is considerably less expensive computationally, yet accurate enough to be considered as a possible alternative. The utility of the approach is demonstrated by computing and analyzing the electrostatic potential generated by full capsid of the tobacco ringspot virus (half a million atoms) at atomic resolution. The details of the potential distribution on the molecular surface sheds light on the mechanism behind the high selectivity of the capsid to the viral RNA. These results are generated with the modest computational power of a desktop PC. The applicability of the analytical approximation as an initial guess for traditional numerical methods as a means of improving the convergence of iterative solutions is investigated and found to be quite promising.
Master of Science

Le VWN est un arbovirus pouvant causer la maladie chez les mammiferes dont l'homme et le cheval. Notre projet a pour but de développer un vaccin vectorisé contre le VWN qui consiste à utiliser mi novirhabdovirus: le virus de la Septicémie Hémorragique Virale (VSHV). Il se réplique à des températures inférieures à 20°C et est naturellement inactivé à des températures au-delà. Un système de génétique inverse développé pour le VSHV, offre la possibilité d'ajouter des gènes dans le génome viral et de générer des virus recombinants rVSHV. Des virus recombinants exprimant d'une part le gène complet de la glycoprotéine d'enveloppe du VWN (Evwn) ou délété de sa région transmembranaire (rVSHV-EvwN et rVSHV-EvwnΔtm) et d'autre part des fragments codant certains domaines de la EvwN (soit le domaine III seul ou fusionné au domaine II) (rVSHV-DIIIvwN et rVSHV-DIIDIIIvwN, respectivement), insérés dans le génome du VSHV ont été générés. Le peptide signal ainsi que la région transmembranaire dérivés de la glycoprotéine G des Novirhabdovirus (PSG and TMG) ont été fusionnés aux antigènes du VWN aux extrémités amino et carboxy terminales respectivement pour optimiser leur adressage à la surface des virions. Nous avons démontré que la EvwN et le DIIIvwN pouvaient être exprimés à la surface du rVSHV lors de l'addition du PSG. Les constructions exprimant la EvwN fusionnée au PSG protégeaient la souris contre l'épreuve avec le VWN et spécifiquement rVHSV-PSgEvwn, qui induisait une réponse d'anticorps neutralisants corrélée avec la protection. Étonnamment, rVSHV exprimant le DIIIvwN ou le DIIDIIIvwN ne protégeaient pas de l'infection, bien qu'ils étaient fortement exprimés à la surface du virus
West Nile Virus (WNV) is an arbovirus that can cause disease in mammals including humans and horses. There is no specific treatment or vaccines for WNV in humans. Our study aims at developing a WNV vectored vaccine which consists in using a fish Novirhabdovirus vector: the Viral Hemorrhagic Septicemia virus (VHSV). VHSV replicates at temperatures lower than 20°C and is naturally inactivated at higher temperatures. A reverse genetics system has recently been developed for VHSV allowing the addition of genes in the viral genome and the generation of the respective recombinant viruses rVHSVs. We have generated rVHSV vectors bearing on the one hand the complete WNV envelope gene (EwNv) (rVHSV-EwNv and rVHSV-EwNΔtm) or deleted of his transmembrane domain and on the other hand, fragments encoding E subdomains (either domain III alone or fused to domain II) (rVHSV-DJIIwNv and rVHSV-DIIDIIIwNv, respectively) in the VHSV genome. With the objective to enhance the targeting of the EwNv protein or EwNv-derived domains to the surface of VHSV virions, Novirhabdovirus G-derived signal peptide and transmembrane domain (SPG and TMG) were fused to EwNv at its amino and carboxy termini, respectively. We demonstrated that both the EWNV and the DIIIwnv could be expressed at the viral surface of rVHSV upon addition of SPG. Constructs expressing EwNv fused to SPG protected mice against WNV lethal challenge and specifically rVHSV-SPGEwNv induced a neutralizing antibody response that correlated with protection. Surprisingly, rVHSV expressing EwNv-derived domain III or II and III were unable to protect mice against WNV challenge, although these domains were highly expressed at the viral surface

