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Sample records for neonatali viral infections

  1. INFEZIONI VIRALI CONGENITE, PERINATALI E NEONATALI VIRAL INFECTIONS OF THE FETUS AND NEWBORN INFANT

    PubMed Central

    Tremolada, Sara; Delbue, Serena; Ferrante, Pasquale

    2009-01-01

    Riassunto Alcuni virus possono essere trasmessi verticalmente da madre a figlio in seguito allo sviluppo, da parte della madre, di un’infezione primaria, ricorrente o cronica. La trasmissione materno-fetale dei virus, che può avvenire in utero (infezione congenita), durante il travaglio del parto (infezione perinatale), oppure attraverso l’allattamento (infezione postnatale), può causare aborto spontaneo, morte fetale, ritardo di crescita intrauterino, anomalie congenite e patologie neonatali o postnatali di diversa entità. Alcuni fattori di rischio sembrano influenzare l’incidenza di trasmissione materno-fetale dei virus, come ad esempio la presenza di altre infezioni virali, la carica virale materna, il tipo di infezione (primaria o ricorrente), la durata della rottura delle membrane, la modalità con cui avviene il parto, le condizioni socio-economiche e l’allattamento. Oggi è possibile prevenire la trasmissione materno-fetale di molti virus grazie all’utilizzo di vaccini, immunizzazione passiva e farmaci antivirali. Il rischio di trasmissione delle infezioni perinatali e postnatali, inoltre, può essere diminuito evitando l’allattamento o ricorrendo ad un parto cesareo. PMID:19216201

  2. 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

  3. VIRAL INFECTIONS DURING PREGNANCY

    PubMed Central

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

    2015-01-01

    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

  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. [Emergent viral infections].

    PubMed

    Galama, J M

    2001-03-31

    The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic infections such as dengue and hepatitis E, but also of hepatitis A, which is no longer endemic. Apart from import diseases new viruses have appeared (Nipah-virus and transfusion-transmitted virus). Existing viruses may suddenly cause more severe diseases, e.g. infection by enterovirus 71. The distribution area of a virus may change, e.g. in case of West Nile virus, an Egyptian encephalitis virus that appears to have established itself in the USA. Furthermore, there is no such thing as a completely new virus; it is always an existing virus that has adapted itself to another host or that was already present in humans but has only recently been discovered. A number of factors facilitate the emergence of new infectious diseases. These include intensive animal husbandry and the transport of animals. The unexpected appearance of West Nile virus in the western hemisphere was possibly due to animal transportation. PMID:11305210

  6. DENGUE VIRAL INFECTIONS

    PubMed Central

    Gurugama, Padmalal; Garg, Pankaj; Perera, Jennifer; Wijewickrama, Ananda; Seneviratne, Suranjith L

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections. PMID:20418983

  7. Viral infection, inflammation and schizophrenia

    PubMed Central

    Kneeland, Rachel E.; Fatemi, S. Hossein

    2012-01-01

    Schizophrenia is a severe neurodevelopmental disorder with genetic and environmental etiologies. Prenatal viral/bacterial infections and inflammation play major roles in the genesis of schizophrenia. In this review, we describe a viral model of schizophrenia tested in mice whereby the offspring of mice prenatally infected with influenza at E7, E9, E16, and E18 show significant gene, protein, and brain structural abnormalities postnatally. Similarly, we describe data on rodents exposed to bacterial infection or injected with a synthetic viral mimic (PolyI:C) also demonstrating brain structural and behavioral abnormalities. Moreover, human serologic data has been indispensible in supporting the viral theory of schizophrenia. Individuals born seropositive for bacterial and viral agents are at a significantly elevated risk of developing schizophrenia. While the specific mechanisms of prenatal viral/bacterial infections and brain disorder are unclear, recent findings suggest that the maternal inflammatory response may be associated with fetal brain injury. Preventive and therapeutic treatment options are also proposed. This review presents data related to epidemiology, human serology, and experimental animal models which support the viral model of schizophrenia. PMID:22349576

  8. Cytokines and persistent viral infections.

    PubMed

    Beltra, Jean-Christophe; Decaluwe, Hélène

    2016-06-01

    Intracellular pathogens such as the human immunodeficiency virus, hepatitis C and B or Epstein-Barr virus often cause chronic viral infections in humans. Persistence of these viruses in the host is associated with a dramatic loss of T-cell immune response due to functional T-cell exhaustion. Developing efficient immunotherapeutic approaches to prevent viral persistence and/or to restore a highly functional T-cell mediated immunity remains a major challenge. During the last two decades, numerous studies aimed to identify relevant host-derived factors that could be modulated to achieve this goal. In this review, we focus on recent advances in our understanding of the role of cytokines in preventing or facilitating viral persistence. We concentrate on the impact of multiple relevant cytokines in T-cell dependent immune response to chronic viral infection and the potential for using cytokines as therapeutic agents in mice and humans. PMID:26907634

  9. Viral infections of rabbits.

    PubMed

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned. PMID:23642871

  10. NLRs, inflammasomes, and viral infection

    PubMed Central

    Jacobs, Sarah R.; Damania, Blossom

    2012-01-01

    NLR proteins are innate immune sensors that respond to microbial infection. Upon pathogen infection, some NLR proteins form large complexes, called inflammasomes, which activate caspase-1 and induce the production of active IL-1β and IL-18. Activation of inflammasomes can also lead to an inflammatory cell death program, named pyroptosis. In this review, we will discuss the role of various NLR proteins in sensing different viral infections, as well as the strategies used by several RNA and DNA viruses to counteract the antiviral effects of NLR-dependent inflammasomes. PMID:22581934

  11. [Oral viral infections].

    PubMed

    Parent, Dominique

    2016-02-01

    Exclude herpes infection in the presence of acute oral ulcers of unknown origin, particularly in patients in poor general condition. Remember that asymptomatic HSV-1 shedding in saliva may result in an oral-genital transmission. Perform an anogenital examination and a screening for other sexually transmitted diseases when oral warts are diagnosed. Search for immunosuppression and monitor the patient (screening for a potential associated carcinoma) when there is rapid growth of oral warts. Consider all the clinical signs (systemic, skin, other mucosa, immunity...) when a patient has an enanthem or oral ulcerations. Ask for a HIV test when an oral Kaposi's sarcoma, a hairy leukoplakia or major aphthae are diagnosed. PMID:26854091

  12. Stochastic models of viral infection

    NASA Astrophysics Data System (ADS)

    Chou, Tom

    2009-03-01

    We develop biophysical models of viral infections from a stochastic process perspective. The entry of enveloped viruses is treated as a stochastic multiple receptor and coreceptor engagement process that can lead to membrane fusion or endocytosis. The probabilities of entry via fusion and endocytosis are computed as functions of the receptor/coreceptor engagement rates. Since membrane fusion and endocytosis entry pathways can lead to very different infection outcomes, we delineate the parameter regimes conducive to each entry pathway. After entry, viral material is biochemically processed and degraded as it is transported towards the nucleus. Productive infections occur only when the material reaches the nucleus in the proper biochemical state. Thus, entry into the nucleus in an infectious state requires the proper timing of the cytoplasmic transport process. We compute the productive infection probability and show its nonmonotonic dependence on both transport speeds and biochemical transformation rates. Our results carry subtle consequences on the dosage and efficacy of antivirals such as reverse transcription inhibitors.

  13. Recycling Endosomes and Viral Infection

    PubMed Central

    Vale-Costa, Sílvia; Amorim, Maria João

    2016-01-01

    Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral–host interactions occurring on the endocytic recycling compartment (ERC), and mediated by its regulatory Ras-related in brain (Rab) GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition. PMID:27005655

  14. 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

  15. Inflammasome control of viral infection

    PubMed Central

    Lupfer, Christopher; Malik, Ankit; Kanneganti, Thirumala-Devi

    2015-01-01

    The inflammasome is a caspase-1 containing complex that activates the proinflammatory cytokines IL-1β and IL-18 and results in the proinflammatory cell death known as pyroptosis. Numerous recent publications have highlighted the importance of inflammasome activation in the control of virus infection. Inflammasome activation during viral infection is dependent on a variety of upstream receptors including the NOD-Like receptor, RIG-I-Like receptor and AIM2-Like receptor families. Various receptors also function in inflammasome activation in different cellular compartments, including the cytoplasm and the nucleus. The effectiveness of inflammasomes at suppressing virus replication is highlighted by the prevalence and diversity of virus encoded inflammasome inhibitors. Also, the host has a myriad of regulatory mechanisms in place to prevent unwanted inflammasome activation and overt inflammation. Finally, recent reports begin to suggest that inflammasome activation and inflammasome modulation may have important clinical applications. Herein, we highlight recent advances and discuss potential future directions toward understanding the role of inflammasomes during virus infection. PMID:25771504

  16. Snapshots: Chromatin Control of Viral Infection

    PubMed Central

    Knipe, David M.; Lieberman, Paul M.; Jung, Jae U.; McBride, Alison A.; Morris, Kevin V.; Ott, Melanie; Margolis, David; Nieto, Amelia; Nevels, Michael; Parks, Robin J.; Kristie, Thomas M.

    2012-01-01

    Like their cellular host counterparts, many invading viral pathogens must contend with, modulate, and utilize the host cell’s chromatin machinery to promote efficient lytic infection or control persistent-latent states. While not intended to be comprehensive, this review represents a compilation of conceptual snapshots of the dynamic interplay of viruses with the chromatin environment. Contributions focus on chromatin dynamics during infection, viral circumvention of cellular chromatin repression, chromatin organization of large DNA viruses, tethering and persistence, viral interactions with cellular chromatin modulation machinery, and control of viral latency-reactivation cycles. PMID:23217624

  17. Illuminating viral infections in the nervous system

    PubMed Central

    McGavern, Dorian B.; Kang, Silvia S.

    2016-01-01

    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 the strategies used by neurotropic viruses to cross the barrier systems of the CNS and on how the immune system detects and responds to viral infections in the CNS. A special emphasis is placed on immune surveillance of persistent and latent viral infections and on recent insights gained from imaging both protective and pathogenic antiviral immune responses. PMID:21508982

  18. Severe Viral Infections and Primary Immunodeficiencies

    PubMed Central

    Cohen, Jeffrey I.

    2011-01-01

    Patients with severe viral infections are often not thoroughly evaluated for immunodeficiencies. In this review, we summarize primary immunodeficiencies that predispose individuals to severe viral infections. Some immunodeficiencies enhance susceptibility to disease with a specific virus or family of viruses, whereas others predispose to diseases with multiple viruses in addition to disease with other microbes. Although the role of cytotoxic T cells in controlling viral infections is well known, a number of immunodeficiencies that predispose to severe viral diseases have recently been ascribed to defects in the Toll-like receptor–interferon signaling pathway. These immunodeficiencies are rare, but it is important to identify them both for prognostic information and for genetic counseling. Undoubtedly, additional mutations in proteins in the innate and adaptive arms of the immune system will be identified in the future, which will reveal the importance of these proteins in controlling infections caused by viruses and other pathogens. PMID:21960712

  19. Oxygen tension level and human viral infections

    SciTech Connect

    Morinet, Frédéric; Casetti, Luana; François, Jean-Hugues; Capron, Claude; Pillet, Sylvie

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

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

    PubMed

    Adışen, 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

  1. [Immunosupression and viral infections in rheumatic diseases].

    PubMed

    Vince, Adriana; Dusek, Davorka

    2007-01-01

    Infections are one of the leading causes of morbidity and mortality in patients with rheumatic diseases. Although bacterial pathogens are the most common cause of infections, a wide variety of viral pathogens can also cause serious clinical manifestations mostly due to immunosupressive therapy primarily targeting cellular immunity (steroids, cyclosporins, cyclophosphamid, leflunomid, TNF-alfa antagonists etc.). Depleted cellular immunity can lead to reactivation of latent viruses such as members of Herpesvirus family, or hepatitis B and C viruses. Symptoms of viral infection may mimic exacerbation of rheumatic disease. In this paper authors present the main clinical characteristics, diagnostics and tretment possibilities for most common viral infections in immunosupressed host with a rheumatic disease. PMID:18351141

  2. Membrane dynamics associated with viral infection.

    PubMed

    de Armas-Rillo, Laura; Valera, María-Soledad; Marrero-Hernández, Sara; Valenzuela-Fernández, Agustín

    2016-05-01

    Viral replication and spreading are fundamental events in the viral life cycle, accounting for the assembly and egression of nascent virions, events that are directly associated with viral pathogenesis in target hosts. These processes occur in cellular compartments that are modified by specialized viral proteins, causing a rearrangement of different cell membranes in infected cells and affecting the ER, mitochondria, Golgi apparatus, vesicles and endosomes, as well as processes such as autophagic membrane flux. In fact, the activation or inhibition of membrane trafficking and other related activities are fundamental to ensure the adequate replication and spreading of certain viruses. In this review, data will be presented that support the key role of membrane dynamics in the viral cycle, especially in terms of the assembly, egression and infection processes. By defining how viruses orchestrate these events it will be possible to understand how they successfully complete their route of infection, establishing viral pathogenesis and provoking disease. © 2015 The Authors Reviews in Medical Virology Published by John Wiley & Sons, Ltd. PMID:26817660

  3. [Microbiological diagnosis of viral respiratory infections].

    PubMed

    Eiros, José M; Ortiz de Lejarazu, Raúl; Tenorio, Alberto; Casas, Inmaculada; Pozo, Francisco; Ruiz, Guillermo; Pérez-Breña, Pilar

    2009-03-01

    Acute respiratory infection is the most common disease occurring over a person's lifetime, with etiological variations determined mainly by age, environmental circumstances, the healthcare setting, and the underlying pathology. More than 200 different viruses distributed in six viral families have been implicated in the pathogenesis of respiratory tract infection. These facts are generating an increasing diagnostic demand that should be incorporated into the healthcare setting without delay. To meet this demand, the Spanish Society of Infectious Diseases and Clinical Microbiology has updated its Standard Procedure for the microbiological diagnosis of viral respiratory infection. This document contains an update primarily of infections caused by influenza viruses, and secondarily, infections due to other conventional and emerging respiratory viruses. In all cases, the methods for direct virological diagnosis (cell culture, and detection of antigens and nucleic acid) are reviewed, with special reference to techniques for molecular detection and genetic characterization. PMID:19306718

  4. Viral enteric infections of poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enteric diseases cause great economic losses to the poultry industry mostly from depressed weight gains, impaired feed efficiency, and decreased flock uniformity. Enteric syndromes have been described in both young turkeys and chickens and likely result from infection by a mixture of pathogenic age...

  5. T cell responses in dengue viral infections.

    PubMed

    Malavige, Gathsaurie Neelika; Ogg, Graham S

    2013-12-01

    Dengue viral infections are the commonest mosquito borne viral infection in the world, affecting more than 100 countries and 390 million individuals annually. Currently, there are no effective antiviral drugs or an effective vaccine to prevent infection. A main hurdle in developing a safe and effective vaccine has been our poor understanding of the complex nature of the protective immune response in acute dengue infection and the presence of four dengue virus (DV) serotypes that are highly homologous. The role of DV specific T cells in the pathogenesis of severe clinical disease in not clear. It has been speculated that highly cross reactive T cells for the previous infecting heterologous DV serotype, which produce pro-inflammatory cytokines, contribute to disease pathogenesis. These cross reactive T cells are believed to be suboptimal in clearing the infection with the current DV-serotype. However, other studies have shown that cross-reactive DV-specific T cells are absent or present in very low frequency during acute infection, appearing only during the convalescent period in the majority of patients. Furthermore, significant apoptosis of T cells occurs in severe acute clinical disease. Overall therefore, it is unclear what role T cells play in contributing to disease pathogenesis during acute dengue infection. Existing data have been complicated by cross-reactivity in T cells assays. These findings can now be re-evaluated in the light of novel technologies to identify serotype-specific T cell responses. PMID:24220605

  6. Claudins and pathogenesis of viral infection.

    PubMed

    Tawar, Rajiv G; Colpitts, Che C; Lupberger, Joachim; El-Saghire, Hussein; Zeisel, Mirjam B; Baumert, Thomas F

    2015-06-01

    Since their discovery, tremendous progress has been made in our understanding of the roles of claudins in tight junction physiology. In addition, interactions between claudins and other cellular proteins have highlighted their novel roles in cell physiology. Moreover, the importance of claudins is becoming apparent in the pathophysiology of several diseases, including viral infections. Notable is the discovery of CLDN1 as an essential host factor for hepatitis C virus (HCV) entry, which led to detailed characterization of CLDN1 and its association with tetraspanin CD81 for the initiation of HCV infection. CLDN1 has also been shown to facilitate dengue virus entry. Furthermore, owing to the roles of claudins in forming anatomical barriers, several viruses have been shown to alter claudin expression at the tight junction. This review summarizes the role of claudins in viral infection, with particular emphasis on HCV. PMID:25960372

  7. Immunological memory to viral infection.

    PubMed

    Slifka, Mark K

    2004-08-01

    Immunological memory is defined by the ability of a host to remember a past encounter with a specific pathogen and to respond to it in an effective manner upon re-exposure. How long immunological memory can be maintained in the absence of re-infection continues to be a subject of great controversy. Recent studies on immunity following smallpox vaccination demonstrate that T-cell memory declines steadily with a half-life of 8-15 years, whereas antiviral antibody responses are maintained for up to 75 years without appreciable decline. By combining recent advances in quantitative immunology with historical accounts of protection against smallpox dating back to the time of Edward Jenner, we are gaining a better understanding of the duration and magnitude of immunological memory and how it relates to protective immunity. PMID:15245737

  8. Visualizing viral transport and host infection

    NASA Astrophysics Data System (ADS)

    Son, Kwangmin; Guasto, Jeffrey; Cubillos-Ruiz, Andres; Sullivan, Matthew; Stocker, Roman; MIT Team

    2013-11-01

    A virus is a non-motile infectious agent that can only replicate inside a living host. They consist of a <100 nm diameter capsid which houses their DNA, and a <20 nm diameter tail used to inject DNA to the host, which are classified into three different morphologies by the tail type: short tail (~ 10 nm, podovirus), rigid contractile tail (~ 100 nm, myovirus), or flexible noncontractile tail (~ 300 nm, siphovirus). Combining microfluidics with epifluorescent microscopy, we studied the simultaneous diffusive transport governing the initial encounter and ultimately the infection of a non-motile cyanobacteria host (~ 1 μm prochlorococcus) and their viral (phage) counterparts in real time. This methodology allows us to quantify the virus-host encounter/adsorption dynamics and subsequently the effectiveness of various tail morphologies for viral infection. Viral transport and the role of viral morphology in host-virus interactions are critical to our understanding of both ecosystem dynamics and human health, as well as to the evolution of virus morphology.

  9. Viral infections of the liver in childhood

    PubMed Central

    Zuckerman, A. J.

    1974-01-01

    Hepatitis A and hepatitis B viruses and yellow fever virus are the most important causes of acute inflammation of the liver. Hepatitis is also frequently associated with other common viral infections such as cytomegalovirus (human herpesvirus 5) and EB virus (human herpesvirus 4). In addition, there are a number of viruses which occasionally display increased hepatotropism producing a clinical picture which is similar to classical hepatitis. PMID:4377172

  10. Spatiotemporal modelling of viral infection dynamics

    NASA Astrophysics Data System (ADS)

    Beauchemin, Catherine

    Viral kinetics have been studied extensively in the past through the use of ordinary differential equations describing the time evolution of the diseased state in a spatially well-mixed medium. However, emerging spatial structures such as localized populations of dead cells might affect the spread of infection, similar to the manner in which a counter-fire can stop a forest fire from spreading. In the first phase of the project, a simple two-dimensional cellular automaton model of viral infections was developed. It was validated against clinical immunological data for uncomplicated influenza A infections and shown to be accurate enough to adequately model them. In the second phase of the project, the simple two-dimensional cellular automaton model was used to investigate the effects of relaxing the well-mixed assumption on viral infection dynamics. It was shown that grouping the initially infected cells into patches rather than distributing them uniformly on the grid reduced the infection rate as only cells on the perimeter of the patch have healthy neighbours to infect. Use of a local epithelial cell regeneration rule where dead cells are replaced by healthy cells when an immediate neighbour divides was found to result in more extensive damage of the epithelium and yielded a better fit to experimental influenza A infection data than a global regeneration rule based on division rate of healthy cell. Finally, the addition of immune cell at the site of infection was found to be a better strategy at low infection levels, while addition at random locations on the grid was the better strategy at high infection level. In the last project, the movement of T cells within lymph nodes in the absence of antigen, was investigated. Based on individual T cell track data captured by two-photon microscopy experiments in vivo, a simple model was proposed for the motion of T cells. This is the first step towards the implementation of a more realistic spatiotemporal model of HIV than

  11. Phylodynamic analysis of a viral infection network

    PubMed Central

    Shiino, Teiichiro

    2012-01-01

    Viral infections by sexual and droplet transmission routes typically spread through a complex host-to-host contact network. Clarifying the transmission network and epidemiological parameters affecting the variations and dynamics of a specific pathogen is a major issue in the control of infectious diseases. However, conventional methods such as interview and/or classical phylogenetic analysis of viral gene sequences have inherent limitations and often fail to detect infectious clusters and transmission connections. Recent improvements in computational environments now permit the analysis of large datasets. In addition, novel analytical methods have been developed that serve to infer the evolutionary dynamics of virus genetic diversity using sample date information and sequence data. This type of framework, termed “phylodynamics,” helps connect some of the missing links on viral transmission networks, which are often hard to detect by conventional methods of epidemiology. With sufficient number of sequences available, one can use this new inference method to estimate theoretical epidemiological parameters such as temporal distributions of the primary infection, fluctuation of the pathogen population size, basic reproductive number, and the mean time span of disease infectiousness. Transmission networks estimated by this framework often have the properties of a scale-free network, which are characteristic of infectious and social communication processes. Network analysis based on phylodynamics has alluded to various suggestions concerning the infection dynamics associated with a given community and/or risk behavior. In this review, I will summarize the current methods available for identifying the transmission network using phylogeny, and present an argument on the possibilities of applying the scale-free properties to these existing frameworks. PMID:22993510

  12. Control Measures for Human Respiratory Viral Infection.

    PubMed

    Bennett, Lesley; Waterer, Grant

    2016-08-01

    New viral respiratory pathogens are emerging with increasing frequency and have potentially devastating impacts on the population worldwide. Recent examples of newly emerged threats include severe acute respiratory syndrome coronavirus, the 2009 H1N1 influenza pandemic, and Middle East respiratory syndrome coronavirus. Experiences with these pathogens have shown up major deficiencies in how we deal globally with emerging pathogens and taught us salient lessons in what needs to be addressed for future pandemics. This article reviews the lessons learnt from past experience and current knowledge on the range of measures required to limit the impact of emerging respiratory infections from public health responses down to individual patient management. Key areas of interest are surveillance programs, political limitations on our ability to respond quickly enough to emerging threats, media management, public information dissemination, infection control, prophylaxis, and individual patient management. Respiratory physicians have a crucial role to play in many of these areas and need to be aware of how to respond as new viral pathogens emerge. PMID:27486741

  13. NKT Cell Immune Responses to Viral Infection

    PubMed Central

    Tessmer, Marlowe S.; Fatima, Ayesha; Paget, Christophe; Trottein, François; Brossay, Laurent

    2010-01-01

    Background Natural killer T (NKT) cells are a heterogeneous population of innate T cells that have attracted recent interest because of their potential to regulate immune responses to a variety of pathogens. The most widely studied NKT cell subset is the invariant (i)NKT cells that recognize glycolipids in the context of the CD1d molecule. The multifaceted methods of activation iNKT cells possess and their ability to produce regulatory cytokines has made them a primary target for therapeutic studies. Objective/Methods This review gives insight into the roles of iNKT cells during infectious diseases, particularly viral infections. We also highlight the different mechanisms leading to iNKT cell activation in response to pathogens. Conclusions The iNKT cell versatility allows them to detect and respond to several viral infections. However, therapeutic approaches to specifically target iNKT cells will require additional research. Notably, examination of the roles of non-invariant NKT cells in response to pathogens warrant further investigations. PMID:19236234

  14. Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections

    PubMed Central

    Chun, Tae-Wook; Lusso, Paolo; Kaplan, Gerardo; Wolfe, Lynne; Memoli, Matthew J.; He, Miao; Vega, Hugo; Kim, Leo J.Y.; Huang, Yan; Hussein, Nadia; Nievas, Elma; Mitchell, Raquel; Garofalo, Mary; Louie, Aaron; Ireland, Derek C.; Grunes, Claire; Cimbro, Raffaello; Patel, Vyomesh; Holzapfel, Genevieve; Salahuddin, Daniel; Bristol, Tyler; Adams, David; Marciano, Beatriz E.; Hegde, Madhuri; Li, Yuxing; Calvo, Katherine R.; Stoddard, Jennifer; Justement, J. Shawn; Jacques, Jerome; Priel, Debra A. Long; Murray, Danielle; Sun, Peter; Kuhns, Douglas B.; Boerkoel, Cornelius F.; Chiorini, John A.; Di Pasquale, Giovanni; Verthelyi, Daniela; Rosenzweig, Sergio D.

    2014-01-01

    Summary Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase (the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorder of glycosylation type IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replication and cellular entry may explain a decreased susceptibility to infections. PMID:24716661

  15. Effects of cannabinoids and their receptors on viral infections.

    PubMed

    Tahamtan, Alireza; Tavakoli-Yaraki, Masoumeh; Rygiel, Tomasz P; Mokhtari-Azad, Talat; Salimi, Vahid

    2016-01-01

    Cannabinoids, the active ingredient in marijuana, and their derivatives have received remarkable attention in the last two decades because they can affect tumor growth and metastasis. There is a large body of evidence from in vivo and in vitro models showing that cannabinoids and their receptors influence the immune system, viral pathogenesis, and viral replication. The present study reviews current insights into the role of cannabinoids and their receptors on viral infections. The results reported here indicate that cannabinoids and their receptors have different sequels for viral infection. Although activation or inhibition of cannabinoid receptors in the majority of viral infections are proper targets for development of safe and effective treatments, caution is required before using pharmaceutical cannabinoids as a treatment agent for patients with viral infections. PMID:26059175

  16. [Viral nosocomial infections: the problem of contemporary hospital management].

    PubMed

    Hermanowska-Szpakowicz, Teresa; Zajkowska, Joanna M; Pancewicz, Sławomir A; Kondrusik, Maciej; Grygorczuk, Sambor S

    2003-01-01

    The most frequent viral pathogens which are the cause of nosocomial infections were presented. Influenza and parainfluenza viruses as well as RS virus affect frequently respiratory tract. So called enteric viruses which are rotaviruses, adenoviruses, small round viruses, astroviruses, caliciviruses, corona viruses, Coxackie, ECHO may be the agents of disorders in digestive tract in the form of intoxications. Viruses of viral hepatitis B, C, D and HIV, CMV, EBV may be the source of nosocomial viral infections transmitted by blood (transfusions). PMID:12910601

  17. Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis

    PubMed Central

    Asner, Sandra A.; Science, Michelle E.; Tran, Dat; Smieja, Marek; Merglen, Arnaud; Mertz, Dominik

    2014-01-01

    Background Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. Methods We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. Results Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) −0.20 days, 95% CI −0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I2 for subgroup analysis 64%, p = 0.04). Conclusions No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation. PMID:24932493

  18. VIRAL INFECTIONS BASED ON CLINICAL SAMPLING AT A SPRAY IRRIGATION SITE

    EPA Science Inventory

    The Lubbock Infection Surveillance Study (LISS) monitored viral and bacterial infections in a semiarid rural American community surrounding a major new land treatment demonstration project. The viral investigation examined the association of new viral infections in residents and ...

  19. Epidemiology of prolonged testicular infections with bovine viral diarrhea virus.

    PubMed

    Givens, M Daniel; Riddell, Kay P; Edmondson, Misty A; Walz, Paul H; Gard, Julie A; Zhang, Yijing; Galik, Patricia K; Brodersen, Bruce W; Carson, Robert L; Stringfellow, David A

    2009-10-20

    Previously, bovine viral diarrhea virus (BVDV) had been found in prolonged testicular infections following acute infection of immunocompetent bulls. The primary purpose of this research was to evaluate the production and maintenance of prolonged testicular infections after exposure to BVDV of seronegative bulls in varying circumstances. The secondary objective was to initiate assessment of the potential for transmission of BVDV via semen of bulls exhibiting a prolonged testicular infection. In total, 10 research trials were conducted. The first trial examined the duration of detectable virus in semen after intranasal inoculation of peri-pubertal bulls. The second to fifth trials examined the potential for prolonged testicular infections resulting from natural exposure of seronegative bulls to persistently infected heifers. In the last five trials, the potential for viral transmission from bulls exhibiting prolonged testicular infections to a small number of exposed animals (n=28) was evaluated. Results of this research demonstrated that prolonged testicular infections could result in detection of viral RNA in semen for 2.75 years with infectious virus grown from testicular tissue 12.5 months after viral exposure. A type 1b strain of BVDV caused prolonged testicular infection after natural exposure of seronegative bulls to a persistently infected heifer. However, transmission of BVDV to susceptible animals was not detected in the final five trials of this research. In conclusion, BVDV can persist in testicular tissue after acute infection for several years, but the potential for viral transmission from these prolonged testicular infections appears to be low. PMID:19473788

  20. Viral Respiratory Infections of Adults in the Intensive Care Unit.

    PubMed

    Nguyen, Christopher; Kaku, Shawn; Tutera, Dominic; Kuschner, Ware G; Barr, Juliana

    2016-08-01

    Viral lower respiratory tract infections (LRTIs) are an underappreciated cause of critical illness in adults. Recent advances in viral detection techniques over the past decade have demonstrated viral LRTIs are associated with rates of morbidity, mortality, and health care utilization comparable to those of seen with bacterial community acquired and nosocomial pneumonias. In this review, we describe the relationship between viral LRTIs and critical illness, as well as discuss relevant clinical features and management strategies for the more prevalent respiratory viral pathogens. PMID:25990273

  1. Studying the immune response to human viral infections using zebrafish

    PubMed Central

    Goody, Michelle F.; Sullivan, Con; Kim, Carol H.

