[Viral hepatitis in travellers].

PubMed

Abreu, Cândida

2007-01-01

Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

Viral meningitis and encephalitis.

PubMed

Tuppeny, Misti

2013-09-01

Meningitis is an inflammation of the meninges, whereas encephalitis is inflammation of the parenchymal brain tissue. The single distinguishing element between the 2 diagnoses is the altered state of consciousness, focal deficits, and seizures found in encephalitis. Consequently meningoencephalitis is a term used when both findings are present in the patient. Viral meningitis is not necessarily reported as it is often underdiagnosed, whereas encephalitis cases are on the increase in various areas of North America. Improved imaging and viral diagnostics, as well as enhanced neurocritical care management, have improved patient outcomes to date. Copyright © 2013 Elsevier Inc. All rights reserved.

Leafhopper viral pathogens

USDA-ARS?s Scientific Manuscript database

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

BIOMARKERS OF VIRAL EXPOSURE

EPA Science Inventory

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

Viral Space Situational Awareness

NASA Astrophysics Data System (ADS)

Gleckler, A.; Butterfield, M. C.

2012-09-01

Viral SSA takes advantage of the amateur astronomy community to provide an extremely low-cost and geographically-diverse network of optical SSA sites. In the spirit of programs such as DARPA's Grand Challenge and the National Weather Service's program of providing amateur meteorologists with weather stations linked to a central professional meteorological facility, we form a cooperative bond with a willing community of technically-minded individuals. We term this program "viral" because we will qualify an initial set of astronomers for SSA operation and then use word of mouth in the astronomy community, as well as an outreach program, to pull in new observers. The use of modern remote controlled telescopes allows the incorporation of certified amateur, university, and commercial telescope systems. The availability of the local Viral SSA member for troubleshooting eliminates most significant costs of operating a large network. In this talk, we discuss the key concepts of Viral SSA and the route to a network of 100+ sites in a three year or less timeframe.

Hepatitis A through E (Viral Hepatitis)

MedlinePlus

... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

Understanding Image Virality

DTIC Science & Technology

2015-06-07

anno - tations for these 5 attributes we achieve (65.18%) accuracy, better than human performance (60.12%) at predicting rel- ative virality directly...Nature, 2005. 1 [3] A. Berg, T. Berg, H. Daume, J . Dodge, A. Goyal, X. Han, A. Mensch, M. Mitchell, A. Sood, K. Stratos, et al. Understanding and...predicting importance in images. In CVPR, 2012. 2 [4] J . Berger. Arousal increases social transmission of information. Psy- chological science, 2011. 1

Viral membrane fusion

SciTech Connect

Harrison, Stephen C., E-mail: harrison@crystal.harvard.edu

2015-05-15

Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formedmore » draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism.« less

[History of viral hepatitis].

PubMed

Fonseca, José Carlos Ferraz da

2010-01-01

The history of viral hepatitis goes back thousands of years and is a fascinating one. When humans were first infected by such agents, a natural repetitive cycle began, with the capacity to infect billions of humans, thus decimating the population and causing sequelae in thousands of lives. This article reviews the available scientific information on the history of viral hepatitis. All the information was obtained through extensive bibliographic review, including original and review articles and consultations on the internet. There are reports on outbreaks of jaundice epidemics in China 5,000 years ago and in Babylon more than 2,500 years ago. The catastrophic history of great jaundice epidemics and pandemics is well known and generally associated with major wars. In the American Civil War, 40,000 cases occurred among Union troops. In 1885, an outbreak of catarrhal jaundice affected 191 workers at the Bremen shipyard (Germany) after vaccination against smallpox. In 1942, 28,585 soldiers became infected with hepatitis after inoculation with the yellow fever vaccine. The number of cases of hepatitis during the Second World War was estimated to be 16 million. Only in the twentieth century were the main agents causing viral hepatitis identified. The hepatitis B virus was the first to be discovered. In this paper, through reviewing the history of major epidemics caused by hepatitis viruses and the history of discovery of these agents, singular peculiarities were revealed. Examples of this include the accidental or chance discovery of the hepatitis B and D viruses.

Diagnosis of viral hepatitis

PubMed Central

Easterbrook, Philippa J.; Roberts, Teri; Sands, Anita; Peeling, Rosanna

2017-01-01

Purpose of review Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and HIV–HBV and HCV coinfection are major causes of chronic liver disease worldwide. Testing and diagnosis is the gateway for access to both treatment and prevention services, but there remains a large burden of undiagnosed infection globally. We review the global epidemiology, key challenges in the current hepatitis testing response, new tools to support the hepatitis global response (2016–2020 Global Hepatitis Health Sector strategy, and 2017 WHO guidelines on hepatitis testing) and future directions and innovations in hepatitis diagnostics. Recent findings Key challenges in the current hepatitis testing response include lack of quality-assured serological and low-cost virological in-vitro diagnostics, limited facilities for testing, inadequate data to guide country-specific hepatitis testing approaches, stigmatization of those with or at risk of viral hepatitis and lack of guidelines on hepatitis testing for resource-limited settings. The new Global Hepatitis Health Sector strategy sets out goals for elimination of viral hepatitis as a public health threat by 2030 and gives outcome targets for reductions in new infections and mortality, as well as service delivery targets that include testing, diagnosis and treatment. The 2017 WHO hepatitis testing guidelines for adults, adolescents and children in low-income and middle-income countries outline the public health approach to strengthen and expand current testing practices for viral hepatitis and addresses who to test (testing approaches), which serological and virological assays to use (testing strategies) as well as interventions to promote linkage to prevention and care. Summary Future directions and innovations in hepatitis testing include strategies to improve access such as through use of existing facility and community-based testing opportunities for hepatitis testing, near-patient or point-of-care assays for

[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.

Viral hepatitis in India.

PubMed

Acharya, S K; Madan, Kaushal; Dattagupta, S; Panda, S K

2006-01-01

Viral hepatitis is a major public health problem in India, which is hyperendemic for HAV and HEV. Seroprevalence studies reveal that 90%-100% of the population acquires anti-HAV antibody and becomes immune by adolescence. Many epidemics of HEV have been reported from India. HAV related liver disease is uncommon in India and occurs mainly in children. HEV is also the major cause of sporadic adult acute viral hepatitis and ALF. Pregnant women and patients with CLD constitute the high risk groups to contract HEV infection, and HEV-induced mortality among them is substantial, which underlines the need for preventive measures for such groups. Children with HAV and HEV coinfection are prone to develop ALF. India has intermediate HBV endemicity, with a carrier frequency of 2%-4%. HBV is the major cause of CLD and HCC. Chronic HBV infection in India is acquired in childhood, presumably before 5 years of age, through horizontal transmission. Vertical transmission of HBV in India is considered to be infrequent. Inclusion of HBV vaccination in the expanded programme of immunization is essential to reduce the HBV carrier frequency and disease burden. HBV genotypes A and D are prevalent in India, which are similar to the HBV genotypes in the West. HCV infection in India has a population prevalence of around 1%, and occurs predominantly through transfusion and the use of unsterile glass syringes. HCV genotypes 3 and 2 are prevalent in 60%-80% of the population and they respond well to a combination of interferon and ribavirin. About 10%-15% of CLD and HCC are associated with HCV infection in India. HCV infection is also a major cause of post-transfusion hepatitis. HDV infection is infrequent in India and is present about 5%-10% of patients with HBV-related liver disease. HCC appears to be less common in India than would be expected from the prevalence rates of HBV and HCV. The high disease burden of viral hepatitis and related CLD in India, calls for the setting up of a

Viral pathogen discovery

PubMed Central

Chiu, Charles Y

2015-01-01

Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease. PMID:23725672

Viral Hemorrhagic Fever Diagnostics

PubMed Central

Racsa, Lori D.; Kraft, Colleen S.; Olinger, Gene G.; Hensley, Lisa E.

2016-01-01

There are 4 families of viruses that cause viral hemorrhagic fever (VHF), including Filoviridae. Ebola virus is one virus within the family Filoviridae and the cause of the current outbreak of VHF in West Africa. VHF-endemic areas are found throughout the world, yet traditional diagnosis of VHF has been performed in large reference laboratories centered in Europe and the United States. The large amount of capital needed, as well as highly trained and skilled personnel, has limited the availability of diagnostics in endemic areas except in conjunction with governmental and nongovernmental entities. However, rapid diagnosis of VHF is essential to efforts that will limit outbreaks. In addition, increased global travel suggests VHF diagnoses may be made outside of the endemic areas. Thus, understanding how to diagnose VHF is imperative for laboratories worldwide. This article reviews traditional and current diagnostic modalities for VHF. PMID:26354968

Viral Quasispecies Evolution

PubMed Central

Sheldon, Julie; Perales, Celia

2012-01-01

Summary: Evolution of RNA viruses occurs through disequilibria of collections of closely related mutant spectra or mutant clouds termed viral quasispecies. Here we review the origin of the quasispecies concept and some biological implications of quasispecies dynamics. Two main aspects are addressed: (i) mutant clouds as reservoirs of phenotypic variants for virus adaptability and (ii) the internal interactions that are established within mutant spectra that render a virus ensemble the unit of selection. The understanding of viruses as quasispecies has led to new antiviral designs, such as lethal mutagenesis, whose aim is to drive viruses toward low fitness values with limited chances of fitness recovery. The impact of quasispecies for three salient human pathogens, human immunodeficiency virus and the hepatitis B and C viruses, is reviewed, with emphasis on antiviral treatment strategies. Finally, extensions of quasispecies to nonviral systems are briefly mentioned to emphasize the broad applicability of quasispecies theory. PMID:22688811

Nuclear targeting of viral and non-viral DNA.