Le danio zébré est un modèle bien établi pour étudier la biologie du développement des vertébrés. Ses larves transparentes sont favorables à des approches de microscopie non invasive, qui permettent de réaliser des observations à l’échelle d’un individu entier à des niveaux de résolution cellulaire et subcellulaire. Ces atouts font du danio zébré un excellent modèle pour étudier les infections virales in vivo. Au cours de mon projet, j’ai etudié l’entrée et la colonisation du système nerveux central (SNC) par le virus Sindbis (SINV) dans le modèle danio zébré. Mon projet présentait plusieurs axes: 1) développer un modèle d’infection du virus Sindbis chez le danio zébré, 2) caractériser l’invasion du SNC par le virus par des techniques d’imagerie à haute résolution, 3) définir la voie d’entrée du virus dans le SNC, 4) évaluer la dynamique de la réponse immunitaire innée par l’étude de la réponse interféron. Le suivi de la propagation du virus a été rendu possible par l’utilisation d’un ARN viral recombinant exprimant la protéine fluorescente verte ‘GFP’. L’utilisation de cette construction m’a permis de caractériser la progression de SINV chez le danio zébré et d’identifier les organes/tissus cibles que sont le vitellus, le foie, le cœur et enfin, le cerveau. Les données rassemblées jusqu'à présent m’ont aussi permis d’identifier le mécanisme par lequel SINV se propage vers le cerveau: le virus se propage par un transport axonal du system nerveux périphérique vers le SNC. Dans le cadre de la réponse immunitaire au niveau cellulaire, j’ai pu observer le rôle joué par les leucocytes, en particulier les neutrophiles, comme cellules productrices d'interféron
The zebrafish (Danio rerio) is an important model organism, particularly for studies of development and more recently host pathogen interactions. As opposed to other vertebrate model organisms, its optical clarity and ease of genetic manipulations allow to visualize highly dynamic cellular processes in vivo at the whole organism scale. These assets make the zebrafish a perfect model for the study of viral infections in vivo, such as those caused by neurotropic viruses. The aim of this project has been to gain insights in some of the interactions that determine encephalitis, by characterizing the neurotropic Sindbis virus (SINV). This Thesis project has consisted therefore in: 1) the development of a SINV infection model in zebrafish larvae, 2) the characterization of SINV neuroinvasion upon its inoculation in the bloodstream, thanks to the use of high resolution microscopy, 3) the study of SINV mechanism of entry in the CNS, 4) the characterization of the innate immune response, both at the whole organism and organ specific level. Thanks to the use of a SINV recombinant strain, engineered to express the green fluorescent protein “GFP” in infected cells upon viral replication, we have been able to follow the onset and the progression of the infection. We have suggested infection of peripheral neurons and subsequent axonal transport to the CNS as SINV entry mechanism. At the cellular level, we have identified neutrophils as the main IFN producing cells

