Effect Of Virus Infection Research Articles

β-Carboline derivatives as novel antivirals for herpes simplex virus

Several commercial and novel synthetic β-carbolines (βCs) were evaluated for their antiviral activity against herpes simplex virus type 1 (HSV-1) using an adapted MTS assay. Of 21 drugs tested, although 11 exerted antiviral activity at non-cytotoxic concentrations, only 3 of them [9-methyl-norharmane (9-Me-nHo), 9-methyl-harmane (9-Me-Ho) and 6-methoxy-harmane (6-MeO-Ho)] completely avoided virus-driven cytopathic effects. Half-maximal effective concentrations (EC50 values) (4.9 ± 0.4, 5.9 ± 0.8 and 19.5 ± 0.3 µM, respectively) and selectivity indexes (88.8, 40.2 and 7.0, respectively) of the latter three βCs against HSV-1 were determined by MTS, flow cytometry and plaque reduction assays. The mode of action of these drugs was also evaluated. According to time-of-addition assays, the selected compounds were not virucidal and did not interfere with attachment or penetration of HSV-1, but interfered with later events of virus infection. Western blot studies showed that early and late protein expression was significantly delayed or even suppressed. Herpes simplex virus type 2 (HSV-2) was also inhibited by the selected substances in a similar manner. Interestingly, 6-MeO-Ho, 9-Me-Ho and 9-Me-nHo restricted HSV-1 ICP0 localisation to the nucleus during later stages of infection, possibly affecting its functionality in the cytoplasm where ICP0 normally inhibits antiviral signalling and promotes viral replication. In silico prediction of ADME (Absorption, Distribution, Metabolism and Excretion) properties showed that all compounds fulfilled Lipinski's rule and their calculated absorptions were >95%.

Enhanced nanoparticle uptake into virus infected cells: Could nanoparticles be useful in antiviral therapy?

Virus infections cause diseases of different severity ranged from mild infection e.g. common cold into life threatening diseases e.g. Human Immunodeficiency virus (HIV), Hepatitis B. Virus infections represent 44% of newly emerging infections. Although there are many efficient antiviral agents, they still have drawbacks due to accumulation at off target organs and developing of virus resistance due to virus mutation. Therefore, developing a delivery system that can selectively target drug into affected organs and avoid off target accumulation would be a highly advantageous strategy to improve antiviral therapy. Nanoparticles (NP) can be effectively targeted to the liver, and therefore it could be used for improving therapy of hepatic virus infections including hepatitis B virus and hepatitis C virus (HCV). Many studies were performed to encapsulate antiviral agents into nano-delivery system to improve their pharmacokinetics parameters to have a better therapeutic efficacy with lower side effects. However, the effect of virus infection on the uptake of NP has not yet been studied in detail. The latter is a crucial area as modulation of endocytic uptake of nanoparticles could impact on reduce potential therapeutic usefulness of antiviral agents loaded into nano-delivery system. In this study, a fluorescently-labelled polymeric nanoparticle was prepared and used to track NP uptake into Huh7.5, human hepatoma cells transfected with replicating HCV genomes, compared with non-transfected cells as a model representing hepatocyte uptake. Confocal microscopy and flow cytometry of virus transfected Huh7.5 cells unexpectedly demonstrated two-fold increase in uptake of NP compared to non-transfected cells. Therefore, virus transfection enhanced NP uptake into Huh7.5 cells and NP could be considered as a promising delivery system for targeted treatment of hepatitis viruses.