PubMed

Chowdhury, E H

2009-07-01

The nuclear envelope presents a major barrier to transgene delivery and expression using a non-viral vector. Virus is capable of overcoming the barrier to deliver their genetic materials efficiently into the nucleus by virtue of the specialized protein components with the unique amino acid sequences recognizing cellular nuclear transport machinery. However, considering the safety issues in the clinical gene therapy for treating critical human diseases, non-viral systems are highly promising compared with their viral counterparts. This review summarizes the progress on exploring the nuclear traffic mechanisms for the prominent viral vectors and the technological innovations for the nuclear delivery of non-viral DNA by mimicking those natural processes evolved for the viruses as well as for many cellular proteins.

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

[Epidemiology of viral hepatitis].

PubMed

Kaić, Bernard; Vilibić-Cavlek, Tatjana; Filipović, Sanja Kurecić; Nemeth-Blazić, Tatjana; Pem-Novosel, Iva; Vucina, Vesna Visekruna; Simunović, Aleksandar; Zajec, Martina; Radić, Ivan; Pavlić, Jasmina; Glamocanin, Marica; Gjenero-Margan, Ira

2013-10-01

Understanding the country-specific epidemiology of disease, which may vary greatly among countries, is crucial for identifying the most appropriate preventive and control measures. An overview of the local epidemiology of viral hepatitis in Croatia is given in this paper. The overall prevalence of hepatitis B in Croatia is low (less than 2% HBsAg carriers in the general population). Hepatitis B incidence and prevalence began to decline significantly following the introduction of universal hepatitis B vaccination in 1999. Information on HBsAg seroprevalence is derived from routine testing of certain subpopulations (pregnant women, blood donors) and seroprevalence studies mostly targeted at high-risk populations. Universal childhood vaccination against hepatitis B remains the main preventive measure. We recommend testing for immunity one to two months after the third dose of hepatitis B vaccine for health-care workers. The incidence and prevalence of hepatitis C have also been declining in the general population. The main preventive measures are ensuring safety of blood products, prevention of drug abuse, and harm reduction programs for intravenous drug users. Hepatitis A incidence has declined dramatically since fifty years ago, when thousands of cases were reported annually. In the last five years, an average of twenty cases have been reported per year. The reduction of hepatitis A is a consequence of improved personal and community hygiene and sanitation. Hepatitis D has not been reported in Croatia. The risk of hepatitis D will get to be even smaller as the proportion of population vaccinated against hepatitis B builds up. Hepatitis E is reported only sporadically in Croatia, mostly in persons occupationally in contact with pigs and in travelers to endemic countries. In conclusion, Croatia is a low prevalence country for hepatitides A, B and C. Hepatitis D has not been reported to occur in Croatia and there are only sporadic cases of hepatitis E. Since hepatitis

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

PubMed Central

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

2012-01-01

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

Insulated Foamy Viral Vectors

PubMed Central

Browning, Diana L.; Collins, Casey P.; Hocum, Jonah D.; Leap, David J.; Rae, Dustin T.; Trobridge, Grant D.

2016-01-01

Retroviral vector-mediated gene therapy is promising, but genotoxicity has limited its use in the clinic. Genotoxicity is highly dependent on the retroviral vector used, and foamy viral (FV) vectors appear relatively safe. However, internal promoters may still potentially activate nearby genes. We developed insulated FV vectors, using four previously described insulators: a version of the well-studied chicken hypersensitivity site 4 insulator (650cHS4), two synthetic CCCTC-binding factor (CTCF)-based insulators, and an insulator based on the CCAAT box-binding transcription factor/nuclear factor I (7xCTF/NF1). We directly compared these insulators for enhancer-blocking activity, effect on FV vector titer, and fidelity of transfer to both proviral long terminal repeats. The synthetic CTCF-based insulators had the strongest insulating activity, but reduced titers significantly. The 7xCTF/NF1 insulator did not reduce titers but had weak insulating activity. The 650cHS4-insulated FV vector was identified as the overall most promising vector. Uninsulated and 650cHS4-insulated FV vectors were both significantly less genotoxic than gammaretroviral vectors. Integration sites were evaluated in cord blood CD34+ cells and the 650cHS4-insulated FV vector had fewer hotspots compared with an uninsulated FV vector. These data suggest that insulated FV vectors are promising for hematopoietic stem cell gene therapy. PMID:26715244

Viral myositis in children.

PubMed

Magee, Haley; Goldman, Ran D

2017-05-01

Question I recently evaluated a child in my clinic after an emergency department visit where she presented having woken up that morning refusing to walk and was crawling around the house. The parents reported she was getting over a cold, and I recall similar cases of myositis during the H1N1 influenza epidemic a few years ago. What are the key features of myositis that I should recognize? Which investigations are needed to confirm the diagnosis and how should affected patients be managed? Answer Benign acute childhood myositis is a mild and self-limited sudden onset of lower extremity pain during or following recovery from a viral illness. Presentation can include tiptoe gait or refusal to walk, secondary to symmetric bilateral lower extremity pain that resolves quickly, usually within 3 days. In general, no investigation is needed except in severe cases for which screening bloodwork and a urine myoglobin test can confirm the diagnosis and rule out complications. Myoglobinuria and highly elevated creatine phosphokinase levels are rare but should be a consideration for admission to hospital. Prognosis is excellent and management might include rest and analgesia. Copyright© the College of Family Physicians of Canada.

Emerging zoonotic viral diseases.

PubMed

Wang, L-F; Crameri, G

2014-08-01

Zoonotic diseases are infectious diseases that are naturally transmitted from vertebrate animals to humans and vice versa. They are caused by all types of pathogenic agents, including bacteria, parasites, fungi, viruses and prions. Although they have been recognised for many centuries, their impact on public health has increased in the last few decades due to a combination of the success in reducing the spread of human infectious diseases through vaccination and effective therapies and the emergence of novel zoonotic diseases. It is being increasingly recognised that a One Health approach at the human-animal-ecosystem interface is needed for effective investigation, prevention and control of any emerging zoonotic disease. Here, the authors will review the drivers for emergence, highlight some of the high-impact emerging zoonotic diseases of the last two decades and provide examples of novel One Health approaches for disease investigation, prevention and control. Although this review focuses on emerging zoonotic viral diseases, the authors consider that the discussions presented in this paper will be equally applicable to emerging zoonotic diseases of other pathogen types.

Viral Hepatitis: A through E and Beyond

MedlinePlus

... National Digestive Diseases Information Clearinghouse What is viral hepatitis? Viral hepatitis is inflammation of the liver caused by ... and serious. Drugs are available to treat chronic hepatitis. 4 Viral Hepatitis: A through E and Beyond What else ...

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

Neuroanatomy goes viral!

PubMed Central

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

2015-01-01

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

Statistical Mechanics of Viral Entry

NASA Astrophysics Data System (ADS)

Zhang, Yaojun; Dudko, Olga K.

2015-01-01

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

Aseptic Meningitis and Viral Myelitis

PubMed Central

Irani, David N.

2008-01-01

SYNOPSIS Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system (CNS), respectively. Indeed, the number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal CNS infections, on the other hand, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with non-infectious disorders that cause acute flaccid paralysis (AFP). This chapter will review some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus will be placed on the diseases caused by enteroviruses (EVs), which as a group account for the vast majority of all aseptic meningitis cases as well as many focal infections of the spinal cord. PMID:18657719

Viral Evolution Core | FNLCR Staging

Cancer.gov

Brandon F. Keele, Ph.D. PI/Senior Principal Investigator, Retroviral Evolution Section Head, Viral Evolution Core Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research Frederick, MD 21702-1201 Tel: 301-846-173

Viral Hepatitis in South Korea

PubMed Central

Alastal, Yaseen; Khan, Zubair; Darr, Umar

2017-01-01

In South Korea (S. Korea), viral hepatitis is a major public health burden. Advances in healthcare policy, evidence-based medicine, and therapeutic strategies in S. Korea have brought a rapid change in the sociodemographic and clinical characteristics of viral hepatitis. This review discusses the innovative approaches that S. Korea has taken to curb the epidemic of viral hepatitis. In addition, the efficacy of various preventive and therapeutic modalities is discussed. This review aims to provide a brief overview to guide future research direction and healthcare policy changes. How to cite this article: Pak SC, Alastal Y, Khan Z, Darr U. Viral Hepatitis in South Korea. Euroasian J Hepato-Gastroenterol 2017;7(2):163-165. PMID:29201801

Aseptic meningitis and viral myelitis.

PubMed

Irani, David N

2008-08-01

Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system, respectively. The number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal central nervous system infections, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with noninfectious disorders that cause acute flaccid paralysis. This article reviews some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus is placed on the diseases caused by enteroviruses, which as a group account for most aseptic meningitis cases and many focal infections of the spinal cord.

FastStats: Viral Hepatitis

MedlinePlus

... Submit What's this? Submit Button NCHS Home Viral Hepatitis Recommend on Facebook Tweet Share Compartir Data are for the U.S. Morbidity Number of new hepatitis A cases: 1,239 (2014) Number of new ...

Viral infections in transplant recipients.

PubMed

Razonable, R R; Eid, A J

2009-12-01

Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. The agents of viral hepatitis B and C present unique challenges particularly among liver transplant recipients. Respiratory viral illnesses due to influenza, respiratory syncytial virus, and parainfluenza virus may affect all types of transplant recipients, although severe clinical disease is observed more commonly among lung and allogeneic hematopoietic stem cell transplant recipients. Less common viral infections affecting transplant recipients include those caused by adenoviruses, parvovirus B19, and West Nile virus. Treatment for viruses with proven effective antiviral drug therapies should be complemented by reduction in the degree of immunosuppression. For others with no proven antiviral drugs for therapy, reduction in the degree of immunosuppression remains as the sole effective strategy for management. Prevention of viral infections is therefore of utmost importance, and this may be accomplished through vaccination, antiviral strategies, and aggressive infection control measures.