Chez les vertébrés à mâchoires, les défenses antivirales innées sont principalement basées sur les interférons (IFN) de type I. Ces cytokines sont sécrétées en cas d'infection virale et induisent l'expression de gènes stimulés par l'IFN (ISGs). Les ISGs codent des protéines aux fonctions diverses dont l'expression conduit à l'établissement d'un état réfractaire à l'infection. Le système IFN de type I est globalement bien conservé entre les mammifères et les poissons, mais le répertoire des ISGs est plus diversifié chez ces derniers, en raison de leur histoire évolutive complexe et de leurs spécificités physiologiques. Par conséquent, la plupart des ISGs de mammifères ont un ou plusieurs orthologues chez les poissons. Il reste, cependant, à déterminer si les ISGs de poisson ont les mêmes fonctions et mécanismes d'action que leurs homologues mammaliens.Dans ce contexte, ma thèse avait pour but de caractériser fonctionnellement deux ISGs de poisson, pkr et viperin, en utilisant une approche in vitro d'invalidation génique. Chez les mammifères, la PKR est principalement impliquée dans l'inhibition de la traduction et l'apoptose, tandis que la Viperin agit en générant des ribonucléotides antiviraux et en modulant certaines voies métaboliques exploitées par les virus. Chez les poissons, ces fonctions restent à explorer en détail. Les objectifs de ma thèse s'articulaient autour de trois axes : (1) développer des lignées cellulaires de poisson pkr-/- et viperin-/- en utilisant la technologie CRISPR/Cas9 ; (2) caractériser fonctionnellement ces lignées, afin d'identifier les mécanismes d'action de la PKR et de la Viperin de poisson et leur rôle dans la régulation de la réponse IFN; (3) évaluer leur permissivité aux infections virales et leur capacité à produire des virus à plus hauts rendements que ceux obtenus en cellules sauvages.En utilisant des approches complémentaires de surexpression et d'invalidation génique, j'ai tout d'abord étudié les mécanismes d'action de la PKR en cellules de saumon Chinook (Oncorhynchus tshawytscha). Nos résultats montrent que la PKR de salmonidés a des fonctions moléculaires conservées : elle est impliquée dans l'activation de l'apoptose et l'inhibition de la synthèse des protéines de l'hôte. Cependant, la PKR n'a pas de rôle majeur lors de l'infection par le virus de la septicémie hémorragique virale (VSHV) : nos résultats suggèrent que le VSHV a développé des stratégies pour échapper aux effets antiviraux de la PKR, en limitant l'expression précoce de pkr, en évitant l'inhibition de la traduction et en tirant partie de l'apoptose médiée par la PKR à un stade d'infection tardif pour favoriser la propagation du virus.En parallèle, nous avons mené une analyse transcriptomique comparative des lignées cellulaires du poisson tête-de-boule (Pimephales promelas), sauvages ou viperin-/-, stimulées ou non par l'IFN de type I, dans le but d'avoir une vue d'ensemble du rôle régulateur de la Viperin chez les cyprinidés. Nos données montrent que la Viperin n'est pas impliquée dans la régulation de la réponse IFN de type I mais qu'elle régule négativement certaines voies inflammatoires. Notre analyse indique aussi que la Viperin a une fonction régulatrice dans d'autres processus métaboliques tels que l'organisation de la matrice extracellulaire, l'adhésion cellulaire et le métabolisme un-carbone.Au cours du processus de développement de lignées cellulaires pkr-/- initiales, deux lignées se sont révélées être infectées de façon persistante par le virus de la nécrose pancréatique infectieuse (IPNV). J'ai entrepris de caractériser ces lignées cellulaires infectées au cours de 40 passages. Nous avons ainsi observé la présence d'oscillations périodiques des titres viraux extracellulaires et des niveaux intracellulaires d'ARN viral au cours des passages. De plus, la réponse IFN de type I n'était pas déclenchée par l'infection, ce qui suggère que l'IPNV persistant est capable d'échapper à la réponse innée de l'hôte
In jawed vertebrates, innate antiviral defenses are primarily based on type I interferons (IFNs). These master cytokines are secreted following virus recognition and induce the expression of hundreds of IFN-stimulated genes (ISGs). ISGs encode proteins with diverse functions, including enhancers of the type I IFN pathway and antiviral effectors, which all work towards establishing an antiviral state refractory to viral infection. Overall, the type I IFN system is well-conserved between mammals and fish but the ISGs repertoire is more diverse in fish, largely due to their complex evolutionary history and physiological specificities. Consequently, most mammalian ISGs have one or more orthologs in fish. However, it is still unclear whether fish ISGs are true functional homologs and their mechanisms of action remain to be explored in detail.In this context, my thesis aimed to functionally characterize two key fish ISGs, namely dsRNA-dependent protein kinase (pkr) and virus inhibitory protein endoplasmic reticulum-associated, interferon-inducible (viperin), by using an in vitro knock-out approach. In mammals, both proteins are primarily regarded as antiviral effectors: PKR is involved in host translation inhibition and apoptosis, while Viperin operates by generating antiviral ribonucleotides and modulating metabolic pathways exploited during viral life cycles. However, the extent to which these functions are conserved in fish remains largely unknown. The objectives of my thesis were articulated along three axes: (1) to develop and validate pkr-/- and viperin-/- fish cell lines using the CRISPR/Cas9 technology; (2) to functionally characterize these cell lines, in order to identify the mechanisms of action of fish PKR and Viperin and their role in regulating the type I IFN response through feedback loops; (3) to assess their permissivity to viral infections and their ability to produce viral particles at higher yields than their wild-type counterparts.Using complementary overexpression and knockout approaches, I first studied the molecular mechanisms of action of PKR in Chinook salmon (Oncorhynchus tshawytscha) CHSE-EC cells. Our findings show that salmonid PKR has conserved molecular functions, including apoptosis activation and inhibition of host protein synthesis. However, endogenous PKR did not play a major antiviral role during viral hemorrhagic septicemia virus (VHSV) infection. In fact, our results suggest that VHSV has evolved strategies to subvert PKR antiviral action, by limiting early induction of pkr expression, evading PKR-mediated translational arrest and taking advantage of PKR-mediated apoptosis at a late infection stage to favor viral spread.In parallel, we conducted a comparative RNA-seq analysis of the viperin-/- and wild-type fathead minnow (Pimephales promelas) EPC-EC cell lines with or without stimulation with recombinant type I IFN to have a global overview of the regulatory role of fish Viperin. Our data show that cyprinid Viperin is not involved in the regulation of the canonical type I IFN but negatively regulates specific inflammatory pathways. Our analysis further indicates that it plays a regulatory role in other metabolic processes, even in non-induced conditions, including extracellular matrix organization, cell adhesion and one carbon metabolism.During the development process of initial pkr-/- cell lines, two CHSE-EC cell lines were found to be persistently infected with infectious pancreatic necrosis virus (IPNV), presumably due to inadvertent contamination. I set out to characterize these persistently IPNV-infected cell lines over the course of 40 passages. A striking feature in both cell lines was the periodic oscillatory pattern of extracellular titers and intracellular viral RNA levels over passages. We further showed that the type I IFN response was not triggered during persistent infection, suggesting that persistent IPNV is able to evade the host innate immune response