Preclinical Testing of an Oncolytic Parvovirus in Ewing Sarcoma: Protoparvovirus H-1 Induces Apoptosis and Lytic Infection In Vitro but Fails to Improve Survival In Vivo

About 70% of all Ewing sarcoma (EWS) patients are diagnosed under the age of 20 years. Over the last decades little progress has been made towards finding effective treatment approaches for primarily metastasized or refractory Ewing sarcoma in young patients. Here, in the context of the search for novel therapeutic options, the potential of oncolytic protoparvovirus H-1 (H-1PV) to treat Ewing sarcoma was evaluated, its safety having been proven previously tested in adult cancer patients and its oncolytic efficacy demonstrated on osteosarcoma cell cultures. The effects of viral infection were tested in vitro on four human Ewing sarcoma cell lines. Notably evaluated were effects of the virus on the cell cycle and its replication efficiency. Within 24 h after infection, the synthesis of viral proteins was induced. Efficient H-1PV replication was confirmed in all four Ewing sarcoma cell lines. The cytotoxicity of the virus was determined on the basis of cytopathic effects, cell viability, and cell lysis. These in vitro experiments revealed efficient killing of Ewing sarcoma cells by H-1PV at a multiplicity of infection between 0.1 and 5 plaque forming units (PFU)/cell. In two of the four tested cell lines, significant induction of apoptosis by H-1PV was observed. H-1PV thus meets all the in vitro criteria for a virus to be oncolytic towards Ewing sarcoma. In the first xenograft experiments, however, although an antiproliferative effect of intratumoral H-1PV injection was observed, no significant improvement of animal survival was noted. Future projects aiming to validate parvovirotherapy for the treatment of pediatric Ewing sarcoma should focus on combinatorial treatments and will require the use of patient-derived xenografts and immunocompetent syngeneic animal models.

Análise do desenvolvimento neuropsicomotor em crianças com síndrome pós–zika vírus: um estudo transversal

INTRODUÇÃO: No Brasil, a epidemia ocasionada pelo Zika Vírus gerou aumento de casos de microcefalia, caracterizando que mulheres infectadas durante o período gestacional transmitiram o vírus ao feto. As consequências da infecção pelo vírus são caracterizadas como síndrome pós Zika, evidenciadas através da microcefalia associada, ou não, às alterações visuais, auditivas e osteomioarticulares, podendo ser reversíveis ou permanentes. OBJETIVO: Detectar atrasos no desenvolvimento neuropsicomotor em crianças acometidas no período pré-natal pelo Zika Vírus através da infecção materna. MATERIAIS E MÉTODOS: Estudo observacional, de corte transversal e análise descritiva, com crianças que foram infectadas pelo Zika Vírus através da genitora durante período gestacional, pertencentes à Associação de Pais de Anjos da Bahia, sendo os participantes submetidos à avaliação com o teste de Denver II e seus responsáveis entrevistados por meio de um questionário semiestruturado. Estudo aprovado sob CAAE: Faculdade de Tecnologia e Ciências da cidade de Salvador, Bahia, com parecer de número 2.064.548 sob CAAE 64655616.2.0000.5032, aprovado em 15 de maio de 2017. RESULTADOS: Foram avaliadas 8 crianças, 5(62,5%) do sexo feminino, com uma média de idade de 1,8±0,11 anos e perímetro cefálico de 29,5±1,5 centímetros. Houve predomínio de diagnóstico de Zika das gestantes no primeiro trimestre (37,5%). Das comorbidades associadas 7 (87,5%) alteração osteomioarticular, 5(62,5%) história prévia de convulsão. Disfunções: 5(62,5%) comprometimento visual e 1(12,5%) déficit auditiva. CONCLUSÃO: É possível constatar que crianças com síndrome pós-Zika apresentam atrasos no desenvolvimento neuropsicomotor com preponderância no aspecto motor grosseiro do teste de Denver II.