Viral-associated lymphoid proliferations☆

PubMed Central

Pittaluga, Stefania

2013-01-01

The histological spectrum of viral-associated lymphoid proliferations is quite broad, ranging from reactive lymphadenitis to atypical proliferations mimicking classical Hodgkin lymphoma or non-Hodgkin lymphoma. Virally associated reactive lesions can appear quite alarming on histological examination, because of direct (cytopathic) and indirect viral-induced changes eliciting a polymorphic cellular host response. In addition, the atypical lymphoid proliferation may show aberrant phenotypic features as well as restricted/clonal gene immunoglobulin or T-cell receptor rearrangements, further complicating the interpretation. In order to achieve an accurate diagnosis, it is important to be aware of the clinical history, including family history and ethnic background, clinical presentation, symptoms, and extent of the disease. Among the clinical data, particular emphasis should be placed on serology and viral load studies, and the use of immunosuppressive drugs. The clinical course and outcome vary greatly, from an indolent, self-limited to aggressive clinical course, blurring at times the distinction between neoplastic and reactive proliferations. It is now recognized that immunosenescence also plays a significant role in the development of these viral-associated lymphoid proliferations, and new entities have been described in recent years. In this review we discuss mostly Epstein–Barr virus-associated viral proliferations that may be confused with lymphomas, which the practicing pathologist may encounter. PMID:23537914

[Neuropsychiatric sequelae of viral meningitis in adults].

PubMed

Damsgaard, Jesper; Hjerrild, Simon; Renvillard, Signe Groth; Leutscher, Peter Derek Christian

2011-10-10

Viral meningitis is considered to be a benign illness with only mild symptoms. In contrast to viral encephalitis and bacterial meningitis, the prognosis is usually good. However, retrospective studies have demonstrated that patients suffering from viral meningitis may experience cognitive impairment following the acute course of infection. Larger controlled studies are needed to elucidate the potential neuropsychiatric adverse outcome of viral meningitis.

Computational mechanics of viral capsids.

PubMed

Gibbons, Melissa M; Perotti, Luigi E; Klug, William S

2015-01-01

Viral capsids undergo significant mechanical deformations during their assembly, maturation, and infective life-span. In order to characterize the mechanics of viral capsids, their response to applied external forces is analyzed in several experimental studies using, for instance, Atomic Force Microscope (AFM) indentation experiments. In recent years, a broader approach to study the mechanics of viral capsids has leveraged the theoretical tools proper of continuum mechanics. Even though the theory of continuum elasticity is most commonly used to study deformable bodies at larger macroscopic length scales, it has been shown that this very rich theoretical field can still offer useful insights into the mechanics of viral structures at the nanometer scale. Here we show the construction of viral capsid continuum mechanics models starting from different forms of experimental data. We will discuss the kinematics assumptions, the issue of the reference configuration, the material constitutive laws, and the numerical discretization necessary to construct a complete Finite Element capsid mechanical model. Some examples in the second part of the chapter will show the predictive capabilities of the constructed models and underline useful practical aspects related to efficiency and accuracy. We conclude each example by collecting several key findings discovered by simulating AFM indentation experiments using the constructed numerical models.

Focal posterior pole viral retinitis.

PubMed

Hazirolan, Dicle; Sungur, Gulten; Demir, Necati; Kasim, Remzi; Duman, Sunay

2010-01-01

To describe the clinical features of an atypical form of viral retinitis in immunocompetent patients. This was a retrospective noncomparative case series. The charts of 8 patients diagnosed with and treated for focal posterior viral retinitis were reviewed. Clinical and demographic features were evaluated. All the patients had extensive laboratory tests, fundus fluorescein angiography, optical coherence tomography of macula, and polymerase chain reaction of vitreous. All the patients were referred to our Uveitis Service from other hospitals, as their uveitis symptoms deteriorated in spite of treatment. The mean age of 4 male and 4 female patients was 32.1 years (range, 22-42 years). The mean follow-up period was 10 months (range, 6-18 months). All of the patients had unilateral disease. Polymerase chain reaction analysis of vitreous specimen was positive for herpes simplex virus-1 in 5 patients and varicella zoster virus in 3 patients. Retinitis resolved after systemic acyclovir treatment in all patients. Viral etiology must be borne in mind in the differential diagnosis of atypical retinitis. It can be a milder form of viral retinitis like focal viral retinitis, as mentioned in this study. The prognosis of this disease is better than the other forms of necrotizing retinopathies involving a larger area of retina.

P‐TEFb goes viral

PubMed Central

Zaborowska, Justyna; Isa, Nur F.

2015-01-01

Positive transcription elongation factor b (P‐TEFb), which comprises cyclin‐dependent kinase 9 (CDK9) kinase and cyclin T subunits, is an essential kinase complex in human cells. Phosphorylation of the negative elongation factors by P‐TEFb is required for productive elongation of transcription of protein‐coding genes by RNA polymerase II (pol II). In addition, P‐TEFb‐mediated phosphorylation of the carboxyl‐terminal domain (CTD) of the largest subunit of pol II mediates the recruitment of transcription and RNA processing factors during the transcription cycle. CDK9 also phosphorylates p53, a tumor suppressor that plays a central role in cellular responses to a range of stress factors. Many viral factors affect transcription by recruiting or modulating the activity of CDK9. In this review, we will focus on how the function of CDK9 is regulated by viral gene products. The central role of CDK9 in viral life cycles suggests that drugs targeting the interaction between viral products and P‐TEFb could be effective anti‐viral agents. PMID:27398404

Noncoding RNPs of viral origin.

PubMed

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

2011-03-01

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

Noncoding RNPs of Viral Origin

PubMed Central

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

2011-01-01

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

Acute bacterial and viral meningitis.

PubMed

Bartt, Russell

2012-12-01

Most cases of acute meningitis are infectious and result from a potentially wide range of bacterial and viral pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Acute meningitis is infectious in most cases and caused by a potentially wide range of bacterial and viral pathogens. Shifts in the epidemiology of bacterial pathogens have been influenced by changes in vaccines and their implementation. Seasonal and environmental changes influence the likely viral and rickettsial pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Pertinent testing and treatment can vary with the clinical presentation, season, and possible exposures. This article reviews the epidemiology, clinical presentation, diagnosis, and treatment of acute meningitis.

[Emerging viral diseases in Europe].

PubMed

Löbermann, M; Gürtler, L G; Eichler-Löbermann, B; Reisinger, E C

2012-04-01

Emergence of viral agents in Europe is influenced by various factors. Climatic changes influencing possible vectors, insufficient vaccination, and travel of man and goods are among the most important reasons to explain these changes. Fever and arthralgia are the leading symptoms in infection with Dengue, Sindbis, or Chikungunya virus. In contrast, tick-born encephalitis (TBE), Toscana, or West Nile virus infections mainly lead to meningo-encephalitis. In Europe, hemorrhagic fever is caused by Crimean Congo and Hanta virus. Protective vaccines are available for emerging viral agents like TBE, influenza and measles. © Georg Thieme Verlag KG Stuttgart · New York.

Recycling Endosomes and Viral Infection.

PubMed

Vale-Costa, Sílvia; Amorim, Maria João

2016-03-08

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.

The Paradigm of Viral Communication.

ERIC Educational Resources Information Center

Welker, Carl B.

2002-01-01

Introduces the concepts of idea viruses and viral communication, a technology-based communication that spreads ideas quickly. Explains its applicability in the area of direct marketing and discusses a technology platform that provides the opportunity of sending a message to a large number of people and emotional or pecuniary incentives to…

Nosocomial Spread of Viral Disease

PubMed Central

Aitken, Celia; Jeffries, Donald J.

2001-01-01

Viruses are important causes of nosocomial infection, but the fact that hospital outbreaks often result from introduction(s) from community-based epidemics, together with the need to initiate specific laboratory testing, means that there are usually insufficient data to allow the monitoring of trends in incidences. The most important defenses against nosocomial transmission of viruses are detailed and continuing education of staff and strict adherence to infection control policies. Protocols must be available to assist in the management of patients with suspected or confirmed viral infection in the health care setting. In this review, we present details on general measures to prevent the spread of viral infection in hospitals and other health care environments. These include principles of accommodation of infected patients and approaches to good hygiene and patient management. They provide detail on individual viral diseases accompanied in each case with specific information on control of the infection and, where appropriate, details of preventive and therapeutic measures. The important areas of nosocomial infection due to blood-borne viruses have been extensively reviewed previously and are summarized here briefly, with citation of selected review articles. Human prion diseases, which present management problems very different from those of viral infection, are not included. PMID:11432812

Autistic disorder and viral infections.

PubMed

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

2005-02-01

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

Small molecules targeting viral RNA.