    2014-01-01

    Humans and viruses have a long co-evolutionary history. Viral illnesses have and will continue to shape human history: from smallpox, to influenza, to HIV, and beyond. Animal models of human viral illnesses are needed in order to generate safe and effective antiviral medicines, adjuvant therapies, and vaccines. These animal models must support the replication of human viruses, recapitulate aspects of human viral illnesses, and respond with conserved immune signaling cascades. The zebrafish is perhaps the simplest, most commonly used laboratory model organism in which innate and/or adaptive immunity can be studied. Herein, we will discuss the current zebrafish models of human viral illnesses and the insights they have provided. We will highlight advantages of early life stage zebrafish and the importance of innate immunity in human viral illnesses. We will also discuss viral characteristics to consider before infecting zebrafish with human viruses as well as predict other human viruses that may be able to infect zebrafish. PMID:24718256

  2. Viral infection of the lung: host response and sequelae.

    PubMed

    Yoo, Jae-Kwang; Kim, Taeg S; Hufford, Matthew M; Braciale, Thomas J

    2013-12-01

    Because of its essential role in gas exchange and oxygen delivery, the lung has evolved a variety of strategies to control inflammation and maintain homeostasis. Invasion of the lung by pathogens (and in some instances exposure to certain noninfectious particulates) disrupts this equilibrium and triggers a cascade of events aimed at preventing or limiting colonization (and more importantly infection) by pathogenic microorganisms. In this review we focus on viral infection of the lung and summarize recent advances in our understanding of the triggering of innate and adaptive immune responses to viral respiratory tract infection, mechanisms of viral clearance, and the well-recognized consequences of acute viral infection complicating underlying lung diseases, such as asthma. PMID:23915713

  3. Harnessing RNA interference for the treatment of viral infections.

    PubMed

    Arbuthnot, Patrick

    2010-01-01

    Exploiting the RNA interference (RNAi) pathway to inhibit viral gene expression has become an active field of research. The approach has potential for therapeutic application and several viruses are susceptible to RNAi-mediated knockdown. Differences in the characteristics of individual viruses require that viral gene silencing be tailored to specific infections. Important considerations are viral tissue tropism, acute or chronic nature of the infection and the efficiency with which antiviral sequences can be delivered to affected tissue. Both synthetic short interfering RNAs (siRNAs) and expressed RNAi activators are being developed for viral therapy. The sustained silencing of expressed antiviral sequences is useful for countering chronic viral infection. siRNAs, which may be chemically modified to improve specificity and stability, are being developed for knockdown of viruses that cause acute or chronic infections. Preventing viral escape from silencing is important and overcoming this problem using combinatorial RNAi or through silencing of host dependency factors is promising. Although improving delivery efficiency and limiting off-target effects remain obstacles, rapid progress continues to be made in the field and it is likely that the goal of achieving licensed RNAi-based viral therapies will soon be realized. PMID:20697601

  4. The Ins and Outs of Viral Infection: Keystone Meeting Review

    PubMed Central

    Bird, Sara W.; Kirkegaard, Karla; Agbandje-McKenna, Mavis; Freed, Eric O.

    2014-01-01

    Newly observed mechanisms for viral entry, assembly, and exit are challenging our current understanding of the replication cycle of different viruses. To address and better understand these mechanisms, a Keystone Symposium was organized in the snowy mountains of Colorado (“The Ins and Outs of Viral Infection: Entry, Assembly, Exit, and Spread”; 30 March–4 April 2014, Beaver Run Resort, Breckenridge, Colorado, organized by Karla Kirkegaard, Mavis Agbandje-McKenna, and Eric O. Freed). The meeting served to bring together cell biologists, structural biologists, geneticists, and scientists expert in viral pathogenesis to discuss emerging mechanisms of viral ins and outs. The conference was organized around different phases of the viral replication cycle, including cell entry, viral assembly and post-assembly maturation, virus structure, cell exit, and virus spread. This review aims to highlight important topics and themes that emerged during the conference. PMID:25256395

  5. Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model

    PubMed Central

    Laurie, Karen L.; Guarnaccia, Teagan A.; Carolan, Louise A.; Yan, Ada W. C.; Aban, Malet; Petrie, Stephen; Cao, Pengxing; Heffernan, Jane M.; McVernon, Jodie; Mosse, Jennifer; Kelso, Anne; McCaw, James M.; Barr, Ian G.

    2015-01-01

    Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1–14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season. PMID:25943206

  6. 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

  7. The Contribution of Viral Genotype to Plasma Viral Set-Point in HIV Infection

    PubMed Central

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

    2014-01-01

    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

  8. Eicosanoids mediate Galaleria mellonella cellular immune response to viral infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nodulation is the predominant insect cellular immune response to bacterial and fungal infections and it can also be induced by viral infection. Treating seventh instar larvae of greater wax moth Galleria mellonella with Bovine herpes simplex virus-1 (BHSV-1) induced nodulation reactions in a dose-d...

  9. Clinical bovine viral diarrhoea virus infection in Jordan.

    PubMed

    Abutarbush, S M; Alqawasmeh, D M

    2010-12-01

    A 1-year-old Holstein Friesian heifer was presented for anorexia and acute diarrhoea. The heifer was born and raised at the farm. Bovine viral diarrhoea virus (BVDV) infection was diagnosed using clinical signs and RT-PCR. Clinical BVDV infection has never been reported in Jordan. PMID:21117287

  10. Emerging infectious diseases with cutaneous manifestations: Viral and bacterial infections.

    PubMed

    Nawas, Zeena Y; Tong, Yun; Kollipara, Ramya; Peranteau, Andrew J; Woc-Colburn, Laila; Yan, Albert C; Lupi, Omar; Tyring, Stephen K

    2016-07-01

    Given increased international travel, immigration, and climate change, bacterial and viral infections that were once unrecognized or uncommon are being seen more frequently in the Western Hemisphere. A delay in diagnosis and treatment of these diseases can lead to significant patient morbidity and mortality. However, the diagnosis and management of these infections is fraught with a lack of consistency because there is a dearth of dermatology literature on the cutaneous manifestations of these infections. We review the epidemiology, cutaneous manifestations, diagnosis, and management of these emerging bacterial and viral diseases. PMID:27317512

  11. Immune responses to viral infections: relevance for asthma.

    PubMed

    Martin, James G; Siddiqui, Sana; Hassan, Muhannad

    2006-01-01

    Severe respiratory viral infections in childhood are associated with the development of asthma later in life. Rhinovirus, respiratory syncytial virus and metapneumovirus are of particular importance as triggers of asthma. Effects of virus infection on dendritic cell function in the airways may predispose children to allergic sensitization. Asthmatic subjects may have impaired interferon responses to viral infection that also predispose to allergic sensitization. Difference in Toll-like receptor expression on airway epithelial cells is a potential mechanism for the altered immune responses of asthmatic children. PMID:16798536

  12. Redox Imbalance and Viral Infections in Neurodegenerative Diseases

    PubMed Central

    Limongi, Dolores

    2016-01-01

    Reactive oxygen species (ROS) are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). PMID:27110325

  13. Redox Imbalance and Viral Infections in Neurodegenerative Diseases.

    PubMed

    Limongi, Dolores; Baldelli, Sara

    2016-01-01

    Reactive oxygen species (ROS) are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). PMID:27110325

  14. 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

  15. NK Cell Subset Redistribution during the Course of Viral Infections

    PubMed Central

    Lugli, Enrico; Marcenaro, Emanuela; Mavilio, Domenico

    2014-01-01

    Natural killer (NK) cells are important effectors of innate immunity that play a critical role in the control of human viral infections. Indeed, given their capability to directly recognize virally infected cells without the need of specific antigen presentation, NK cells are on the first line of defense against these invading pathogens. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify anti-viral adaptive immune responses. In turn, viruses evolved and developed several mechanisms to evade NK cell-mediated immune activity. It has been reported that certain viral diseases, including human immunodeficiency virus-1 as well as human cytomegalovirus infections, are associated with a pathologic redistribution of NK cell subsets in the peripheral blood. In particular, it has been observed the expansion of unconventional CD56neg NK cells, whose effector functions are significantly impaired as compared to that of conventional CD56pos NK cells. In this review, we address the impact of these two chronic viral infections on the functional and phenotypic perturbations of human NK cell compartment. PMID:25177322

  16. 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

  17. Patterns of viral infection in honey bee queens.

    PubMed

    Francis, Roy Mathew; Nielsen, Steen Lykke; Kryger, Per

    2013-03-01

    The well-being of a colony and replenishment of the workers depends on a healthy queen. Diseases in queens are seldom reported, and our knowledge on viral infection in queens is limited. In this study, 86 honey bee queens were collected from beekeepers in Denmark. All queens were tested separately by two real-time PCRs: one for the presence of deformed wing virus (DWV), and one that would detect sequences of acute bee-paralysis virus, Kashmir bee virus and Israeli acute paralysis virus (AKI complex). Worker bees accompanying the queen were also analysed. The queens could be divided into three groups based on the level of infection in their head, thorax, ovary, intestines and spermatheca. Four queens exhibited egg-laying deficiency, but visually all queens appeared healthy. Viral infection was generally at a low level in terms of AKI copy numbers, with 134/430 tissues (31 %) showing the presence of viral infection ranging from 10(1) to 10(5) copies. For DWV, 361/340 tissues (84 %) showed presence of viral infection (DWV copies ranging from 10(2) to 10(12)), with 50 tissues showing viral titres >10(7) copies. For both AKI and DWV, the thorax was the most frequently infected tissue and the ovaries were the least frequently infected. Relative to total mass, the spermatheca showed significantly higher DWV titres than the other tissues. The ovaries had the lowest titre of DWV. No significant differences were found among tissues for AKI. A subsample of 14 queens yielded positive results for the presence of negative-sense RNA strands, thus demonstrating active virus replication in all tissues. PMID:23223622

  18. Patterns of viral infection in honey bee queens

    PubMed Central

    Francis, Roy Mathew; Nielsen, Steen Lykke

    2013-01-01

    The well-being of a colony and replenishment of the workers depends on a healthy queen. Diseases in queens are seldom reported, and our knowledge on viral infection in queens is limited. In this study, 86 honey bee queens were collected from beekeepers in Denmark. All queens were tested separately by two real-time PCRs: one for the presence of deformed wing virus (DWV), and one that would detect sequences of acute bee-paralysis virus, Kashmir bee virus and Israeli acute paralysis virus (AKI complex). Worker bees accompanying the queen were also analysed. The queens could be divided into three groups based on the level of infection in their head, thorax, ovary, intestines and spermatheca. Four queens exhibited egg-laying deficiency, but visually all queens appeared healthy. Viral infection was generally at a low level in terms of AKI copy numbers, with 134/430 tissues (31 %) showing the presence of viral infection ranging from 101 to 105 copies. For DWV, 361/340 tissues (84 %) showed presence of viral infection (DWV copies ranging from 102 to 1012), with 50 tissues showing viral titres >107 copies. For both AKI and DWV, the thorax was the most frequently infected tissue and the ovaries were the least frequently infected. Relative to total mass, the spermatheca showed significantly higher DWV titres than the other tissues. The ovaries had the lowest titre of DWV. No significant differences were found among tissues for AKI. A subsample of 14 queens yielded positive results for the presence of negative-sense RNA strands, thus demonstrating active virus replication in all tissues. PMID:23223622

  19. MAIT cells are activated during human viral infections

    PubMed Central

    van Wilgenburg, Bonnie; Scherwitzl, Iris; Hutchinson, Edward C.; Leng, Tianqi; Kurioka, Ayako; Kulicke, Corinna; de Lara, Catherine; Cole, Suzanne; Vasanawathana, Sirijitt; Limpitikul, Wannee; Malasit, Prida; Young, Duncan; Denney, Laura; Barnes, Eleanor; Ball, Jonathan; Burgess, Gary; Cooke, Graham; Dillon, John; Gore, Charles; Foster, Graham; Guha, Neil; Halford, Rachel; Herath, Cham; Holmes, Chris; Howe, Anita; Hudson, Emma; Irving, William; Khakoo, Salim; Koletzki, Diana; Martin, Natasha; Mbisa, Tamyo; McKeating, Jane; McLauchlan, John; Miners, Alec; Murray, Andrea; Shaw, Peter; Simmonds, Peter; Spencer, Chris; Targett-Adams, Paul; Thomson, Emma; Vickerman, Peter; Zitzmann, Nicole; Moore, Michael D.; Fabris, Paolo; Giordani, Maria Teresa; Oo, Ye Htun; Laidlaw, Stephen M.; Dustin, Lynn B.; Ho, Ling-Pei; Thompson, Fiona M.; Ramamurthy, Narayan; Mongkolsapaya, Juthathip; Willberg, Christian B.; Screaton, Gavin R.; Klenerman, Paul

    2016-01-01

    Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation—driving cytokine release and Granzyme B upregulation—is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-α leads to specific MAIT cell activation in vivo in parallel with an enhanced therapeutic response. Moreover, TCR-independent activation of MAIT cells leads to a reduction of HCV replication in vitro mediated by IFN-γ. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology. PMID:27337592

  20. MAIT cells are activated during human viral infections.

    PubMed

    van Wilgenburg, Bonnie; Scherwitzl, Iris; Hutchinson, Edward C; Leng, Tianqi; Kurioka, Ayako; Kulicke, Corinna; de Lara, Catherine; Cole, Suzanne; Vasanawathana, Sirijitt; Limpitikul, Wannee; Malasit, Prida; Young, Duncan; Denney, Laura; Moore, Michael D; Fabris, Paolo; Giordani, Maria Teresa; Oo, Ye Htun; Laidlaw, Stephen M; Dustin, Lynn B; Ho, Ling-Pei; Thompson, Fiona M; Ramamurthy, Narayan; Mongkolsapaya, Juthathip; Willberg, Christian B; Screaton, Gavin R; Klenerman, Paul

    2016-01-01

    Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation-driving cytokine release and Granzyme B upregulation-is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-α leads to specific MAIT cell activation in vivo in parallel with an enhanced therapeutic response. Moreover, TCR-independent activation of MAIT cells leads to a reduction of HCV replication in vitro mediated by IFN-γ. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology. PMID:27337592

  1. Emerging viral infections with special reference to India.

    PubMed

    Banerjee, K

    1996-04-01

    An emerging viral infection may be a totally new disease with undescribed symptomatology as it was in the case of Kyasanur forest disease in Karnataka, but more often it is an introduction of a known or little known disease in an area where the disease did not occur earlier e.g. yellow fever in Kenya or Rift valley fever in Egypt. The virus may show altered degree of virulence due to many changing factors as in the case of the different haemorrhagic fevers. Many factors may contribute to the emergence of viral infections which may be genetic exchanges or mutations; adaptation to new hosts or vectors; and changed social patterns of humans like urbanization, rapid transport, trade, migration of people or of vectors, strain on civic facilities or changing moral values and life-styles. Large scale changes in ecology due to global warming, deforestation or afforestation, building of dams or canals, changed agricultural practices, rearing of livestock or birds may also contribute to emergence of viral diseases. A number of emergent virus infections relatively important to India have been discussed. To combat emergent virus infections, a comprehensive strategy needs to be evolved. A national viral surveillance system needs to be established. Epidemiology of virus diseases needs to be studied in depth. Development of diagnostic reagents and their supply to investigating centres, a Central serum bank, and a virus respository are important factors. Research and development on viruses, as regards the epidemiology, diagnosis, pathogenesis and vaccinology of virus infections need to be strengthened. An international network of databases of virus infections needs to be instituted. A global network for the diagnosis and containment of emerging viral diseases is advocated. PMID:8935739

  2. Current Approaches on Viral Infection: Proteomics and Functional Validations

    PubMed Central

    Zheng, Jie; Tan, Boon Huan; Sugrue, Richard; Tang, Kai

    2012-01-01

    Viruses could manipulate cellular machinery to ensure their continuous survival and thus become parasites of living organisms. Delineation of sophisticated host responses upon virus infection is a challenging task. It lies in identifying the repertoire of host factors actively involved in the viral infectious cycle and characterizing host responses qualitatively and quantitatively during viral pathogenesis. Mass spectrometry based proteomics could be used to efficiently study pathogen-host interactions and virus-hijacked cellular signaling pathways. Moreover, direct host and viral responses upon infection could be further investigated by activity-based functional validation studies. These approaches involve drug inhibition of secretory pathway, immunofluorescence staining, dominant negative mutant of protein target, real-time PCR, small interfering siRNA-mediated knockdown, and molecular cloning studies. In this way, functional validation could gain novel insights into the high-content proteomic dataset in an unbiased and comprehensive way. PMID:23162545

  3. Novel approaches and challenges to treatment of CNS viral infections

    PubMed Central

    Nath, Avindra; Tyler, Kenneth L.

    2014-01-01

    Existing and emerging viral CNS infections are major sources of human morbidity and mortality. Treatments of proven efficacy are currently limited predominantly to herpesviruses and human immunodeficiency virus. Development of new therapies has been hampered by the lack of appropriate animal model systems for some important viruses and by the difficulty in conducting human clinical trials for diseases that may be rare, or in the case of arboviral infections, often have variable seasonal and geographic incidence. Nonetheless, many novel approaches to antiviral therapy are available including candidate thiazolide and purazinecarboxamide derivatives with potential broad-spectrum antiviral efficacy. New herpesvirus drugs include viral helicase-primase and terminase inhibitors. The use of antisense oligonucleotides and other strategies to interfere with viral RNA translation has shown efficacy in experimental models of CNS viral disease. Identifying specific molecular targets within viral replication cycles has led to many existing antivirals and will undoubtedly continue to be the basis of future drug design. A promising new area of research involves therapies based on enhanced understanding of host antiviral immune responses. Toll-like receptor agonists, and drugs that inhibit specific cytokines as well as interferon preparations have all shown potential therapeutic efficacy. Passive transfer of virus-specific cytotoxic T-lymphocytes have been used in humans and may provide an effective therapies for some herpesvirus infections and potentially for progressive multifocal leukoencephalopathy. Humanized monoclonal antibodies directed against specific viral proteins have been developed and in several cases evaluated in humans in settings including West Nile virus and HIV infection and in pre-exposure prophylaxis for rabies. PMID:23913580

  4. Emerging Viral Infections of the Central Nervous System

    PubMed Central

    Tyler, Kenneth L.

    2010-01-01

    The first part of this review ended with a discussion of new niches for known viruses as illustrated by viral central nervous system (CNS) disease associated with organ transplant and the syndrome of human herpesvirus 6–associated posttransplant acute limbic encephalitis. In this part, we begin with a continuation of this theme, reviewing the association of JC virus–associated progressive multifocal leukoencephalopathy (PML) with novel immunomodulatory agents. This part then continues with emerging viral infections associated with importation of infected animals (monkeypox virus), then spread of vectors and enhanced vector competence (chikungunya virus [CHIK]), and novel viruses causing CNS infections including Nipah and Hendra viruses and bat lyssaviruses (BLV). PMID:19752295

  5. Neuroinvasion and Inflammation in Viral Central Nervous System Infections

    PubMed Central

    Schroten, Horst

    2016-01-01

    Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) have been described as relevant sites of entry for specific viruses as well as for leukocytes, which are recruited during the proinflammatory response in the course of CNS infection. In this review, we illustrate examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed. Furthermore, we highlight the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections. We discuss in detail the link between specific cytokines and chemokines and leukocyte migration profiles. The thorough understanding of the complex and interrelated inflammatory mechanisms as well as identifying universal mediators promoting CNS inflammation is essential for the development of new diagnostic and treatment strategies. PMID:27313404

  6. Molecular Imaging of Influenza and Other Emerging Respiratory Viral Infections

    PubMed Central

    Lawler, James; Paragas, Jason; Jahrling, Peter B.; Mollura, Daniel J.

    2011-01-01

    Research on the pathogenesis and therapy of influenza and other emerging respiratory viral infections would be aided by methods that directly visualize pathophysiologic processes in patients and laboratory animals. At present, imaging of diseases, such as swine-origin H1N1 influenza, is largely restricted to chest radiograph and computed tomography (CT), which can detect pulmonary structural changes in severely ill patients but are more limited in characterizing the early stages of illness, differentiating inflammation from infection or tracking immune responses. In contrast, imaging modalities, such as positron emission tomography, single photon emission CT, magnetic resonance imaging, and bioluminescence imaging, which have become useful tools for investigating the pathogenesis of a range of disease processes, could be used to advance in vivo studies of respiratory viral infections in patients and animals. Molecular techniques might also be used to identify novel biomarkers of disease progression and to evaluate new therapies. PMID:21422476

  7. Viral lesions of the mouth in HIV-infected patients.

    PubMed

    Itin, P H; Lautenschlager, S

    1997-01-01

    Viral lesions of the mouth in patients with HIV infection are common and these diseases any be a marker for HIV and disease progression. We review the spectrum of oral viral manifestations and discuss treatment modalities. The most common Epstein-Barr virus (EBV)-induced disorder in HIV-infected patients is oral hairy leukoplakia. EBV-related oral B-cell and T-cell lymphoma in AIDS patients has been described repeatedly. Herpes virus type 1 and rarely type 2 may lead to painful and resistant oral ulcers, and systemic treatment with acyclovir, valaciclovir or famciclovir is indicated. In acyclovir-resistant cases foscarnet is the treatment of choice. In recent years it has been documented that Kaposi's sarcoma, which often affects oral mucosa, is probably induced by herpesvirus type 8. Cytomegalovirus was found in 53% of cases with herpesviridae-induced mucosal ulcers as the only ulcerogenic viral agent in AIDS patients. In severe cytomegalovirus infection treatment with ganciclovir is helpful. Viral warts induced by different HPV may occur in the mouth. Several physical treatment modalities are possible in the oral mucosa. In AIDS patients mollusca contagiosa may occur as large and atypical lesions in the face and lips and rarely in the oral cavity. Cryotherapy is a bloodless treatment in such patients. PMID:9031782

  8. Viral infections and the development of asthma in children

    PubMed Central

    2013-01-01

    Viral aetiology, host susceptibility (in particular allergic predisposition and sensitization), and illness severity, timing and frequency all appear to contribute as synergistic factors to the risk of developing asthma. Experimental models have shown both innate and adaptive immune responses contribute to this risk with lung inflammatory cells showing marked differences in phenotype and function in young compared with older animals, and these differences are further enhanced following virus infection. Findings to date strongly suggest that the impact of infant and preschool viral infections on the maturing immune system and developing lung that subsequently result in an asthma phenotype occur during a critical susceptibility period, and in a genetically susceptible host. There are currently no therapeutic strategies that allow primary or secondary prevention of asthma following early life viral respiratory infections in high-risk children, thus a focus on understanding the mechanisms of progression from viral wheezing in infants and preschool children to asthma development are urgently needed. This review summarizes the data reporting the role of the two most common viruses, that is, respiratory syncytial virus and human rhinovirus, that result in asthma development, comparing risk factors for disease progression, and providing insight into strategies that might be adopted to prevent asthma development. PMID:25165549

  9. Viral infections and the development of asthma in children.

    PubMed

    Saglani, Sejal

    2013-08-01

    Viral aetiology, host susceptibility (in particular allergic predisposition and sensitization), and illness severity, timing and frequency all appear to contribute as synergistic factors to the risk of developing asthma. Experimental models have shown both innate and adaptive immune responses contribute to this risk with lung inflammatory cells showing marked differences in phenotype and function in young compared with older animals, and these differences are further enhanced following virus infection. Findings to date strongly suggest that the impact of infant and preschool viral infections on the maturing immune system and developing lung that subsequently result in an asthma phenotype occur during a critical susceptibility period, and in a genetically susceptible host. There are currently no therapeutic strategies that allow primary or secondary prevention of asthma following early life viral respiratory infections in high-risk children, thus a focus on understanding the mechanisms of progression from viral wheezing in infants and preschool children to asthma development are urgently needed. This review summarizes the data reporting the role of the two most common viruses, that is, respiratory syncytial virus and human rhinovirus, that result in asthma development, comparing risk factors for disease progression, and providing insight into strategies that might be adopted to prevent asthma development. PMID:25165549

  10. Exosome Biogenesis, Regulation, and Function in Viral Infection

    PubMed Central

    Alenquer, Marta; Amorim, Maria João

    2015-01-01

    Exosomes are extracellular vesicles released upon fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. They originate as intraluminal vesicles (ILVs) during the process of MVB formation. Exosomes were shown to contain selectively sorted functional proteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in the physiology of the healthy and diseased organism. Challenges in the field include the identification of mechanisms sustaining packaging of membrane-bound and soluble material to these vesicles and the understanding of the underlying processes directing MVBs for degradation or fusion with the plasma membrane. The investigation into the formation and roles of exosomes in viral infection is in its early years. Although still controversial, exosomes can, in principle, incorporate any functional factor, provided they have an appropriate sorting signal, and thus are prone to viral exploitation. This review initially focuses on the composition and biogenesis of exosomes. It then explores the regulatory mechanisms underlying their biogenesis. Exosomes are part of the endocytic system, which is tightly regulated and able to respond to several stimuli that lead to alterations in the composition of its sub-compartments. We discuss the current knowledge of how these changes affect exosomal release. We then summarize how different viruses exploit specific proteins of endocytic sub-compartments and speculate that it could interfere with exosome function, although no direct link between viral usage of the endocytic system and exosome release has yet been reported. Many recent reports have ascribed functions to exosomes released from cells infected with a variety of animal viruses, including viral spread, host immunity, and manipulation of the microenvironment, which are discussed. Given the ever-growing roles and importance of exosomes in viral infections, understanding what regulates their composition and levels, and

  11. A Child with Acute Encephalopathy Associated with Quadruple Viral Infection

    PubMed Central

    Nakata, Keiko; Kashiwagi, Mitsuru; Masuda, Midori; Shigehara, Seiji; Oba, Chizu; Murata, Shinya; Kase, Tetsuo; Komano, Jun A.

    2015-01-01

    Pediatric acute encephalopathy (AE) was sometimes attributed to virus infection. However, viral infection does not always result in AE. The risk factors for developing infantile AE upon virus infection remain to be determined. Here, we report an infant with AE co-infected with human herpesvirus-6 (HHV-6) and three picornaviruses, including coxsackievirus A6 (CVA6), Enterovirus D68 (EV-D68), and human parechovirus (HPeV). EV-D68 was vertically transmitted to the infant from his mother. CVA6 and HPeV were likely transmitted to the infant at the nursery school. HHV-6 might be re-activated in the patient. It remained undetermined, which pathogen played the central role in the AE pathogenesis. However, active, simultaneous infection of four viruses should have evoked the cytokine storm, leading to the pathogenesis of AE. Conclusion: an infant case with active quadruple infection of potentially AE-causing viruses was seldom reported partly because systematic nucleic acid-based laboratory tests on picornaviruses were not common. We propose that simultaneous viral infection may serve as a risk factor for the development of AE. PMID:25883930

  12. Detection of viral infections using colloidal quantum dots

    NASA Astrophysics Data System (ADS)

    Bentzen, Elizabeth L.; House, Frances S.; Utley, Thomas J.; Crowe, James E., Jr.; Wright, David W.

    2006-02-01

    Fluorescence is a tool widely employed in biological assays. Fluorescent semiconducting nanocrystals, quantum dots (QDs), are beginning to find their way into the tool box of many biologist, chemist and biochemist. These quantum dots are an attractive alternative to the traditional organic dyes due to their broad excitation spectra, narrow emission spectra and photostability. Quantum dots were used to detect and monitor the progession of viral glycoproteins, F (fusion) and G (attachment), from Respiratory Syncytial Virus (RSV) in HEp-2 cells. Additionally, oligo-Qdot RNA probes have been developed for identification and detection of mRNA of the N(nucleocapsid) protein for RSV. The use of quantum dot-FISH probes provides another confirmatory route to diagnostics as well as a new class of probes for monitoring the flux and fate of viral RNA RSV is the most common cause of lower respiratory tract infection in children worldwide and the most common cause of hospitalization of infants in the US. Antiviral therapy is available for treatment of RSV but is only effective if given within the first 48 hours of infection. Existing test methods require a virus level of at least 1000-fold of the amount needed for infection of most children and require several days to weeks to obtain results. The use of quantum dots may provide an early, rapid method for detection and provide insight into the trafficking of viral proteins during the course of infection.

  13. Opioids and Viral Infections: A Double-Edged Sword

    PubMed Central

    Tahamtan, Alireza; Tavakoli-Yaraki, Masoumeh; Mokhtari-Azad, Talat; Teymoori-Rad, Majid; Bont, Louis; Shokri, Fazel; Salimi, Vahid

    2016-01-01

    Opioids and their receptors have received remarkable attention because they have the ability to alter immune function, which affects disease progression. In vitro and in vivo findings as well as observations in humans indicate that opioids and their receptors positively or negatively affect viral replication and virus-mediated pathology. The present study reviews recent insights in the role of opioids and their receptors in viral infections and discusses possible therapeutic opportunities. This review supports the emerging concept that opioids and their receptors have both favorable and unfavorable effects on viral disease, depending on the type of virus. Targeting of the opioid system is a potential option for developing effective therapies; however caution is required in relation to the beneficial functions of opioid systems. PMID:27446011

  14. West Nile viral infection of equids

    PubMed Central

    Angenvoort, J.; Brault, A.C.; Bowen, R.A.; Groschup, M.H.

    2015-01-01

    West Nile virus (WNV) is a flavivirus transmitted between certain species of birds and mosquito vectors. Tangential infections of equids and subsequent equine epizootics have occurred historically. Although the attack rate has been estimated to be below 10%, mortality rates can approach 50% in horses that present clinical disease. Symptoms are most commonly presenting in the form of encephalitis with ataxia as well as limb weakness, recumbency and muscle fasciculation. The most effective strategy for prevention of equine disease is proper vaccination with one of the numerous commercially available vaccines available in North America or the European Union. Recently, WNV has been increasingly associated with equine epizootics resulting from novel non-lineage-1a viruses in expanding geographic areas. However, specific experimental data on the virulence of these novel virus strains is lacking and questions remain as to the etiology of the expanded epizootics: whether it be a function of inherent virulence or ecological and/or climactic factors that could precipitate the altered epidemiological patterns observed. PMID:24035480

  15. Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN-I responses.