Le danio zébré est un modèle bien établi pour étudier la biologie du développement des vertébrés. Ses larves transparentes sont favorables à des approches de microscopie non invasive, qui permettent de réaliser des observations à l’échelle d’un individu entier à des niveaux de résolution cellulaire et subcellulaire. Ces atouts font du danio zébré un excellent modèle pour étudier les infections virales in vivo. Au cours de mon projet, j’ai etudié l’entrée et la colonisation du système nerveux central (SNC) par le virus Sindbis (SINV) dans le modèle danio zébré. Mon projet présentait plusieurs axes: 1) développer un modèle d’infection du virus Sindbis chez le danio zébré, 2) caractériser l’invasion du SNC par le virus par des techniques d’imagerie à haute résolution, 3) définir la voie d’entrée du virus dans le SNC, 4) évaluer la dynamique de la réponse immunitaire innée par l’étude de la réponse interféron. Le suivi de la propagation du virus a été rendu possible par l’utilisation d’un ARN viral recombinant exprimant la protéine fluorescente verte ‘GFP’. L’utilisation de cette construction m’a permis de caractériser la progression de SINV chez le danio zébré et d’identifier les organes/tissus cibles que sont le vitellus, le foie, le cœur et enfin, le cerveau. Les données rassemblées jusqu'à présent m’ont aussi permis d’identifier le mécanisme par lequel SINV se propage vers le cerveau: le virus se propage par un transport axonal du system nerveux périphérique vers le SNC. Dans le cadre de la réponse immunitaire au niveau cellulaire, j’ai pu observer le rôle joué par les leucocytes, en particulier les neutrophiles, comme cellules productrices d'interféron
The zebrafish (Danio rerio) is an important model organism, particularly for studies of development and more recently host pathogen interactions. As opposed to other vertebrate model organisms, its optical clarity and ease of genetic manipulations allow to visualize highly dynamic cellular processes in vivo at the whole organism scale. These assets make the zebrafish a perfect model for the study of viral infections in vivo, such as those caused by neurotropic viruses. The aim of this project has been to gain insights in some of the interactions that determine encephalitis, by characterizing the neurotropic Sindbis virus (SINV). This Thesis project has consisted therefore in: 1) the development of a SINV infection model in zebrafish larvae, 2) the characterization of SINV neuroinvasion upon its inoculation in the bloodstream, thanks to the use of high resolution microscopy, 3) the study of SINV mechanism of entry in the CNS, 4) the characterization of the innate immune response, both at the whole organism and organ specific level. Thanks to the use of a SINV recombinant strain, engineered to express the green fluorescent protein “GFP” in infected cells upon viral replication, we have been able to follow the onset and the progression of the infection. We have suggested infection of peripheral neurons and subsequent axonal transport to the CNS as SINV entry mechanism. At the cellular level, we have identified neutrophils as the main IFN producing cells