PubMed

Hermann, Thomas

2016-11-01

Highly conserved noncoding RNA (ncRNA) elements in viral genomes and transcripts offer new opportunities to expand the repertoire of drug targets for the development of antiinfective therapy. Ligands binding to ncRNA architectures are able to affect interactions, structural stability or conformational changes and thereby block processes essential for viral replication. Proof of concept for targeting functional RNA by small molecule inhibitors has been demonstrated for multiple viruses with RNA genomes. Strategies to identify antiviral compounds as inhibitors of ncRNA are increasingly emphasizing consideration of drug-like properties of candidate molecules emerging from screening and ligand design. Recent efforts of antiviral lead discovery for RNA targets have provided drug-like small molecules that inhibit viral replication and include inhibitors of human immunodeficiency virus (HIV), hepatitis C virus (HCV), severe respiratory syndrome coronavirus (SARS CoV), and influenza A virus. While target selectivity remains a challenge for the discovery of useful RNA-binding compounds, a better understanding is emerging of properties that define RNA targets amenable for inhibition by small molecule ligands. Insight from successful approaches of targeting viral ncRNA in HIV, HCV, SARS CoV, and influenza A will provide a basis for the future exploration of RNA targets for therapeutic intervention in other viral pathogens which create urgent, unmet medical needs. Viruses for which targeting ncRNA components in the genome or transcripts may be promising include insect-borne flaviviruses (Dengue, Zika, and West Nile) and filoviruses (Ebola and Marburg). WIREs RNA 2016, 7:726-743. doi: 10.1002/wrna.1373 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Viral Immunotherapy to Eradicate Subclinical Brain Metastases

DTIC Science & Technology

2012-09-01

1 AD_________________ Award Number: W81XWH-11-1-0124 TITLE: Viral Immunotherapy to...Annual 3. DATES COVERED 1 September 2011 – 31 August 2012 4. TITLE AND SUBTITLE Viral Immunotherapy to Eradicate Subclinical Brain Metastases...re-activated to enter and destroy early BM by viral infection of Her2-positive breast BM by a recombinant vesicular stomatitis virus (VSV), which

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2012-07-01

will in due course approach DOD for approval of the animal protocol. 15. SUBJECT TERMS Viral oncolysis, neoplastic meningitis , cell lines, HSV-1...proposed study is to develop novel, safe and efficient therapy for neoplastic meningitis – that of HSV-1 oncolysis. The viral genome is genetically...1 AD_________________ Award Number: W81XWH-11-1-0388 TITLE: Viral Oncolytic Therapeutics for Neoplastic

Prospects for new viral vaccines.

PubMed

Marmion, B P

1980-08-11

Animal virology has made outstanding contributions to preventive medicine by the development of vaccines for the control of infectious disease in man and animals. Cost-benefit analysis indicates substantial savings in health care costs from the control of diseases such as smallpox, poliomyelitis, yellow fever and measels. Areas for further development include vaccines for influenza (living, attenuated virus), the herpes group (varicella: cytomegalovirus), respiratory syncytial virus, rotavirus and hepatitis A, B, and non A/non B. The general options for vaccine formulation are discussed with particular emphasis on approaches with the use of viral genetics to 'tailor make' vaccine viruses with defined growth potential in laboratory systems, low pathogenicity, and defined antigens. Current progress with the development of an inactivated hepatitis B vaccine is reviewed as a case study in vaccine development. The impact of recent experiments in cloning hepatitis B virus DNA in E. coli on the production of a purified viral polypeptide vaccine is assessed.

[Immunotherapy for refractory viral infections].

PubMed

Morio, Tomohiro; Fujita, Yuriko; Takahashi, Satoshi

Various antiviral agents have been developed, which are sometimes associated with toxicity, development of virus-resistant strain, and high cost. Virus-specific T-cell (VST) therapy provides an alternative curative therapy that can be effective for a prolonged time without eliciting drug resistance. VSTs can be directly separated using several types of capture devices and can be obtained by stimulating peripheral blood mononuclear cells with viral antigens (virus, protein, or peptide) loaded on antigen-presenting cells (APC). APC can be transduced with virus-antigen coding plasmid or pulsed with overlapping peptides. VST therapy has been studied in drug non-responsive viral infections after hematopoietic cell transplantation (HCT). Several previous studies have demonstrated the efficacy of VST therapy without significant severe GVHD. In addition, VSTs from a third-party donor have been prepared and administered for post-HCT viral infection. Although target viruses of VSTs include herpes virus species and polyomavirus species, a wide variety of pathogens, such as papillomavirus, intracellular bacteria, and fungi, can be treated by pathogen-specific T-cells. Perhaps, these specific T-cells could be used for opportunistic infections in other immunocompromised hosts in the near future.

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

Laboratory procedures to generate viral metagenomes.

PubMed

Thurber, Rebecca V; Haynes, Matthew; Breitbart, Mya; Wegley, Linda; Rohwer, Forest

2009-01-01

This collection of laboratory protocols describes the steps to collect viruses from various samples with the specific aim of generating viral metagenome sequence libraries (viromes). Viral metagenomics, the study of uncultured viral nucleic acid sequences from different biomes, relies on several concentration, purification, extraction, sequencing and heuristic bioinformatic methods. No single technique can provide an all-inclusive approach, and therefore the protocols presented here will be discussed in terms of hypothetical projects. However, care must be taken to individualize each step depending on the source and type of viral-particles. This protocol is a description of the processes we have successfully used to: (i) concentrate viral particles from various types of samples, (ii) eliminate contaminating cells and free nucleic acids and (iii) extract, amplify and purify viral nucleic acids. Overall, a sample can be processed to isolate viral nucleic acids suitable for high-throughput sequencing in approximately 1 week.

Viral diseases of marine invertebrates

NASA Astrophysics Data System (ADS)

Johnson, P. T.

1984-03-01

Approximately 40 viruses are known from marine sponges; turbellarian and monogenetic flatworms; cephalopod, bivalve, and gastropod mollusks; nereid polychaetes; and isopod and decapod crustaceans. Most of the viruses can be tentatively assigned to the Herpesviridae, Baculoviridae, Iridoviridae, Adenoviridae, Papovaviridae, Reoviridae, “Birnaviridae”, Bunyaviridae, Rhabdoviridae, and Picornaviridae. Viruslike particles found in oysters might be representatives of the Togaviridae and Retroviridae. Enveloped single-stranded RNA viruses from crustaceans have developmental and morphological characteristics intermediate between families, and some show evidence of relationships to the Paramyxoviridae as well as the Bunyaviridae or Rhabdoviridae. Certain small viruses of shrimp cannot be assigned, even tentatively, to a particular family. Some viruses cause disease in wild and captive hosts, others are associated with disease states but may not be primary instigators, and many occur in apparently normal animals. The frequency of viral disease in natural populations of marine invertebrates is unknown. Several viruses that cause disease in captive animals, with or without experimental intervention, have also been found in diseased wild hosts, including herpeslike viruses of crabs and oysters, iridovirus of octopus, and reolike and bunyalike viruses of crabs. Iridolike viruses have been implicated in massive mortalities of cultured oysters. Baculoviruses, and IHHN virus, which is of uncertain affinities, cause economically damaging diseases in cultured penaeid shrimp. Double or multiple viral infection is common in crabs. For example, a reolike virus and associated rhabdolike virus act synergistically to cause paralytic and fatal disease in Callinectes sapidus. Information on host range, most susceptible stage, and viral latency is available only for viruses of shrimp. One baculovirus attacks five species of New World penaeid shrimp. IHHN virus infects three species of

Population Dynamics of Viral Inactivation

NASA Astrophysics Data System (ADS)

Freeman, Krista; Li, Dong; Behrens, Manja; Streletzky, Kiril; Olsson, Ulf; Evilevitch, Alex

We have investigated the population dynamics of viral inactivation in vitrousing time-resolved cryo electron microscopy combined with light and X-ray scattering techniques. Using bacteriophage λ as a model system for pressurized double-stranded DNA viruses, we found that virions incubated with their cell receptor eject their genome in a stochastic triggering process. The triggering of DNA ejection occurs in a non synchronized manner after the receptor addition, resulting in an exponential decay of the number of genome-filled viruses with time. We have explored the characteristic time constant of this triggering process at different temperatures, salt conditions, and packaged genome lengths. Furthermore, using the temperature dependence we determined an activation energy for DNA ejections. The dependences of the time constant and activation energy on internal DNA pressure, affected by salt conditions and encapsidated genome length, suggest that the triggering process is directly dependent on the conformational state of the encapsidated DNA. The results of this work provide insight into how the in vivo kinetics of the spread of viral infection are influenced by intra- and extra cellular environmental conditions. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1252522.

Sequencing Needs for Viral Diagnostics

SciTech Connect

Gardner, S N; Lam, M; Mulakken, N J

2004-01-26

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

Commercialization of veterinary viral vaccines.

PubMed

Flore, P H

2004-12-01

If vaccines are to reliably prevent disease, they must be developed, produced and quality-controlled according to very strict regulations and procedures. Veterinary viral vaccine registrations are governed by different rules in different countries, but these rules all emphasize that the quality of the raw materials--the cells, eggs, animals or plants that are used in production--need to be carefully controlled. The veterinary vaccine business is also very cost-conscious. Emphasis over the last 5-10 years has therefore been to develop culture systems that minimize labor and sterility problems and thus provide for reliable and cost-effective production. Implementing these often more complex systems in a production environment takes considerable effort, first in scale-up trials and further down the line in convincing production personnel to change their familiar system for something new and possibly untried. To complete scale-up trials successfully, it is absolutely necessary to understand the biochemistry of the cells and the influence of the virus on the cells under scale-up and later production conditions. Once a viral product can be produced on a large scale, it is imperative that the quality of the end-product is controlled in an intelligent way. One needs to know whether the end-product performs in the animal as was intended during its conception in the research and development department. The development of the appropriate tests to demonstrate this plays an important role in the successful development of a vaccine.

Oncolytic Viral Therapy for Mesothelioma

PubMed Central

Pease, Daniel F.; Kratzke, Robert A.