    PubMed

    Honke, Nadine; Shaabani, Namir; Merches, Katja; Gassa, Asmae; Kraft, Anke; Ehrhardt, Katrin; Häussinger, Dieter; Löhning, Max; Dittmer, Ulf; Hengel, Hartmut; Recher, Mike; Lang, Philipp A; Lang, Karl S

    2016-02-01

    Acute or chronic viral infections can lead to generalized immunosuppression. Several mechanisms, such as immunopathology of CD8(+) T cells, inhibitory receptors, or regulatory T (Treg) cells, contribute to immune dysfunction. Moreover, patients with chronic viral infections usually do not respond to vaccination, a finding that has not been previously explained. Recently, we reported that CD169(+) macrophages enforce viral replication, which is essential for guaranteeing antigen synthesis and efficient adaptive immune responses. In the present study, we used a chronic lymphocytic choriomeningitis virus infection mouse model to determine whether this mechanism is affected by chronic viral infection, which may impair the activation of adaptive immunity. We found that enforced viral replication of a superinfecting virus is completely blunted in chronically infected mice. This absence of enforced viral replication in CD169(+) macrophages is not explained by CD8(+) T-cell-mediated immunopathology but rather by prolonged IFN-I responses. Consequently, the absence of viral replication impairs both antigen production and the adaptive immune response against the superinfecting virus. These findings indicate that chronic infection leads to sustained IFN-I action, which is responsible for the absence of an antiviral immune response against a secondary viral infection. PMID:26507703

  16. Aptamers in Diagnostics and Treatment of Viral Infections

    PubMed Central

    Wandtke, Tomasz; Woźniak, Joanna; Kopiński, Piotr

    2015-01-01

    Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), SARS (Severe Acute Respiratory Syndrome), H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases. PMID:25690797

  17. A review of hepatitis viral infections in Pakistan.

    PubMed

    Bosan, Altaf; Qureshi, Huma; Bile, Khalif Mohamud; Ahmad, Irtaza; Hafiz, Rehan

    2010-12-01

    A review of published literature on viral hepatitis infections in Pakistan is presented. A total of 220 abstracts available in the Pakmedinet and Medline have been searched. All relevant articles were reviewed to determine the prevalence of hepatitis viral infections in Pakistan. Two hundred and three (203) relevant articles/abstracts including twenty nine supporting references are included in this review. Of the articles on prevalence of hepatitis infection, seven were related to Hepatitis A, fifteen to Hepatitis E while the remaining articles were on frequency of hepatitis B and C in different disease and healthy population groups. These included eight studies on healthy children, three on vertical transmission, nineteen on pregnant women, fifteen on healthy individuals, six on army recruits, thirty one on blood donors, thirteen on health care workers, five on unsafe injections, seventeen on high risk groups, five on patients with provisional diagnosis of hepatitis, thirty three on patients with chronic liver disease, four on genotypes of HBV and five on genotypes of HCV. This review highlights the lack of community-based epidemiological work as the number of subjects studied were predominantly patients, high risk groups and healthy blood donors. High level of Hepatitis A seroconversion was found in children and this viral infection accounts for almost 50%-60% of all cases of acute viral hepatitis in children in Pakistan. Hepatitis E is endemic in the country affecting mostly the adult population and epidemic situations have been reported from many parts of the country. The mean results of HBsAg and Anti-HCV prevalence on the basis of data aggregated from several studies was calculated which shows 2.3% and 2.5% prevalence of HBsAg and Anti-HCV in children, 2.5% and 5.2% among pregnant women, 2.6% and 5.3% in general population, 3.5% and 3.1% in army recruits, 2.4% and 3.6% in blood donors, 6.0% and 5.4% in health care workers, 13.0% and 10.3% in high risk groups

  18. Vaccine to Control the Viral Infection of Fish.

    DOEpatents

    Leong, JoAnn Ching

    1994-10-11

    Subunit vaccines and their use for immunizing fish against infection by viruses are disclosed. In particular, plasmid pG8 is constructed by joining, with the plasmid pUC8, DNA which encodes the glycoprotein of infectious hematopoietic necrosis virus (IHNV). E. coli cells are transformed by pG8, whereby pure viral antigen is produced to provide a vaccine for the control of IHNV in fish. 10 figs.

  19. Vaccine to control the viral infection of fish

    DOEpatents

    Leong, Jo-Ann C.

    1994-10-11

    Subunit vaccines and their use for immunizing fish against infection by viruses are disclosed. In particular, plasmid pG8 is constructed by joining, with the plasmid pUC8, DNA which encodes the glycoprotein of infectious hematopoietic necrosis virus (IHNV). E. coli cells are transformed by pG8, whereby pure viral antigen is produced to provide a vaccine for the control of IHNV in fish.

  20. Viral Co-infection and Leprosy Outcomes: A Cohort Study

    PubMed Central

    Machado, Paulo R. L.; Machado, Lídia M.; Shibuya, Mayume; Rego, Jamile; Johnson, Warren D.; Glesby, Marshall J.

    2015-01-01

    Background The role of the host immunity in determining leprosy clinical forms and complications is well recognized, implying that changes in the immune status may interfere with several aspects of the disease. Therefore, we hypothesized that the presence of viral co-infections and associated immunological changes will have a clinical impact on leprosy outcomes. The aim of our study was to determine the clinical impact of human immunodeficiency virus (HIV), human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection on the development of reactions, neuritis, neuropathy and relapses. Methodology/Principal Findings Cohort study in 245 leprosy subjects from Bahia, Brazil. Patients were followed from the time of diagnosis until at least the end of multidrug therapy. Viral co-infection was detected in 36 out of the 245 patients (14.7%). Specific co-infection rates were 10.6% for HBV, 2.9% for HIV, 2.5% for HTLV-1 and 0.8% for HCV. All four groups of co-infected patients had higher rates of neuritis and nerve function impairment compared to non co-infected leprosy subjects. The relapse rate was also higher in the co-infected group (8.3%) versus patients without co-infection (1.9%); relative risk 4.37, 95% confidence interval 1.02–18.74. Conclusions/Significance Leprosy patients should be screened for HBV, HCV, HIV and HTLV-1 co-infections. Besides contributing to better health care, this measure will facilitate the early detection of severe complications through targeting of higher risk patients. PMID:26267882

  1. A survey of overlooked viral infections in biological experiment systems.

    PubMed

    Wang, Yajing; Wang, Hui; Xu, Kunhan; Ni, Peixiang; Zhang, Huan; Ma, Jinmin; Yang, Huanming; Xu, Feng

    2014-01-01

    It is commonly accepted that there are many unknown viruses on the planet. For the known viruses, do we know their prevalence, even in our experimental systems? Here we report a virus survey using recently published small (s)RNA sequencing datasets. The sRNA reads were assembled and contigs were screened for virus homologues against the NCBI nucleotide (nt) database using the BLASTn program. To our surprise, approximately 30% (28 out of 94) of publications had highly scored viral sequences in their datasets. Among them, only two publications reported virus infections. Though viral vectors were used in some of the publications, virus sequences without any identifiable source appeared in more than 20 publications. By determining the distributions of viral reads and the antiviral RNA interference (RNAi) pathways using the sRNA profiles, we showed evidence that many of the viruses identified were indeed infecting and generated host RNAi responses. As virus infections affect many aspects of host molecular biology and metabolism, the presence and impact of viruses needs to be actively investigated in experimental systems. PMID:25144530

  2. Sunscreens Cause Coral Bleaching by Promoting Viral Infections

    PubMed Central

    Danovaro, Roberto; Bongiorni, Lucia; Corinaldesi, Cinzia; Giovannelli, Donato; Damiani, Elisabetta; Astolfi, Paola; Greci, Lucedio; Pusceddu, Antonio

    2008-01-01

    Background Coral bleaching (i.e., the release of coral symbiotic zooxanthellae) has negative impacts on biodiversity and functioning of reef ecosystems and their production of goods and services. This increasing world-wide phenomenon is associated with temperature anomalies, high irradiance, pollution, and bacterial diseases. Recently, it has been demonstrated that personal care products, including sunscreens, have an impact on aquatic organisms similar to that of other contaminants. Objectives Our goal was to evaluate the potential impact of sunscreen ingredients on hard corals and their symbiotic algae. Methods In situ and laboratory experiments were conducted in several tropical regions (the Atlantic, Indian, and Pacific Oceans, and the Red Sea) by supplementing coral branches with aliquots of sunscreens and common ultraviolet filters contained in sunscreen formula. Zooxanthellae were checked for viral infection by epifluorescence and transmission electron microscopy analyses. Results Sunscreens cause the rapid and complete bleaching of hard corals, even at extremely low concentrations. The effect of sunscreens is due to organic ultraviolet filters, which are able to induce the lytic viral cycle in symbiotic zooxanthellae with latent infections. Conclusions We conclude that sunscreens, by promoting viral infection, potentially play an important role in coral bleaching in areas prone to high levels of recreational use by humans. PMID:18414624

  3. A Survey of Overlooked Viral Infections in Biological Experiment Systems

    PubMed Central

    Wang, Yajing; Wang, Hui; Xu, Kunhan; Ni, Peixiang; Zhang, Huan; Ma, Jinmin; Yang, Huanming; Xu, Feng

    2014-01-01

    It is commonly accepted that there are many unknown viruses on the planet. For the known viruses, do we know their prevalence, even in our experimental systems? Here we report a virus survey using recently published small (s)RNA sequencing datasets. The sRNA reads were assembled and contigs were screened for virus homologues against the NCBI nucleotide (nt) database using the BLASTn program. To our surprise, approximately 30% (28 out of 94) of publications had highly scored viral sequences in their datasets. Among them, only two publications reported virus infections. Though viral vectors were used in some of the publications, virus sequences without any identifiable source appeared in more than 20 publications. By determining the distributions of viral reads and the antiviral RNA interference (RNAi) pathways using the sRNA profiles, we showed evidence that many of the viruses identified were indeed infecting and generated host RNAi responses. As virus infections affect many aspects of host molecular biology and metabolism, the presence and impact of viruses needs to be actively investigated in experimental systems. PMID:25144530

  4. Severe hindrance of viral infection propagation in spatially extended hosts.

    PubMed

    Capitán, José A; Cuesta, José A; Manrubia, Susanna C; Aguirre, Jacobo

    2011-01-01

    The production of large progeny numbers affected by high mutation rates is a ubiquitous strategy of viruses, as it promotes quick adaptation and survival to changing environments. However, this situation often ushers in an arms race between the virus and the host cells. In this paper we investigate in depth a model for the dynamics of a phenotypically heterogeneous population of viruses whose propagation is limited to two-dimensional geometries, and where host cells are able to develop defenses against infection. Our analytical and numerical analyses are developed in close connection to directed percolation models. In fact, we show that making the space explicit in the model, which in turn amounts to reducing viral mobility and hindering the infective ability of the virus, connects our work with similar dynamical models that lie in the universality class of directed percolation. In addition, we use the fact that our model is a multicomponent generalization of the Domany-Kinzel probabilistic cellular automaton to employ several techniques developed in the past in that context, such as the two-site approximation to the extinction transition line. Our aim is to better understand propagation of viral infections with mobility restrictions, e.g., in crops or in plant leaves, in order to inspire new strategies for effective viral control. PMID:21912595

  5. Viral infections in beta-thalassemia/hemoglobin E patients.

    PubMed

    Wasi, C; Kuntang, R; Louisirirotchanakul, S; Siritantikorn, S; Fucharoen, S; Aswapokee, P; Aswapokee, N; Hirunraks, A; Wasi, P

    1987-01-01

    One hundred ten patients with beta-thal/Hb E disease and 60 normal controls matched for age and socioeconomic status were followed for 1.5 years. They were examined clinically, and blood and plasma were studied for Coxsackie B viruses and others. The findings suggest that the patients are more susceptible to Coxsackie B virus but not to rubella, herpes simplex, cytomegalovirus, adenovirus, and M. pneumoniae. In contrast to bacterial infections, splenectomized patients did not show evidence of increased viral infections. PMID:2825835

  6. Respiratory Viral Infections and Subversion of Cellular Antioxidant Defenses

    PubMed Central

    Komaravelli, Narayana; Casola, Antonella

    2014-01-01

    Reactive oxygen species (ROS) formation is part of normal cellular aerobic metabolism, due to respiration and oxidation of nutrients in order to generate energy. Low levels of ROS are involved in cellular signaling and are well controlled by the cellular antioxidant defense system. Elevated levels of ROS generation due to pollutants, toxins and radiation exposure, as well as infections, are associated with oxidative stress causing cellular damage. Several respiratory viruses, including respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and influenza, induce increased ROS formation, both intracellularly and as a result of increased inflammatory cell recruitment at the site of infection. They also reduce antioxidant enzyme (AOE) levels and/or activity, leading to unbalanced oxidative-antioxidant status and subsequent oxidative cell damage. Expression of several AOE is controlled by the activation of the nuclear transcription factor NF-E2-related factor 2 (Nrf2), through binding to the antioxidant responsive element (ARE) present in the AOE gene promoters. While exposure to several pro-oxidant stimuli usually leads to Nrf2 activation and upregulation of AOE expression, respiratory viral infections are associated with inhibition of AOE expression/activity, which in the case of RSV and hMPV is associated with reduced Nrf2 nuclear localization, decreased cellular levels and reduced ARE-dependent gene transcription. Therefore, administration of antioxidant mimetics or Nrf2 inducers represents potential viable therapeutic approaches to viral-induced diseases, such as respiratory infections and other infections associated with decreased cellular antioxidant capacity. PMID:25584194

  7. New Insights into IDO Biology in Bacterial and Viral Infections

    PubMed Central

    Schmidt, Susanne V.; Schultze, Joachim L.

    2014-01-01

    Initially, indoleamine-2,3-dioxygenase (IDO) has been introduced as a bactericidal effector mechanism and has been linked to T-cell immunosuppression and tolerance. In recent years, evidence has been accumulated that IDO also plays an important role during viral infections including HIV, influenza, and hepatitis B and C. Moreover, novel aspects about the role of IDO in bacterial infections and sepsis have been revealed. Here, we review these recent findings highlighting the central role of IDO and tryptophan metabolism in many major human infections. Moreover, we also shed light on issues concerning human-specific and mouse-specific host–pathogen interactions that need to be considered when studying the biology of IDO in the context of infections. PMID:25157255

  8. Tissue myeloid cells in SIV-infected primates acquire viral DNA through phagocytosis of infected T cells.

    PubMed

    Calantone, Nina; Wu, Fan; Klase, Zachary; Deleage, Claire; Perkins, Molly; Matsuda, Kenta; Thompson, Elizabeth A; Ortiz, Alexandra M; Vinton, Carol L; Ourmanov, Ilnour; Loré, Karin; Douek, Daniel C; Estes, Jacob D; Hirsch, Vanessa M; Brenchley, Jason M

    2014-09-18

    The viral accessory protein Vpx, expressed by certain simian and human immunodeficiency viruses (SIVs and HIVs), is thought to improve viral infectivity of myeloid cells. We infected 35 Asian macaques and African green monkeys with viruses that do or do not express Vpx and examined viral targeting of cells in vivo. While lack of Vpx expression affected viral dynamics in vivo, with decreased viral loads and infection of CD4⁺ T cells, Vpx expression had no detectable effect on infectivity of myeloid cells. Moreover, viral DNA was observed only within myeloid cells in tissues not massively depleted of CD4⁺ T cells. Myeloid cells containing viral DNA also showed evidence of T cell phagocytosis in vivo, suggesting that their viral DNA may be attributed to phagocytosis of SIV-infected T cells. These data suggest that myeloid cells are not a major source of SIV in vivo, irrespective of Vpx expression. PMID:25238099

  9. Functional Role of Infective Viral Particles on Metal Reduction

    SciTech Connect

    Coates, John D.

    2014-04-01

    A proposed strategy for the remediation of uranium (U) contaminated sites was based on the immobilization of U by reducing the oxidized soluble U, U(VI), to form a reduced insoluble end product, U(IV). Previous studies identified Geobacter sp., including G. sulfurreducens and G. metallireducens, as predominant U(VI)-reducing bacteria under acetate-oxidizing and U(VI)-reducing conditions. Examination of the finished genome sequence annotation of the canonical metal reducing species Geobacter sulfurreducens strain PCA and G. metallireduceans strain GS-15 as well as the draft genome sequence of G. uraniumreducens strain Rf4 identified phage related proteins. In addition, the completed genome for Anaeromyxobacter dehalogenans and the draft genome sequence of Desulfovibrio desulfuricans strain G20, two more model metal-reducing bacteria, also revealed phage related sequences. The presence of these gene sequences indicated that Geobacter spp., Anaeromyxobacter spp., and Desulfovibrio spp. are susceptible to viral infection. Furthermore, viral populations in soils and sedimentary environments in the order of 6.4×10{sup 6}–2.7×10{sup 10} VLP’s cm{sup -3} have been observed. In some cases, viral populations exceed bacterial populations in these environments suggesting that a relationship may exist between viruses and bacteria. Our preliminary screens of samples collected from the ESR FRC indicated that viral like particles were observed in significant numbers. The objective of this study was to investigate the potential functional role viruses play in metal reduction specifically Fe(III) and U(VI) reduction, the environmental parameters affecting viral infection of metal reducing bacteria, and the subsequent effects on U transport.

  10. Experimental infection of mice with bovine viral diarrhea virus.

    PubMed

    Seong, Giyong; Oem, Jae-Ku; Lee, Kyung-Hyun; Choi, Kyoung-Seong

    2015-06-01

    The objective of this study was to test the ability of bovine viral diarrhea virus (BVDV) to infect mice. Two mice each were either mock infected or inoculated with one of three BVDV strains by the intraperitoneal (IP) (n = 8) or intranasal (IN) (n = 8) route. All mice were euthanized at day 7 postinfection (p.i.). None of the infected mice exhibited any clinical signs of illness; however, the tissues harvested after BVDV challenge showed significant histopathological changes. Blood samples from five mice that were injected IP and one mouse that was inoculated IN were positive for BVDV by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry (IHC) was used to assess the presence of viral antigen in the organs of mice infected with three BVDV strains. In IP-injected mice, BVDV antigen was detected in the spleen (5/6), mesenteric lymph nodes (4/6), lymphatic tissue of the lung (3/6), lung (1/6), and stomach (1/6) of the infected mice; however, it was not detected in the liver (0/6) or kidney (0/6). In IN-inoculated mice, BVDV antigen was detected in the lung and mesenteric lymph nodes of one BVDV-infected mouse but was not detected in other tissues. The results of this study suggest that the spleen is the most reliable tissue for BVDV antigen detection using IHC in the IP-injected group. Our study demonstrates that mice can be infected by BVDV. This is the first report of BVDV infection in mice. PMID:25850760

  11. Mixed Viral Infections Circulating in Hospitalized Patients with Respiratory Tract Infections in Kuwait

    PubMed Central

    Essa, Sahar; Owayed, Abdullah; Altawalah, Haya; Khadadah, Mousa; Behbehani, Nasser; Al-Nakib, Widad

    2015-01-01

    The aim of this study was to determine the frequency of viral mixed detection in hospitalized patients with respiratory tract infections and to evaluate the correlation between viral mixed detection and clinical severity. Hospitalized patients with respiratory tract infections (RTI) were investigated for 15 respiratory viruses by using sensitive molecular techniques. In total, 850 hospitalized patients aged between 3 days and 80 years were screened from September 2010 to April 2014. Among the 351 (47.8%) patients diagnosed with viral infections, viral mixed detection was identified in 49 patients (14%), with human rhinovirus (HRV) being the most common virus associated with viral mixed detection (7.1%), followed by adenovirus (AdV) (4%) and human coronavirus-OC43 (HCoV-OC43) (3.7%). The highest combination of viral mixed detection was identified with HRV and AdV (2%), followed by HRV and HCoV-OC43 (1.4%). Pneumonia and bronchiolitis were the most frequent reason for hospitalization with viral mixed detection (9.1%). There were statistical significance differences between mixed and single detection in patients diagnosed with bronchiolitis (P = 0.002) and pneumonia (P = 0.019). Our findings might indicate a significant association between respiratory virus mixed detection and the possibility of developing more severe LRTI such as bronchiolitis and pneumonia when compared with single detection. PMID:25983755

  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. 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

  14. Defensins Potentiate a Neutralizing Antibody Response to Enteric Viral Infection

    PubMed Central

    Treuting, Piper M.; Bromme, Beth A.; Wilson, Sarah S.; Wiens, Mayim E.; Lu, Wuyuan; Ouellette, André J.; Spindler, Katherine R.; Parks, William C.; Smith, Jason G.

    2016-01-01

    α-defensins are abundant antimicrobial peptides with broad, potent antibacterial, antifungal, and antiviral activities in vitro. Although their contribution to host defense against bacteria in vivo has been demonstrated, comparable studies of their antiviral activity in vivo are lacking. Using a mouse model deficient in activated α-defensins in the small intestine, we show that Paneth cell α-defensins protect mice from oral infection by a pathogenic virus, mouse adenovirus 1 (MAdV-1). Survival differences between mouse genotypes are lost upon parenteral MAdV-1 infection, strongly implicating a role for intestinal defenses in attenuating pathogenesis. Although differences in α-defensin expression impact the composition of the ileal commensal bacterial population, depletion studies using broad-spectrum antibiotics revealed no effect of the microbiota on α-defensin-dependent viral pathogenesis. Moreover, despite the sensitivity of MAdV-1 infection to α-defensin neutralization in cell culture, we observed no barrier effect due to Paneth cell α-defensin activation on the kinetics and magnitude of MAdV-1 dissemination to the brain. Rather, a protective neutralizing antibody response was delayed in the absence of α-defensins. This effect was specific to oral viral infection, because antibody responses to parenteral or mucosal ovalbumin exposure were not affected by α-defensin deficiency. Thus, α-defensins play an important role as adjuvants in antiviral immunity in vivo that is distinct from their direct antiviral activity observed in cell culture. PMID:26933888

  15. How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

    PubMed Central

    Cori, Anne; de Wolf, Frank; Anderson, Roy M.

    2016-01-01

    Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements. PMID:27367230

  16. Discovery of host-viral protein complexes during infection

    PubMed Central

    Rowles, Daniell L.; Terhune, Scott S.; Cristea, Ileana M.

    2014-01-01

    Summary Viruses have co-evolved with their hosts, developing effective approaches for hijacking and manipulating host cellular processes. Therefore, for their efficient replication and spread, viruses depend on dynamic and temporally-regulated interactions with host proteins. The rapid identification of host proteins targeted by viral proteins during infection provides significant insights into mechanisms of viral protein function. The resulting discoveries often lead to unique and innovative hypotheses on viral protein function. Here, we describe a robust method for identifying virus-host protein interactions and protein complexes, which we have successfully utilized to characterize spatial-temporal protein interactions during infections with either DNA or RNA viruses, including human cytomegalovirus (HCMV), herpes simplex virus type 1 (HSV-1), pseudorabies virus (PRV), human immunodeficiency virus (HIV-1), Sindbis, and West Nile virus (WNV). This approach involves cryogenic cell lysis, rapid immunoaffinity purification targeting a virus or host protein, followed by identification of associated proteins using mass spectrometry. Like most proteomic approaches, this methodology has evolved over the past few years and continues to evolve. We are presenting here the updated approaches for each step, and discuss alternative strategies allowing for the protocol to be optimized for different biological systems. PMID:23996249

  17. Emerging viral infections of the central nervous system: part 1.

    PubMed

    Tyler, Kenneth L

    2009-08-01

    In this 2-part review, I will focus on emerging virus infections of the central nervous system (CNS). Part 1 will introduce the basic features of emerging infections, including their definition, epidemiology, and the frequency of CNS involvement. Important mechanisms of emergence will be reviewed, including viruses spreading into new host ranges as exemplified by West Nile virus (WNV), Japanese encephalitis (JE) virus, Toscana virus, and enterovirus 71 (EV71). Emerging infections also result from opportunistic spread of viruses into known niches, often resulting from attenuated host resistance to infection. This process is exemplified by transplant-associated cases of viral CNS infection caused by WNV, rabies virus, lymphocytic choriomeningitis, and lymphocytic choriomeningitis-like viruses and by the syndrome of human herpesvirus 6 (HHV6)-associated posttransplantation acute limbic encephalitis. The second part of this review begins with a discussion of JC virus and the occurrence of progressive multifocal leukoencephalopathy in association with novel immunomodulatory therapies and then continues with an overview of the risk of infection introduced by imported animals (eg, monkeypox virus) and examples of emerging diseases caused by enhanced competence of viruses for vectors and the spread of vectors (eg, chikungunya virus) and then concludes with examples of novel viruses causing CNS infection as exemplified by Nipah and Hendra viruses and bat lyssaviruses. PMID:19667214

  18. Emerging Viral Infections of the Central Nervous System

    PubMed Central

    Tyler, Kenneth L.

    2010-01-01

    In this 2-part review, I will focus on emerging virus infections of the central nervous system (CNS). Part 1 will introduce the basic features of emerging infections, including their definition, epidemiology, and the frequency of CNS involvement. Important mechanisms of emergence will be reviewed, including viruses spreading into new host ranges as exemplified by West Nile virus (WNV), Japanese encephalitis (JE) virus, Toscana virus, and enterovirus 71 (EV71). Emerging infections also result from opportunistic spread of viruses into known niches, often resulting from attenuated host resistance to infection. This process is exemplified by transplant-associated cases of viral CNS infection caused by WNV, rabies virus, lymphocytic choriomeningitis, and lymphocytic choriomeningitis–like viruses and by the syndrome of human herpesvirus 6 (HHV6)–associated posttransplantation acute limbic encephalitis. The second part of this review begins with a discussion of JC virus and the occurrence of progressive multifocal leukoencephalopathy in association with novel immunomodulatory therapies and then continues with an overview of the risk of infection introduced by imported animals (eg, monkeypox virus) and examples of emerging diseases caused by enhanced competence of viruses for vectors and the spread of vectors (eg, chikungunya virus) and then concludes with examples of novel viruses causing CNS infection as exemplified by Nipah and Hendra viruses and bat lyssaviruses. PMID:19667214

  19. Human NK Cell Diversity in Viral Infection: Ramifications of Ramification

    PubMed Central

    Strauss-Albee, Dara M.; Blish, Catherine A.

    2016-01-01

    Natural killer (NK) cells are a unique lymphocyte lineage with remarkable agility in the rapid destruction of virus-infected cells. They are also the most poorly understood class of lymphocyte. A spectrum of activating and inhibitory receptors at the NK cell surface leads to an unusual and difficult-to-study mechanism of cellular recognition, as well as a very high capacity for diversity at the single-cell level. Here, we review the evidence for the role of NK cells in the earliest stage of human viral infection, and in its prevention. We argue that single-cell diversity is a logical evolutionary adaptation for their position in the immune response and contributes to their ability to kill virus-infected cells. Finally, we look to the future, where emerging single-cell technologies will enable a new generation of rigorous and clinically relevant studies on NK cells accounting for all of their unique and diverse characteristics. PMID:26973646

  20. Persistent or Slow Viral Infections and Related Diseases

    PubMed Central

    Adams, John M.

    1975-01-01

    The discovery of persistent transmissible agents by veterinarians has led to striking advances in the infectious cause of neuropathies of human beings. There is evidence for persisting infection in congenital rubella and the herpes group of viruses including cytomegalovirus infections. Hepatitis types A and B are candidates for inclusion in the category of persisting viral infections. The rubeola or measles virus is established as a persistent virus which causes elevated antibodies in the serum and cerebrospinal fluid of many patients with severe demyelinating disease such as subacute sclerosing panencephalitis and multiple sclerosis. Elevated antibodies against vaccinia virus have been found in the cerebrospinal fluid of some patients with multiple sclerosis and neuromyelitis optica, a rare form of multiple sclerosis. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7. PMID:165638

  1. Innate and Adaptive Immune Regulation During Chronic Viral Infections

    PubMed Central

    Zuniga, Elina I.; Macal, Monica; Lewis, Gavin M.; Harker, James A.