Le virus de l’hépatite C (VHC) est une des principales causes d’hépatite chronique. La protéine F du VHC est codée par un cadre de lecture alternatif du gène de la capside, Core. La protéine F a été découverte après que l’on ait associé Core à plusieurs des fonctions pathogènes du VHC. Nous proposons donc que certaines fonctions biologiques et pathogènes attribuées à la protéine Core résultent de l’activité de la protéine F. Nous avons choisi de développer trois lignées de poissons zébrés (Danio rerio) qui expriment différentes versions de la protéine F afin d’étudier les effets de la protéine F et leur incidence dans la pathogenèse du VHC. Deux versions de la séquence codant pour la protéine F (AF11 et AUG26) et une version mutante du gène core (CoremutI) ont été introduites sur les vecteurs d’un système d’expression répressible spécifique au foie. Ces vecteurs ont été co-injectés dans des embryons unicellulaires de poissons zébrés pour générer les poissons fondateurs des lignées transgéniques. 19, 21 et 36 poissons ont été choisis comme fondateurs pour les lignées AF11, AUG26 et CoremutI respectivement. De ce nombre, 9, 11 et 11 poissons ont atteint la maturité, dans l’ordre pour les mêmes lignées, et seront croisés pour donner naissance à des lignées transgéniques stables. Les résultats de ces expériences nous permettront de mieux cerner les propriétés biologiques de la protéine F et de définir son rôle dans la pathogenèse du VHC.
Hepatitis C virus (HCV) is a major cause of liver steatosis, fibrosis and hepatocellular carcinoma. HCV F protein is expressed from an alternative reading frame within the Core sequence. F protein was discovered after many of the pathogenic determinants of HCV had been associated with the effects of Core. Hence, we propose that a part of the functions attributed to Core result from the activity of the F protein. We produced and selected 19, 21 and 36 transgenic zebrafish (Danio rerio) to give rise to 3 independent lines expressing different versions of the F protein. Of these founders, 9, 11 and 11 were raised to maturity and will be bred to generate stable transgenic lines. Characterizing the phenotype of these transgenic fish will help determine the precise role of the F protein in the pathogenesis of hepatitis C.

La protéine core du virus de l’hépatite C (VHC) serait responsable des principaux effets pathogènes du VHC, dont le développement de fibrose, stéatose, cirrhose et carcinome hépatocellulaire. Un cadre de lecture alternatif existe dans le gène de core, permettant la synthèse d’une autre protéine appelée ARFP (pour alternatate reading frame protein) ou protéine F (pour frameshift), dont le rôle reste encore mal compris. La présence de la protéine F lors de l’étude des fonctions biologiques de core ne pouvant être exclue, il est possible que certains rôles attribués à core reflètent en réalité l’activité de la protéine F. Afin de déterminer les fonctions biologiques de la protéine F dans les hépatocytes et son influence dans la pathogenèse associée au VHC, nous avons généré des lignées transgéniques de poissons zébrés (Danio rerio) dans lesquelles l’expression de deux versions de la protéine F (AF11opti et AUG26opti) a été ciblée au foie par l’utilisation du promoteur de la liver fatty acid binding protein (L-FABP). Le phénotype des poissons transgéniques de génération F2 a été analysé au niveau morphologique, histologique et microscopique afin de rechercher des signes de pathologie hépatique. Nos résultats ont démontré l’implication de la protéine F dans le développement de stéatose hépatique chez les deux lignées transgéniques, mais aucun signe de fibrose ou d’oncogenèse n’a été détecté. L’identification des mécanismes cellulaires et moléculaires responsables de l’accumulation lipidique induite par la protéine F pourrait permettre de mieux comprendre son rôle dans la pathogenèse du VHC, et mener au développement de nouvelles stratégies antivirales.
Hepatitis C virus (HCV) core protein is thought to be responsible for the major pathogenic effects of HCV, including the development of fibrosis, steatosis, cirrhosis, and hepatocellular carcinoma. An alternate translational open reading frame exists in the core gene that allows the synthesis of another protein called ARFP (alternate reading frame protein) or F protein (frameshift), the role of which remains poorly understood. Since we cannot exclude the presence of F protein in most studies of core biological functions, it is possible that the roles attributed to core reflect the activity of ARFP. To determine the biological functions of F protein in hepatocytes and their influence on HCV-associated pathogenesis, we generated transgenic lines of zebrafish (Danio rerio) in which the liver fatty acid binding protein (L-FABP) promoter was used to direct liver-specific expression of two forms of ARFP (AF11opti and AUG26opti). The phenotype of F2 transgenic zebrafish was analyzed for morphological, histological and microscopic signs of liver-associated pathology. Our results demonstrated the implication of the HCV F protein in the development of hepatic steatosis in transgenic zebrafish liver but not fibrosis or oncogenesis. Identification of the cellular and molecular mechanisms underlying F protein-induced lipid accumulation will lead to a better understanding of the role of ARFP in HCV-associated pathology, which could lead to the development of novel antiviral strategies.