2017-01-01

The limited effectiveness of conventional therapy for malignant pleural mesothelioma demands innovative approaches to this difficult disease. Even with aggressive multimodality treatment of surgery, radiation, and/or chemotherapy, the median survival is only 1–2 years depending on stage and histology. Oncolytic viral therapy has emerged in the last several decades as a rapidly advancing field of immunotherapy studied in a wide spectrum of malignancies. Mesothelioma makes an ideal candidate for studying oncolysis given the frequently localized pattern of growth and pleural location providing access to direct intratumoral injection of virus. Therefore, despite being a relatively uncommon disease, the multitude of viral studies for mesothelioma can provide insight for applying such therapy to other malignancies. This article will begin with a review of the general principles of oncolytic therapy focusing on antitumor efficacy, tumor selectivity, and immune system activation. The second half of this review will detail results of preclinical models and human studies for oncolytic virotherapy in mesothelioma. PMID:28884088

Viral Organization of Human Proteins

PubMed Central

Wuchty, Stefan; Siwo, Geoffrey; Ferdig, Michael T.

2010-01-01

Although maps of intracellular interactions are increasingly well characterized, little is known about large-scale maps of host-pathogen protein interactions. The investigation of host-pathogen interactions can reveal features of pathogenesis and provide a foundation for the development of drugs and disease prevention strategies. A compilation of experimentally verified interactions between HIV-1 and human proteins and a set of HIV-dependency factors (HDF) allowed insights into the topology and intricate interplay between viral and host proteins on a large scale. We found that targeted and HDF proteins appear predominantly in rich-clubs, groups of human proteins that are strongly intertwined among each other. These assemblies of proteins may serve as an infection gateway, allowing the virus to take control of the human host by reaching protein pathways and diversified cellular functions in a pronounced and focused way. Particular transcription factors and protein kinases facilitate indirect interactions between HDFs and viral proteins. Discerning the entanglement of directly targeted and indirectly interacting proteins may uncover molecular and functional sites that can provide novel perspectives on the progression of HIV infection and highlight new avenues to fight this virus. PMID:20827298

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2013-07-01

SUBTITLE 5a. CONTRACT NUMBER Viral Oncolytic Therapeutics for Neoplastic Meningitis 5b. GRANT NUMBER W81XWH-11-1-0388 5c. PROGRAM ELEMENT NUMBER... viral and cellular kinetics with bioluminescence and PET are being written up for publication. 15. SUBJECT TERMS Neoplastic meningitis , mouse...model of meningeal metastases, breast cancer, bioluminescence, MRI, viral oncolysis, HSV- 1. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

Viral Activation of Cellular Metabolism

PubMed Central

Sanchez, Erica L.; Lagunoff, Michael

2015-01-01

To ensure optimal environments for their replication and spread, viruses have evolved to alter many host cell pathways. In the last decade, metabolomic studies have shown that eukaryotic viruses induce large-scale alterations in host cellular metabolism. Most viruses examined to date induce aerobic glycolysis also known as the Warburg effect. Many viruses tested also induce fatty acid synthesis as well as glutaminolysis. These modifications of carbon source utilization by infected cells can increase available energy for virus replication and virion production, provide specific cellular substrates for virus particles and create viral replication niches while increasing infected cell survival. Each virus species also likely requires unique metabolic changes for successful spread and recent research has identified additional virus-specific metabolic changes induced by many virus species. A better understanding of the metabolic alterations required for each virus may lead to novel therapeutic approaches through targeted inhibition of specific cellular metabolic pathways. PMID:25812764

Ferret models of viral pathogenesis.

PubMed

Enkirch, T; von Messling, V

2015-05-01

Emerging and well-known viral diseases remain one the most important global public health threats. A better understanding of their pathogenesis and mechanisms of transmission requires animal models that accurately reproduce these aspects of the disease. Here we review the role of ferrets as an animal model for the pathogenesis of different respiratory viruses with an emphasis on influenza and paramyxoviruses. We will describe the anatomic and physiologic characteristics that contribute to the natural susceptibility of ferrets to these viruses, and provide an overview of the approaches available to analyze their immune responses. Recent insights gained using this model will be highlighted, including the development of new prophylactic and therapeutic approaches. To provide decision criteria for the use of this animal model, its strengths and limitations will be discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Viral ancestors of antiviral systems.

PubMed

Villarreal, Luis P

2011-10-01

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

Viral Ancestors of Antiviral Systems

PubMed Central

Villarreal, Luis P.

2011-01-01

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

Viral hepatitis in the elderly.

PubMed

Carrion, Andres F; Martin, Paul

2012-05-01

As life expectancy continues to rise, elderly adults represent a rapidly growing proportion of the population. The likelihood of complications of acute and chronic liver disease and overall mortality are higher in elderly populations. Several physiological changes associated with aging, greater prevalence of co-morbid conditions, and cumulative exposure to hepatotropic viruses and environmental hepatotoxins may contribute to worse outcomes of viral hepatitis in the elderly. Although pharmacotherapy for hepatitis B and C continues to evolve, the efficacy, tolerability, and side effects of these agents have not been studied extensively in elderly adults. Immunization against hepatitis A and B in naïve elderly adults is an important public health intervention that needs to be revised and broadened.

Viral hepatitis vaccination during pregnancy.

PubMed

Zhao, Yueyuan; Jin, Hui; Zhang, Xuefeng; Wang, Bei; Liu, Pei

2016-04-02

Viral hepatitis is a serious global public health problem. It is also a common cause of jaundice and gestational complications in pregnant women. Moreover, infected mothers can transmit the virus to their fetus or neonate, which may increase disease burden and decrease quality of life. To date, commercial vaccines have been developed for hepatitis A, B, and E and are available to the general population. The Advisory Committee on Immunization Practices currently accepts emergency vaccination against hepatitis A and B during pregnancy due to benefits that overweight the potential risks. While there are limited data from trials with limited numbers of samples that suggest the efficacy or safety of hepatitis B and E vaccines in pregnant women, additional data are necessary to provide evidence of vaccination during pregnancy.

Viral hepatitis vaccination during pregnancy

PubMed Central

Zhao, Yueyuan; Jin, Hui; Zhang, Xuefeng; Wang, Bei; Liu, Pei

2016-01-01

Abstract Viral hepatitis is a serious global public health problem. It is also a common cause of jaundice and gestational complications in pregnant women. Moreover, infected mothers can transmit the virus to their fetus or neonate, which may increase disease burden and decrease quality of life. To date, commercial vaccines have been developed for hepatitis A, B, and E and are available to the general population. The Advisory Committee on Immunization Practices currently accepts emergency vaccination against hepatitis A and B during pregnancy due to benefits that overweight the potential risks. While there are limited data from trials with limited numbers of samples that suggest the efficacy or safety of hepatitis B and E vaccines in pregnant women, additional data are necessary to provide evidence of vaccination during pregnancy. PMID:26833263

Macrophages and the Viral Dissemination Super Highway

PubMed Central

Klepper, Arielle; Branch, Andrea D

2016-01-01

Monocytes and macrophages are key components of the innate immune system yet they are often the victims of attack by infectious agents. This review examines the significance of viral infection of macrophages. The central hypothesis is that macrophage tropism enhances viral dissemination and persistence, but these changes may come at the cost of reduced replication in cells other than macrophages. PMID:26949751

Computational clustering for viral reference proteomes

PubMed Central

Chen, Chuming; Huang, Hongzhan; Mazumder, Raja; Natale, Darren A.; McGarvey, Peter B.; Zhang, Jian; Polson, Shawn W.; Wang, Yuqi; Wu, Cathy H.

2016-01-01

Motivation: The enormous number of redundant sequenced genomes has hindered efforts to analyze and functionally annotate proteins. As the taxonomy of viruses is not uniformly defined, viral proteomes pose special challenges in this regard. Grouping viruses based on the similarity of their proteins at proteome scale can normalize against potential taxonomic nomenclature anomalies. Results: We present Viral Reference Proteomes (Viral RPs), which are computed from complete virus proteomes within UniProtKB. Viral RPs based on 95, 75, 55, 35 and 15% co-membership in proteome similarity based clusters are provided. Comparison of our computational Viral RPs with UniProt’s curator-selected Reference Proteomes indicates that the two sets are consistent and complementary. Furthermore, each Viral RP represents a cluster of virus proteomes that was consistent with virus or host taxonomy. We provide BLASTP search and FTP download of Viral RP protein sequences, and a browser to facilitate the visualization of Viral RPs. Availability and implementation: http://proteininformationresource.org/rps/viruses/ Contact: chenc@udel.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153712

Production of non viral DNA vectors.

PubMed

Schleef, Martin; Blaesen, Markus; Schmeer, Marco; Baier, Ruth; Marie, Corinne; Dickson, George; Scherman, Daniel

2010-12-01

After some decades of research, development and first clinical approaches to use DNA vectors in gene therapy, cell therapy and DNA vaccination, the requirements for the pharmaceutical manufacturing of gene vectors has improved significantly step by step. Even the expression level and specificity of non viral DNA vectors were significantly modified and followed the success of viral vectors. The strict separation of "viral" and "non viral" gene transfer are historic borders between scientist and we will show that both fields together are able to allow the next step towards successful prevention and therapy. Here we summarize the features of producing and modifying these non-viral gene vectors to ensure the required quality to modify cells and to treat human and animals.

Origins and challenges of viral dark matter.