    2015-01-01

    Chronic viral infections represent a unique challenge to the infected host. Persistently replicating viruses outcompete or subvert the initial antiviral response, allowing the establishment of chronic infections that result in continuous stimulation of both the innate and adaptive immune compartments. This causes a profound reprogramming of the host immune system, including attenuation and persistent low levels of type I interferons, progressive loss (or exhaustion) of CD8+ T cell functions, and specialization of CD4+ T cells to produce interleukin-21 and promote antibody-mediated immunity and immune regulation. Epigenetic, transcriptional, posttranscriptional, and metabolic changes underlie this adaptation or recalibration of immune cells to the emerging new environment in order to strike an often imperfect balance between the host and the infectious pathogen. In this review we discuss the common immunological hallmarks observed across a range of different persistently replicating viruses and host species, the underlying molecular mechanisms, and the biological and clinical implications. PMID:26958929

  2. Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests

    PubMed Central

    Mehraj, Vikram; Routy, Jean-Pierre

    2015-01-01

    l-Tryptophan (l-Trp) is an essential amino acid that possesses diverse metabolic, neurological, and immunological roles spanning from the synthesis of proteins, neurotransmitter serotonin, and neurohormone melatonin, to its degradation into immunosuppressive catabolites by indoleamine-2, 3-dioxygenase (IDO) in the kynurenine pathway (KP). Trp catabolites, by activating aryl hydrocarbon receptor (AhR), play an important role in antimicrobial defense and immune regulation. IDO/AhR acts as a double-edged sword by both depleting l-Trp to starve the invaders and by contributing to the state of immunosuppression with microorganisms that were not cleared during acute infection. Pathogens experiencing Trp deprivation by IDO-mediated degradation include certain bacteria, parasites, and less likely viruses. However, chronic viral infections highjack the host immune response to create a state of disease tolerance via kynurenine catabolites. This review covers the latest data involving chronic viral infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes, and cytomegalovirus (CMV) and their cellular interplay with Trp catabolites. Strategies developed by viruses to escape immune control also represent new avenues for therapeutic interventions based on Trp metabolism. PMID:26309411

  3. Animal models for viral infection and cell exhaustion

    PubMed Central

    McGary, Colleen S.; Silvestri, Guido; Paiardini, Mirko

    2014-01-01

    Purpose of review Despite eliciting an early antiviral T cell response, HIV-specific T cells are unable to prevent disease progression, partly due to their loss of effector functions, known as T cell exhaustion. Restoring this T cell functionality represents a critical step for regaining immunological control of HIV-1 replication, and may be fundamental for the development of a functional cure for HIV. In this context, the use of animal models is invaluable for evaluating the efficacy and mechanisms of novel therapeutics aimed at reinvigorating T cell functions. Recent findings While non-human primates continue to be a mainstay for studying HIV pathogenesis and therapies, recent advances in humanized mouse models have improved their ability to recapitulate the features of cell exhaustion during HIV infection. Targeting coinhibitory receptors in HIV- and SIV-infected animals has resulted in viral load reductions, presumably by reinvigorating the effector functions of T cells. Additionally, studies combining PD-1 blockade with suppressive ART provide further support of the use of coinhibitory receptor blockades in restoring T cell function by delaying viral load rebound upon ART interruption. Future in vivo studies should build on recent in vitro data supporting the simultaneous targeting of multiple regulators of cell exhaustion. Summary In this review, we describe the most recent advances in the use of animal models for the study of cell exhaustion following HIV/SIV infection. These findings suggest that the use of animal models is increasingly critical in translating immunotherapeutics into clinical practice. PMID:25023622

  4. RNase L Activates the NLRP3 Inflammasome During Viral Infections

    PubMed Central

    Chakrabarti, Arindam; Banerjee, Shuvojit; Franchi, Luigi; Loo, Yueh-Ming; Gale, Michael; Núñez, Gabriel; Silverman, Robert H.

    2015-01-01

    SUMMARY The NLRP3 inflammasome assembles in response to danger signals, triggering self-cleavage of procaspase-1 and production of the proinflammatory cytokine IL-1β. Although virus infection activates the NLRP3 inflammasome, the underlying events remain incompletely understood. We report that virus activation of the NLRP3 inflammasome involves the 2′,5′-oligoadenylate (2-5A) synthetase (OAS)/RNase L system, a component of the interferon-induced antiviral response that senses double stranded RNA and activates endoribonuclease RNase L to cleave viral and cellular RNAs. The absence of RNase L reduces IL-1β production in influenza A virus-infected mice. RNA cleavage products generated by RNase L enhance IL-1β production but require the presence of 2′,3′-cyclic phosphorylated termini characteristic of RNase L activity. Additionally, these cleavage products stimulate NLRP3 complex formation with the DExD/H-box helicase, DHX33, and mitochondrial adapter protein, MAVS, which are each required for effective NLRP3 inflammasome activation. Thus, RNA cleavage events catalyzed by RNase L are required for optimal inflammasome activation during viral infections. PMID:25816776

  5. Type I IFN Signaling Is Dispensable during Secondary Viral Infection.

    PubMed

    Hosking, Martin P; Flynn, Claudia T; Whitton, J Lindsay

    2016-08-01

    Innate immune responses in general, and type I interferons (T1IFNs) in particular, play an important and often essential role during primary viral infections, by directly combatting the virus and by maximizing the primary adaptive immune response. Several studies have suggested that T1IFNs also contribute very substantially to the secondary (recall) response; they are thought (i) to be required to drive the early attrition of memory T cells, (ii) to support the subsequent expansion of surviving virus-specific memory cells, and (iii) to assist in the suppression and clearance of the infectious agent. However, many of these observations were predicated upon models in which T1IFN signaling was interrupted prior to a primary immune response, raising the possibility that the resulting memory cells might be intrinsically abnormal. We have directly addressed this by using an inducible-Cre model system in which the host remains genetically-intact during the primary response to infection, and in which T1IFN signaling can be effectively ablated prior to secondary viral challenge. We report that, in stark contrast to primary infection, T1IFN signaling is not required during the recall response. IFNαβR-deficient memory CD8+ and CD4+ memory T cells undergo attrition and expansion with kinetics that are indistinguishable from those of receptor-sufficient cells. Moreover, even in the absence of functional T1IFN signaling, the host's immune capacity to rapidly suppress, and then to eradicate, a secondary infection remains intact. Thus, this study shows that T1IFN signaling is dispensable during the recall response to a virus infection. Moreover, two broader implications may be drawn. First, a T cell's requirement for a cytokine is highly dependent on the cell's maturation / differentiation status. Consequently, second, these data underscore the importance of evaluating a gene's impact by modulating its expression or function in a temporally-controllable manner. PMID:27580079

  6. Synaptic Plasticity and Neurological Disorders in Neurotropic Viral Infections

    PubMed Central

    Atluri, Venkata Subba Rao; Hidalgo, Melissa; Samikkannu, Thangavel; Kurapati, Kesava Rao Venkata; Nair, Madhavan

    2015-01-01

    Based on the type of cells or tissues they tend to harbor or attack, many of the viruses are characterized. But, in case of neurotropic viruses, it is not possible to classify them based on their tropism because many of them are not primarily neurotropic. While rabies and poliovirus are considered as strictly neurotropic, other neurotropic viruses involve nervous tissue only secondarily. Since the AIDS pandemic, the interest in neurotropic viral infections has become essential for all clinical neurologists. Although these neurotropic viruses are able to be harbored in or infect the nervous system, not all the neurotropic viruses have been reported to cause disrupted synaptic plasticity and impaired cognitive functions. In this review, we have discussed the neurotropic viruses, which play a major role in altered synaptic plasticity and neurological disorders. PMID:26649202

  7. A common viral infection can change nickel target organ distribution

    SciTech Connect

    Ilbaeck, N.G.F.; Fohlman, J.; Friman, G. )

    1992-05-01

    The autoradiographic distribution of the toxic heavy metal nickel (Ni) was studied at 4 and 7 days post-coxsackievirus B3 (CB3) infection in Balb/c mice. The distribution of the iv injected 63Ni was studied 10 min, 4 hr, and 24 hr after administration. Results clearly show that the site of 63Ni accumulation is greatly changed during this viral infection. This newly discovered distribution was mainly visible as a greatly increased accumulation in the pancreas and the wall of the ventricular myocardium. Healthy animals showed almost no 63Ni accumulation in these tissues. These results for the first time show that an invading microorganism can change the distribution of an environmental pollutant.

  8. The role of natural killer cells in viral infections.

    PubMed

    See, D M; Khemka, P; Sahl, L; Bui, T; Tilles, J G

    1997-09-01

    Natural killer (NK) cells are important effectors for the lysis of both neoplastic and virus-infected cells. Lectin-like receptors on human NK cells, such as NKR-PIA and CD94, bind to target cell carbohydrate ligands and initiate the lytic process. In addition, P58 and P70 bind to major histocompatibility class I antigens on targets and mediate negative signals. Models using NK cell-deficient mice have proven useful in elaborating the role of NK cells in the immune defence against multiple viral agents. In addition, studies in humans have suggested a vital role of NK cells in the host defence against human immunodeficiency virus, herpesviruses, hepatitis B and C and other viruses. Several genetic disorders, chronic illnesses and infections have been associated with decreased NK function. PMID:9315107

  9. Serum amyloid A protein in acute viral infections.

    PubMed Central

    Miwata, H; Yamada, T; Okada, M; Kudo, T; Kimura, H; Morishima, T

    1993-01-01

    Concentrations of serum amyloid A protein (SAA) were measured in 254 children with viral diseases, including measles, varicella, rubella, mumps, echo-30 meningitis, chronic hepatitis B and C, and in eight with Kawasaki disease. Latex agglutination nephelometric immunoassay was used for assaying SAA. In 191 out of 195 patients (98%), SAA concentrations became markedly raised in the acute phase of the viral disease: measles (97%), varicella (100%), mumps (95%), and echo-30 meningitis (99%) with mean titres of 82.4, 80.5, 60.2, 75.2, and 101.1 micrograms/ml respectively. This increase in SAA was followed by a rapid return to normal concentrations (< 5 micrograms/ml) during convalescence. Remarkably higher concentrations of SAA (mean 1630 micrograms/ml) were detected in the acute phase of patients with Kawasaki disease, but in most of the children with chronic hepatitis B or C, the titres of SAA remained normal. There was no close correlation between SAA and serum concentrations for alpha 1-acid glycoprotein, beta 2-microglobulin, transferrin, and IgG. There was a clear correlation between SAA and C reactive protein concentrations, although SAA showed a greater incremental change than C reactive protein in the acute phase. In the acute phase of these viral diseases, 56% of the patients had raised SAA concentrations (> or = 5 micrograms/ml) with normal C reactive protein concentrations (< 5 micrograms/ml). These results indicate that SAA could be useful as an inflammatory marker in children with acute viral infections. PMID:8481043

  10. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  11. Dietary selenium in adjuvant therapy of viral and bacterial infections.

    PubMed

    Steinbrenner, Holger; Al-Quraishy, Saleh; Dkhil, Mohamed A; Wunderlich, Frank; Sies, Helmut

    2015-01-01

    Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply has been proposed to confer health benefits for patients suffering from some viral diseases, most notably with respect to HIV and influenza A virus (IAV) infections. In addition, selenium-containing multimicronutrient supplements improved several clinical and lifestyle variables in patients coinfected with HIV and Mycobacterium tuberculosis. Selenium status may affect the function of cells of both adaptive and innate immunity. Supranutritional selenium promotes proliferation and favors differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus supporting the acute cellular immune response, whereas excessive activation of the immune system and ensuing host tissue damage are counteracted through directing macrophages toward the M2 phenotype. This review provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M. tuberculosis, Helicobacter pylori). Data from epidemiologic studies and intervention trials, with selenium alone or in combination with other micronutrients, and animal experiments are discussed against the background of dietary selenium requirements to alter immune functions. PMID:25593145

  12. Sensors of Infection: Viral Nucleic Acid PRRs in Fish

    PubMed Central

    Poynter, Sarah; Lisser, Graeme; Monjo, Andrea; DeWitte-Orr, Stephanie

    2015-01-01

    Viruses produce nucleic acids during their replication, either during genomic replication or transcription. These nucleic acids are present in the cytoplasm or endosome of an infected cell, or in the extracellular space to be sensed by neighboring cells during lytic infections. Cells have mechanisms of sensing virus-generated nucleic acids; these nucleic acids act as flags to the cell, indicating an infection requiring defense mechanisms. The viral nucleic acids are called pathogen-associated molecular patterns (PAMPs) and the sensors that bind them are called pattern recognition receptors (PRRs). This review article focuses on the most recent findings regarding nucleic acids PRRs in fish, including: Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), cytoplasmic DNA sensors (CDSs) and class A scavenger receptors (SR-As). It also discusses what is currently known of the downstream signaling molecules for each PRR family and the resulting antiviral response, either type I interferons (IFNs) or pro-inflammatory cytokine production. The review highlights what is known but also defines what still requires elucidation in this economically important animal. Understanding innate immune systems to virus infections will aid in the development of better antiviral therapies and vaccines for the future. PMID:26184332

  13. Predicting Viral Infection From High-Dimensional Biomarker Trajectories

    PubMed Central

    Chen, Minhua; Zaas, Aimee; Woods, Christopher; Ginsburg, Geoffrey S.; Lucas, Joseph; Dunson, David; Carin, Lawrence

    2013-01-01

    There is often interest in predicting an individual’s latent health status based on high-dimensional biomarkers that vary over time. Motivated by time-course gene expression array data that we have collected in two influenza challenge studies performed with healthy human volunteers, we develop a novel time-aligned Bayesian dynamic factor analysis methodology. The time course trajectories in the gene expressions are related to a relatively low-dimensional vector of latent factors, which vary dynamically starting at the latent initiation time of infection. Using a nonparametric cure rate model for the latent initiation times, we allow selection of the genes in the viral response pathway, variability among individuals in infection times, and a subset of individuals who are not infected. As we demonstrate using held-out data, this statistical framework allows accurate predictions of infected individuals in advance of the development of clinical symptoms, without labeled data and even when the number of biomarkers vastly exceeds the number of individuals under study. Biological interpretation of several of the inferred pathways (factors) is provided. PMID:23704802

  14. Mathematical models of immune effector responses to viral infections: Virus control versus the development of pathology

    NASA Astrophysics Data System (ADS)

    Wodarz, Dominik

    2005-12-01

    This article reviews mathematical models which have investigated the importance of lytic and non-lytic immune responses for the control of viral infections. Lytic immune responses fight the virus by killing infected cells, while non-lytic immune responses fight the virus by inhibiting viral replication while leaving the infected cell alive. The models suggest which types or combinations of immune responses are required to resolve infections which vary in their characteristics, such as the rate of viral replication and the rate of virus-induced target cell death. This framework is then applied to persistent infections and viral evolution. It is investigated how viral evolution and antigenic escape can influence the relative balance of lytic and non-lytic responses over time, and how this might correlate with the transition from an asymptomatic infection to pathology. This is discussed in the specific context of hepatitis C virus infection.

  15. A Mathematical Model of T1D Acceleration and Delay by Viral Infection.

    PubMed

    Moore, James R; Adler, Fred

    2016-03-01

    Type 1 diabetes (T1D) is often triggered by a viral infection, but the T1D prevalence is rising among populations that have a lower exposure to viral infection. In an animal model of T1D, the NOD mouse, viral infection at different ages may either accelerate or delay disease depending on the age of infection and the type of virus. Viral infection may affect the progression of T1D via multiple mechanisms: triggering inflammation, bystander activation of self-reactive T-cells, inducing a competitive immune response, or inducing a regulatory immune response. In this paper, we create mathematical models of the interaction of viral infection with T1D progression, incorporating each of these four mechanisms. Our goal is to understand how each viral mechanism interacts with the age of infection. The model predicts that each viral mechanism has a unique pattern of interaction with disease progression. Viral inflammation always accelerates disease, but the effect decreases with age of infection. Bystander activation has little effect at younger ages and actually decreases incidence at later ages while accelerating disease in mice that do get the disease. A competitive immune response to infection can decrease incidence at young ages and increase it at older ages, with the effect decreasing over time. Finally, an induced Treg response decreases incidence at any age of infection, but the effect decreases with age. Some of these patterns resemble those seen experimentally. PMID:27030351

  16. Viral infection of the pregnant cervix predisposes to ascending bacterial infection

    PubMed Central

    Racicot, Karen; Cardenas, Ingrid; Wünsche, Vera; Aldo, Paulomi; Guller, Seth; Means, Robert; Romero, Roberto; Mor, Gil

    2014-01-01

    Preterm birth is the major cause of neonatal mortality and morbidity, and bacterial infections that ascend from the lower female reproductive tract (FRT) are the most common route of uterine infection leading to preterm birth. The uterus and growing fetus are protected from ascending infection by the cervix, which controls and limits microbial access by the production of mucus, cytokines and anti-microbial peptides (AMPs). If this barrier is compromised, bacteria may enter the uterine cavity leading to preterm birth. Using a mouse model, we demonstrate, for the first time, that viral infection of the cervix, during pregnancy, reduces the capacity of the FRT to prevent bacterial infection of the uterus. This is due to differences in susceptibility of the cervix to infection by virus during pregnancy and the associated changes in TLR and AMP expression and function. We suggest that preterm labor is a polymicrobial disease, which requires a multifactorial approach for its prevention and treatment. PMID:23752614

  17. Viral respiratory infections among Hajj pilgrims in 2013.

    PubMed

    Barasheed, Osamah; Rashid, Harunor; Alfelali, Mohammad; Tashani, Mohamed; Azeem, Mohammad; Bokhary, Hamid; Kalantan, Nadeen; Samkari, Jamil; Heron, Leon; Kok, Jen; Taylor, Janette; El Bashir, Haitham; Memish, Ziad A; Haworth, Elizabeth; Holmes, Edward C; Dwyer, Dominic E; Asghar, Atif; Booy, Robert

    2014-12-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged in the Arabian Gulf region, with its epicentre in Saudi Arabia, the host of the 'Hajj' which is the world's the largest mass gathering. Transmission of MERS-CoV at such an event could lead to its rapid worldwide dissemination. Therefore, we studied the frequency of viruses causing influenza-like illnesses (ILI) among participants in a randomised controlled trial at the Hajj 2013. We recruited 1038 pilgrims from Saudi Arabia, Australia and Qatar during the first day of Hajj and followed them closely for four days. A nasal swab was collected from each pilgrim who developed ILI. Respiratory viruses were detected using multiplex RT-PCR. ILI occurred in 112/1038 (11%) pilgrims. Their mean age was 35 years, 49 (44%) were male and 35 (31%) had received the influenza vaccine pre-Hajj. Forty two (38%) pilgrims had laboratory-confirmed viral infections; 28 (25%) rhinovirus, 5 (4%) influenza A, 2 (2%) adenovirus, 2 (2%) human coronavirus OC43/229E, 2 (2%) parainfluenza virus 3, 1 (1%) parainfluenza virus 1, and 2 (2%) dual infections. No MERS-CoV was detected in any sample. Rhinovirus was the commonest cause of ILI among Hajj pilgrims in 2013. Infection control and appropriate vaccination are necessary to prevent transmission of respiratory viruses at Hajj and other mass gatherings. PMID:25413828

  18. Epidemiological investigation of selected pigeon viral infections in Poland.

    PubMed

    Stenzel, T A; Pestka, D; Tykałowski, B; Śmiałek, M; Koncicki, A

    2012-12-01

    Due to a lack of data in regard to the spread of viral infections in Polish pigeon populations, studies were undertaken to assess the frequency of adeno-, circo- and herpesvirus infections in flocks of pigeons across the entire country. In total, 107 flocks were examined, of which 61 per cent consisted of racing and 39 per cent of fancy pigeons. The flocks were divided into groups according to breed (racing and fancy pigeons) as well as physical condition (healthy and sick). In the studied pigeon flocks, the pigeon circovirus (PiCV) genetic material was the most frequently detected (44.5-100 per cent depending on the group), pigeon herpesvirus genetic material was second in frequency (0-30 per cent depending on the group), while genetic material of pigeon adenovirus was found only in two flocks of young birds with clinical symptoms of Young Pigeon Disease Syndrome (YPDS). The presence of fowl adenovirus (FAdV) genetic material was not detected in any of the studied flocks. Results obtained demonstrate a wide spread of circovirus in pigeon flocks in Poland, and substantiate earlier theories proposed by other authors, that immunosuppression evoked by PiCV infection is one of the main causative agents of YPDS. PMID:23118041

  19. Comparative transcriptome response in swine tracheobronchial lymph nodes to viral infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The tracheobronchial lymph node (TBLN) transcriptome response was evaluated following viral infection using Digital Gene Expression Tag Profiling (DGETP). Pigs were sham-treated or infected intranasally with porcine reproductive and respiratory syndrome virus, porcine circovirus type 2, pseudorabies...

  20. Exacerbation of allergic inflammation in mice exposed to diesel exhaust particles prior to viral infection.

    EPA Science Inventory

    Background: Viral infections and exposure to oxidant air pollutants are two ofthe most important inducers ofasthma exacerbation. Our previous studies have demonstrated that exposure to diesel exhaust increases the susceptibility to influenza virus infections both in epithelial ce...

  1. Natural FCoV infection: cats with FIP exhibit significantly higher viral loads than healthy infected cats.

    PubMed

    Kipar, Anja; Baptiste, Keith; Barth, Andreas; Reinacher, Manfred

    2006-02-01

    Natural feline coronavirus (FCoV) infection has been shown to not only induce intestinal infection with viral shedding, but also systemic infection which either remains without clinical signs or leads to feline infectious peritonitis (FIP). As systemic infection is not the key event in the development of FIP, the question arises as to whether a potential difference in viral load might be of importance. Therefore, the purpose of this study was to quantitatively assess feline coronavirus (FCoV) RNA loads in haemolymphatic tissues of healthy, long-term FCoV-infected cats and cats with FIP. In cats that died from FIP, viral loads were significantly higher, indicating a higher rate of viral replication or a reduced capacity for viral clearance in cats developing and/or suffering from FIP. PMID:16213766

  2. The stability analysis of a general viral infection model with distributed delays and multi-staged infected progression

    NASA Astrophysics Data System (ADS)

    Wang, Jinliang; Liu, Shengqiang

    2015-01-01

    We investigate an in-host model with general incidence and removal rate, as well as distributed delays in virus infections and in productions. By employing Lyapunov functionals and LaSalle's invariance principle, we define and prove the basic reproductive number R0 as a threshold quantity for stability of equilibria. It is shown that if R0 > 1 , then the infected equilibrium is globally asymptotically stable, while if R0 ⩽ 1 , then the infection free equilibrium is globally asymptotically stable under some reasonable assumptions. Moreover, n + 1 distributed delays describe (i) the time between viral entry and the transcription of viral RNA, (ii) the n - 1 -stage time needed for activated infected cells between viral RNA transcription and viral release, and (iii) the time necessary for the newly produced viruses to be infectious (maturation), respectively. The model can describe the viral infection dynamics of many viruses such as HIV-1, HCV and HBV.

  3. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Associated with Acetaminophen Use during Viral Infections.

    PubMed

    Ban, Ga-Young; Ahn, Seun-Joo; Yoo, Hye-Soo; Park, Hae-Sim; Ye, Young-Min

    2016-08-01

    An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN. PMID:27574505

  4. Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Associated with Acetaminophen Use during Viral Infections

    PubMed Central

    Ban, Ga-Young; Ahn, Seun-Joo; Yoo, Hye-Soo; Park, Hae-Sim

    2016-01-01

    An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN. PMID:27574505

  5. The Association between Invasive Group A Streptococcal Diseases and Viral Respiratory Tract Infections

    PubMed Central

    Herrera, Andrea L.; Huber, Victor C.; Chaussee, Michael S.

    2016-01-01

    Viral infections of the upper respiratory tract are associated with a variety of invasive diseases caused by Streptococcus pyogenes, the group A streptococcus, including pneumonia, necrotizing fasciitis, toxic shock syndrome, and bacteremia. While these polymicrobial infections, or superinfections, are complex, progress has been made in understanding the molecular basis of disease. Areas of investigation have included the characterization of virus-induced changes in innate immunity, differences in bacterial adherence and internalization following viral infection, and the efficacy of vaccines in mitigating the morbidity and mortality of superinfections. Here, we briefly summarize viral-S. pyogenes superinfections with an emphasis on those affiliated with influenza viruses. PMID:27047460

  6. Pseudo-nitzschia Challenged with Co-occurring Viral Communities Display Diverse Infection Phenotypes

    PubMed Central

    Carlson, Michael C. G.; McCary, Nicolette D.; Leach, Terence S.; Rocap, Gabrielle

    2016-01-01

    Viruses are catalysts of biogeochemical cycling, architects of microbial community structure, and terminators of phytoplankton blooms. Viral lysis of diatoms, a key group of eukaryotic phytoplankton, has the potential to impact carbon export and marine food webs. However, the impact of viruses on diatom abundance and community composition is unknown. Diatom-virus dynamics were explored by sampling every month at two coastal and estuarine locations in Washington state, USA resulting in 41 new isolates of the pennate diatom Pseudo-nitzschia and 20 environmental virus samples. We conducted a total of 820 pair-wise crosses of the Pseudo-nitzschia isolates and viral communities. Viral communities infected Pseudo-nitzschia isolates in 8% of the crosses overall and 16% of crosses when the host and viral communities were isolated from the same sample. Isolates ranged in their permissivity to infection with some isolates not infected by any viral samples and others infected by up to 10 viral communities. Isolates that were infected by the most viral communities also had the highest maximum observed viral titers (as high as 16000 infectious units ml-1). Titers of the viral communities were host dependent, as titers for one viral sample on eight different hosts spanned four orders of magnitude. Sequencing of the Pseudo-nitzschia Internal Transcribed Spacer 1 (ITS1) of the revealed multiple subgroups of hosts with 100% ITS1 identities that were infected by different viral communities. Indeed, we repeatedly isolated groups of isolates with identical ITS1 sequences from the same water sample that displayed different viral infection phenotypes. The interactions between Pseudo-nitzschia and the viral communities highlight the diversity of diatoms and emphasize the complexity and variability of diatom-virus dynamics in the ocean. PMID:27148216

  7. Pseudo-nitzschia Challenged with Co-occurring Viral Communities Display Diverse Infection Phenotypes.

    PubMed

    Carlson, Michael C G; McCary, Nicolette D; Leach, Terence S; Rocap, Gabrielle

    2016-01-01

    Viruses are catalysts of biogeochemical cycling, architects of microbial community structure, and terminators of phytoplankton blooms. Viral lysis of diatoms, a key group of eukaryotic phytoplankton, has the potential to impact carbon export and marine food webs. However, the impact of viruses on diatom abundance and community composition is unknown. Diatom-virus dynamics were explored by sampling every month at two coastal and estuarine locations in Washington state, USA resulting in 41 new isolates of the pennate diatom Pseudo-nitzschia and 20 environmental virus samples. We conducted a total of 820 pair-wise crosses of the Pseudo-nitzschia isolates and viral communities. Viral communities infected Pseudo-nitzschia isolates in 8% of the crosses overall and 16% of crosses when the host and viral communities were isolated from the same sample. Isolates ranged in their permissivity to infection with some isolates not infected by any viral samples and others infected by up to 10 viral communities. Isolates that were infected by the most viral communities also had the highest maximum observed viral titers (as high as 16000 infectious units ml(-1)). Titers of the viral communities were host dependent, as titers for one viral sample on eight different hosts spanned four orders of magnitude. Sequencing of the Pseudo-nitzschia Internal Transcribed Spacer 1 (ITS1) of the revealed multiple subgroups of hosts with 100% ITS1 identities that were infected by different viral communities. Indeed, we repeatedly isolated groups of isolates with identical ITS1 sequences from the same water sample that displayed different viral infection phenotypes. The interactions between Pseudo-nitzschia and the viral communities highlight the diversity of diatoms and emphasize the complexity and variability of diatom-virus dynamics in the ocean. PMID:27148216

  8. Graft-versus-host disease and sialodacryoadenitis viral infection in bone marrow transplanted rats

    SciTech Connect

    Rossie, K.M.; Sheridan, J.F.; Barthold, S.W.; Tutschka, P.J.

    1988-06-01

    The effect of a localized viral infection on the occurrence of graft-vs.-host disease (GVHD) was examined in allogeneic rat bone marrow chimeras (ACI/LEW). Animals without clinical evidence of GVHD, 62 days after bone marrow transplant, were infected in salivary and lacrimal glands with sialodacryoadenitis virus (SDAV), and sacrificed 8-25 days postinfection. Using established histologic criteria, GVHD was found more frequently in salivary and lacrimal glands of SDAV-infected chimeras than uninfected chimeras. Skin and oral mucosa, tissues not infected by the virus, showed no differences in occurrence of GVHD, suggesting that the viral infection induced only local and not systemic GVHD. GVHD and SDAV infection, which are histologically similar, were differentiated by examining tissues for SDAV antigen using immunoperoxidase technique. Histologic changes were present for at least 1 week longer than viral antigen, suggesting they represented GVHD rather than viral infection. GVHD and SDAV infection were also differentiated by looking for a histologic feature characteristic of GVHD and not found in SDAV infection (periductal lymphocytic infiltrate). This was found in SDAV-infected chimeras more frequently than uninfected chimeras, suggesting that the viral infection somehow induced GVHD. Results showed a localized increase in the occurrence of GVHD subsequent to localized viral infection.

  9. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    SciTech Connect

    Kohio, Hinissan P.; Adamson, Amy L.

    2013-09-15

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells.

  10. Blockade of interferon Beta, but not interferon alpha, signaling controls persistent viral infection.

    PubMed

    Ng, Cherie T; Sullivan, Brian M; Teijaro, John R; Lee, Andrew M; Welch, Megan; Rice, Stephanie; Sheehan, Kathleen C F; Schreiber, Robert D; Oldstone, Michael B A

    2015-05-13

    Although type I interferon (IFN-I) is thought to be beneficial against microbial infections, persistent viral infections are characterized by high interferon signatures suggesting that IFN-I signaling may promote disease pathogenesis. During persistent lymphocytic choriomeningitis virus (LCMV) infection, IFNα and IFNβ are highly induced early after infection, and blocking IFN-I receptor (IFNAR) signaling promotes virus clearance. We assessed the specific roles of IFNβ versus IFNα in controlling LCMV infection. While blockade of IFNβ alone does not alter early viral dissemination, it is important in determining lymphoid structure, lymphocyte migration, and anti-viral T cell responses that lead to accelerated virus clearance, approximating what occurs during attenuation of IFNAR signaling. Comparatively, blockade of IFNα was not associated with improved viral control, but with early dissemination of virus. Thus, despite their use of the same receptor, IFNβ and IFNα have unique and distinguishable biologic functions, with IFNβ being mainly responsible for promoting viral persistence. PMID:25974304

  11. [Novel treatments for hepatitis C viral infection and the hepatic fibrosis].

    PubMed

    Lugo-Baruqui, Alejandro; Bautista López, Carlos Alfredo; Armendáriz-Borunda, Juan

    2009-02-01

    Hepatitis C virus (HCV) infection represents a global health problem due to its evolution to hepatic cirrhosis and hepatocellular carcinoma. The viral pathogenesis and infectious processes are not yet fully understood. The development of natural viral resistance towards the host immune system represents a mayor challenge for the design of alternative therapeutic interventions and development of viral vaccines. The molecular mechanisms of hepatic fibrosis are well described. New alternatives for the treatment of patients with HCV infection and hepatic cirrhosis are under intensive research. New drugs such as viral protease inhibitors and assembly inhibitors, as well as immune modulators have been studied in clinical trials. Additional alternatives include antifibrotic drugs, which reverse the hepatic cellular damage caused by HCV infection. This review makes reference to viral infective mechanisms, molecular pathways of liver fibrosis and overviews conventional and new treatments for HCV infection and liver fibrosis. PMID:19543653

  12. Global Analysis of Mouse Polyomavirus Infection Reveals Dynamic Regulation of Viral and Host Gene Expression and Promiscuous Viral RNA Editing

    PubMed Central

    Garren, Seth B.; Kondaveeti, Yuvabharath; Duff, Michael O.; Carmichael, Gordon G.