HIV and the Macrophage: From Cell Reservoirs to Drug Delivery to Viral Eradication

Macrophages serve as host cells, inflammatory disease drivers and drug runners for human immunodeficiency virus infection and treatments. Low-level viral persistence continues in these cells in the absence of macrophage death. However, the cellular microenvironment changes as a consequence of viral infection with aberrant production of pro-inflammatory factors and promotion of oxidative stress. These herald viral spread from macrophages to neighboring CD4+ T cells and end organ damage. Virus replicates in tissue reservoir sites that include the nervous, pulmonary, cardiovascular, gut, and renal organs. However, each of these events are held in check by antiretroviral therapy. A hidden and often overlooked resource of the macrophage rests in its high cytoplasmic nuclear ratios that allow the cell to sense its environment and rid it of the cellular waste products and microbial pathogens it encounters. These phagocytic and intracellular killing sensing mechanisms can also be used in service as macrophages serve as cellular carriage depots for antiretroviral nanoparticles and are able to deliver medicines to infectious disease sites with improved therapeutic outcomes. These undiscovered cellular functions can lead to reductions in persistent infection and may potentially facilitate the eradication of residual virus to eliminate disease.

P.1.016 - Molecular linking of influenza infection to cellular pathology of protein misassembly: the case of Disrupted-in-Schizophrenia 1 (DISC1)

Chronic mental illnesses such as schizophrenia or recurrent affective disorders are heterogeneous in their biological causes behind the clinical, syndromatic diagnosis. Viral infection has been linked to chronic mental illnesses both by direct mechanisms and indirect mechanisms through immune stimulation. For example, studies showed that intrauterine influenza infection could be a risk factor for chronic mental illness [1]. It is also established that viral infection can lead to a change in proteostasis impairing regulatory protein networks and leading to disease. The most dramatic consequences of disrupted proteostasis are the so-called protein misfolding diseases that show as a phenotypical hallmark, microscopically visible deposits of one or several proteins, and cell degeneration. More subtle forms of proteostatic imbalance exist where protein deposits are not microscopically visible and the neurons do not die but remain functionally impaired, for example in some forms of chronic mental illness such as schizophrenia [2]. We previously reported insoluble Disrupted-in-schizophrenia 1 (DISC1) protein in a subpopulation of patients with chronic mental illness [3]. This gene/protein is involved in vulnerability to chronic mental disorders, and was discovered mutant and segregating in a large Scottish pedigree with a chromosomal translocation leading to a 3′ truncation of the gene [4]. Subsequent genetic association studies in multiple populations of different ethnicities also support the involvement of this protein in mental illness. For the present study, our hypothesis was that influenza infection could cause significant long-term impairments of specific proteostatic pathways leading to aggregated DISC1 protein in chronic mental illness patients [5]. Neuroblastoma cell lines expressing inducible full-length, non-mutant DISC1 protein were infected with WSN33 influenza (H1N1 strain). The effect of viral infection was investigated by immunocytochemistry, biochemical and functional assays. Furthermore, infected mice with WSN33 influenza where investigated for insoluble DISC1 deposits by immunohistochemistry. Antiviral drugs were tested in order to reverse the influenza-induced DISC1 aggregates. Influenza infection of cell lines induced DISC1 misassembly but not misassembly of the protein TDP43 known to be mislocalized in ALS, but not in mental illness or influenza, and therefore serving as a control for specificity of DISC1 mis-assembly upon influenza infection in cellular models. Appearance of DISC1 deposits was dependent on infectious influenza virus titer, and the infection time. Functional consequences of influenza-induced DISC1 misassembly will be reported, as well as our investigations of influenza-infected mice that are still ongoing. We conclude that influenza infection leads to a very specific proteostatic change, including the misassembly of DISC1, which has functional consequences for dopamine homeostasis. Thus a selective reprogramming of cellular homeostasis, as measured by proteostasis, may be a novel molecular mechanism by which influenza infection can lead to brain disease.

The Effects of Viral Infection on Lymphocyte Metabolism: A New Perspective on Disease Characterization.