PubMed

Krishnamurthy, Siddharth R; Wang, David

2017-07-15

The accurate classification of viral dark matter - metagenomic sequences that originate from viruses but do not align to any reference virus sequences - is one of the major obstacles in comprehensively defining the virome. Depending on the sample, viral dark matter can make up from anywhere between 40 and 90% of sequences. This review focuses on the specific nature of dark matter as it relates to viral sequences. We identify three factors that contribute to the existence of viral dark matter: the divergence and length of virus sequences, the limitations of alignment based classification, and limited representation of viruses in reference sequence databases. We then discuss current methods that have been developed to at least partially circumvent these limitations and thereby reduce the extent of viral dark matter. Copyright © 2017 Elsevier B.V. All rights reserved.

Ethical Considerations in Research Participation Virality.

PubMed

Ellis-Barton, Carol

2016-07-01

This article seeks to commence and encourage discussion around the upcoming ethical challenges of virality in network structures. When the call for participation in a research project on lupus in Ireland went from an advertisement in a newsletter to a meme (unit of transmissible information) on a closed Facebook page, the ethical considerations of virality were raised. The article analyzes the Association of Internet Researchers guidelines, Facebook policies, and the context of privacy in relation to virality. Virality creates the leverage for methodological pluralism. The nature of the inquiry can determine the method rather than the other way around. Viral ethical considerations are evolving due to the cyber world becoming the primary meme of communication, with flexibility in the researcher's protocol providing opportunities for efficient, cost-effective, and diverse recruitment. © The Author(s) 2016.

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

PubMed

Weber, E P Scott

2013-09-01

Viral dermatopathies of fish bear clinical signs similar to those of dermatopathies from other causes. This article offers an overview to approaching dermatologic presentations in fish, with an emphasis on sampling, diagnosis, and management of viral dermatopathies, building on previous publications. It is vital to recognize clinical signs associated with viral dermatopathies because there are currently no treatments available. Avoidance and prevention is the key to controlling viral diseases in fish. Optimizing husbandry practices and providing appropriate quarantine procedures can help prevent viral disease outbreaks in collection and aquaculture stocks. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Viral kinetic modeling: state of the art

DOE PAGES

Canini, Laetitia; Perelson, Alan S.

2014-06-25

Viral kinetic modeling has led to increased understanding of the within host dynamics of viral infections and the effects of therapy. Here we review recent developments in the modeling of viral infection kinetics with emphasis on two infectious diseases: hepatitis C and influenza. We review how viral kinetic modeling has evolved from simple models of viral infections treated with a drug or drug cocktail with an assumed constant effectiveness to models that incorporate drug pharmacokinetics and pharmacodynamics, as well as phenomenological models that simply assume drugs have time varying-effectiveness. We also discuss multiscale models that include intracellular events in viralmore » replication, models of drug-resistance, models that include innate and adaptive immune responses and models that incorporate cell-to-cell spread of infection. Overall, viral kinetic modeling has provided new insights into the understanding of the disease progression and the modes of action of several drugs. In conclusion, we expect that viral kinetic modeling will be increasingly used in the coming years to optimize drug regimens in order to improve therapeutic outcomes and treatment tolerability for infectious diseases.« less

New Metrics for Evaluating Viral Respiratory Pathogenesis

PubMed Central

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

2015-01-01

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

Viral Evasion of Natural Killer Cell Activation

PubMed Central

Ma, Yi; Li, Xiaojuan; Kuang, Ersheng

2016-01-01

Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections. PMID:27077876

Viral Evasion of Natural Killer Cell Activation.

PubMed

Ma, Yi; Li, Xiaojuan; Kuang, Ersheng

2016-04-12

Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent

PubMed Central

Li, Linlin; Deng, Xutao; Mee, Edward T.; Collot-Teixeira, Sophie; Anderson, Rob; Schepelmann, Silke; Minor, Philip D.; Delwart, Eric

2014-01-01

Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries on the efficiency of viral detection and virus genome coverage were compared. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces. PMID:25497414

Structure and Function of Viral Deubiquitinating Enzymes.

PubMed

Bailey-Elkin, Ben A; Knaap, Robert C M; Kikkert, Marjolein; Mark, Brian L

2017-11-10

Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including innate and adaptive immune responses. Ubiquitin-mediated control over these processes can be reversed by cellular deubiquitinating enzymes (DUBs), which remove ubiquitin from cellular targets and depolymerize polyubiquitin chains. The importance of protein ubiquitination to host immunity has been underscored by the discovery of viruses that encode proteases with deubiquitinating activity, many of which have been demonstrated to actively corrupt cellular ubiquitin-dependent processes to suppress innate antiviral responses and promote viral replication. DUBs have now been identified in diverse viral lineages, and their characterization is providing valuable insights into virus biology and the role of the ubiquitin system in host antiviral mechanisms. Here, we provide an overview of the structural biology of these fascinating viral enzymes and their role innate immune evasion and viral replication. Copyright © 2017 Elsevier Ltd. All rights reserved.

Viral fitness: definitions, measurement, and current insights

USGS Publications Warehouse

Wargo, Andrew R.; Kurath, Gael

2012-01-01

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

Immunity: Insect Immune Memory Goes Viral.

PubMed

Ligoxygakis, Petros

2017-11-20

Adaptive memory in insect immunity has been controversial. In this issue, Andino and co-workers propose that acquisition of viral sequences in the host genome gives rise to anti-sense, anti-viral piRNAs. Such sequences can be regarded as both a genomic archive of past infections and as an armour of potential heritable memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rapid and highly fieldable viral diagnostic

DOEpatents

McKnight, Timothy E.

2016-12-20

The present invention relates to a rapid, highly fieldable, nearly reagentless diagnostic to identify active RNA viral replication in a live, infected cells, and more particularly in leukocytes and tissue samples (including biopsies and nasal swabs) using an array of a plurality of vertically-aligned nanostructures that impale the cells and introduce a DNA reporter construct that is expressed and amplified in the presence of active viral replication.

Oxygen tension level and human viral infections

SciTech Connect

Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr; Université Denis Diderot, Sorbonne Paris Cité Paris, Paris; Casetti, Luana

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 andmore » 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.« less

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.

Viral proteases: an emerging therapeutic target.

PubMed

Korant, B D

1988-01-01

Only a few viral diseases are presently treatable because of our limited knowledge of specific viral target molecules. An attractive class of viral molecules toward which chemotherapeutic agents could be aimed are proteases coded by some virus groups such as retro- or picornaviruses (poliomyelitis, common cold virus). The picornavirus enzymes were discovered first, and they have now been characterized by a combination of molecular-genetic and biochemical approaches. Several laboratories have expressed the picornaviral enzymes in heterologous systems and have reported proteolytic activity, as well as the high cleavage fidelity diagnostic of the viral proteases. After dealing with several technical difficulties often encountered in standard genetic engineering approaches, one viral protease is now available to us in quantity and is amendable to mutagenic procedures. The initial outcome of the mutagenesis studies has been the confirmation of our earlier work with inhibitors, which suggested a cysteine active-site class. There is a clustering of active-site residues which may be unique to these viruses. The requirement for an active-site cysteine-histidine pair in combination with detailed information on the viral cleavage sites has permitted design of selective inhibitors with attractive antiviral properties. Future goals include investigation of the structural basis for selective processing and application of the cleavage specificity to general problems in genetic engineering.

An Odyssey to Viral Pathogenesis.

PubMed

Oldstone, Michael B A

2016-05-23

polishing by Karl Habel (a superb senior virologist who left the National Institutes of Health and came to Scripps), and the gifted postdoctoral fellows who joined my laboratory over four decades form the log of my scientific voyage. The strong friendships and collaborations developed with other young but growing experimentalists like Bernie Fields and Abner Notkins are the fabric of the tale I will weave and were pivotal in the establishment of viral pathogenesis as a discipline.

Viral Hepatitis: Information for Gay and Bisexual Men

MedlinePlus

VIRAL HEPATITIS Information for Gay and Bisexual Men What is viral hepatitis? Viral hepatitis is an infection of the liver caused by one of several ... each virus is spread in different ways. Are gay and bisexual men at risk for viral hepatitis? ...

Raw Sewage Harbors Diverse Viral Populations

PubMed Central

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

2011-01-01

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

Lactoferrin for prevention of common viral infections.

PubMed

Wakabayashi, Hiroyuki; Oda, Hirotsugu; Yamauchi, Koji; Abe, Fumiaki

2014-11-01

Although lactoferrin has many biological functions, the host-protective effects against pathogenic microorganisms including bacteria, fungi, and viruses are regarded as one of the most important. Here, we review research on the protective role of lactoferrin administration against common viral infections. Many studies have shown the in vitro antiviral activity of lactoferrin against viral pathogens that cause common infections such as the common cold, influenza, gastroenteritis, summer cold, and herpes, where lactoferrin inhibits mainly viral attachment to the target cells. Recently, studies indicating the in vivo protective effects of lactoferrin by oral administration against common viral infections have been increasing. For instance, norovirus is an extremely important emerging human pathogen that causes a majority of gastroenteritis outbreaks worldwide that may be a target candidate for lactoferrin. Lactoferrin consumption reduced the incidence of noroviral gastroenteritis in children and a similar effect was observed in a wide range of ages in a preliminary survey. A recent in vitro study reported that lactoferrin inhibits both cellular attachment of the murine norovirus, a virus closely-related to the human norovirus, and viral replication in the cells by inducing antiviral cytokines interferon (IFN)-α/β. Lactoferrin administration also enhances NK cell activity and Th1 cytokine responses, which lead to protection against viral infections. In conclusion, lactoferrin consumption may protect the host from viral infections through inhibiting the attachment of a virus to the cells, replication of the virus in the cells, and enhancement of systemic immune functions. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Chronic viral hepatitis: the histology report.