    2015-01-01

    Mouse polyomavirus (MPyV) lytically infects mouse cells, transforms rat cells in culture, and is highly oncogenic in rodents. We have used deep sequencing to follow MPyV infection of mouse NIH3T6 cells at various times after infection and analyzed both the viral and cellular transcriptomes. Alignment of sequencing reads to the viral genome illustrated the transcriptional profile of the early-to-late switch with both early-strand and late-strand RNAs being transcribed at all time points. A number of novel insights into viral gene expression emerged from these studies, including the demonstration of widespread RNA editing of viral transcripts at late times in infection. By late times in infection, 359 host genes were seen to be significantly upregulated and 857 were downregulated. Gene ontology analysis indicated transcripts involved in translation, metabolism, RNA processing, DNA methylation, and protein turnover were upregulated while transcripts involved in extracellular adhesion, cytoskeleton, zinc finger binding, SH3 domain, and GTPase activation were downregulated. The levels of a number of long noncoding RNAs were also altered. The long noncoding RNA MALAT1, which is involved in splicing speckles and used as a marker in many late-stage cancers, was noticeably downregulated, while several other abundant noncoding RNAs were strongly upregulated. We discuss these results in light of what is currently known about the MPyV life cycle and its effects on host cell growth and metabolism. PMID:26407100

  13. Mycobacterium avium infection in HIV-1-infected subjects increases monokine secretion and is associated with enhanced viral load and diminished immune response to viral antigens.

    PubMed Central

    Denis, M; Ghadirian, E

    1994-01-01

    The complex interaction between HIV-1 infection and Mycobacterium avium was studied. Viral burden was assessed, as well as immune response to HIV-1 in the context of Myco. avium infections. We also examined serum cytokine levels and cytokine release by blood mononuclear cells in HIV-1-infected subjects, infected or not with Myco. avium. Undetectable serum levels of IL-1, tumour necrosis factor-alpha (TNF-alpha) and IL-6 were found in normal controls and in groups I, II and III of HIV-1-infected subjects. Moderate levels of TNF-alpha, IL-1 and IL-6 were found in the sera of group IV patients. When group IV was subdivided into subjects with and without Myco. avium infections, subjects with Myco, avium infections were shown to have higher serum levels of TNF-alpha, IL-1 beta and IL-6 than those with other infections. Blood mononuclear cells from controls and HIV subjects were stimulated with bacterial lipopolysaccharide, and cytokine levels assessed. Cells from group II patients were shown to secrete normal levels of TNF-alpha and IL-6, and lower levels of IL-1 beta; group III subjects released higher levels of IL-6. Patients in group IV had blood cells that released elevated levels of IL-6 and TNF-alpha, and lower levels of IL-1 beta. Group IV subjects with Myco. avium infections had blood cells that released higher levels of TNF-alpha, IL-6 and IL-1 than group IV subjects with other infections. Assessment of viral burden in cells of HIV-1-infected subjects revealed that Myco. avium-infected subjects had a higher level of virus burden and a lower level of lymphoproliferative response to an inactivated gp120-depleted HIV-1 antigen than AIDS subjects with other infections. These data suggest that Myco. avium infections in HIV-1-infected subjects hasten the progression of viral disease, enhance cytokine release and contribute to the anergy to viral antigens. PMID:8033423

  14. A trend towards increasing viral load in newly diagnosed HIV-infected inpatients in southeast China.

    PubMed

    Chen, Y; Wang, Z; Huang, A; Yuan, J; Wei, D; Ye, H

    2016-06-01

    Peripheral blood viral load is an important indicator of viral production and clearance. Previous studies have suggested that viral load might predict the rate of decrease in CD4+ cell count and progression to AIDS and death. Here, we conducted a retrospective analysis of the trends in HIV-1 viral load in southeast China. Among inpatients newly diagnosed with HIV infection, we found that viral load has increased over the past decade from 4·20 log10 copies/ml in 2002 to 6·61 log10 copies/ml in 2014, with a mean increase of 0·19 log10 copies/ml each year. However, the CD4+ cell count was stable and insensitive to changes in viral load. Thus, increasing viral load appears to be an emerging trend in newly diagnosed HIV-infected inpatients. PMID:26732896

  15. Exploitation of Lipid Components by Viral and Host Proteins for Hepatitis C Virus Infection

    PubMed Central

    Moriishi, Kohji; Matsuura, Yashiharu

    2012-01-01

    Hepatitis C virus (HCV), which is a major causative agent of blood-borne hepatitis, has chronically infected about 170 million individuals worldwide and leads to chronic infection, resulting in development of steatosis, cirrhosis, and eventually hepatocellular carcinoma. Hepatocellular carcinoma associated with HCV infection is not only caused by chronic inflammation, but also by the biological activity of HCV proteins. HCV core protein is known as a main component of the viral nucleocapsid. It cooperates with host factors and possesses biological activity causing lipid alteration, oxidative stress, and progression of cell growth, while other viral proteins also interact with host proteins including molecular chaperones, membrane-anchoring proteins, and enzymes associated with lipid metabolism to maintain the efficiency of viral replication and production. HCV core protein is localized on the surface of lipid droplets in infected cells. However, the role of lipid droplets in HCV infection has not yet been elucidated. Several groups recently reported that other viral proteins also support viral infection by regulation of lipid droplets and core localization in infected cells. Furthermore, lipid components are required for modification of host factors and the intracellular membrane to maintain or up-regulate viral replication. In this review, we summarize the current status of knowledge regarding the exploitation of lipid components by viral and host proteins in HCV infection. PMID:22347882

  16. DNA cleavage enzymes for treatment of persistent viral infections: Recent advances and the pathway forward

    SciTech Connect

    Weber, Nicholas D.; Aubert, Martine; Dang, Chung H.; Stone, Daniel; Jerome, Keith R.

    2014-04-15

    Treatment for most persistent viral infections consists of palliative drug options rather than curative approaches. This is often because long-lasting viral DNA in infected cells is not affected by current antivirals, providing a source for viral persistence and reactivation. Targeting latent viral DNA itself could therefore provide a basis for novel curative strategies. DNA cleavage enzymes can be used to induce targeted mutagenesis of specific genes, including those of exogenous viruses. Although initial in vitro and even in vivo studies have been carried out using DNA cleavage enzymes targeting various viruses, many questions still remain concerning the feasibility of these strategies as they transition into preclinical research. Here, we review the most recent findings on DNA cleavage enzymes for human viral infections, consider the most relevant animal models for several human viral infections, and address issues regarding safety and enzyme delivery. Results from well-designed in vivo studies will ideally provide answers to the most urgent remaining questions, and allow continued progress toward clinical application. - Highlights: • Recent in vitro and in vivo results for DNA cleavage enzymes targeting persistent viral infections. • Analysis of the best animal models for testing enzymes for HBV, HSV, HIV and HPV. • Challenges facing in vivo delivery of therapeutic enzymes for persistent viral infections. • Safety issues to be addressed with proper animal studies.

  17. Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infection in Humans

    PubMed Central

    Zaas, Aimee K.; Chen, Minhua; Varkey, Jay; Veldman, Timothy; Hero, Alfred O.; Lucas, Joseph; Huang, Yongsheng; Turner, Ronald; Gilbert, Anthony; Lambkin-Williams, Robert; Øien, N. Christine; Nicholson, Bradly; Kingsmore, Stephen; Carin, Lawrence; Woods, Christopher W.; Ginsburg, Geoffrey S.

    2010-01-01

    Summary Acute respiratory infections (ARI) are a common reason for seeking medical attention and the threat of pandemic influenza will likely add to these numbers. Using human viral challenge studies with live rhinovirus, respiratory syncytial virus, and influenza A, we developed peripheral blood gene expression signatures that distinguish individuals with symptomatic ARI from uninfected individuals with > 95% accuracy. We validated this “acute respiratory viral” signature - encompassing genes with a known role in host defense against viral infections - across each viral challenge. We also validated the signature in an independently acquired dataset for influenza A and classified infected individuals from healthy controls with 100% accuracy. In the same dataset, we could also distinguish viral from bacterial ARIs (93% accuracy). These results demonstrate that ARIs induce changes in human peripheral blood gene expression that can be used to diagnose a viral etiology of respiratory infection and triage symptomatic individuals. PMID:19664979

  18. Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

    DOE PAGESBeta

    Graw, Frederik; Balagopal, Ashwin; Kandathil, Abraham J.; Ray, Stuart C.; Thomas, David L.; Ribeiro, Ruy M.; Perelson, Alan S.; Yates, Andrew J.

    2014-11-13

    Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, wemore » are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Lastly, our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.« less

  19. Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

    SciTech Connect

    Graw, Frederik; Balagopal, Ashwin; Kandathil, Abraham J.; Ray, Stuart C.; Thomas, David L.; Ribeiro, Ruy M.; Perelson, Alan S.; Yates, Andrew J.

    2014-11-13

    Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, we are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Lastly, our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.

  20. Extensive multiplex PCR diagnostics reveal new insights into the epidemiology of viral respiratory infections.

    PubMed

    Nickbakhsh, S; Thorburn, F; VON Wissmann, B; McMENAMIN, J; Gunson, R N; Murcia, P R

    2016-07-01

    Viral respiratory infections continue to pose a major global healthcare burden. At the community level, the co-circulation of respiratory viruses is common and yet studies generally focus on single aetiologies. We conducted the first comprehensive epidemiological analysis to encompass all major respiratory viruses in a single population. Using extensive multiplex PCR diagnostic data generated by the largest NHS board in Scotland, we analysed 44230 patient episodes of respiratory illness that were simultaneously tested for 11 virus groups between 2005 and 2013, spanning the 2009 influenza A pandemic. We measured viral infection prevalence, described co-infections, and identified factors independently associated with viral infection using multivariable logistic regression. Our study provides baseline measures and reveals new insights that will direct future research into the epidemiological consequences of virus co-circulation. In particular, our study shows that (i) human coronavirus infections are more common during influenza seasons and in co-infections than previously recognized, (ii) factors associated with co-infection differ from those associated with viral infection overall, (iii) virus prevalence has increased over time especially in infants aged <1 year, and (iv) viral infection risk is greater in the post-2009 pandemic era, likely reflecting a widespread change in the viral population that warrants further investigation. PMID:26931455

  1. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction

    PubMed Central

    Cyr, Derek D.; Lucas, Joseph E.; Zaas, Aimee K.; Woods, Christopher W.; Newby, L. Kristin; Kraus, William E.; Ginsburg, Geoffrey S.

    2015-01-01

    Background Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. Methods A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. Results In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). Conclusions A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection

  2. Viral infection in community-acquired pneumonia: a systematic review and meta-analysis.

    PubMed

    Burk, Michael; El-Kersh, Karim; Saad, Mohamed; Wiemken, Timothy; Ramirez, Julio; Cavallazzi, Rodrigo

    2016-06-01

    The advent of PCR has improved the identification of viruses in patients with community-acquired pneumonia (CAP). Several studies have used PCR to establish the importance of viruses in the aetiology of CAP.We performed a systematic review and meta-analysis of the studies that reported the proportion of viral infection detected via PCR in patients with CAP. We excluded studies with paediatric populations. The primary outcome was the proportion of patients with viral infection. The secondary outcome was short-term mortality.Our review included 31 studies. Most obtained PCR via nasopharyngeal or oropharyngeal swab. The pooled proportion of patients with viral infection was 24.5% (95% CI 21.5-27.5%). In studies that obtained lower respiratory samples in >50% of patients, the proportion was 44.2% (95% CI 35.1-53.3%). The odds of death were higher in patients with dual bacterial and viral infection (OR 2.1, 95% CI 1.32-3.31).Viral infection is present in a high proportion of patients with CAP. The true proportion of viral infection is probably underestimated because of negative test results from nasopharyngeal or oropharyngeal swab PCR. There is increased mortality in patients with dual bacterial and viral infection. PMID:27246595

  3. Detection Of Viral And Bacterial Pathogens In Acute Respiratory Infections

    PubMed Central

    Obasi, Chidi N.; Barrett, Bruce; Brown, Roger; Vrtis, Rose; Barlow, Shari; Muller, Daniel; Gern, James

    2013-01-01

    Objectives The role of bacteria in acute respiratory illnesses (ARI) of adults and interactions with viral infections is incompletely understood. This study tested the hypothesis that bacterial co-infection during ARI adds to airway inflammation and illness severity. Methods Two groups of 97 specimens each were randomly selected from multiplex-PCR identified virus-positive and virus-negative nasal specimens obtained from adults with new onset ARI, and 40 control specimens were collected from healthy adults. All specimens were analyzed for Haemophilus influenza(HI), Moraxella catarrhalis(MC) and Streptococcus pneumonia(SP) by quantitative-PCR. General linear models tested for relationships between respiratory pathogens, biomarkers (nasal wash neutrophils and CXCL8), and ARI-severity. Results Nasal specimens from adults with ARIs were more likely to contain bacteria (37% overall; HI=28%, MC=14%, SP=7%) compared to specimens from healthy adults (5% overall; HI=0%, MC=2.5%, SP=2.5%;p<0.001). Among ARI specimens, bacteria were more likely to be detected among virus-negative specimens compared to virus-positive specimens (46% vs. 27%;p=0.0046). The presence of bacteria was significantly associated with increased CXCL8 and neutrophils, but not increased symptoms. Conclusion Pathogenic bacteria were more often detected in virus-negative ARI, and also associated with increased inflammatory biomarkers. These findings suggest the possibility that bacteria may augment virus-induced ARI and contribute to airway inflammation. Summary We tested whether bacterial pathogens were associated with ARI illness and inflammation. Bacteria were detected more often in nasal secretions during ARI, especially in samples without detectable viruses, and were associated with increased airway inflammation, but not increased symptoms. PMID:24211414

  4. Incubation periods of acute respiratory viral infections: a systematic review

    PubMed Central

    Lessler, Justin; Reich, Nicholas G; Brookmeyer, Ron; Perl, Trish M; Nelson, Kenrad E; Cummings, Derek A T

    2015-01-01

    Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8–6·3) for adenovirus, 3·2 days (95% CI 2·8–3·7) for human coronavirus, 4·0 days (95% CI 3·6–4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3–1·5) for influenza A, 0·6 days (95% CI 0·5–0·6) for influenza B, 12·5 days (95% CI 11·8–13·3) for measles, 2·6 days (95% CI 2·1–3·1) for parainfluenza, 4·4 days (95% CI 3·9–4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4–2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications. PMID:19393959

  5. Protection of Insects against Viral Infection by Apoptosis-Dependent Phagocytosis.

    PubMed

    Nainu, Firzan; Tanaka, Yumiko; Shiratsuchi, Akiko; Nakanishi, Yoshinobu

    2015-12-15

    We investigated whether phagocytosis participates in the protection of insects from viral infection using the natural host-virus interaction between Drosophila melanogaster and Drosophila C virus (DCV). Drosophila S2 cells were induced to undergo apoptotic cell death upon DCV infection. However, UV-inactivated virus was unable to cause apoptosis, indicating the need for productive infection for apoptosis induction. S2 cells became susceptible to phagocytosis by hemocyte-derived l(2)mbn cells after viral infection, and the presence of phagocytes in S2 cell cultures reduced viral proliferation. Phagocytosis depended, in part, on caspase activity in S2 cells, as well as the engulfment receptors Draper and integrin βν in phagocytes. To validate the in vivo situation, adult flies were abdominally infected with DCV, followed by the analysis of fly death and viral growth. DCV infection killed flies in a dose-responding manner, and the activation of effector caspases was evident, as revealed by the cleavage of a target protein ectopically expressed in flies. Furthermore, hemocytes isolated from infected flies contained DCV-infected cells, and preinjection of latex beads to inhibit the phagocytic activity of hemocytes accelerated fly death after viral infection. Likewise, viral virulence was exaggerated in flies lacking the engulfment receptors, and was accompanied by the augmented proliferation of virus. Finally, phagocytosis of DCV-infected cells in vitro was inhibited by phosphatidylserine-containing liposome, and virus-infected flies died early when a phosphatidylserine-binding protein was ectopically expressed. Collectively, our study demonstrates that the apoptosis-dependent, phosphatidylserine-mediated phagocytosis of virus-infected cells plays an important role in innate immune responses against viral infection in Drosophila. PMID:26546607

  6. Synaptic transmission and the susceptibility of HIV infection to anti-viral drugs

    NASA Astrophysics Data System (ADS)

    Komarova, Natalia L.; Levy, David N.; Wodarz, Dominik

    2013-07-01

    Cell-to-cell viral transmission via virological synapses has been argued to reduce susceptibility of the virus population to anti-viral drugs through multiple infection of cells, contributing to low-level viral persistence during therapy. Using a mathematical framework, we examine the role of synaptic transmission in treatment susceptibility. A key factor is the relative probability of individual virions to infect a cell during free-virus and synaptic transmission, a currently unknown quantity. If this infection probability is higher for free-virus transmission, then treatment susceptibility is lowest if one virus is transferred per synapse, and multiple infection of cells increases susceptibility. In the opposite case, treatment susceptibility is minimized for an intermediate number of virions transferred per synapse. Hence, multiple infection via synapses does not simply lower treatment susceptibility. Without further experimental investigations, one cannot conclude that synaptic transmission provides an additional mechanism for the virus to persist at low levels during anti-viral therapy.

  7. Synthesis of minus-strand copies of a viral transgene during viral infections of transgenic plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants can be genetically engineered to express viral sequences, often resulting in resistance to the virus from which the sequence was derived. The generally accepted mechanism for this pathogen induced resistance is gene silencing. Previous work has demonstrated that viral transgenes can be incorp...

  8. Extracellular vesicles are the Trojan horses of viral infection.

    PubMed

    Altan-Bonnet, Nihal

    2016-08-01

    Extracellular vesicles have recently emerged as a novel mode of viral propagation exploited by both enveloped and non-enveloped viruses. In particular non-enveloped viruses utilize the hosts' production of extracellular vesicles to exit from cells non-lytically and to hide and manipulate the immune system. Moreover, challenging the long held idea that viruses behave as independent genetic units, extracellular vesicles enable multiple viral particles and genomes to collectively traffic in and out of cells, which can promote genetic cooperativity among viral quasispecies and enhance the fitness of the overall viral population. PMID:27232382

  9. Experimental infection of pregnant goats with bovine viral diarrhea virus (BVDV)1 or 2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. ...

  10. Epidemiology and prevention of pediatric viral respiratory infections in health-care institutions.

    PubMed Central

    Goldmann, D. A.

    2001-01-01

    Nosocomial viral respiratory infections cause considerable illness and death on pediatric wards. Common causes of these infections include respiratory syncytial virus and influenza. Although primarily a community pathogen, rhinovirus also occasionally results in hospitalization and serious sequelae. This article reviews effective infection control interventions for these three pathogens, as well as ongoing controversies. PMID:11294717

  11. Enhanced enteroviral infectivity via viral protease-mediated cleavage of Grb2-associated binder 1.

    PubMed

    Deng, Haoyu; Fung, Gabriel; Shi, Junyan; Xu, Suowen; Wang, Chen; Yin, Meimei; Hou, Jun; Zhang, Jingchun; Jin, Zheng-Gen; Luo, Honglin

    2015-11-01

    Coxsackievirus B3 (CVB3), an important human causative pathogen for viral myocarditis, pancreatitis, and meningitis, has evolved different strategies to manipulate the host signaling machinery to ensure successful viral infection. We previously revealed a crucial role for the ERK1/2 signaling pathway in regulating viral infectivity. However, the detail mechanism remains largely unknown. Grb2-associated binder 1 (GAB1) is an important docking protein responsible for intracellular signaling assembly and transduction. In this study, we demonstrated that GAB1 was proteolytically cleaved after CVB3 infection at G175 and G436 by virus-encoded protease 2A(pro), independent of caspase activation. Knockdown of GAB1 resulted in a significant reduction of viral protein expression and virus titers. Moreover, we showed that virus-induced cleavage of GAB1 is beneficial to viral growth as the N-terminal proteolytic product of GAB1 (GAB1-N1-174) further enhances ERK1/2 activation and promotes viral replication. Our results collectively suggest that CVB3 targets host GAB1 to generate a GAB1-N1-174 fragment that enhances viral infectivity, at least in part, via activation of the ERK pathway. The findings in this study suggest a novel mechanism that CVB3 employs to subvert the host signaling and facilitate consequent viral replication. PMID:26183772

  12. INCREASED SUSCEPTIBILITY TO PENTOBARBITAL FOLLOWING MOUSE CYTOMEGALOVIRUS INFECTION: ROLE OF VIRAL-INDUCED INTERFERON

    EPA Science Inventory

    The purpose of this study was to determine the relative roles of viral induced interferon (IFN) and viral infection of the liver in mouse cytomegalovirus (MCMV)-induced depression of cytochrome P-450 (cyt P-450) levels and enhancement of pentobarbital-induced sleeping time (PEN-S...

  13. HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders

    PubMed Central

    Janes, Holly; Herbeck, Joshua T.; Tovanabutra, Sodsai; Thomas, Rasmi; Frahm, Nicole; Duerr, Ann; Hural, John; Corey, Lawrence; Self, Steve G.; Buchbinder, Susan P.; McElrath, M. Juliana; O'Connell, Robert J.; Paris, Robert M.; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Pitisuttihum, Punnee; Kaewkungwal, Jaranit; Robb, Merlin L.; Michael, Nelson L.; Mullins, James I.; Kim, Jerome H.; Gilbert, Peter B.; Rolland, Morgane

    2015-01-01

    Given the wide differences in HIV-1 viral load (VL) setpoint across subjects as opposed to fairly stable VL over time within an infected individual, it is important to identify host and viral characteristics that affect VL setpoint. While recently-infected individuals with multiple phylogenetically-linked HIV-1 founder variants represent a minority of HIV-1 infections, we found in two different cohorts that more diverse HIV-1 populations in early infection were associated with significantly higher VL one year after HIV-1 diagnosis. PMID:26322580

  14. Impact of cell regeneration in human respiratory tract on simultaneous viral infections

    NASA Astrophysics Data System (ADS)

    Pinky, Lubna Jahan Rashid; Dobrovolny, Hana

    2015-03-01

    Studies have found that ~ 40% of patients hospitalized with influenza-like illness are infected with at least two different viruses. In these longer infections, we need to consider the role of cell regeneration. Several mathematical models have been used to describe cell regeneration in infection models, though the effect of model choice on the predicted time course of simultaneous viral infections is not clear. We investigate a series of mathematical models of cell regeneration during simultaneous respiratory virus infections to determine the effect of cell regeneration on infection dynamics. We perform a nonlinear stability analysis for each model. The analysis suggests that coexistence of two viral species is not possible for any form of regeneration. We find that chronic illness is possible, but with only one viral species.

  15. CD4 T Cell Responses in Latent and Chronic Viral Infections

    PubMed Central

    Walton, Senta; Mandaric, Sanja; Oxenius, Annette

    2013-01-01

    The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

  16. Alpha-Synuclein Expression Restricts RNA Viral Infections in the Brain

    PubMed Central

    Beatman, Erica L.; Massey, Aaron; Shives, Katherine D.; Burrack, Kristina S.; Chamanian, Mastooreh; Morrison, Thomas E.

    2015-01-01

    ABSTRACT We have discovered that native, neuronal expression of alpha-synuclein (Asyn) inhibits viral infection, injury, and disease in the central nervous system (CNS). Enveloped RNA viruses, such as West Nile virus (WNV), invade the CNS and cause encephalitis, yet little is known about the innate neuron-specific inhibitors of viral infections in the CNS. Following WNV infection of primary neurons, we found that Asyn protein expression is increased. The infectious titer of WNV and Venezuelan equine encephalitis virus (VEEV) TC83 in the brains of Asyn-knockout mice exhibited a mean increase of 104.5 infectious viral particles compared to the titers in wild-type and heterozygote littermates. Asyn-knockout mice also exhibited significantly increased virus-induced mortality compared to Asyn heterozygote or homozygote control mice. Virus-induced Asyn localized to perinuclear, neuronal regions expressing viral envelope protein and the endoplasmic reticulum (ER)-associated trafficking protein Rab1. In Asyn-knockout primary neuronal cultures, the levels of expression of ER signaling pathways, known to support WNV replication, were significantly elevated before and during viral infection compared to those in Asyn-expressing primary neuronal cultures. We propose a model in which virus-induced Asyn localizes to ER-derived membranes, modulates virus-induced ER stress signaling, and inhibits viral replication, growth, and injury in the CNS. These data provide a novel and important functional role for the expression of native alpha-synuclein, a protein that is closely associated with the development of Parkinson's disease. IMPORTANCE Neuroinvasive viruses such as West Nile virus are able to infect neurons and cause severe disease, such as encephalitis, or infection of brain tissue. Following viral infection in the central nervous system, only select neurons are infected, implying that neurons exhibit innate resistance to viral infections. We discovered that native neuronal

  17. Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

    PubMed

    Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

    2015-11-01

    Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. PMID:26401005

  18. Antivirals for Respiratory Viral Infections: Problems and Prospects.

    PubMed

    Liu, Qiang; Zhou, Yuan-Hong; Ye, Feng; Yang, Zhan-Qiu

    2016-08-01

    In the past two decades, several newly emerging and reemerging viral respiratory pathogens including several influenza viruses (avian influenza and pandemic influenza), severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV), have continued to challenge medical and public health systems. Thereafter, the development of cost-effective, broad-spectrum antiviral agents is the urgent mission of both virologists and pharmacologists. Current antiviral developments have focused targets on viral entry, replication, release, and intercellular pathways essential for viral life cycle. Here, we review the current literature on challenges and prospects in the development of these antivirals. PMID:27486742

  19. Who Regulates Whom? An Overview of RNA Granules and Viral Infections

    PubMed Central

    Poblete-Durán, Natalia; Prades-Pérez, Yara; Vera-Otarola, Jorge; Soto-Rifo, Ricardo; Valiente-Echeverría, Fernando

    2016-01-01

    After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis) and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs), which are translationally silent sites of RNA triage and processing bodies (PBs), which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs). PMID:27367717

  20. Temporal pathogenesis of experimental neonatal woodchuck hepatitis virus infection: increased initial viral load and decreased severity of acute hepatitis during the development of chronic viral infection.

    PubMed

    Cote, P J; Toshkov, I; Bellezza, C; Ascenzi, M; Roneker, C; Ann Graham, L; Baldwin, B H; Gaye, K; Nakamura, I; Korba, B E; Tennant, B C; Gerin, J L

    2000-10-01

    Acute hepatitis B virus (HBV) infections either resolve or progress to chronicity. Identification of early deviations in host-virus responses associated with these outcomes can further differentiate cause-effect mechanisms that initiate and maintain chronicity. Neonatal woodchucks were infected experimentally with the woodchuck hepatitis virus (WHV) at 3 days of age. At 8 or 14 weeks of age (i.e. , the early- or mid-acute stage of infection), whole blood and large surgical biopsies of the liver were obtained from infected animals and uninfected controls. These were stored for later correlating histopathologic responses and viral load with the subsequently determined outcome of infection. As of 1 year postinfection, half of the surgically treated infected woodchucks had developed self-limited infections, while the other half developed chronic infections. The self-limited outcome was characterized by decreased viral load in acute-phase liver and plasma and a generally robust acute hepatic inflammatory response. Comparisons at the same early time points revealed that the chronic outcome was characterized by increasing initial viral load in liver and plasma, and a detectable, but diminished, acute hepatic inflammation. These cotemporal comparisons indicate that there is an early host-response deviation during the acute phase of a developing chronic infection. Continued analysis of the tissues banked from this study will facilitate further temporal characterization of acute-phase mechanisms that determine resolution versus chronicity in WHV infection. Understanding such mechanisms may be useful in the rational design of therapy for established chronic HBV infection. PMID:11003627

  1. Human papillomavirus type 16 viral load measurement as a predictor of infection clearance

    PubMed Central

    Schlecht, Nicolas F.; Ramanakumar, Agnihotram V.; Villa, Luisa L.; Franco, Eduardo L.

    2013-01-01

    Viral load measurements may predict whether human papillomavirus (HPV) type 16 infections may become persistent and eventually lead to cervical lesions. Today, multiple PCR methods exist to estimate viral load. We tested three protocols to investigate viral load as a predictor of HPV clearance. We measured viral load in 418 HPV16-positive cervical smears from 224 women participating in the Ludwig–McGill Cohort Study by low-stringency PCR (LS-PCR) using consensus L1 primers targeting over 40 known HPV types, and quantitative real-time PCR (qRT-PCR) targeting the HPV16 E6 and L1 genes. HPV16 clearance was determined by MY09/11 and PGMY PCR testing on repeated smears collected over 5 years. Correlation between viral load measurements by qRT-PCR (E6 versus L1) was excellent (Spearman’s rank correlation, ρ = 0.88), but decreased for L1 qRT-PCR versus LS-PCR (ρ = 0.61). Viral load by LS-PCR was higher for HPV16 and related types independently of other concurrent HPV infections. Median duration of infection was longer for smears with high copy number by all three PCR protocols (log rank P<0.05). Viral load is inversely related to HPV16 clearance independently of concurrent HPV infections and PCR protocol. PMID:23677791

  2. Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies.