Over the past decade, metabolic dysfunction has been re-examined as an area of interest in a variety of atopic, malignant, and autoimmune conditions. The unique immune and, specifically, lymphocyte metabolic dysfunctions in disease are starting to be more clearly classified. Exploring the lymphocyte metabolic profiles of these diseases in the current literature, we characterize these diseases into two distinct metabolic groups. The influence of viral infection on immune metabolic dysfunction is explored. During an acute or chronic infection, there is a varied rapid shift in nutrients available to immune cells. This article explores the effect of these changes in nutrient availability and the resulting outcome on immune cell function. From this, a new hypothesis is proposed that these two groups of conditions, characterized by two unique immune profiles, are caused by either acute or chronic viral infections. The physiology behind this is explored, which proposes a new step between a healthy immune system and that of disease, in a unique working model.

Breeding consequences of flavivirus infection in the collared flycatcher

BackgroundThe breeding consequences of virus infections have rarely been studied in avian natural breeding populations. In this paper we investigated the links between humoral immunity following a natural flavivirus infection and reproduction in a wild bird population of collared flycatcher (Ficedula albicollis). We analyzed plasma from 744 birds for antibodies and correlated these results to a number of reproductive components.ResultsNearly one third (27.8%) of the sampled collared flycatchers were found seropositive for flavivirus. Males had significantly more frequently flavivirus antibodies (32.3%) than females (25.1%). Seropositive females differed significantly from seronegative females in four traits: they had earlier lay date, higher body weight, higher survival rate and were older than seronegative females. The females did not differ in clutch size, number of fledged young or number of recruited young. Seropositive males had female partners with earlier lay date, i.e. the males bred earlier and they also produced more fledged young than seronegative males. In contrast, the males did not differ in clutch size, number of recruited young, male weight, age or survival. Interestingly, seropositive males had larger ornament, forehead badge size, than seronegative males.ConclusionsCollared flycatchers with an antibody response against flavivirus were more successful than birds with no antibody response, for any of the measured life history traits. The positive link between flavivirus antibody presence and life-history trait levels suggest that it is condition dependent in the collared flycatcher.

The Effect of Viral Infections and Allergic Inflammation in Asthmatic Patients on Immunotherapy

The Effect of Viral Infections and Allergic Inflammation in Asthmatic Patients on Immunotherapy

Virus resistance in potato: Current state and prospects

The potato (Solanum tuberosum), one of the world’s most important food crops, is infected by numerous viruses, nine of which are of major economic importance as they cause significant yield losses and reduce the quality of the crop. To mitigate the consequences of viral infections, countries with highly developed agriculture are improving and promoting sanitary measures, which include constantly monitoring viruses and certification of potato seed material based on virus diagnostics and improved potato cultivars. However, the development of virus-resistant potato cultivars seems to be a preferable choice in the long term. By employing conventional breeding techniques and genetic engineering approaches using natural virus resistance genes, normally obtained from the wild growing Solanum species, or virus-specific sequences, a number of potato cultivars/lines, which are resistant to the majority of known potato viruses, have already been obtained. However, the above-mentioned techniques have certain limitations, which are determined, in particular, by the high virus specificity of the acquired resistance (against certain viruses only), its short duration, and the ability of the virus to overcome it, as well as the regularly declared bans on the use of genetically modified plants. In the modern era, the novel technologies allowing us to edit genomes for the purposes of gene design have created the possibility to engineer a new generation of resistance genes. The most promising approaches are thought to be the directed mutagenesis of resistance genes, which allows broadening the spectrum of the effects of the gene and the use of nonhost resistance (NHR) (nonspecific resistance) genes, allowing engineering plants resistant to unrelated viruses and in certain cases, to other pathogens and even abiotic stresses. The identification of genes involved in the mechanisms of NHR has only just begun. The nucleus is now being considered as a new source of still unknown factors involved in diverse signal pathways controlling the plant’s defensive response against virus infection. The review describes the approaches which are used to generate virus-resistant potato plants and the challenges faced in this path.