In light of the last chapter, this one considers the limitations of “toxic” and recommends “viral masculinity” as a metaphor suited to the challenge ahead. A poison control frame does not address the transnational movement of manly grievance because it concentrates on the substance (ideology) instead of how it gets passed around (feeling). Viral mitigation better captures a pandemic of feeling and redirects focus accordingly: from stopping individual ingestion to slowing communal transmission. Viral masculinity is more than a metaphor, in fact. Short of a biomedical virus, it is a physical transfer of social feeling through bodies, technologies, and other material means. Aggrieved masculinity is a genuine sociophysical pandemic.

Abstract The most notable member of The Primrose family was Gilbert, a Scot (b. 1573) head of The reformed church in France, and later chaplain in ordinary to James The relationship of Diana Primrose to this man (if any, but The name is uncommon) is unknown. Her long poem in praise of Elizabeth I is apparently intended as an oblique criticism of The personal rule of Charles I. The motto, Dat Rosa me/ apibus, qua sugit Aranea virus [The Rose, from which The Spider sucks poison, gives honey to The bee] seems to imply a reading strategy: The poem, or The author (Prim-rose) is The rose, from which The virtuous reader will extract nectar, and The vicious one poison, a definite suggestion that her work carries double meanings. Dat Rosa me/ apibus is a Rosicrucian slogan used by Robert Fludd: Rosicrucian texts were always intended to mean one thing to initiates and anoTher to outsiders.

Citrus are cultivated in a vast area worldwide and many countries grow it. Citrus fruits are delicious and everybody can eat it easily so many farmers like to grow them because of the good market. This plant has many diseases that induce various kinds of agents like fungi, bacteria, nematodes, and viruses. In this chapter, we discussed some citrus viral diseases that are very important and dangerous for fields. First, the Citrus Tristeza virus is explained that exists around the world. After that, you will know about other viruses like the Citrus psorosis virus. Viroids are another agent that causes diseases and reduces the amount of production. You learn some of them in this chapter like Hop stunt viroid, Citrus exocortis viroid, etc. The significant point of knowing citrus viral diseases is in the management of diseases. The control of viral diseases is difficult because there are no poisons or combinations to remove viruses from infected plants. If farmers or experts know about symptoms that cause viruses or viroids, they can report it to the related office and do some work to control it and it is important to the agriculture industry.

Traditional medicine offers a wide range of application for in silico study techniques. This drug research and development strategy is embryonic in the West African context, particularly in Burkina Faso, which is increasingly faced with emerging diseases such as dengue fever. Circulation of the 4 serotypes of this virus has been documented in the country. This study aims to evaluate the therapeutic potential of phytocompounds contained in the West African pharmacopoeia against dengue virus NS2B/NS3 protein, using computational methods integrating several software packages and databases. Based on a literature review, we identified 191 molecules from 30 plants known for their antiviral effects. Five met the inclusion criteria for molecular docking: patulin from calotropis procera, resiniferonol from Euphorbia poissonii, Securinol A from Flueggea virosa, Shikimic acid and Methyl gallate from Terminalia macroptera. The best binding scores were observed between resiniferonol and the serotypes 1, 2 and 4 NS2B/NS3 protease, with binding energies of -7.4 Kcal/mol, -6.8 Kcal/mol and -7.3 Kcal/mol respectively; while the NS2B/NS3 protease of serotype 3 had the best affinity for securinol A (-7 Kcal/mol). This study points the way to further research in computer aided drug design field and calls for multidisciplinary collaboration to promote West African medicinal plants against health challenges.

The uniform distribution of charged amino acids along the exterior surface of the tobacco mosaic virus (TMV) along with its unusual structural stability over a large pH and temperature range has made it a model organism for inorganic deposition and nanostructure fabrication studies on biomolecules. However, the potential engineering applications of the virus’s central pore, which is about 300 nm long and 4 nm in diameter, has been overlooked. We aim to expand TMV applications by understanding the surface characteristics of its central pore. We have identified the set of amino acids and atoms that create the surface of the pore, mapped the partial charge distribution of the pore using AMBER9 force fields, and determined the electrostatic potential of the pore surface through Coulomb’s law and Poisson-Boltzmann Equation (PBE). Our analysis has revealed that the pore contains a dense helical distribution of negatively charged glutamic amino acid residues, which results in a strong negative electrostatic potential across the pore. This can potentially be used for water filtration by creating overlapping electric double layer within the central pore.