    PubMed

    Ramanan, Vyas; Trehan, Kartik; Ong, Mei-Lyn; Luna, Joseph M; Hoffmann, Hans-Heinrich; Espiritu, Christine; Sheahan, Timothy P; Chandrasekar, Hamsika; Schwartz, Robert E; Christine, Kathleen S; Rice, Charles M; van Oudenaarden, Alexander; Bhatia, Sangeeta N

    2016-07-01

    Hepatitis C virus (HCV) is a positive single-stranded RNA virus of enormous global health importance, with direct-acting antiviral therapies replacing an immunostimulatory interferon-based regimen. The dynamics of HCV positive and negative-strand viral RNAs (vRNAs) under antiviral perturbations have not been studied at the single-cell level, leaving a gap in our understanding of antiviral kinetics and host-virus interactions. Here, we demonstrate quantitative imaging of HCV genomes in multiple infection models, and multiplexing of positive and negative strand vRNAs and host antiviral RNAs. We capture the varying kinetics with which antiviral drugs with different mechanisms of action clear HCV infection, finding the NS5A inhibitor daclatasvir to induce a rapid decline in negative-strand viral RNAs. We also find that the induction of host antiviral genes upon interferon treatment is positively correlated with viral load in single cells. This study adds smFISH to the toolbox available for analyzing the treatment of RNA virus infections. PMID:27128351

  3. Coral Mucus Is a Hot Spot for Viral Infections.

    PubMed

    Nguyen-Kim, Hanh; Bettarel, Yvan; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Nguyen-Thanh, Thuy; Tran-Quang, Huy; Brune, Justine

    2015-09-01

    There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are dominant among coral-associated viral communities. Mucosal viruses also exhibited significant differences in their main features between the two coral species and were also remarkably contrasted with their planktonic counterparts. For example, their abundance (inferred from epifluorescence counts), lytic production rates (KCN incubations), and the proportion of lysogenic cells (mitomycin C inductions) were, respectively, 2.6-, 9.5-, and 2.2-fold higher in mucus than in the surrounding water. Both lytic and lysogenic indicators were tightly coupled with temperature and salinity, suggesting that the life strategy of viral epibionts is strongly dependent upon environmental circumstances. Finally, our results suggest that coral mucus may represent a highly favorable habitat for viral proliferation, promoting the development of both temperate and virulent phages. Here, we discuss how such an optimized viral arsenal could be crucial for coral viability by presumably forging complex links with both symbiotic and adjacent nonsymbiotic microorganisms. PMID:26092456

  4. Coral Mucus Is a Hot Spot for Viral Infections

    PubMed Central

    Nguyen-Kim, Hanh; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Nguyen-Thanh, Thuy; Tran-Quang, Huy; Brune, Justine

    2015-01-01

    There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are dominant among coral-associated viral communities. Mucosal viruses also exhibited significant differences in their main features between the two coral species and were also remarkably contrasted with their planktonic counterparts. For example, their abundance (inferred from epifluorescence counts), lytic production rates (KCN incubations), and the proportion of lysogenic cells (mitomycin C inductions) were, respectively, 2.6-, 9.5-, and 2.2-fold higher in mucus than in the surrounding water. Both lytic and lysogenic indicators were tightly coupled with temperature and salinity, suggesting that the life strategy of viral epibionts is strongly dependent upon environmental circumstances. Finally, our results suggest that coral mucus may represent a highly favorable habitat for viral proliferation, promoting the development of both temperate and virulent phages. Here, we discuss how such an optimized viral arsenal could be crucial for coral viability by presumably forging complex links with both symbiotic and adjacent nonsymbiotic microorganisms. PMID:26092456

  5. Viral infections in type 1 diabetes mellitus--why the β cells?

    PubMed

    de Beeck, Anne Op; Eizirik, Decio L

    2016-05-01

    Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection--particularly by enteroviruses (for example, coxsackievirus)--as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review. PMID:27020257

  6. The Toll-Dorsal Pathway Is Required for Resistance to Viral Oral Infection in Drosophila

    PubMed Central

    Ferreira, Álvaro Gil; Naylor, Huw; Esteves, Sara Santana; Pais, Inês Silva; Martins, Nelson Eduardo; Teixeira, Luis

    2014-01-01

    Pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. Drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. Here we investigate the role of the Toll pathway in resistance to oral viral infection in D. melanogaster. We show that several Toll pathway components, including Spätzle, Toll, Pelle and the NF-kB-like transcription factor Dorsal, are required to resist oral infection with Drosophila C virus. Furthermore, in the fat body Dorsal is translocated from the cytoplasm to the nucleus and a Toll pathway target gene reporter is upregulated in response to Drosophila C Virus infection. This pathway also mediates resistance to several other RNA viruses (Cricket paralysis virus, Flock House virus, and Nora virus). Compared with control, viral titres are highly increased in Toll pathway mutants. The role of the Toll pathway in resistance to viruses in D. melanogaster is restricted to oral infection since we do not observe a phenotype associated with systemic infection. We also show that Wolbachia and other Drosophila-associated microbiota do not interact with the Toll pathway-mediated resistance to oral infection. We therefore identify the Toll pathway as a new general inducible pathway that mediates strong resistance to viruses with a route-specific role. These results contribute to a better understanding of viral oral infection resistance in insects, which is particularly relevant in the context of transmission of arboviruses by insect vectors. PMID:25473839

  7. The Toll-dorsal pathway is required for resistance to viral oral infection in Drosophila.

    PubMed

    Ferreira, Álvaro Gil; Naylor, Huw; Esteves, Sara Santana; Pais, Inês Silva; Martins, Nelson Eduardo; Teixeira, Luis

    2014-12-01

    Pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. Drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. Here we investigate the role of the Toll pathway in resistance to oral viral infection in D. melanogaster. We show that several Toll pathway components, including Spätzle, Toll, Pelle and the NF-kB-like transcription factor Dorsal, are required to resist oral infection with Drosophila C virus. Furthermore, in the fat body Dorsal is translocated from the cytoplasm to the nucleus and a Toll pathway target gene reporter is upregulated in response to Drosophila C Virus infection. This pathway also mediates resistance to several other RNA viruses (Cricket paralysis virus, Flock House virus, and Nora virus). Compared with control, viral titres are highly increased in Toll pathway mutants. The role of the Toll pathway in resistance to viruses in D. melanogaster is restricted to oral infection since we do not observe a phenotype associated with systemic infection. We also show that Wolbachia and other Drosophila-associated microbiota do not interact with the Toll pathway-mediated resistance to oral infection. We therefore identify the Toll pathway as a new general inducible pathway that mediates strong resistance to viruses with a route-specific role. These results contribute to a better understanding of viral oral infection resistance in insects, which is particularly relevant in the context of transmission of arboviruses by insect vectors. PMID:25473839

  8. Bovine viral diarrhea virus infections: manifestations of infection and recent advances in understanding pathogenesis and control.

    PubMed

    Brodersen, B W

    2014-03-01

    Bovine viral diarrhea virus (BVDV) continues to be of economic significance to the livestock industry in terms of acute disease and fetal loss. Many of the lesions relating to BVDV infection have been well described previously. The virus is perpetuated in herds through the presence of calves that are persistently infected. Relationships between various species and biotypes of BVDV and host defenses are increasingly understood. Understanding of the host defense mechanisms of innate immunity and adaptive immunity continues to improve, and the effects of the virus on these immune mechanisms are being used to explain how persistent infection develops. The noncytopathic biotype of BVDV plays the major role in its effects on the host defenses by inhibiting various aspects of the innate immune system and creation of immunotolerance in the fetus during early gestation. Recent advances have allowed for development of affordable test strategies to identify and remove persistently infected animals. With these improved tests and removal strategies, the livestock industry can begin more widespread effective control programs. PMID:24476940

  9. Cotton Leaf Curl Multan Virus-Derived Viral Small RNAs Can Target Cotton Genes to Promote Viral Infection.

    PubMed

    Wang, Jinyan; Tang, Yafei; Yang, Yuwen; Ma, Na; Ling, Xitie; Kan, Jialiang; He, Zifu; Zhang, Baolong

    2016-01-01

    RNA silencing is a conserved mechanism in plants that targets viruses. Viral small RNAs (vsiRNAs) can be generated from viral double-stranded RNA replicative intermediates within the infected host, or from host RNA-dependent RNA polymerases activity on viral templates. The abundance and profile of vsiRNAs in viral infections have been reported previously. However, the involvement of vsiRNAs during infection of the Geminiviridae family member cotton leaf curl virus (CLCuD), which causes significant economic losses in cotton growing regions, remains largely uncharacterized. Cotton leaf curl Multan virus (CLCuMuV) associated with a betasatellite called Cotton leaf curl Multan betasatellite (CLCuMuB) is a major constraint to cotton production in South Asia and is now established in Southern China. In this study, we obtained the profiles of vsiRNAs from CLCuMV and CLCuMB in infected upland cotton (Gossypium hirsutum) plants by deep sequencing. Our data showed that vsiRNA that were derived almost equally from sense and antisense CLCuD DNA strands accumulated preferentially as 21- and 22-nucleotide (nt) small RNA population and had a cytosine bias at the 5'-terminus. Polarity distribution revealed that vsiRNAs were almost continuously present along the CLCuD genome and hotspots of sense and antisense strands were mainly distributed in the Rep proteins region of CLCuMuV and in the C1 protein of CLCuMuB. In addition, hundreds of host transcripts targeted by vsiRNAs were predicted, many of which encode transcription factors associated with biotic and abiotic stresses. Quantitative real-time polymerase chain reaction analysis of selected potential vsiRNA targets showed that some targets were significantly down-regulated in CLCuD-infected cotton plants. We also verified the potential function of vsiRNA targets that may be involved in CLCuD infection by virus-induced gene silencing (VIGS) and 5'-rapid amplification of cDNA end (5'-RACE). Here, we provide the first report on vsi

  10. Cotton Leaf Curl Multan Virus-Derived Viral Small RNAs Can Target Cotton Genes to Promote Viral Infection

    PubMed Central

    Wang, Jinyan; Tang, Yafei; Yang, Yuwen; Ma, Na; Ling, Xitie; Kan, Jialiang; He, Zifu; Zhang, Baolong

    2016-01-01

    RNA silencing is a conserved mechanism in plants that targets viruses. Viral small RNAs (vsiRNAs) can be generated from viral double-stranded RNA replicative intermediates within the infected host, or from host RNA-dependent RNA polymerases activity on viral templates. The abundance and profile of vsiRNAs in viral infections have been reported previously. However, the involvement of vsiRNAs during infection of the Geminiviridae family member cotton leaf curl virus (CLCuD), which causes significant economic losses in cotton growing regions, remains largely uncharacterized. Cotton leaf curl Multan virus (CLCuMuV) associated with a betasatellite called Cotton leaf curl Multan betasatellite (CLCuMuB) is a major constraint to cotton production in South Asia and is now established in Southern China. In this study, we obtained the profiles of vsiRNAs from CLCuMV and CLCuMB in infected upland cotton (Gossypium hirsutum) plants by deep sequencing. Our data showed that vsiRNA that were derived almost equally from sense and antisense CLCuD DNA strands accumulated preferentially as 21- and 22-nucleotide (nt) small RNA population and had a cytosine bias at the 5′-terminus. Polarity distribution revealed that vsiRNAs were almost continuously present along the CLCuD genome and hotspots of sense and antisense strands were mainly distributed in the Rep proteins region of CLCuMuV and in the C1 protein of CLCuMuB. In addition, hundreds of host transcripts targeted by vsiRNAs were predicted, many of which encode transcription factors associated with biotic and abiotic stresses. Quantitative real-time polymerase chain reaction analysis of selected potential vsiRNA targets showed that some targets were significantly down-regulated in CLCuD-infected cotton plants. We also verified the potential function of vsiRNA targets that may be involved in CLCuD infection by virus-induced gene silencing (VIGS) and 5′-rapid amplification of cDNA end (5′-RACE). Here, we provide the first report

  11. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

    PubMed Central

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

  12. Productive infection of human immunodeficiency virus type 1 in dendritic cells requires fusion-mediated viral entry

    SciTech Connect

    Janas, Alicia M.; Dong, Chunsheng; Wang Jianhua; Wu Li

    2008-06-05

    Human immunodeficiency virus type 1 (HIV-1) enters dendritic cells (DCs) through endocytosis and viral receptor-mediated fusion. Although endocytosis-mediated HIV-1 entry can generate productive infection in certain cell types, including human monocyte-derived macrophages, productive HIV-1 infection in DCs appears to be dependent on fusion-mediated viral entry. It remains to be defined whether endocytosed HIV-1 in DCs can initiate productive infection. Using HIV-1 infection and cellular fractionation assays to measure productive viral infection and entry, here we show that HIV-1 enters monocyte-derived DCs predominately through endocytosis; however, endocytosed HIV-1 cannot initiate productive HIV-1 infection in DCs. In contrast, productive HIV-1 infection in DCs requires fusion-mediated viral entry. Together, these results provide functional evidence in understanding HIV-1 cis-infection of DCs, suggesting that different pathways of HIV-1 entry into DCs determine the outcome of viral infection.

  13. TLR and RLR Signaling Are Reprogrammed in Opposite Directions after Detection of Viral Infection.

    PubMed

    Hotz, Christian; Roetzer, Laurin C; Huber, Thomas; Sailer, Andreas; Oberson, Anne; Treinies, Marina; Heidegger, Simon; Herbst, Tina; Endres, Stefan; Bourquin, Carole

    2015-11-01

    Innate immune recognition of RNA is key for the initiation of immunity in response to viral infection. Although the factors controlling the detection of viral RNA by innate immune receptors in host cells are increasingly well understood, little is known about the dynamic changes in signaling after the initial triggering of these receptors. In this study, we report that preconditioning with the synthetic dsRNA polyinosinic-polycytidylic acid [poly(I:C)], a mimetic of viral RNA, rapidly reprograms murine APCs by simultaneously augmenting sensitivity of endosomal TLRs and inhibiting activation of RIG-I-like receptors (RLRs) in an IFN-β-dependent manner. These changes in receptor sensitivity were also seen in vivo after treatment of mice with poly(I:C). Mechanistically, the increased sensitivity of the TLR pathway was associated with elevated MAPK and NF-κB activity. The RLR response was inhibited downstream of TANK-binding kinase-1, resulting in decreased IFN regulatory factor 3 phosphorylation. Reprogramming of pattern-recognition receptor signaling also occurred after viral infection, because infection of host cells with Sendai virus or their exposure to supernatant from virus-infected cells induced the same changes in TLR and RLR sensitivity as poly(I:C). Thus, innate recognition of viral infection critically modifies responses to pattern-recognition receptor stimulation. These dynamic adaptations to infection may reinforce antiviral immunity and at the same time serve to limit pathological inflammation. PMID:26392465

  14. TCF1 Is Required for the T Follicular Helper Cell Response to Viral Infection.

    PubMed

    Wu, Tuoqi; Shin, Hyun Mu; Moseman, E Ashley; Ji, Yun; Huang, Bonnie; Harly, Christelle; Sen, Jyoti M; Berg, Leslie J; Gattinoni, Luca; McGavern, Dorian B; Schwartzberg, Pamela L

    2015-09-29

    T follicular helper (TFH) and T helper 1 (Th1) cells generated after viral infections are critical for the control of infection and the development of immunological memory. However, the mechanisms that govern the differentiation and maintenance of these two distinct lineages during viral infection remain unclear. We found that viral-specific TFH and Th1 cells showed reciprocal expression of the transcriptions factors TCF1 and Blimp1 early after infection, even before the differential expression of the canonical TFH marker CXCR5. Furthermore, TCF1 was intrinsically required for the TFH cell response to viral infection; in the absence of TCF1, the TFH cell response was severely compromised, and the remaining TCF1-deficient TFH cells failed to maintain TFH-associated transcriptional and metabolic signatures, which were distinct from those in Th1 cells. Mechanistically, TCF1 functioned through forming negative feedback loops with IL-2 and Blimp1. Our findings demonstrate an essential role of TCF1 in TFH cell responses to viral infection. PMID:26365183

  15. Progress in Treatment of Viral Infections in Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Moschovi, Maria; Adamaki, Maria; Vlahopoulos, Spiros A.

    2016-01-01

    In children, the most commonly encountered type of leukemia is acute lymphoblastic leukemia (ALL). An important source of morbidity and mortality in ALL are viral infections. Even though allogeneic transplantations, which are often applied also in ALL, carry a recognized risk for viral infections, there are multiple factors that make ALL patients susceptible to viral infections. The presence of those factors has an influence in the type and severity of infections. Currently available treatment options do not guarantee a positive outcome for every case of viral infection in ALL, without significant side effects. Side effects can have very serious consequences for the ALL patients, which include nephrotoxicity. For this reason a number of strategies for personalized intervention have been already clinically tested, and experimental approaches are being developed. Adoptive immunotherapy, which entails administration of ex vivo grown immune cells to a patient, is a promising approach in general, and for transplant recipients in particular. The ex vivo grown cells are aimed to strengthen the immune response to the virus that has been identified in the patients’ blood and tissue samples. Even though many patients with weakened immune system can benefit from progress in novel approaches, a viral infection still poses a very significant risk for many patients. Therefore, preventive measures and supportive care are very important for ALL patients. PMID:27471584

  16. Rapid, targeted and culture-free viral infectivity assay in drop-based microfluidics.

    PubMed

    Tao, Ye; Rotem, Assaf; Zhang, Huidan; Chang, Connie B; Basu, Anindita; Kolawole, Abimbola O; Koehler, Stephan A; Ren, Yukun; Lin, Jeffrey S; Pipas, James M; Feldman, Andrew B; Wobus, Christiane E; Weitz, David A

    2015-10-01

    A key viral property is infectivity, and its accurate measurement is crucial for the understanding of viral evolution, disease and treatment. Currently viral infectivity is measured using plaque assays, which involve prolonged culturing of host cells, and whose measurement is unable to differentiate between specific strains and is prone to low number fluctuation. We developed a rapid, targeted and culture-free infectivity assay using high-throughput drop-based microfluidics. Single infectious viruses are incubated in a large number of picoliter drops with host cells for one viral replication cycle followed by in-drop gene-specific amplification to detect infection events. Using murine noroviruses (MNV) as a model system, we measure their infectivity and determine the efficacy of a neutralizing antibody for different variants of MNV. Our results are comparable to traditional plaque-based assays and plaque reduction neutralization tests. However, the fast, low-cost, highly accurate genomic-based assay promises to be a superior method for drug screening and isolation of resistant viral strains. Moreover our technique can be adapted to measuring the infectivity of other pathogens, such as bacteria and fungi. PMID:26304791

  17. Early lymphoreticular viral tropism and antigen persistence. Tamiami virus infection in the cotton rat.

    PubMed

    Murphy, F A; Winn, W C; Walker, D H; Flemister, M R; Whitfield, S G

    1976-02-01

    Tamiami virus was inoculated into its natural reservoir host, the cotton rat (Sigmodon hispidus), and the course of infection was followed by sequential organ titrations, frozen-section immunofluorescence, and light and electron microscopy. In animals infected at 2 days of age, there was an early lymphoreticular tropism with peak concentrations of virus and viral antigen in lymph nodes, splenic white pulp, thymus, and bone marrow at 16 days postinoculation. Megakaryocyte infection was early and pronounced. Viral antigen concentration peaked in liver and salivary glands at day 30 and in kidney, adrenal cortex, respiratory tract, and bladder epithelium at day 60-long after viral infectivity in these organs had disappeared. Central nervous system infection was only modestly productive of infectious virus, but viral antigen continued to increase in the brain until day 90 and then did not decline throughout the 360-day study. Reticuloendothelial hyperplastic foci were found late in some target organs, but there was never any histologic or ultrastructural evidence of cytonecrosis. Older animals were virtually uninfectable; therefore, this susceptibility of newborns and their slow termination of infection represent the key to virus transmission and perpetuation in nature. These aspects of viral natural history contribute to an understanding of human exposure to the pathogenic arenaviruses which exist in similar rodent niches. PMID:1249916

  18. Eicosanoids mediate melantoic nodulation reactions to viral infection in larvae of the parasitic wasp, Pimpla turionellae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nodulation is the predominant insect cellular immune response to bacterial and fungal infections and it can also be induced by viral infection. Treating seventh instar larvae of greater wax moth Galleria mellonella with Bovine herpes simplex virus-1 (BHSV-1) induced nodulation reactions in a dose-d...

  19. Evidence for persistent bovine viral diarrhea virus infection in a captive mountain goat (Oreamnos americanus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea viruses (BVDV) are pestiviruses that have been isolated from domestic and wild ruminants, and there is serologic evidence of pestiviral infection in more than 40 species of free-ranging and captive mammals. Vertical transmission can produce persistently infected animals that ar...

  20. Identification of Genetic Regions Associated with Bovine Viral Diarrhea-Persistently Infected Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is one of the etiologies involved in bovine respiratory disease (BRD). BVDV infection can also cause reproductive disorders and acute fatal hemorrhagic disease resulting in poor performance and economic losses to the cattle industry. Infection with BVDV can be tra...

  1. Long-term clincopathological characteristics of alpacas naturally infected with bovine viral diarrhea virus type Ib

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Substantial bovine viral diarrhea virus (BVDV)-related production losses in North American alpaca herds have been associated with BVDV type Ib infection. Objectives: To classify and differentiate the long-term clinicopathological characteristics of BVDV type Ib infection of alpaca crias,...

  2. The effects of exposure of susceptible alpacas to alpacas persistently infected with bovine viral diarrhea virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reports of bovine viral diarrhea virus (BVDV) infections in alpacas have been increasing over the past several years but much is still unknown about the mechanisms of disease in this species. This report describes research performed to characterize the transmission of BVDV from persistently infected...

  3. First report of bovine viral diarrhoea virus-2 infection in cattle in Poland.

    PubMed

    Polak, Mirosław P; Kuta, Aleksandra; Rybałtowski, Wiesław; Rola, Jerzy; Larska, Magdalena; Zmudziński, Jan F

    2014-12-01

    This report describes the first identification in Poland of bovine viral diarrhoea virus (BVDV)-2 in a dairy herd where severe clinical disease with losses of young animals was observed. The virus was readily cultivated in cell culture and a phylogenetic analysis of the nucleotide sequences and secondary structures of the viral genomic 5' untranslated region confirmed virus identity. The economic impact of the infection was significant compared to the previously prevalent BVDV-1 infections confirming that this genotype of BVDV can cause severe sickness in affected herds. The use of BVDV-1 vaccine did not prevent the infection with the BVDV-2 genotype. PMID:25457262

  4. Diagnostic classification, viral sexually transmitted infections and discourses of femininity: limits of normalisation to erase stigma.

    PubMed

    Cook, Catherine

    2013-06-01

    Clinicians in the field of women's sexual health typically classify the two most common viral sexually transmitted infections (STIs), the human papilloma virus and the herpes simplex virus, as relatively innocuous infections. Teaching interventions include 'normalising' adult sexual activity and the epidemiological ordinariness of infection. Normalising is intended to disarm the potential stigma of the diagnosis. In this study, in-depth email interviews were conducted with 26 women with a viral STI diagnosis and 12 sexual health clinicians. Data were analysed thematically using a feminist, poststructuralist approach. Normalising is contextualised as an example of the workings of western philosophical thought whereby dualistic classifications privilege certain terms and subordinate other terms. In this instance, the relative medical normalcy of viral STIs is given primacy compared to the social abnormality experienced by women. Although these viral STIs infect women and men, this research concentrates on women's learning about viral STIs. For women, beliefs about femininity, sexuality, health, morality and responsibility influence effects of a viral STI diagnosis. These discourses are clinically significant because beliefs that specifically link to ideas about how to be a woman are overlooked when clinicians devise educational interventions. PMID:22333002

  5. Activating KIRs and NKG2C in Viral Infections: Toward NK Cell Memory?

    PubMed Central

    Della Chiesa, Mariella; Sivori, Simona; Carlomagno, Simona; Moretta, Lorenzo; Moretta, Alessandro

    2015-01-01

    Natural killer (NK) cells are important players in the immune defense against viral infections. The contribution of activating killer immunoglobulin-like receptors (KIRs) and CD94/NKG2C in regulating anti-viral responses has recently emerged. Thus, in the hematopoietic stem cell transplantation setting, the presence of donor activating KIRs (aKIRs) may protect against viral infections, while in HIV-infected individuals, KIR3DS1, in combination with HLA-Bw4-I80, results in reduction of viral progression. Since, studies have been performed mainly at the genetic or transcriptional level, the effective size, the function, and the “licensing” status of NK cells expressing aKIRs, as well as the nature of their viral ligands, require further investigation. Certain viral infections, mainly due to Human cytomegalovirus (HCMV), can deeply influence the NK cell development and function by inducing a marked expansion of mature NKG2C+ NK cells expressing self-activating KIRs. This suggests that NKG2C and/or aKIRs are involved in the selective proliferation of this subset. The persistent, HCMV-induced, imprinting suggests that NK cells may display unexpected adaptive immune traits. The role of aKIRs and NKG2C in regulating NK cell responses and promoting a memory-like response to certain viruses is discussed. PMID:26617607

  6. 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

  7. JP-8 jet fuel exposure suppresses the immune response to viral infections.

    PubMed

    Harris, D T; Sakiestewa, D; Titone, D; He, X; Hyde, J; Witten, M

    2008-05-01

    The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has reported that JP-8 exposure is immunosuppressive. Exposure of mice to JP-8 for 1A h/day resulted in immediate secretion of two immunosuppressive agents, namely, interleukin-10 and prostaglandin E2. Thus, it was of interest to determine if jet fuel exposure might alter the immune response to infectious agents. The Hong Kong influenza model was used for these studies. Mice were exposed to 1000A mg/m(3) JP-8 (1A h/day) for 7A days before influenza viral infection. Animals were infected intra-nasally with virus and followed in terms of overall survival as well as immune responses. All surviving animals were killed 14A days after viral infection. In the present study, JP-8 exposure increased the severity of the viral infection by suppressing the anti-viral immune responses. That is, exposure of mice to JP-8 for 1A h/day for 7A days before infection resulted in decreased immune cell viability after exposure and infection, a greater than fourfold decrease in immune proliferative responses to mitogens, as well as an overall loss of CD3(+), CD4(+), and CD8(+) T cells from the lymph nodes, but not the spleens, of infected animals. These changes resulted in decreased survival of the exposed and infected mice, with only 33% of animals surviving as compared with 50% of mice infected but not jet fuel-exposed (and 100% of mice exposed only to JP-8). Thus, short-term, low-concentration JP-8 jet fuel exposures have significant suppressive effects on the immune system which can result in increased severity of viral infections. PMID:19022873

  8. Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I

    PubMed Central

    Wang, Penghua; Arjona, Alvaro; Zhang, Yue; Sultana, Hameeda; Dai, Jianfeng; Yang, Long; LeBlanc, Philippe M; Doiron, Karine; Saleh, Maya; Fikrig, Erol

    2013-01-01

    Caspase-12 has been shown to negatively modulate inflammasome signaling during bacterial infection. Its function in viral immunity, however, has not been characterized. We now report an important role for caspase-12 in controlling viral infection via the pattern-recognition receptor RIG-I. After challenge with West Nile virus (WNV), caspase-12-deficient mice had greater mortality, higher viral burden and defective type I interferon response compared with those of challenged wild-type mice. In vitro studies of primary neurons and mouse embryonic fibroblasts showed that caspase-12 positively modulated the production of type I interferon by regulating E3 ubiquitin ligase TRIM25–mediated ubiquitination of RIG-I, a critical signaling event for the type I interferon response to WNV and other important viral pathogens. PMID:20818395

  9. An accurate two-phase approximate solution to the acute viral infection model

    SciTech Connect

    Perelson, Alan S

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  10. Viral infection and aging as cofactors for the development of pulmonary fibrosis

    PubMed Central

    Naik, Payal K; Moore, Bethany B

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a disease of unknown origin and progression that primarily affects older adults. Accumulating clinical and experimental evidence suggests that viral infections may play a role, either as agents that predispose the lung to fibrosis or exacerbate existing fibrosis. In particular, herpesviruses have been linked with IPF. This article summarizes the evidence for and against viral cofactors in IPF pathogenesis. In addition, we review mechanistic studies in animal models that highlight the fibrotic potential of viral infection, and explore the different mechanisms that might be responsible. We also review early evidence to suggest that the aged lung may be particularly susceptible to viral-induced fibrosis and make recommendations for future research directions. PMID:21128751

  11. The impact of bacterial and viral co‐infection in severe influenza

    PubMed Central

    Blyth, Christopher C.; Webb, Steve A. R.; Kok, Jen; Dwyer, Dominic E.; van Hal, Sebastiaan J.; Foo, Hong; Ginn, Andrew N.; Kesson, Alison M.; Seppelt, Ian; Iredell, Jonathan R.

    2013-01-01

    Please cite this paper as: Blyth et al. (2013) The impact of bacterial and viral co‐infection in severe influenza. Influenza and Other Respiratory Viruses 7(2) 168–176. Background  Many questions remain concerning the burden, risk factors and impact of bacterial and viral co‐infection in patients with pandemic influenza admitted to the intensive care unit (ICU). Objectives  To examine the burden, risk factors and impact of bacterial and viral co‐infection in Australian patients with severe influenza. Patients/Methods  A cohort study conducted in 14 ICUs was performed. Patients with proven influenza A during the 2009 influenza season were eligible for inclusion. Demographics, risk factors, clinical data, microbiological data, complications and outcomes were collected. Polymerase chain reaction for additional bacterial and viral respiratory pathogens was performed on stored respiratory samples. Results  Co‐infection was identified in 23·3–26·9% of patients with severe influenza A infection: viral co‐infection, 3·2–3·4% and bacterial co‐infection, 20·5–24·7%. Staphylococcus aureus was the most frequent bacterial co‐infection followed by Streptococcus pneumoniae and Haemophilus influenzae. Patients with co‐infection were younger [mean difference in age = 8·46 years (95% CI: 0·18–16·74 years)], less likely to have significant co‐morbidities (32·0% versus 66·2%, P = 0·004) and less frequently obese [mean difference in body mass index = 6·86 (95% CI: 1·77–11·96)] compared to those without co‐infection. Conclusions  Bacterial or viral co‐infection complicated one in four patients admitted to ICU with severe influenza A infection. Despite the co‐infected patients being younger and with fewer co‐morbidities, no significant difference in outcomes was observed. It is likely that co‐infection contributed to a need for ICU admission in those without other risk factors for severe influenza disease

  12. Spatiotemporal dynamics of insect pest population under viral infection.

    PubMed

    Ghosh, Suma; Bhattacharyya, Samit

    2013-07-01

    The interrelationship between pathogen infection and host mobility is of great importance for successful spread of disease in spatial pest population. As spread of infection depends on horizontal transmission of pathogen, there are numerous factors like susceptibility, latent period, host movement that influence overall effectiveness of the control policy. Initiation of new infection cycle depends on density of infected inoculum in the site. So, spatial movement of infected hosts during the course of infection influence the dynamics. Also, infected individuals are more vulnerable to predators and hence production of virus particles in the site depends on predation to some extent. We derive a four dimensional delayed reaction-diffusion model in one spatial dimension and compute the minimum travelling speed of transmission of infection. We show that the minimum speed is sensitive to several parameters of the system. For example, the minimum speed decreases only with increase in delay in lysis process, but otherwise it increases with increase in force of infection, diffusivity of infectives or per capita virus production. A concluding discussion with numerical simulation is presented in the end. PMID:23562890

  13. Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver.