Effects of virus infection on plant growth, root development and phytohormone levels in in vitro-cultured pear plants

Virus infection is common in pear (Pyrus spp.) trees commercially cultivated in China. In this study, the growth speed, root development and phytohormone levels of virus-free and virus-infected pear cultures were comparatively investigated. Results showed that the co-infection of Apple stem grooving virus (ASGV) and Apple stem pitting virus (ASPV) significantly decreased the growth and proliferation of in vitro plants of P. communis cv. ‘Confenence’, but showed relatively less effect for P. pyrifolia cv. ‘Jinshui no. 2’, P. communis cv. ‘Red Clapp Favonite’ and P. sinkiangensis cv. ‘Korla’. Strong inhibition of ASGV infection to root development was observed for in vitro plants of ‘Jinshui no. 2’, but not for ‘Confenence’. Furthermore, during root induction, ASGV infection significantly increased CTKs/IAA ratio and decreased IAA/ABA ratio in the rooting region of in vitro plants of ‘Jinshui no. 2’. Nevertheless, for in vitro plants of ‘Confenence’, these values were rarely influenced by ASGV and ASPV infection. The result indicated that the changes of CTKs/IAA and IAA/ABA ratios might be responsible for rooting inhibition of in vitro plants of ‘Jinshui no. 2’.

Metabolomics of Rhabdomyosarcoma Cell During Echovirus 30 Infection

BackgroundEchovirus 30 (E30) causes acute aseptic meningitis. Viral replication requires energy and macromolecular precursors derived from the metabolic network of the host cell. The effect of viral infection within a host cell metabolic activity remains unclear.MethodsTo gain an insight into cell-virus interaction during E30 infection we used a human rhabdomyosarcoma cell line. In a new approach to metabolomics, 1H NMR was used to measure the level of various cellular metabolites at different times of infection and morphological examination of the cells. Statistical analysis was done by using Confidence interval (CI) 95% and One-way ANOVA test.ResultsThe1H NMR metabolite spectrum signals were observed between mock infected and virus infected cells. Both mock infected and virus infected cells utilized glucose through metabolic pathways and released metabolic end products. Upon infection, the concentration of Alanine, Lactate, Acetate, Glutamate, Tyrosine, Histidine, Phenylalanine, Creatine, Choline and Formate, increased. Interestingly, all of these augmented metabolites were decreased during later stage of infection. The cells showed wide-ranging lipid signals at the end of infection, which correlates with the morphological changes as apoptosis (programmed cell death) of cells was observed. A significant association was found between time interval (12 h, 24 h, and 48 h) and metabolites likewise Alanin, Lactate, Acetate, Glutamate, Tyrosine, Histidine, Phenylalanine, Creatine, Choline and Formate respectively released by cell during infection, which is highly significant (p < 0.01).ConclusionProgressive breakdown and utilization of all cellular components were observed as the infection increased. This study is useful for monitoring the cellular metabolic changes during viral infection.

Anticancer drug-loaded quantum dots engineered polymeric nanoparticles: Diagnosis/therapy combined approach

Primary Effusion Lymphoma (PEL) is an HHV-8-related non Hodgkin lymphoma localized in body cavities (as pleural, peritoneal and pericardial) presenting lymphomatous effusion that, until now, lack of an effective therapy. Curcumin was reported to display pro-apoptotic effect via the inhibition of the JAK/STAT pathway, that is overexpressed in PEL cells, as consequence of virus infection. The administration of curcumin is severely restricted by its physicochemical properties, mainly its low solubility in biological fluid and consequently low bioavailability. Encapsulation into biocompatible and biodegradable PLGA nanoparticles (NPs) could be a strategy to overcome biological limits of curcumin, offering a valuable step forward for its clinical application. In this study we described single-emulsion process for curcumin loading into NPs (encapsulation efficiency about 35%). We applied a post-formulation strategy (NHS/EDC reaction) to decorate the surface of the curcumin-loaded NPs with quantum dots (QDs) as imaging agents (QDs-NPs-Cur, 24pmol of QDs per 100mg of NPs) obtaining tools useful for possible application in theranostic approach.Bifunctionalized NPs were tested in vitro on two PEL's cell line (BCBL-1 and HBL-6). The efficacy of the treatment was evaluated by cytofluorimetric assay by measuring both cell viability and cell density. We found that the NPs significantly improve the cellular effect of curcumin (respect to free drug). Moreover, by means of confocal microscopy, both the localization of bifunctional NPs and of the released drug were easily detectable.Thus, we conclude that the delivery of curcumin using bifunctional traceable NPs is a promising future approach for the diagnosis and the treatment of PEL.