PubMed

Guido, Maria; Mangia, Alessandra; Faa, Gavino

2011-03-01

In chronic viral hepatitis, the role of liver biopsy as a diagnostic test has seen a decline, paralleled by its increasing importance for prognostic purposes. Nowadays, the main indication for liver biopsy in chronic viral hepatitis is to assess the severity of the disease, in terms of both necro-inflammation (grade) and fibrosis (stage), which is important for prognosis and therapeutic management. Several scoring systems have been proposed for grading and staging chronic viral hepatitis and there is no a general consensus on the best system to be used in the daily practice. All scoring systems have their drawbacks and all may be affected by sampling and observer variability. Whatever the system used, a histological score is a reductive approach since damage in chronic viral hepatitis is a complex biological process. Thus, scoring systems are not intended to replace the detailed, descriptive, pathology report. In fact, lesions other than those scored for grading and staging may have clinical relevance and should be assessed and reported. This paper aims to provide a systematic approach to the interpretation of liver biopsies obtained in cases of chronic viral hepatitis, with the hope of helping general pathologists in their diagnostic practice. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

Viral assembly of oriented quantum dot nanowires.

PubMed

Mao, Chuanbin; Flynn, Christine E; Hayhurst, Andrew; Sweeney, Rozamond; Qi, Jifa; Georgiou, George; Iverson, Brent; Belcher, Angela M

2003-06-10

The highly organized structure of M13 bacteriophage was used as an evolved biological template for the nucleation and orientation of semiconductor nanowires. To create this organized template, peptides were selected by using a pIII phage display library for their ability to nucleate ZnS or CdS nanocrystals. The successful peptides were expressed as pVIII fusion proteins into the crystalline capsid of the virus. The engineered viruses were exposed to semiconductor precursor solutions, and the resultant nanocrystals that were templated along the viruses to form nanowires were extensively characterized by using high-resolution analytical electron microscopy and photoluminescence. ZnS nanocrystals were well crystallized on the viral capsid in a hexagonal wurtzite or a cubic zinc blende structure, depending on the peptide expressed on the viral capsid. Electron diffraction patterns showed single-crystal type behavior from a polynanocrystalline area of the nanowire formed, suggesting that the nanocrystals on the virus were preferentially oriented with their [001] perpendicular to the viral surface. Peptides that specifically directed CdS nanocrystal growth were also engineered into the viral capsid to create wurtzite CdS virus-based nanowires. Lastly, heterostructured nucleation was achieved with a dual-peptide virus engineered to express two distinct peptides within the same viral capsid. This work represents a genetically controlled biological synthesis route to a semiconductor nanoscale heterostructure.

Viral assembly of oriented quantum dot nanowires

NASA Astrophysics Data System (ADS)

Mao, Chuanbin; Flynn, Christine E.; Hayhurst, Andrew; Sweeney, Rozamond; Qi, Jifa; Georgiou, George; Iverson, Brent; Belcher, Angela M.

2003-06-01

The highly organized structure of M13 bacteriophage was used as an evolved biological template for the nucleation and orientation of semiconductor nanowires. To create this organized template, peptides were selected by using a pIII phage display library for their ability to nucleate ZnS or CdS nanocrystals. The successful peptides were expressed as pVIII fusion proteins into the crystalline capsid of the virus. The engineered viruses were exposed to semiconductor precursor solutions, and the resultant nanocrystals that were templated along the viruses to form nanowires were extensively characterized by using high-resolution analytical electron microscopy and photoluminescence. ZnS nanocrystals were well crystallized on the viral capsid in a hexagonal wurtzite or a cubic zinc blende structure, depending on the peptide expressed on the viral capsid. Electron diffraction patterns showed single-crystal type behavior from a polynanocrystalline area of the nanowire formed, suggesting that the nanocrystals on the virus were preferentially oriented with their [001] perpendicular to the viral surface. Peptides that specifically directed CdS nanocrystal growth were also engineered into the viral capsid to create wurtzite CdS virus-based nanowires. Lastly, heterostructured nucleation was achieved with a dual-peptide virus engineered to express two distinct peptides within the same viral capsid. This work represents a genetically controlled biological synthesis route to a semiconductor nanoscale heterostructure.

Viral quasispecies inference from 454 pyrosequencing

PubMed Central

2013-01-01

Background Many potentially life-threatening infectious viruses are highly mutable in nature. Characterizing the fittest variants within a quasispecies from infected patients is expected to allow unprecedented opportunities to investigate the relationship between quasispecies diversity and disease epidemiology. The advent of next-generation sequencing technologies has allowed the study of virus diversity with high-throughput sequencing, although these methods come with higher rates of errors which can artificially increase diversity. Results Here we introduce a novel computational approach that incorporates base quality scores from next-generation sequencers for reconstructing viral genome sequences that simultaneously infers the number of variants within a quasispecies that are present. Comparisons on simulated and clinical data on dengue virus suggest that the novel approach provides a more accurate inference of the underlying number of variants within the quasispecies, which is vital for clinical efforts in mapping the within-host viral diversity. Sequence alignments generated by our approach are also found to exhibit lower rates of error. Conclusions The ability to infer the viral quasispecies colony that is present within a human host provides the potential for a more accurate classification of the viral phenotype. Understanding the genomics of viruses will be relevant not just to studying how to control or even eradicate these viral infectious diseases, but also in learning about the innate protection in the human host against the viruses. PMID:24308284

Neutral Theory and Rapidly Evolving Viral Pathogens.

PubMed

Frost, Simon D W; Magalis, Brittany Rife; Kosakovsky Pond, Sergei L

2018-06-01

The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, adaptive evolution is largely confined to small parts of information-packed viral genomes, and the majority of observed variation is effectively neutral. The predictions and implications of the neutral theory have proven immensely useful in this context, with applications spanning understanding within-host population structure, tracing the origins and spread of viral pathogens, predicting evolutionary dynamics, and modeling the emergence of drug resistance. We highlight the multiple ways in which the neutral theory has had an impact, which has been accelerated in the age of high-throughput, high-resolution genomics.

Molecular basis of viral and microbial pathogenesis

SciTech Connect

Rott, R.; Goebel, W.

1988-01-01

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

Viral haemorrhagic fever and vascular alterations.

PubMed

Aleksandrowicz, P; Wolf, K; Falzarano, D; Feldmann, H; Seebach, J; Schnittler, H

2008-02-01

Pathogenesis of viral haemorrhagic fever (VHF) is closely associated with alterations of the vascular system. Among the virus families causing VHF, filoviruses (Marburg and Ebola) are the most fatal, and will be focused on here. After entering the body, Ebola primarily targets monocytes/macrophages and dendritic cells. Infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. Monocytes/macrophages, however, immediately activate after viral contact and release reasonable amounts of cytokines that target the vascular system, particularly the endothelial cells. Some underlying molecular mechanisms such as alteration of the vascular endothelial cadherin/catenin complex, tyrosine phosphorylation, expression of cell adhesion molecules, tissue factor and the effect of soluble viral proteins released from infected cells to the blood stream will be discussed.

[Viral retinitis following intravitreal triamcinolone injection].

PubMed

Zghal, I; Malek, I; Amel, C; Soumaya, O; Bouguila, H; Nacef, L

2013-09-01

Necrotizing viral retinitis is associated with infection by the Herpes family of viruses, especially herpes simplex virus (HSV), varicella zoster virus (VZV) and occasionally cytomegalovirus (CMV). When the diagnosis is suspected clinically, antiviral therapy must be instituted immediately. We report the case of a patient presenting with necrotizing viral retinitis 3 months following intravitreal injection of triamcinolone acetonide for diabetic macular edema. Fluorescein angiography demonstrated a superior temporal occlusive vasculitis. A diagnostic anterior chamber paracentesis was performed to obtain deoxyribo-nucleic acid (DNA) for a polymerase chain reaction (PCR) test for viral retinitis. PCR was positive for CMV. The patient was placed on intravenous ganciclovir. CMV retinitis is exceedingly rare in immunocompetent patients; however, it remains the most common cause of posterior uveitis in immunocompromised patients. The incidence of this entity remains unknown. Local immunosuppression, the dose and the frequency of injections may explain the occurrence of this severe retinitis. Copyright © 2013. Published by Elsevier Masson SAS.

Viral vector-based influenza vaccines.

PubMed

de Vries, Rory D; Rimmelzwaan, Guus F

2016-11-01

Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors.

Viral vector-based influenza vaccines

PubMed Central

de Vries, Rory D.; Rimmelzwaan, Guus F.

2016-01-01

ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

Hepatitis C Virus: Viral Quasispecies and Genotypes.

PubMed

Tsukiyama-Kohara, Kyoko; Kohara, Michinori

2017-12-22

Hepatitis C virus (HCV) mainly replicates in the cytoplasm, where it easily establishes persistent infection, resulting in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Due to its high rate of mutation, HCV forms viral quasispecies, categorized based on the highly variable regions in the envelope protein and nonstructural 5A protein. HCV possesses seven major genotypes, among which genotype 1 is the most prevalent globally. The distribution of HCV genotypes varies based on geography, and each genotype has a different sensitivity to interferon treatment. Recently-developed direct-acting antivirals (DAAs), which target viral proteases or polymerases, mediate drastically better antiviral effects than previous therapeutics. Although treatment with DAAs has led to the development of drug-resistant HCV mutants, the most recently approved DAAs show improved pan-genomic activity, with a higher barrier to viral resistance.