Introduction. Epstein-Barr virus (EBV) causes recurrent infectious mononucleosis-like symptoms. Today poisons of insects and animals were shown to be rich sources of antimicrobial substances (peptides) and contain a wide range of active biological compounds. Antimicrobial peptides play an important role in the immune response of the host’s innate immunity to pathogenic microorganisms. Based on antimicrobial peptides in Russia, an antiviral drug Allokin-alpha has been developed. The active ingredient of the drug is cytokine-like peptide alloferon. The purpose of the study is to evaluate the effect of Allokin-alpha therapy on the amount of EBV DNA in saliva samples and clinical complaints in patients with chronic Epstein-Barr viral infection (EBI). Material and methods. 59 chronic EBI patients (45 women and 14 men; mean age 32.52 ± 1.75 years) were examined. Patients were subjected to quantitative determination of Epstein-Barr virus DNA in saliva samples by the method of polymerase chain reaction (PCR) with real-time hybridization-fluorescence detection. The analytical sensitivity of the test system is 400 copies/ ml. The patients were divided into two groups: 26 patients who received Allokin-alpha therapy (9 injections subcutaneously with 1.0 mg every other day) were included in the 1st group; the 2nd group included 33 patients who received Valtrex (500 mg 2 times/day, orally) for 2 months. Results. After treatment with allocin-alpha, negative results of PCR were obtained in 59.67% of patients. After two months of Valtrex therapy, negative PCR results were obtained in only 27.27% of patients. The correlation analysis revealed a significant effect of the initial number of copies of EBV DNA on the severity of clinical complaints in the general group of EBV patients. Discussion. Allokin-alpha improves the recognition of virus-infected cells and helps to suppress viral replication. Conclusion. Allokin-alpha therapy can be recommended for the treatment of chronic EBV infection in a dose of 1 mg subcutaneously every other day with a course dose of at least 9 injections.

In various practically relevant incompressible flow problems, such as polymer flow or biomedicalengineering applications, the dependence of fluid viscosity on the local shear rate plays an impor-tant role. Standard techniques using inf-sup stable finite elements lead to saddle-point systemsposing a challenge even for state-of-the-art solvers and preconditioners.For efficiency, projection schemes or time-splitting methods decouple the governing equations forvelocity and pressure, resulting in more, but easier to solve linear systems. Doing so, boundaryconditions and correction terms at intermediate steps have to be carefully considered in order toprohibit spoiling accuracy. In the case of Newtonian incompressible fluids, pressure and velocitycorrection schemes of high-order accuracy have been devised (see, e.g. [1, 2]). However, the exten-sion to generalised Newtonian fluids is a non-trivial task and considered an open question. Deteixet al. [3] successfully adapted the popular rotational correction scheme to consider for shear-ratedependent viscosity, but this resulted in substantial numerical overhead caused by necessarily pro-jecting viscous stress components.In this contribution we address this shortcoming and present a split-step scheme, extending pre-vious work by Liu [4]. The new method is based on an explicit-implicit treatment of pressure,convection and viscous terms combined with a Pressure-Poisson equation equipped with fully con-sistent Neumann and Dirichlet boundary conditions. Through proper reformulation, the use ofstandard continuous finite element spaces is enabled due to low regularity requirements. Addition-ally, equal-order velocity-pressure pairs are applicable as in the original scheme.The stability, accuracy and efficiency of the higher-order splitting scheme is showcased in challeng-ing numerical examples of practical interest.[1] Karniadakis, G. E., Israeli, M. and Orszag, S. A. High-order splitting methods for the incom-pressible Navier-Stokes equations. J. Comput. Phys., (1991).[2] Timmermans, L.J.P., Minev, P.D. and Van de Vosse, F. N. An approximate projection schemefor incompressible flow using spectral elements. Internat. J. Numer. Methods Fluids, Vol.22(7), pp. 673–688, (1996).[3] Deteix, J. and Yakoubi, D. Shear rate projection schemes for non-Newtonian fluids, Comput.Methods Appl. Mech. Engrg., Vol. 354, pp. 620–636, (2019).[4] Liu, J. Open and traction boundary conditions for the incompressible NavierStokesequations.J. Comput. Phys., Vol. 228(19), pp. 7250..7267, (2009).