Unexpected evolutionarily conserved rapid effects of viral infection on oxytocin receptor and TGF-\u03b2/pSmad3

BackgroundshRNA lentiviral vectors are extensively used for gene knockdowns in mammalian cells, and non-target shRNAs typically are considered the proper experimental control for general changes caused by RNAi. However, the effects of non-target lentivirus controls on the modulation of cell signaling pathways remain largely unknown. In this study, we evaluated the effect of control lentiviral transduction on oxytocin receptor (OXTR) expression through the ERK/MAPK pathway in mouse and human skeletal muscle cells, on myogenic activity, and in vivo on mouse muscle regeneration. Furthermore, we mined published data for the influence of viral infections on OXTR levels in human populations and found that unrelated viral pathologies have a common consequence: diminished levels of OXTR.MethodsWe examined the change in OXTR mRNA expression upon transduction with control and Smad3-targeting viral vectors through real time RT-PCR and Western blotting, and confirmed with immunofluorescence. Changes in Smad3 and OXTR expression were examined both in vitro with mouse and human myoblasts and in vivo in mouse satellite cells. The general effects of viral infections on OXTR downregulation in humans were also examined by analyzing published Gene Expression Omnibus (GEO) datasets. The change in myoblast myogenic activity caused by the viral transduction (the percent of Pax7 + Ki67+ cells) was examined by immunofluorescence.ResultsResults shown in this work establish that lentiviral control vectors significantly downregulate OXTR expression at mRNA and protein levels and diminish key downstream effectors of OXTR, ERK signaling, reducing the myogenic proliferation of infected cells. This effect is evolutionarily conserved between mouse and human myogenic cells, and it manifests in satellite cells after control lentiviral transduction of mice in vivo. Furthermore, an examination of published datasets uncovered similar OXTR downregulation in humans that are afflicted with different viral infections. Additionally, cells transduced with Smad3-targeting shRNA downregulate OXTR even more than cells transduced with control viruses.ConclusionsOur work suggests that experimental cohorts transduced with control viruses may not behave the same as un-transduced cells and animals, specifically that control viral vectors significantly change the intensity of key cell-signaling pathways, such as OXTR/ERK. Our results further demonstrate that lentiviral transduction significantly decreases myogenic proliferation and suggest that viral infections in general may play a role in decreasing muscle health and regeneration, a decline in metabolic health, and a lower sense of well-being, as these rely on effective OXTR signaling. Additionally, our data suggest pathway crosstalk between TGF-β/pSmad3 and OXTR, implying that sustained attenuation of the TGF-β/pSmad3 pathway will reduce pro-regenerative OXTR/pERK signaling.