    PubMed Central

    Guidotti, L G; Borrow, P; Hobbs, M V; Matzke, B; Gresser, I; Oldstone, M B; Chisari, F V

    1996-01-01

    Hepatitis B virus (HBV) infection is thought to be controlled by virus-specific cytotoxic T lymphocytes (CTL). We have recently shown that HBV-specific CTL can abolish HBV replication noncytopathically in the liver of transgenic mice by secreting tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) after antigen recognition. We now demonstrate that hepatocellular HBV replication is also abolished noncytopathically during lymphocytic choriomeningitis virus (LCMV) infection, and we show that this process is mediated by TNF-alpha and IFN-alpha/beta produced by LCMV-infected hepatic macrophages. These results confirm the ability of these inflammatory cytokines to abolish HBV replication; they elucidate the mechanism likely to be responsible for clearance of HBV in chronically infected patients who become superinfected by other hepatotropic viruses; they suggest that pharmacological activation of intrahepatic macrophages may have therapeutic value in chronic HBV infection; and they raise the possibility that conceptually similar events may be operative in other viral infections as well. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8643448

  14. Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Firdous, Shamaraz; Anwar, Shahzad

    2015-08-01

    Raman spectroscopy has been found useful for monitoring the dengue patient diagnostic and recovery after infection. In the present work, spectral changes that occurred in the blood sera of a dengue infected patient and their possible utilization for monitoring of infection and recovery were investigated using 532 nm wavelength of light. Raman spectrum peaks for normal and after recovery of dengue infection are observed at 1527, 1170, 1021 cm-1 attributed to guanine, adenine, TRP (protein) carbohydrates peak for solids, and skeletal C-C stretch of lipids acyl chains. Where in the dengue infected patient Raman peaks are at 1467, 1316, 1083, and 860 attributed to CH2/CH3 deformation of lipids and collagen, guanine (B, Z-marker), lipids and protein bands. Due to antibodies and antigen reactions the portions and lipids concentration totally changes in dengue viral infection compared to normal blood. These chemical changes in blood sera of dengue viral infection in human blood may be used as possible markers to indicate successful remission and suggest that Raman spectroscopy may provide a rapid optical method for continuous monitoring or evaluation of a protein bands and an antibodies population. Accumulate acquisition mode was used to reduce noise and thermal fluctuation and improve signal to noise ratio. This in vitro dengue infection monitoring methodology will lead in vivo noninvasive on-line monitoring and screening of viral infected patients and their recovery.

  15. Stimulation of viral infection of bacterioplankton during a mesoscale iron fertilization experiment in the Southern Ocean

    NASA Astrophysics Data System (ADS)

    Weinbauer, M. G.; Arrieta, J.-M.; Herndl, G. J.

    2003-04-01

    A mesoscale iron fertilization in the Southern Ocean (Eisenex ) induced a phytoplankton bloom within three weeks observation as well as in an increased bacterial abundance and production. Viral abundance and viral production were stimulated as well. A virus-dilution approach was used to estimate the frequency of infected cells (FIC) and the frequency of lysogenic cells (FLC), i.e. cells with a dormant viral genome. While the FLC did not vary strongly within the iron-enriched patch and did not differ from waters outside the patch, FIC increased significantly within the iron fertilized patch. This suggests that induction of the lytic cycle in lysogenic cells was not significant. Rather, the stimulated bacterial production and abundance within the patch resulted in higher and more successful encounters between viruses and hosts and thus in higher FIC values. Consequently, the iron fertilization enhanced the influence of viral infection in the microbial food web. According to the current model, this should result a stimulation of bacterial production, since lysed bacterial cells cannot be consumed up by protists and transferred to higher trophic level; lysis products can be taken up by bacteria and thus organic carbon spins within this viral loop. Viral infection is a significant and previously overlooked factor in the carbon flow during iron fertilization experiments.

  16. Balancing viral replication in spleen and liver determines the outcome of systemic virus infection.

    PubMed

    Lang, K S; Lang, P A

    2015-12-01

    The innate immune system limits virus replication during systemic infection by producing type I interferons (IFN-I) but still has to allow viral replication to achieve maximal innate and adaptive immune activation. Some spleen and lymph node resident antigen presenting cells (APCs) show limited response to IFN-I due to expression of the endogenous inhibitor of IFN-I signaling, Usp18. Therefore, virus in this spleen niche replicates despite high levels of IFN-I. This enforced viral replication leads to an exorbitant propagation of viral antigens and viral RNA. Viral antigen leads to massive activation of the adaptive immune system, while viral RNA to activated innate immunity. In contrast to these APCs, liver resident Kupffer cells, take up most of the systemic virus and suppress its replication in response to IFN-I. In addition, virus specific CD8 + T cells which are primed in the spleen migrate to the liver and kill virus infected cells. In this review we discuss the different mechanisms, which influence immune activation in spleen and antiviral mechanisms in the liver and how they determine the outcome of virus infection. PMID:26666281

  17. MAVS: a new weapon in the fight against viral infections.

    PubMed

    Boga, Jose A; de Oña, Maria; Melon, Santiago; Alvarez-Arguelles, Marta E; Morilla, Ana; Coto-Montes, Ana

    2013-05-01

    In addition to their participation in metabolic processes and control of programmed cell death, the role of mitochondria as a fundamental hub for innate anti-viral immunity is now emerging. The participation of the mitochondrial antiviral signaling protein (MAVS) as a central regulator of a complex signaling cascade, which results in the induction of antiviral and inflammatory responses has been described. A patent based on this role of MAVS is highlighted in this review. PMID:23432157

  18. Methamphetamine mediates immune dysregulation in a murine model of chronic viral infection

    PubMed Central

    Sriram, Uma; Haldar, Bijayesh; Cenna, Jonathan M.; Gofman, Larisa; Potula, Raghava

    2015-01-01

    Methamphetamine (METH) is a highly addictive psychostimulant that not only affects the brain and cognitive functions but also greatly impacts the host immune system, rendering the body susceptible to infections and exacerbating the severity of disease. Although there is gathering evidence about METH abuse and increased incidence of HIV and other viral infections, not much is known about the effects on the immune system in a chronic viral infection setting. We have used the lymphocytic choriomeningitis virus (LCMV) chronic mouse model of viral infection in a chronic METH environment and demonstrate that METH significantly increases CD3 marker on splenocytes and programmed death-1 (PD-1) expression on T cells, a cell surface signaling molecule known to inhibit T cell function and cause exhaustion in a lymphoid organ. Many of these METH effects were more pronounced during early stage of infection, which are gradually attenuated during later stages of infection. An essential cytokine for T-lymphocyte homeostasis, Interleukin-2 (IL-2) in serum was prominently reduced in METH-exposed infected mice. In addition, the serum pro-inflammatory (TNF, IL12 p70, IL1β, IL-6, and KC-GRO) and Th2 (IL-2, IL-10, and IL-4) cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice. Similarly, compared to only infected mice, epidermal growth factor receptor (EGFR) in METH exposed LCMV infected mice were up regulated. Collectively, our data suggest that METH alters systemic, peripheral immune responses and modulates key markers on T cells involved in pathogenesis of chronic viral infection. PMID:26322025

  19. Early Cytokine Dysregulation and Viral Replication Are Associated with Mortality During Lethal Influenza Infection

    PubMed Central

    Vogel, Alexander J.; Harris, Seth; Marsteller, Nathan; Condon, Shirley A.

    2014-01-01

    Abstract Infection with influenza A virus (IAV) leads to acute lung injury and possibly fatal complications, especially in immunocompromised, elderly, or chronically infected individuals. Therefore, it is important to study the factors that lead to pathology and mortality in infected hosts. In this report, we analyze immune responses to infection at a sublethal (0.1 LD50) and lethal (1 LD50) dose of the highly pathogenic IAV A/Puerto Rico/8/34 (PR8). Our experiments revealed that infection with a 1 LD50 dose induced peak viral titers at day 2 compared to day 4 in the 0.1 LD50 dose. Moreover, early cytokine dysregulation was observed in the lethal dose with significantly elevated levels of IFN-α, TNF-α, CXCL9, IL-6, and MCP-1 produced at day 2. Early inflammatory responses following infection with 1 LD50 correlated with a greater influx of neutrophils into the lung. However, depletion of neutrophils enhanced morbidity following IAV infection. Though no differences in CD8+ cell function were observed, CD4+ effector responses were impaired in the lungs 8 days after infection with 1 LD50. Histological analysis revealed significant pathology in lethally infected mice at day 2 and day 6 postinfection, when viral titers remained high. Treating lethally infected mice with oseltamivir inhibited viral titers to sublethal levels, and abrogated the pathology associated with the lethal dose. Together, these results suggest that early cytokine dysregulation and viral replication play a role in pulmonary damage and high mortality in lethally infected mice. PMID:24787235

  20. Viral respiratory infection increases alveolar macrophage cytoplasmic motility in rats: role of NO.

    PubMed

    Fukushima, T; Sekizawa, K; Yamaya, M; Okinaga, S; Satoh, M; Sasaki, H

    1995-03-01

    Ingested ferrimagnetic (Fe3O4) particles were used to estimate noninvasively the motion of organelles in alveolar macrophages (AM) in intact rats during viral respiratory infection by parainfluenza type 1 (Sendai) virus. Four days after instillation of Fe3O4 particles (3 mg/kg) into the lung, remnant field strength (RFS) was measured at the body surface immediately after magnetization of Fe3O4 particles by an externally applied magnetic field. RFS decreases with time, due to particle rotation (relaxation) which is related to cytoplasmic motility of AM. Viral infection increased the relaxation rate (lambda o per min), and increases in lambda o reached a maximum 3 days after nasal inoculation (day 3). Viral infection (day 3)-induced increases in lambda o were dose dependently inhibited by either the L-arginine analogue N-nitro-L-arginine or by methylene blue, an inhibitor of guanylate cyclase activity. Bronchoalveolar lavage fluid obtained from infected rats contained significantly higher levels of nitrite than that from control rats (P < 0.01). In in vitro experiments, AM from infected rats showed significantly higher lambda o, nitrite production, and intracellular guanosine 3',5'-cyclic monophosphate levels than those from control rats (P < 0.01). Sodium nitroprusside, known to release nitric oxide concentration dependently, increased lambda o of AM from noninfected rats in vitro. These results suggest that nitric oxide plays an important role in AM cytoplasmic motility during viral respiratory infection. PMID:7900821

  1. Contrasting life strategies of viruses that infect photo- and heterotrophic bacteria, as revealed by viral tagging.

    PubMed

    Deng, Li; Gregory, Ann; Yilmaz, Suzan; Poulos, Bonnie T; Hugenholtz, Philip; Sullivan, Matthew B

    2012-01-01

    Ocean viruses are ubiquitous and abundant and play important roles in global biogeochemical cycles by means of their mortality, horizontal gene transfer, and manipulation of host metabolism. However, the obstacles involved in linking viruses to their hosts in a high-throughput manner bottlenecks our ability to understand virus-host interactions in complex communities. We have developed a method called viral tagging (VT), which combines mixtures of host cells and fluorescent viruses with flow cytometry. We investigated multiple viruses which infect each of two model marine bacteria that represent the slow-growing, photoautotrophic genus Synechococcus (Cyanobacteria) and the fast-growing, heterotrophic genus Pseudoalteromonas (Gammaproteobacteria). Overall, viral tagging results for viral infection were consistent with plaque and liquid infection assays for cyanobacterial myo-, podo- and siphoviruses and some (myo- and podoviruses) but not all (four siphoviruses) heterotrophic bacterial viruses. Virus-tagged Pseudoalteromonas organisms were proportional to the added viruses under varied infection conditions (virus-bacterium ratios), while no more than 50% of the Synechococcus organisms were virus tagged even at viral abundances that exceeded (5 to 10×) that of their hosts. Further, we found that host growth phase minimally impacts the fraction of virus-tagged Synechococcus organisms while greatly affecting phage adsorption to Pseudoalteromonas. Together these findings suggest that at least two contrasting viral life strategies exist in the oceans and that they likely reflect adaptation to their host microbes. Looking forward to the point at which the virus-tagging signature is well understood (e.g., for Synechococcus), application to natural communities should begin to provide population genomic data at the proper scale for predictively modeling two of the most abundant biological entities on Earth. Viral study suffers from an inability to link viruses to hosts en

  2. Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study

    PubMed Central

    Zhai, Yijie; Franco, Luis M.; Atmar, Robert L.; Quarles, John M.; Arden, Nancy; Bucasas, Kristine L.; Wells, Janet M.; Niño, Diane; Wang, Xueqing; Zapata, Gladys E.; Shaw, Chad A.; Belmont, John W.; Couch, Robert B.

    2015-01-01

    To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. PMID:26070066

  3. Surveillance for persistent bovine viral diarrhea virus infection in four artificial insemination centers.

    PubMed

    Howard, T H; Bean, B; Hillman, R; Monke, D R

    1990-06-15

    Four large bovine artificial insemination centers implemented a program of surveillance of resident and newly acquired bulls for persistent bovine viral diarrhea virus infection. Infection was identified in 12 of 1,538 bulls. Several clinical abnormalities, including acute and chronic mucosal disease, were evident among the persistently infected bulls. Semen produced by such bulls consistently contained bovine viral diarrhea virus, and such contamination was not always accompanied by diminished seminal quality. Infected bulls were detected by means of virus isolation tests performed on blood specimens, but not by use of serologic testing. Ten of the 12 persistently infected bulls were results of embryo transfer. Virologic surveillance of breeding herds, artificial insemination and embryo transfer centers, and the cattle trade is necessary to prevent spread of this virus by modern cattle breeding practices. Attention is also necessary to prevent contamination by this virus of the fluids used for recovery, in vitro manipulation, and transfer of bovine embryos. PMID:2163996

  4. Influence of viral infection on essential oil composition of Ocimum basilicum (Lamiaceae).

    PubMed

    Nagai, Alice; Duarte, Ligia M L; Santos, Déborah Y A C

    2011-08-01

    Ocimum basilicum L., popularly known as sweet basil, is a Lamiaceae species whose essential oil is mainly composed of monoterpenes, sesquiterpenes and phenylpropanoids. The contents of these compounds can be affected by abiotic and biotic factors such as infections caused by viruses. The main goal of this research was an investigation of the effects of viral infection on the essential oil profile of common basil. Seeds of O. basilicum L. cv. Genovese were sowed and kept in a greenhouse. Plants presenting two pairs of leaves above the cotyledons were inoculated with an unidentified virus isolated from a field plant showing chlorotic yellow spots and foliar deformation. Essential oils of healthy and infected plants were extracted by hydrodistillation and analyzed by GCMS. Changes in essential oil composition due to viral infection were observed. Methyleugenol and p-cresol,2,6-di-tert-butyl were the main constituents. However, methyleugenol contents were significantly decreased in infected plants. PMID:21922932

  5. Long-range transport and universality classes in in vitro viral infection spread

    NASA Astrophysics Data System (ADS)

    Manrubia, S. C.; García-Arriaza, J.; Domingo, E.; Escarmís, C.

    2006-05-01

    Dispersal mechanisms play a main role in the dynamics of infection spread. Recent experimental results with in vitro infections of foot-and-mouth disease virus reveal that the time needed for the virus to kill a cellular monolayer depends qualitatively on the number of viral particles required to initiate infection in a susceptible cell. A two-dimensional susceptible-infected-removed (SIR) model based on the experimental setting agrees with the observations only when viral particles are subject to long-range transport. Numerical and analytical results show that this long-range transport plays a role when a single particle causes infection, while it is inefficient when complementation between two or more particles is necessary.

  6. [Consequences of extrahepatic manifestations of hepatitis C viral infection (HCV)].

    PubMed

    Pawełczyk, Agnieszka

    2016-01-01

    The hepatitis C virus (HCV) is a primarily hepatotropic virus. However, numerous extrahepatic symptoms are observed in patients chronically infected with HCV, e.g. cryoglobulinemia, lymphoproliferative disorders, kidney diseases, disturbances of the central and peripheral nervous system, thyroid gland, pancreas, lymph nodes and pituitary gland, that develop at various times after the infection. Complex mechanisms underlie these processes, both molecular, related to direct effects of the virus on cells or tissues and indirect mechanisms, resulting from the response of the immune system to infection (via cytokines or oxidative stress), and from the antiviral treatment used. Understanding these mechanisms may contribute to the definition of new prognostic factors, important for the early diagnosis of the infection, which in turn may improve treatment efficacy. This paper is a review of the incidence of selected extrahepatic manifestations of HCV infection and their underlying pathogenetic mechanisms and risk factors. PMID:27117111

  7. Final Technical Report: Viral Infection of Subsurface Microorganisms and Metal/Radionuclide Transport

    SciTech Connect

    Weber, Karrie A.; Bender, Kelly S.; Li, Yusong

    2013-09-28

    Microbially mediated metabolisms have been identified as a significant factor either directly or indirectly impacting the fate and transport of heavy metal/radionuclide contaminants. To date microorganisms have been isolated from contaminated environments. Examination of annotated finished genome sequences of many of these subsurface isolates from DOE sites, revealed evidence of prior viral infection. To date the role that viruses play influencing microbial mortality and the resulting community structure which directly influences biogeochemical cycling in soils and sedimentary environments remains poorly understood. The objective of this exploratory study was to investigate the role of viral infection of subsurface bacteria and the formation of contaminant-bearing viral particles. This objective was approached by examining the following working hypotheses: (i) subsurface microorganisms are susceptible to viral infections by the indigenous subsurface viral community, and (ii) viral surfaces will adsorb heavy metals and radionuclides. Our results have addressed basic research needed to accomplish the BER Long Term Measure to provide sufficient scientific understanding such that DOE sites would be able to incorporate coupled physical, chemical and biological processes into decision making for environmental remediation or natural attenuation and long-term stewardship by establishing viral-microbial relationships on the subsequent fate and transport of heavy metals and radionuclides. Here we demonstrated that viruses play a significant role in microbial mortality and community structure in terrestrial subsurface sedimentary systems. The production of viral-like particles within subsurface sediments in response to biostimulation with dissolved organic carbon and a terminal electron acceptor resulted in the production of viral-like particles. Organic carbon alone did not result in significant viral production and required the addition of a terminal electron acceptor

  8. Respiratory Viral Infections among Pediatric Inpatients and Outpatients in Taiwan from 1997 to 1999

    PubMed Central

    Tsai, Huey-Pin; Kuo, Pin-Hwa; Liu, Ching-Chuan; Wang, Jen-Ren

    2001-01-01

    The present study examined the association of specific virus infections with acute respiratory tract conditions among hospitalized and outpatient children in a subtropical country. A total of 2,295 virus infections were detected in 6,986 patients between 1997 and 1999, including infections caused by respiratory syncytial virus (RSV) (1.7%), parainfluenza virus (2.0%), influenza B virus (2.6%), adenovirus (4.0%), herpes simplex virus type 1 (4.4%), influenza A virus (5.5%), and enterovirus (12.7%). There were 61 mixed infections, and no consistent seasonal variation was found. One or more viruses were detected among 24.8% of hospitalized patients and 35.0% of outpatients. The frequencies and profiles of detection of various viruses among in- and outpatients were different. The occurrence of enterovirus infections exceeded that of other viral infections detected in 1998 and 1999 due to outbreaks of enterovirus 71 and coxsackievirus A10. RSV was the most prevalent virus detected among hospitalized children, whereas influenza virus was the most frequently isolated virus in the outpatient group. Most respiratory viral infections (39.3%) occurred in children between 1 and 3 years old. RSV (P < 0.025) and influenza A virus (P < 0.05) infections were dominant in the male inpatient group. In addition, most pneumonia and bronchiolitis (48.4%) was caused by RSV among hospitalized children less than 6 months old. Adenovirus was the most common agent associated with pharyngitis and tonsilitis (45.5%). These data expand our understanding of the etiology of acute respiratory tract viral infections among in- and outpatients in a subtropical country and may contribute to the prevention and control of viral respiratory tract infections. PMID:11136758

  9. Respiratory viral infections among pediatric inpatients and outpatients in Taiwan from 1997 to 1999.

    PubMed

    Tsai, H P; Kuo, P H; Liu, C C; Wang, J R

    2001-01-01

    The present study examined the association of specific virus infections with acute respiratory tract conditions among hospitalized and outpatient children in a subtropical country. A total of 2,295 virus infections were detected in 6,986 patients between 1997 and 1999, including infections caused by respiratory syncytial virus (RSV) (1.7%), parainfluenza virus (2.0%), influenza B virus (2.6%), adenovirus (4.0%), herpes simplex virus type 1 (4. 4%), influenza A virus (5.5%), and enterovirus (12.7%). There were 61 mixed infections, and no consistent seasonal variation was found. One or more viruses were detected among 24.8% of hospitalized patients and 35.0% of outpatients. The frequencies and profiles of detection of various viruses among in- and outpatients were different. The occurrence of enterovirus infections exceeded that of other viral infections detected in 1998 and 1999 due to outbreaks of enterovirus 71 and coxsackievirus A10. RSV was the most prevalent virus detected among hospitalized children, whereas influenza virus was the most frequently isolated virus in the outpatient group. Most respiratory viral infections (39.3%) occurred in children between 1 and 3 years old. RSV (P < 0.025) and influenza A virus (P < 0.05) infections were dominant in the male inpatient group. In addition, most pneumonia and bronchiolitis (48.4%) was caused by RSV among hospitalized children less than 6 months old. Adenovirus was the most common agent associated with pharyngitis and tonsilitis (45.5%). These data expand our understanding of the etiology of acute respiratory tract viral infections among in- and outpatients in a subtropical country and may contribute to the prevention and control of viral respiratory tract infections. PMID:11136758

  10. Correlation of CD4 T Cell Count and Plasma Viral Load with Reproductive Tract Infections/Sexually Transmitted Infections in HIV Infected Females

    PubMed Central

    Bhattar, Sonali; Rawat, Deepti; Tripathi, Reva; Kaur, Ravinder; Sardana, Kabir

    2014-01-01

    Background: Sexually transmitted infections (STIs) plays a major role in the spread of Human immunodeficiency virus (HIV) due to common route of transmission. These infections display an epidemiological synergy with HIV. Aim: The aim of this study was to analyse the correlation of CD4 T lymphocyte cell count, HIV-1 plasma viral load with Reproductive tract infections/Sexually transmitted infections (RTIs/STIs) in HIV infected females. Materials and Methods: The study included 60 HIV infected females. An informed consent was taken from all the study subjects. Relevant specimens (genital specimen and blood) were collected for laboratory diagnosis of various RTIs/STIs, CD4 cell count and plasma viral load estimation. Results: Mean CD4 count of females with bacterial vaginosis, vaginal candidiasis, trichomoniasis, syphilis and herpes simplex infection were lower as compared to other HIV infected cases and mean plasma viral load of bacterial vaginosis, vaginal candidiasis, trichomoniasis and syphilis were higher as compared to other HIV infected cases but this difference was not statistically significant. Conclusion: This study highlights the importance of routine screening for STIs/RTIs of all the HIV infected females for RTIs/STIs irrespective of CD4 cell count and plasma viral load. PMID:25478342

  11. Hepatitis C Viral Infection in Children: Updated Review

    PubMed Central

    2016-01-01

    Hepatitis C virus (HCV) infection is a major medical challenge affecting around 200 million people worldwide. The main site of HCV replication is the hepatocytes of the liver. HCV is a positive enveloped RNA virus from the flaviviridae family. Six major HCV genotypes are implicated in the human infection. In developed countries the children are infected mainly through vertical transmission during deliveries, while in developing countries it is still due to horizontal transmission from adults. Minimal nonspecific and brief symptoms are initially found in approximately 15% of children. Acute and chronic HCV infection is diagnosed through the recognition of HCV RNA. The main objective for treatment of chronic HCV is to convert detected HCV viremia to below the detection limit. Children with chronic HCV infection are usually asymptomatic and rarely develop severe liver damage. Therefore, the benefits from current therapies, pegylated-Interferon plus ribavirin, must be weighed against their adverse effects. This combined treatment offers a 50-90% chance of clearing HCV infection according to several studies and on different HCV genotype. Recent direct acting antiviral (DAA) drugs which are well established for adults have not yet been approved for children and young adults below 18 years. The most important field for the prevention of HCV infection in children would be the prevention of perinatal and parenteral transmission. There are areas of focus for new lines of research in pediatric HCV-related disease that can be addressed in the near future. PMID:27437184

  12. Complexities in Isolation and Purification of Multiple Viruses from Mixed Viral Infections: Viral Interference, Persistence and Exclusion

    PubMed Central

    Kumar, Naveen; Barua, Sanjay; Riyesh, Thachamvally; Chaubey, Kundan K.; Rawat, Krishan Dutt; Khandelwal, Nitin; Mishra, Anil K.; Sharma, Nitika; Chandel, Surender S.; Sharma, Shalini; Singh, Manoj K.; Sharma, Dinesh K.; Singh, Shoor V.; Tripathi, Bhupendra N.

    2016-01-01

    Successful purification of multiple viruses from mixed infections remains a challenge. In this study, we investigated peste des petits ruminants virus (PPRV) and foot-and-mouth disease virus (FMDV) mixed infection in goats. Rather than in a single cell type, cytopathic effect (CPE) of the virus was observed in cocultured Vero/BHK-21 cells at 6th blind passage (BP). PPRV, but not FMDV could be purified from the virus mixture by plaque assay. Viral RNA (mixture) transfection in BHK-21 cells produced FMDV but not PPRV virions, a strategy which we have successfully employed for the first time to eliminate the negative-stranded RNA virus from the virus mixture. FMDV phenotypes, such as replication competent but noncytolytic, cytolytic but defective in plaque formation and, cytolytic but defective in both plaque formation and standard FMDV genome were observed respectively, at passage level BP8, BP15 and BP19 and hence complicated virus isolation in the cell culture system. Mixed infection was not found to induce any significant antigenic and genetic diversity in both PPRV and FMDV. Further, we for the first time demonstrated the viral interference between PPRV and FMDV. Prior transfection of PPRV RNA, but not Newcastle disease virus (NDV) and rotavirus RNA resulted in reduced FMDV replication in BHK-21 cells suggesting that the PPRV RNA-induced interference was specifically directed against FMDV. On long-term coinfection of some acute pathogenic viruses (all possible combinations of PPRV, FMDV, NDV and buffalopox virus) in Vero cells, in most cases, one of the coinfecting viruses was excluded at passage level 5 suggesting that the long-term coinfection may modify viral persistence. To the best of our knowledge, this is the first documented evidence describing a natural mixed infection of FMDV and PPRV. The study not only provides simple and reliable methodologies for isolation and purification of two epidemiologically and economically important groups of viruses, but

  13. Complexities in Isolation and Purification of Multiple Viruses from Mixed Viral Infections: Viral Interference, Persistence and Exclusion.

    PubMed

    Kumar, Naveen; Barua, Sanjay; Riyesh, Thachamvally; Chaubey, Kundan K; Rawat, Krishan Dutt; Khandelwal, Nitin; Mishra, Anil K; Sharma, Nitika; Chandel, Surender S; Sharma, Shalini; Singh, Manoj K; Sharma, Dinesh K; Singh, Shoor V; Tripathi, Bhupendra N

    2016-01-01

    Successful purification of multiple viruses from mixed infections remains a challenge. In this study, we investigated peste des petits ruminants virus (PPRV) and foot-and-mouth disease virus (FMDV) mixed infection in goats. Rather than in a single cell type, cytopathic effect (CPE) of the virus was observed in cocultured Vero/BHK-21 cells at 6th blind passage (BP). PPRV, but not FMDV could be purified from the virus mixture by plaque assay. Viral RNA (mixture) transfection in BHK-21 cells produced FMDV but not PPRV virions, a strategy which we have successfully employed for the first time to eliminate the negative-stranded RNA virus from the virus mixture. FMDV phenotypes, such as replication competent but noncytolytic, cytolytic but defective in plaque formation and, cytolytic but defective in both plaque formation and standard FMDV genome were observed respectively, at passage level BP8, BP15 and BP19 and hence complicated virus isolation in the cell culture system. Mixed infection was not found to induce any significant antigenic and genetic diversity in both PPRV and FMDV. Further, we for the first time demonstrated the viral interference between PPRV and FMDV. Prior transfection of PPRV RNA, but not Newcastle disease virus (NDV) and rotavirus RNA resulted in reduced FMDV replication in BHK-21 cells suggesting that the PPRV RNA-induced interference was specifically directed against FMDV. On long-term coinfection of some acute pathogenic viruses (all possible combinations of PPRV, FMDV, NDV and buffalopox virus) in Vero cells, in most cases, one of the coinfecting viruses was excluded at passage level 5 suggesting that the long-term coinfection may modify viral persistence. To the best of our knowledge, this is the first documented evidence describing a natural mixed infection of FMDV and PPRV. The study not only provides simple and reliable methodologies for isolation and purification of two epidemiologically and economically important groups of viruses, but

  14. HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders.

    PubMed

    Janes, Holly; Herbeck, Joshua T; Tovanabutra, Sodsai; Thomas, Rasmi; Frahm, Nicole; Duerr, Ann; Hural, John; Corey, Lawrence; Self, Steve G; Buchbinder, Susan P; McElrath, M Juliana; O'Connell, Robert J; Paris, Robert M; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Pitisuttihum, Punnee; Kaewkungwal, Jaranit; Robb, Merlin L; Michael, Nelson L; Mullins, James I; Kim, Jerome H; Gilbert, Peter B; Rolland, Morgane

    2015-10-01

    Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically linked HIV-1 founder variants represent a minority of HIV-1 infections, we found--n two different cohorts--hat more diverse HIV-1 populations in early infection were associated with significantly higher VL 1 year after HIV-1 diagnosis. PMID:26322580

  15. Cullin4 Is Pro-Viral during West Nile Virus Infection of Culex Mosquitoes

    PubMed Central

    Paradkar, Prasad N.; Duchemin, Jean-Bernard; Rodriguez-Andres, Julio; Trinidad, Lee; Walker, Peter J.