Influence of OSHV-1 oyster mortality episode on dissolved inorganic fluxes: An ex situ experiment at the individual scale

Ostreid herpesvirus 1 (OsHV-1 μvar) infection has caused significant mortalities in juvenile oysters (Crassostrea gigas). In contrast to the practices of other animal production industries, sick and dead oysters are not separated from live ones and are left to decay in the surrounding environment, with unknown consequences on fluxes of dissolved materials. A laboratory approach was used in this study to test the influence of oyster mortality episode on dissolved inorganic fluxes at the oyster interface, dissociating (i) the effect of viral infection on metabolism of juvenile oysters and (ii) the effect of flesh decomposition on oxygen consumption and nutrient releases at the individual scale. Nine batches of juvenile oysters (Individual Total wet weight 1g) were infected via injection of OsHV-1 enriched inoculums at different viral loads (108 and 109 OsHV-1 DNA copies per oyster) to explore infection thresholds. Oysters injected with filtered seawater were used as controls (C). Oysters were maintained under standard conditions to avoid stress linked to hypoxia, starvation, or ammonia excess. Before, after the injection and during the mortality episode, i.e. at days 1, 3, 7, 10 and 14, nine oysters per treatment were incubated in individual metabolic chambers to quantify oxygen, ammonium and phosphate fluxes at the seawater-oyster interface. Nine empty chambers served as a reference. Injections of the two viral loads of OsHV-1 induced similar mortality rates (38%), beginning at day 3 and lasting until day 14. The observed mortality kinetics were slower than those reported in previous experimental pathology studies, but comparable to those observed in the field (Thau lagoon, France). This study highlights that oxygen and nutrient fluxes significantly varied during mortality episode. Indeed (i) OsHV-1 infection firstly modifies oyster metabolism, with significant decreases in oxygen consumption and ammonium excretion, and (ii) dead oysters lead to a strong increase of ammonium (6 fold) and phosphate (41 fold) fluxes and a decrease in the N/P ratio due to mineralisation of their flesh. The latter may modify the structure of the planktonic community in the field during mortality episode. This study is a first step of the MORTAFLUX program. The second step was to in situ confirm this abnormal nutrient loading during a mortality episode and show its impact on bacterio-, phyto- and protozoo-plankton.

Virus-Bacteria Interactions: An Emerging Topic in Human Infection.

Bacteria and viruses often occupy the same niches, however, interest in their potential collaboration in promoting wellness or disease states has only recently gained traction. While the interaction of some bacteria and viruses is well characterized (e.g., influenza virus), researchers are typically more interested in the location of the infection than the manner of cooperation. There are two overarching types of bacterial-virus disease causing interactions: direct interactions that in some way aid the viruses, and indirect interactions aiding bacteria. The virus-promoting direct interactions occur when the virus exploits a bacterial component to facilitate penetration into the host cell. Conversely, indirect interactions result in increased bacterial pathogenesis as a consequence of viral infection. Enteric viruses mainly utilize the direct pathway, while respiratory viruses largely affect bacteria in an indirect fashion. This review focuses on some key examples of how virus-bacteria interactions impact the infection process across the two organ systems, and provides evidence supporting this as an emerging theme in infectious disease.

The impact of Zika virus in the brain

The recent outbreak of ZIKV in Brazil called the attention of the world because the effects of viral infection in the brain under development in fetuses. Consequences of vertical infection comprise brain malformation, especially microcephaly, eye and musculoskeletal abnormalities, among others. In adults, outcomes of infection include meningoencephalitis and Guillain-Barré Syndrome. Recent data specific suggest that neural progenitor cells are the main targets of ZIKV infection, causing massive cellular death and impairment in the neurogenesis process. Here we review the fetal and adult brain damage after ZIKV exposure, exploring models to study the mechanisms underlying the pathways related to microcephaly and cell death.

Cellular Metabolomics of Rhabdomyosarcoma Cell during Echovirus 30 Infection

The Human echovirus 30 causes acute aseptic meningitis. Viral replication requires energy and macromolecular precursors derived from the metabolic network of the host cell. The effect of viral infection within a host cell metabolic activity remains unclear. To study an insight of cell-virus interaction during echovirus 30 infection we used human rhabdomyosarcoma cell line. The new approach of metabolomics the 1H NMR was used to measure the level of various cellular metabolites at different times of infections and morphological examination of the cells. The 1H NMR metabolite spectrum signals were observed between uninfected and infected cells. Both uninfected and infected cells utilized the glucose through metabolic pathways and released the metabolic end products. After infection the concentration of Alanine, Lactate, Acetate, Glutamate, Tyrosine, Histidine, Phenylalanine, Creatine, Choline and Formate, were increased and all these augmented metabolites were decreased at the end of the infection. The cells showed wide-ranging lipid signals at the end of the infections, which correlates with the morphological changes as apoptosis of cells was observed. Progressive breakdown and utilization of all cellular components were observed as the infections were increased. This study is useful for monitoring the cellular metabolic changes during virus infection.

Molecular Detection of Bean Yellow Mosaic Virus in Lupinus albus Plants and its Associated Alterations in Biochemical and Physiological Parameters

Bean yellow mosaic virus is one of the most devastating diseases of cultivated Leguminosae plants worldwide causing mosaic, mottling, malformation and distortion in infected cultivar plants. Present study was conducted to investigate the possibility of infection of Lupinus albus (Lupine) with Bean yellow mosaic virus. Virus isolate was identified by detection of the coat protein gene amplified by reverse transcription polymerase chain reaction and also via Chenopodium Amaranticolor as a diagnostic host plant. Results showed that infection can be induced under greenhouse conditions and infected plants showed a considerable level of mosaic symptoms. As disease development in infected plants is always associated with physiological and chemical changes, some metabolic alterations parameters have been evaluated like photosynthetic pigment contents, total carbohydrate content, total soluble protein, total protein, total free amino acid, proline induction, total phenolics, salicylic acid, and abscisic acid content in healthy and infected lupine plants. Results showed a great variation in all the biochemical categories in Lupinus albus infected with bean yellow mosaic virus as compared to healthy plants. Chlorophyll a of virus inoculated Lupinus albus decreased to 27%, whereas Chlorophyll b content decreased to 19.5% and carbohydrate content decreased to 36% when compared to healthy control plant corresponding values. Results also showed many metabolic changes in virus infected Lupine plants. The effect of virus infection on the induction of plant growth regulators like abscisic acid was determined, as well as the relationship between abscisic acid activation, accumulation of the virus, and symptoms development was discussed, and the effect of abscisic acid inhibitor application on virus infection and Lupine primary and secondary metabolism was elucidated, as this effect is a neglected field of research.

Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36.

Macrophages are essential to maintaining lung homoeostasis and recent work has demonstrated that influenza-infected lung macrophages downregulate their expression of the scavenger receptor CD36. This receptor has also been shown to be involved in phagocytosis of Streptococcus pneumoniae, a primary agent associated with pneumonia secondary to viral infection. The aim of this study was to investigate the role of CD36 in the effects of viral infection on macrophage phagocytic function. Human monocyte-derived macrophages (MDM) were exposed to H3N2 X31 influenza virus, M37 respiratory syncytial virus (RSV) or UV-irradiated virus. No infection of MDM was seen upon exposure to UV-irradiated virus but incubation with live X31 or M37 resulted in significant levels of viral detection by flow cytometry or RT-PCR respectively. Infection resulted in significantly diminished uptake of S. pneumoniae by MDM and significantly decreased expression of CD36 at both the cell surface and mRNA level. Concurrently, there was a significant increase in IFNβ gene expression in response to infection and we observed a significant decrease in bacterial phagocytosis (p = 0.031) and CD36 gene expression (p = 0.031) by MDM cultured for 24 h in 50IU/ml IFNβ. Knockdown of CD36 by siRNA resulted in decreased phagocytosis, but this was mimicked by transfection reagent alone. When MDM were incubated with CD36 blocking antibodies no effect on phagocytic ability was observed. These data indicate that autologous IFNβ production by virally-infected cells can inhibit bacterial phagocytosis, but that decreased CD36 expression by these cells does not play a major role in this functional deficiency.