    2015-01-01

    Although mosquitoes serve as vectors of many pathogens of public health importance, their response to viral infection is poorly understood. It also remains to be investigated whether viruses deploy some mechanism to be able to overcome this immune response. Here, we have used an RNA-Seq approach to identify differentially regulated genes in Culex quinquefasciatus cells following West Nile virus (WNV) infection, identifying 265 transcripts from various cellular pathways that were either upregulated or downregulated. Ubiquitin-proteasomal pathway genes, comprising 12% of total differentially regulated genes, were selected for further validation by real time RT-qPCR and functional analysis. It was found that treatment of infected cells with proteasomal inhibitor, MG-132, decreased WNV titers, indicating importance of this pathway during infection process. In infection models, the Culex ortholog of mammalian Cul4A/B (cullin RING ubiquitin ligase) was found to be upregulated in vitro as well as in vivo, especially in midguts of mosquitoes. Gene knockdown using dsRNA and overexpression studies indicated that Culex Cul4 acts as a pro-viral protein by degradation of CxSTAT via ubiquitin-proteasomal pathway. We also show that gene knockdown of Culex Cul4 leads to activation of the Jak-STAT pathway in mosquitoes leading to decrease viral replication in the body as well as saliva. Our results suggest a novel mechanism adopted by WNV to overcome mosquito immune response and increase viral replication. PMID:26325027

  16. Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity

    SciTech Connect

    Du, Lanying; Kao, Richard Y.; Zhou, Yusen; He, Yuxian; Zhao, Guangyu; Wong, Charlotte; Jiang, Shibo; Yuen, Kwok-Yung; Jin, Dong-Yan; Zheng, Bo-Jian . E-mail: bzheng@hkucc.hku.hk

    2007-07-20

    The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitate fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection.

  17. 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

  18. The role of IL-10 in regulating immunity to persistent viral infections

    PubMed Central

    Wilson, Elizabeth B.; Brooks, David G.

    2012-01-01

    The immune system has evolved multipronged responses that are critical to effectively defend the body from invading pathogens and to clear infection. However, the same weapons employed to eradicate infection can have caustic effects on normal bystander cells. Therefore, tight regulation is vital and the host must balance engendering correct and sufficient immune responses to pathogens while limiting errant and excessive immunopathology. To accomplish this task a complex network of positive and negative immune signals are delivered that in most instances successfully eliminate pathogen. However, in response to some viral infections, immune function is rapidly suppressed leading to viral persistence. Immune suppression is a critical obstacle to the control of many persistent virus infections such as HIV, hepatitis C and hepatitis B virus, which together affect more than 500 million individuals worldwide. Thus, the ability to therapeutically enhance immunity is a potentially powerful approach to resolve persistent infections. The host derived cytokine IL-10 is a key player in the establishment and perpetuation of viral persistence. This chapter discusses the role of IL-10 in viral persistence and explores the exciting prospect of therapeutically blocking IL-10 to increase antiviral immunity and vaccine efficacy. PMID:20703965

  19. Exacerbation of Autoantibody-Mediated Hemolytic Anemia by Viral Infection

    PubMed Central

    Meite, Mory; Léonard, Sabine; Idrissi, Mohammed El Azami El; Izui, Shozo; Masson, Pierre L.; Coutelier, Jean-Paul

    2000-01-01

    Strong enhancement of the pathogenicity of an antierythrocyte monoclonal antibody was observed after infection of mice with lactate dehydrogenase-elevating virus. While injection of the antierythrocyte antibody alone induced only moderate anemia, concomitant infection with this virus, which is harmless in most normal mice, led to a dramatic drop in the hematocrit and to death of infected animals. In vitro and in vivo analyses showed a dramatic increase in the ability of macrophages from infected mice to phagocytose antibody-coated erythrocytes. These results indicate that viruses can trigger the onset of autoimmune disease by enhancing the pathogenicity of autoantibodies. They may explain how unrelated viruses could be implicated in the etiology of autoantibody-mediated autoimmune diseases. PMID:10846087

  20. Epidemiology, Co-Infections, and Outcomes of Viral Pneumonia in Adults: An Observational Cohort Study.

    PubMed

    Crotty, Matthew P; Meyers, Shelby; Hampton, Nicholas; Bledsoe, Stephanie; Ritchie, David J; Buller, Richard S; Storch, Gregory A; Micek, Scott T; Kollef, Marin H

    2015-12-01

    Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described. This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48  h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model. Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk. PMID:26683973

  1. Epidemiology and aetiology of maternal bacterial and viral infections in low- and middle-income countries

    PubMed Central

    Velu, Prasad Palani; Gravett, Courtney A.; Roberts, Tom K.; Wagner, Thor A.; Zhang, Jian Shayne F.; Rubens, Craig E.; Gravett, Michael G.; Campbell, Harry; Rudan, Igor

    2011-01-01

    Background Maternal morbidity and mortality in low- and middle-income countries has remained exceedingly high. However, information on bacterial and viral maternal infections, which are important contributors to poor pregnancy outcomes, is sparse and poorly characterised. This review aims to describe the epidemiology and aetiology of bacterial and viral maternal infections in low- and middle-income countries. Methods A systematic search of published literature was conducted and data on aetiology and epidemiology of maternal infections was extracted from relevant studies for analysis. Searches were conducted in parallel by two reviewers (using OVID) in the following databases: Medline (1950 to 2010), EMBASE (1980 to 2010) and Global Health (1973 to 2010). Results Data from 158 relevant studies was used to characterise the epidemiology of the 10 most extensively reported maternal infections with the following median prevalence rates: Treponema pallidum (2.6%), Neisseria gonorrhoeae (1.5%), Chlamydia trachomatis (5.8%), Group B Streptococcus (8.6%), bacterial vaginosis (20.9%), hepatitis B virus (4.3%), hepatitis C virus (1.4%), Cytomegalovirus (95.7% past infection), Rubella (8.9% susceptible) and Herpes simplex (20.7%). Large variations in the prevalence of these infections between countries and regions were noted. Conclusion This review confirms the suspected high prevalence of maternal bacterial and viral infections and identifies particular diseases and regions requiring urgent attention in public health policy planning, setting research priorities and donor funding towards reducing maternal morbidity and mortality in low- and middle-income countries. PMID:23198117

  2. Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

  3. Double-stranded RNA viral infection of Trichomonas vaginalis and correlation with genetic polymorphism of isolates.

    PubMed

    Fraga, Jorge; Rojas, Lazara; Sariego, Idalia; Fernández-Calienes, Ayme

    2011-02-01

    Trichomonas vaginalis can be infected with double-stranded RNA (dsRNA) viruses known as T. vaginalis virus (TVV). This viral infection may have important implications for trichomonal virulence and disease pathogenesis. The objective of this study was to determine the possible correlation between the T. vaginalis genetic polymorphism and the isolate infection with TVV. The Random Amplified Polymorphic DNA (RAPD) technique was used to determine genetic differences among 37 isolates of T. vaginalis using a panel of 30 random primers and these genetic data were correlated with the infection of isolates with TVV. The trees drawn based on RAPD data showed significantly association with the presence of TVV (P = 0.028) demonstrating the existence of concordance between the genetic relatedness and the presence of TVV in T. vaginalis isolates. This result could point to a predisposition of T. vaginalis for the viral enters and/or survival. PMID:20875411

  4. [WASTE WATERS AS THE RESERVOIR OF INTESTINAL ENTERIC VIRAL INFECTIONS].

    PubMed

    Nedachin, A E; Dmitrieva, R A; Doskina, T V; Dolgin, V A; Chulanov, V P; Pimenov, N N

    2015-01-01

    In the paper there are presented data of field observations of the spectrum of viruses, contained in the waste waters. The studies were performed on the territory of the city and the territory unfavorable for hepatitis A. In the territory of the big city by RT-PCR in the waste liquid the enterovirus RNA was detected in 45% of samples; astroviruses--90%; noroviruses--80% and 15% of rotaviruses. Samples from 2 wells were slightly positive for the presence of HCV RNA A. In the waste liquid on the territory, unfavorable for viral hepatitis A, in 100% of the samples there were determined noro- and astroviruses RNA and adenovirus DNA, in 75%--enterovirus RNA; 50%--HAV RNA and a 25%--rotavirus RNA. PMID:26856138

  5. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    PubMed Central

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

    2016-01-01

    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

  6. Management of respiratory viral infections in hematopoietic cell transplant recipients.

    PubMed

    Shah, Dimpy P; Ghantoji, Shashank S; Mulanovich, Victor E; Ariza-Heredia, Ella J; Chemaly, Roy F

    2012-01-01

    Advances in stem cell transplantation procedures and the overall improvement in the clinical management of hematopoietic cell transplant (HCT) recipients over the past 2 decades have led to an increase in survival duration, in part owing to better strategies for prevention and treatment of post-transplant complications, including opportunistic infections. However, post-HCT infections remain a concern for HCT recipients, particularly infections caused by community respiratory viruses (CRVs), which can lead to significant morbidity and mortality. These viruses can potentially cause lower respiratory tract illness, which is associated with a higher mortality rate among HCT recipients. Clinical management of CRV infections in HCT recipients includes supportive care and antiviral therapy, especially in high-risk individuals, when available. Directed antiviral therapy is only available for influenza infections, where successful use of neuraminidase inhibitors (oseltamivir or zanamivir) and/or M2 inhibitors (amantadine or rimantadine) has been reported. Data on the successful use of ribavirin, with or without immunomodulators, for respiratory syncytial virus infections in HCT recipients has emerged over the past 2 decades but is still controversial at best because of a lack of randomized controlled trials. Because of the lack of directed antiviral therapy for most of these viruses, prevention should be emphasized for healthcare workers, patients, family, and friends and should include the promotion of the licensed inactivated influenza vaccine for HCT recipients, when indicated. In this review, we discuss the clinical management of respiratory viruses in this special patient population, focusing on commercially available antivirals, adjuvant therapy, and novel drugs under investigation, as well as on available means for prevention. PMID:23226621

  7. Management of respiratory viral infections in hematopoietic cell transplant recipients

    PubMed Central

    Shah, Dimpy P; Ghantoji, Shashank S; Mulanovich, Victor E; Ariza-heredia, Ella J; Chemaly, Roy F

    2012-01-01

    Advances in stem cell transplantation procedures and the overall improvement in the clinical management of hematopoietic cell transplant (HCT) recipients over the past 2 decades have led to an increase in survival duration, in part owing to better strategies for prevention and treatment of post-transplant complications, including opportunistic infections. However, post-HCT infections remain a concern for HCT recipients, particularly infections caused by community respiratory viruses (CRVs), which can lead to significant morbidity and mortality. These viruses can potentially cause lower respiratory tract illness, which is associated with a higher mortality rate among HCT recipients. Clinical management of CRV infections in HCT recipients includes supportive care and antiviral therapy, especially in high-risk individuals, when available. Directed antiviral therapy is only available for influenza infections, where successful use of neuraminidase inhibitors (oseltamivir or zanamivir) and/or M2 inhibitors (amantadine or rimantadine) has been reported. Data on the successful use of ribavirin, with or without immunomodulators, for respiratory syncytial virus infections in HCT recipients has emerged over the past 2 decades but is still controversial at best because of a lack of randomized controlled trials. Because of the lack of directed antiviral therapy for most of these viruses, prevention should be emphasized for healthcare workers, patients, family, and friends and should include the promotion of the licensed inactivated influenza vaccine for HCT recipients, when indicated. In this review, we discuss the clinical management of respiratory viruses in this special patient population, focusing on commercially available antivirals, adjuvant therapy, and novel drugs under investigation, as well as on available means for prevention. PMID:23226621

  8. Nuclear Sensing of Viral DNA, Epigenetic Regulation of Herpes Simplex Virus Infection, and Innate Immunity

    PubMed Central

    Knipe, David M.

    2015-01-01

    Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. Herpes viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related. PMID:25742715

  9. New treatment strategies against hepatitis C viral infection

    PubMed Central

    Bilodeau, Marc; Lamarre, Daniel

    2006-01-01

    Treatment of hepatitis C virus infection is currently based on a combination of pegylated interferon and ribavirin. Because efficacy of this therapy remains suboptimal and side effects sometimes problematic, major efforts have been put forward by scientists and the pharmaceutical industry to develop alternative treatments for this chronic infection. Over the past few years, clinical studies performed with some of these new agents have been presented at major international meetings. The present paper aims to review the rationale underlying the development of these new forms of treatment as well as the current available data concerning their clinical efficacy. PMID:17111056

  10. Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality.

    PubMed

    Khoury-Hanold, William; Yordy, Brian; Kong, Philip; Kong, Yong; Ge, William; Szigeti-Buck, Klara; Ralevski, Alexandra; Horvath, Tamas L; Iwasaki, Akiko

    2016-06-01

    Herpes simplex virus 1 (HSV-1), a leading cause of genital herpes, infects oral or genital mucosal epithelial cells before infecting the peripheral sensory nervous system. The spread of HSV-1 beyond the sensory nervous system and the resulting broader spectrum of disease are not well understood. Using a mouse model of genital herpes, we found that HSV-1-infection-associated lethality correlated with severe fecal and urinary retention. No inflammation or infection of the brain was evident. Instead, HSV-1 spread via the dorsal root ganglia to the autonomic ganglia of the enteric nervous system (ENS) in the colon. ENS infection led to robust viral gene transcription, pathological inflammatory responses, and neutrophil-mediated destruction of enteric neurons, ultimately resulting in permanent loss of peristalsis and the development of toxic megacolon. Laxative treatment rescued mice from lethality following genital HSV-1 infection. These results reveal an unexpected pathogenesis of HSV associated with ENS infection. PMID:27281569

  11. BOVINE VIRAL DIARRHEA VIRUS IN CAMELIDS: AN EMERGING PATHOGEN AND WAYS TO MONITOR HERD INFECTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The subject of this report will attempt to tie in several aspects of bovine viral diarrhea virus (BVDV) and its most recent incursion into the camelid family, namely llamas and alpacas. We have known that both llamas and alpacas are susceptible to BVDV infections for over 20 years. In some cases, ...

  12. Effects of Viral Infection on Blood-Feeding Behavior in Culicoides sonorensis (Diptera: Ceratopogonidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Culicoides sonorensis (Diptera: Ceratopogonidae) is the primary vector of bluetongue virus (BTV) in North America and a competent vector of vesicular stomatitis virus (VSV). Little is known about how viral infection of this midge affects its blood feeding behavior. Midges were intrathoracically inoc...

  13. ModeLang: A New Approach for Experts-Friendly Viral Infections Modeling

    PubMed Central

    Blazewicz, Jacek

    2013-01-01

    Computational modeling is an important element of systems biology. One of its important applications is modeling complex, dynamical, and biological systems, including viral infections. This type of modeling usually requires close cooperation between biologists and mathematicians. However, such cooperation often faces communication problems because biologists do not have sufficient knowledge to understand mathematical description of the models, and mathematicians do not have sufficient knowledge to define and verify these models. In many areas of systems biology, this problem has already been solved; however, in some of these areas there are still certain problematic aspects. The goal of the presented research was to facilitate this cooperation by designing seminatural formal language for describing viral infection models that will be easy to understand for biologists and easy to use by mathematicians and computer scientists. The ModeLang language was designed in cooperation with biologists and its computer implementation was prepared. Tests proved that it can be successfully used to describe commonly used viral infection models and then to simulate and verify them. As a result, it can make cooperation between biologists and mathematicians modeling viral infections much easier, speeding up computational verification of formulated hypotheses. PMID:24454531

  14. Comment on ‘Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy’

    NASA Astrophysics Data System (ADS)

    Darvin, Maxim E.; Lademann, Juergen; Brandt, Nikolay N.

    2016-04-01

    The results of the letter ‘Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy’ authored by Firdous and Anwar (2015 Laser Phys. Lett. 12 085601) are discussed. We show that the original interpretation of the results is not correct and does not correspond to data in the literature.

  15. The Contribution of Infections with Bovine Viral Diarrhea Viruses to Bovine Respiratory Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The contribution of bovine viral diarrhea viruses (BVDV) to the development of bovine respiratory disease is the sum of a number of different factors. These factors include the contribution of acute uncomplicated BVDV infections, the high incidence of respiratory disease in animals persistently inf...

  16. Effects of Viral Infection on Blood Feeding Behavior and Fecundity in Culicoides Sonorensis (Diptera: Ceratopogonidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Culicoides sonorensis (Diptera: Ceratopogonidae) is the primary vector of bluetongue virus (BTV) in North America and a competent vector of vesicular stomatitis virus (VSV). Little is known about how viral infection of this midge affects its blood feeding behavior and fecundity. Blood feeding succes...

  17. Bovine viral diarrhea virus infection alters global transcription profiles in bovine endothelial cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea viruses (BVDV) are significant pathogens of cattle worldwide. These viruses exist in both non-cytopathic and cytopathic biotypes. Non-cytopathic BVDV can establish persistent lifelong infections in cattle and are a frequent contaminant of biological reagents such as cell cultur...

  18. At the crossroads of autophagy and infection: Noncanonical roles for ATG proteins in viral replication.

    PubMed

    Solvik, Tina; Debnath, Jayanta

    2016-08-29

    Autophagy-related (ATG) proteins have increasingly demonstrated functions other than cellular self-eating. In this issue, Mauthe et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201602046) conduct an unbiased RNA interference screen of the ATG proteome to reveal numerous noncanonical roles for ATG proteins during viral infection. PMID:27573461

  19. The paradox of simian immunodeficiency virus infection in sooty mangabeys: active viral replication without disease progression.

    PubMed

    Chakrabarti, Lisa A

    2004-01-01

    Simian immunodeficiency virus SIVsm causes an asymptomatic infection in its natural host, the sooty mangabey, but induces an immunodeficiency syndrome very similar to human AIDS when transferred to a new host species such as the rhesus macaque. Unexpectedly, SIVsm replication dynamics is comparable in the two species, with rapid accumulation of viral mutations and a high viral load detected in both mangabeys and macaques. In contrast, clear differences are observed in immune parameters. Pathogenic SIV infection in macaques is associated with decreased CD4+ T cell numbers and signs of generalized immune activation, such as increased numbers of cycling and apoptotic T cells, hyperplasic lymphoid tissues, and exacerbated immune responses. Mangabeys with asymptomatic SIV infection show normal T cell regeneration parameters and signs of a moderate immune response, appropriate in the setting of chronic viral infection. The comparative analysis of simian models thus suggests that viral load alone cannot account for progression to disease, and that the capacity of primate lentiviruses to induce abnormal immune activation underlies AIDS pathogenesis. PMID:14766388

  20. Case Report: Emergence of bovine viral diarrhea virus persistently infected calves in a closed herd

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) continues to have significant economic impact on the cattle industry worldwide. The virus is primarily maintained in the cattle population due to persistently infected animals. Herd surveillance along with good vaccination programs and biosecurity practices are the...

  1. Resolving bovine viral diarrhea virus subtypes from persistently infected US beef calves with complete genome sequence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is classified into 2 genotypes, BVDV-1 and BVDV-2, each of which contains distinct subtypes with genetic and antigenic differences. Currently, three major subtypes circulate in the United States: BVDV-1a, 1b, and 2a. In addition, a single case of BVDV-2b infection ...

  2. Novel approaches and challenges to treatment of central nervous system viral infections.

    PubMed

    Nath, Avindra; Tyler, Kenneth L

    2013-09-01

    Existing and emerging viral central nervous system (CNS) infections are major sources of human morbidity and mortality. Treatments of proven efficacy are currently limited predominantly to herpesviruses and human immunodeficiency virus (HIV). Development of new therapies has been hampered by the lack of appropriate animal model systems for some important viruses and by the difficulty in conducting human clinical trials for diseases that may be rare, or in the case of arboviral infections, often have variable seasonal and geographic incidence. Nonetheless, many novel approaches to antiviral therapy are available, including candidate thiazolide and pyrazinecarboxamide derivatives with potential broad-spectrum antiviral efficacy. New herpesvirus drugs include viral helicase-primase and terminase inhibitors. The use of antisense oligonucleotides and other strategies to interfere with viral RNA translation has shown efficacy in experimental models of CNS viral disease. Identifying specific molecular targets within viral replication cycles has led to many existing antiviral agents and will undoubtedly continue to be the basis of future drug design. A promising new area of research involves therapies based on enhanced understanding of host antiviral immune responses. Toll-like receptor agonists and drugs that inhibit specific cytokines as well as interferon preparations have all shown potential therapeutic efficacy. Passive transfer of virus-specific cytotoxic T lymphocytes has been used in humans and may provide an effective therapy for some herpesvirus infections and potentially for progressive multifocal leukoencephalopathy. Humanized monoclonal antibodies directed against specific viral proteins have been developed and in several cases evaluated in humans in settings including West Nile virus and HIV infection and in pre-exposure prophylaxis for rabies. PMID:23913580

  3. Modelling and analysis of dynamics of viral infection of cells and of interferon resistance

    NASA Astrophysics Data System (ADS)

    Getto, Ph.; Kimmel, M.; Marciniak-Czochra, A.

    2008-08-01

    Interferons are active biomolecules, which help fight viral infections by spreading from infected to uninfected cells and activate effector molecules, which confer resistance from the virus on cells. We propose a new model of dynamics of viral infection, including endocytosis, cell death, production of interferon and development of resistance. The novel element is a specific biologically justified mechanism of interferon action, which results in dynamics different from other infection models. The model reflects conditions prevailing in liquid cultures (ideal mixing), and the absence of cells or virus influx from outside. The basic model is a nonlinear system of five ordinary differential equations. For this variant, it is possible to characterise global behaviour, using a conservation law. Analytic results are supplemented by computational studies. The second variant of the model includes age-of-infection structure of infected cells, which is described by a transport-type partial differential equation for infected cells. The conclusions are: (i) If virus mortality is included, the virus becomes eventually extinct and subpopulations of uninfected and resistant cells are established. (ii) If virus mortality is not included, the dynamics may lead to extinction of uninfected cells. (iii) Switching off the interferon defense results in a decrease of the sum total of uninfected and resistant cells. (iv) Infection-age structure of infected cells may result in stabilisation or destabilisation of the system, depending on detailed assumptions. Our work seems to constitute the first comprehensive mathematical analysis of the cell-virus-interferon system based on biologically plausible hypotheses.

  4. Differentiation between viral and bacterial acute infections using chemiluminescent signatures of circulating phagocytes.

    PubMed

    Prilutsky, Daria; Shneider, Evgeni; Shefer, Alex; Rogachev, Boris; Lobel, Leslie; Last, Mark; Marks, Robert S

    2011-06-01

    Oftentimes the etiological diagnostic differentiation between viral and bacterial infections is problematic, while clinical management decisions need to be made promptly upon admission. Thus, alternative rapid and sensitive diagnostic approaches need to be developed. Polymorphonuclear leukocytes (PMNs) or phagocytes act as major players in the defense response of the host during an episode of infection, and thereby undergo functional changes that differ according to the infections. PMNs functional activity can be characterized by quantification and localization of respiratory burst production and assessed by chemiluminescent (CL) byproduct reaction. We have assessed the functional states of PMNs of patients with acute infections in a luminol-amplified whole blood system using the component CL approach. In this study, blood was drawn from 69 patients with fever (>38 °C), and diagnosed as mainly viral or bacterial infections in origin. Data mining algorithms (C4.5, Support Vector Machines (SVM) and Naïve Bayes) were used to induce classification models to distinguish between clinical groups. The model with the best predictive accuracy was induced using C4.5 algorithm, resulting in 94.7% accuracy on the training set and 88.9% accuracy on the testing set. The method demonstrated a high predictive diagnostic value and may assist the clinician one day in the distinction between viral and bacterial infections and the choice of proper medication. PMID:21517122

  5. Clinical and Associated Immunological Manifestations of HFMD Caused by Different Viral Infections in Children

    PubMed Central

    Wang, Jingjing; Pu, Jing; Liu, Longding; Che, Yanchun; Liao, Yun; Wang, Lichun; Guo, Lei; Feng, Min; Liang, Yan; Fan, Shengtao; Cai, Lukui; Zhang, Ying; Li, Qihan

    2016-01-01

    Hand, foot, and mouth disease (HFMD), with vesiculae on the hands, feet and mouth, is an infectious disease caused by many viral pathogens. However, the differences of immune response induced by these pathogens are unclear. We compared the clinical manifestations and the levels of immunologic indicators from 60 HFMD patients caused by different viral pathogens to analyze the differences in the immune response. It was shown that Th2 cytokines (IL-4 and IL-10) increased significantly in EV71-infected children; Th1 cytokines (IL-2 and IFN-γ) rose in CA16-infected children; both Th1 and Th2 cytokines elevated in non-EVG-infected children; only individual cytokines (such as IL-10) went up in EVG-infected children. Meanwhile, the antibodies induced by viral infection could not cross-interfere between the different pathogens. These differences might be due to variations in the immune response induced by the individual pathogens or to the pathogenesis of the infections by the individual pathogens. PMID:27336013

  6. Clinical and Associated Immunological Manifestations of HFMD Caused by Different Viral Infections in Children.

    PubMed

    Wang, Jingjing; Pu, Jing; Liu, Longding; Che, Yanchun; Liao, Yun; Wang, Lichun; Guo, Lei; Feng, Min; Liang, Yan; Fan, Shengtao; Cai, Lukui; Zhang, Ying; Li, Qihan

    2016-01-01

    Hand, foot, and mouth disease (HFMD), with vesiculae on the hands, feet and mouth, is an infectious disease caused by many viral pathogens. However, the differences of immune response induced by these pathogens are unclear. We compared the clinical manifestations and the levels of immunologic indicators from 60 HFMD patients caused by different viral pathogens to analyze the differences in the immune response. It was shown that Th2 cytokines (IL-4 and IL-10) increased significantly in EV71-infected children; Th1 cytokines (IL-2 and IFN-γ) rose in CA16-infected children; both Th1 and Th2 cytokines elevated in non-EVG-infected children; only individual cytokines (such as IL-10) went up in EVG-infected children. Meanwhile, the antibodies induced by viral infection could not cross-interfere between the different pathogens. These differences might be due to variations in the immune response induced by the individual pathogens or to the pathogenesis of the infections by the individual pathogens. PMID:27336013

  7. Chronic and persistent viral hemorrhagic septicemia virus infections in Pacific herring

    USGS Publications Warehouse

    Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Cortney A.; Taylor, L.

    2010-01-01

    Chronic viral hemorrhagic septicemia virus (VHSV) infections were established in a laboratory stock of Pacific herring Clupea pallasii held in a large-volume tank supplied with pathogen-free seawater at temperatures ranging from 6.8 to 11.6°C. The infections were characterized by viral persistence for extended periods and near-background levels of host mortality. Infectious virus was recovered from mortalities occurring up to 167 d post-exposure and was detected in normal-appearing herring for as long as 224 d following initial challenge. Geometric mean viral titers were generally as high as or higher in brain tissues than in pools of kidney and spleen tissues, with overall prevalence of infection being higher in the brain. Upon re-exposure to VHSV in a standard laboratory challenge, negligible mortality occurred among groups of herring that were either chronically infected or fully recovered, indicating that survival from chronic manifestations conferred protection against future disease. However, some survivors of chronic VHS infections were capable of replicating virus upon re-exposure. Demonstration of a chronic manifestation of VHSV infection among Pacific herring maintained at ambient seawater temperatures provides insights into the mechanisms by which the virus is maintained among populations of endemic hosts.

  8. Chronic and persistent viral hemorrhagic septicemia virus infections in Pacific herring

    USGS Publications Warehouse

    Hershberger, P.K.; Gregg, J.L.; Grady, C.A.; Taylor, L.; Winton, J.R.

    2010-01-01

    Chronic viral hemorrhagic septicemia virus (VHSV) infections were established in a laboratory stock of Pacific herring Clupea pallasii held in a large-volume tank supplied with pathogenfree seawater at temperatures ranging from 6.8 to 11.6??C. The infections were characterized by viral persistence for extended periods and near-background levels of host mortality. Infectious virus was recovered from mortalities occurring up to 167 d post-exposure and was detected in normal-appearing herring for as long as 224 d following initial challenge. Geometric mean viral titers were generally as high as or higher in brain tissues than in pools of kidney and spleen tissues, with overall prevalence of infection being higher in the brain. Upon re-exposure to VHSV in a standard laboratory challenge, negligible mortality occurred among groups of herring that were either chronically infected or fully recovered, indicating that survival from chronic manifestations conferred protection against future disease. However, some survivors of chronic VHS infections were capable of replicating virus upon re-exposure. Demonstration of a chronic manifestation of VHSV infection among Pacific herring maintained at ambient seawater temperatures provides insights into the mechanisms by which the virus is maintained among populations of endemic hosts. ?? 2010 Inter-Research.

  9. TYPE A VIRAL HEPATITIS: EFFECT OF CHLORINE ON INFECTIVITY

    EPA Science Inventory

    The objective of this study was to determine the effect of (HOCl) treatment on the infectivity of hepatitis A virus (HAV). Prodromal chimpanzee feces, shown to induce hepatitis in marmosets (Saginus sp.), was clarified (JA 20/8K/30 min/5C), the virus precipitated with 7% PEG 6000...

  10. Nutrition, immunity and viral infections in honey bees

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Honey bees can be infected with viruses that can spread rapidly in colonies. Here we discuss how honey bees decrease the risk of disease outbreaks by a combination of behaviors (social immunity) and individual immunity. The effectiveness of both social and individual immunity relies on nutrition. Ho...