Hepatitis C Virus: Viral Quasispecies and Genotypes

PubMed Central

Tsukiyama-Kohara, Kyoko; Kohara, Michinori

2017-01-01

Hepatitis C virus (HCV) mainly replicates in the cytoplasm, where it easily establishes persistent infection, resulting in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Due to its high rate of mutation, HCV forms viral quasispecies, categorized based on the highly variable regions in the envelope protein and nonstructural 5A protein. HCV possesses seven major genotypes, among which genotype 1 is the most prevalent globally. The distribution of HCV genotypes varies based on geography, and each genotype has a different sensitivity to interferon treatment. Recently-developed direct-acting antivirals (DAAs), which target viral proteases or polymerases, mediate drastically better antiviral effects than previous therapeutics. Although treatment with DAAs has led to the development of drug-resistant HCV mutants, the most recently approved DAAs show improved pan-genomic activity, with a higher barrier to viral resistance. PMID:29271914

Shedding new light on viral photosynthesis.

PubMed

Puxty, Richard J; Millard, Andrew D; Evans, David J; Scanlan, David J

2015-10-01

Viruses infecting the environmentally important marine cyanobacteria Prochlorococcus and Synechococcus encode 'auxiliary metabolic genes' (AMGs) involved in the light and dark reactions of photosynthesis. Here, we discuss progress on the inventory of such AMGs in the ever-increasing number of viral genome sequences as well as in metagenomic datasets. We contextualise these gene acquisitions with reference to a hypothesised fitness gain to the phage. We also report new evidence with regard to the sequence and predicted structural properties of viral petE genes encoding the soluble electron carrier plastocyanin. Viral copies of PetE exhibit extensive modifications to the N-terminal signal peptide and possess several novel residues in a region responsible for interaction with redox partners. We also highlight potential knowledge gaps in this field and discuss future opportunities to discover novel phage-host interactions involved in the photosynthetic process.

IFITM Proteins Restrict Viral Membrane Hemifusion

PubMed Central

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

2013-01-01

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

The Fecal Viral Flora of Wild Rodents

PubMed Central

Phan, Tung G.; Kapusinszky, Beatrix; Wang, Chunlin; Rose, Robert K.; Lipton, Howard L.; Delwart, Eric L.

2011-01-01

The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat) collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in mammals. PMID:21909269

Latent Herpes Viral Reactivation in Astronauts

NASA Technical Reports Server (NTRS)

Pierson, D. L.; Mehta, S. K.; Stowe, R.

2008-01-01

Latent viruses are ubiquitous and reactivate during stressful periods with and without symptoms. Latent herpes virus reactivation is used as a tool to predict changes in the immune status in astronauts and to evaluate associated health risks. Methods: Viral DNA was detected by real time polymerase chain reaction in saliva and urine from astronauts before, during and after short and long-duration space flights. Results and Discussion: EpsteinBarr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivated, and viral DNA was shed in saliva (EBV and VZV) or urine (CMV). EBV levels in saliva during flight were 10fold higher than baseline levels. Elevations in EBV specific CD8+ T-cells, viral antibody titers, and specific cytokines were consistent with viral reactivation. Intracellular levels of cytokines were reduced in EBVspecific Tcells. CMV, rarely present in urine of healthy individuals, was shed in urine of 27% of astronauts during all phases of spaceflight. VZV, not found in saliva of asymptomatic individuals, was found in saliva of 50% of astronauts during spaceflight and 35 days after flight. VZV recovered from astronaut saliva was found to be live, infectious virus. DNA sequencing demonstrated that the VZV recovered from astronauts was from the common European strain of VZV. Elevation of stress hormones accompanied viral reactivation indicating involvement of the hypothalmic-pituitary-adrenal and sympathetic adrenal-medullary axes in the mechanism of viral reactivation in astronauts. A study of 53 shingles patients found that all shingles patients shed VZV DNA in their saliva and the VZV levels correlated with the severity of the disease. Lower VZV levels in shingles patients were similar to those observed in astronauts. We proposed a rapid, simple, and cost-effective assay to detect VZV in saliva of patients with suspected shingles. Early detection of VZV infection allows early medical intervention.

The Art of Engineering Viral Nanoparticles

PubMed Central

Pokorski, Jonathan K.; Steinmetz, Nicole F.

2011-01-01

Viral nanotechnology is an emerging and highly interdisciplinary field in which viral nanoparticles (VNPs) are applied in diverse areas such as electronics, energy and next-generation medical devices. VNPs have been developed as candidates for novel materials, and are often described as “programmable” because they can be modified and functionalized using a number of techniques. In this review, we discuss the concepts and methods that allow VNPs to be engineered, including (i) bioconjugation chemistries, (ii) encapsulation techniques, (iii) mineralization strategies, and (iv) film and hydrogel development. With all these techniques in hand, the potential applications of VNPs are limited only by the imagination. PMID:21047140

Temporary divergence paralysis in viral meningitis.

PubMed

Bakker, Stef L M; Gan, Ivan M

2008-06-01

A 43-year-old woman who reported diplopia and headache was found to have comitant esotropia at distance fixation and normal alignment at reading distance (divergence paralysis). Eye movement, including abduction, was normal as was the rest of the neurologic examination. Brain MRI was normal. Lumbar puncture showed an elevated opening pressure and a cerebrospinal fluid formula consistent with viral meningitis. The patient was treated with intravenous fluids and analgesics and with a temporary prism to alleviate diplopia. Within 3 weeks, she had fully recovered. This is the first report of divergence palsy in viral meningitis.

High viral abundance as a consequence of low viral decay in the Baltic Sea redoxcline

PubMed Central

Scharnreitner, Lisa; Jürgens, Klaus; Labrenz, Matthias; Herndl, Gerhard J.; Winter, Christian

2017-01-01

Throughout the Baltic Sea redoxcline, virus production and the frequency of lytically-infected prokaryotic cells were estimated from parallel incubations of undiluted seawater and seawater that contained prokaryotes with substantially reduced numbers of viruses (virus dilution approach), effectively preventing viral reinfection during the incubation period. Undiluted seawater incubations resulted in much higher estimates of virus production (6–35×104 mL-1 h-1) and the frequency of infected cells (5–84%) than the virus dilution approach (virus production: 1–3×104 mL-1 h-1; frequency of infected cells: 1–11%). Viral production and the frequency of infected cells from both approaches, however, cannot be directly compared, as data obtained from undiluted incubations were biased by viral reinfection and other uncontrollable processes during the incubation period. High in situ viral abundance (1–2×107 mL-1) together with low virus production rates based on the virus dilution approach resulted in some of the longest viral turnover times (24–84 d) ever reported for the epipelagial. Throughout a wide range of environmental conditions, viral turnover time and burst size were negatively correlated. Given that viral decay estimated in ultra-filtered water was below the detection limit and the burst size was low (1–17), we conclude that prokaryotic viruses in the Baltic Sea redoxcline are investing most of their resources into stress defense (strong capsids) rather than proliferation (high burst size). In summary, the Baltic Sea redoxcline constitutes an environment where low virus production is found in combination with low viral decay, resulting in high viral abundance. PMID:28594863

Optimal Cytoplasmic Transport in Viral Infections

PubMed Central

D'Orsogna, Maria R.; Chou, Tom

2009-01-01

For many viruses, the ability to infect eukaryotic cells depends on their transport through the cytoplasm and across the nuclear membrane of the host cell. During this journey, viral contents are biochemically processed into complexes capable of both nuclear penetration and genomic integration. We develop a stochastic model of viral entry that incorporates all relevant aspects of transport, including convection along microtubules, biochemical conversion, degradation, and nuclear entry. Analysis of the nuclear infection probabilities in terms of the transport velocity, degradation, and biochemical conversion rates shows how certain values of key parameters can maximize the nuclear entry probability of the viral material. The existence of such “optimal” infection scenarios depends on the details of the biochemical conversion process and implies potentially counterintuitive effects in viral infection, suggesting new avenues for antiviral treatment. Such optimal parameter values provide a plausible transport-based explanation of the action of restriction factors and of experimentally observed optimal capsid stability. Finally, we propose a new interpretation of how genetic mutations unrelated to the mechanism of drug action may nonetheless confer novel types of overall drug resistance. PMID:20046829

Neutron diffraction studies of viral fusion peptides

NASA Astrophysics Data System (ADS)

Bradshaw, Jeremy P.; J. M. Darkes, Malcolm; Katsaras, John; Epand, Richard M.

2000-03-01

Membrane fusion plays a vital role in a large and diverse number of essential biological processes. Despite this fact, the precise molecular events that occur during fusion are still not known. We are currently engaged on a study of membrane fusion as mediated by viral fusion peptides. These peptides are the N-terminal regions of certain viral envelope proteins that mediate the process of fusion between the viral envelope and the membranes of the host cell during the infection process. As part of this study, we have carried out neutron diffraction measurements at the ILL, BeNSC and Chalk River, on a range of viral fusion peptides. The peptides, from simian immunodeficiency virus (SIV), influenza A and feline leukaemia virus (FeLV), were incorporated into stacked phospholipid bilayers. Some of the peptides had been specifically deuterated at key amino acids. Lamellar diffraction data were collected and analysed to yield information on the peptide conformation, location and orientation relative to the bilayer.

Diagnosis and treatment of viral encephalitis

PubMed Central

Chaudhuri, A; Kennedy, P

2002-01-01

Acute encephalitis constitutes a medical emergency. In most cases, the presence of focal neurological signs and focal seizures will distinguish encephalitis from encephalopathy. Acute disseminated encephalomyelitis is a non-infective inflammatory encephalitis that may require to be treated with steroids. Acute infective encephalitis is usually viral. Herpes simplex encephalitis (HSE) is the commonest sporadic acute viral encephalitis in the Western world. Magnetic resonance imaging of brain is the investigation of choice in HSE and the diagnosis may be confirmed by the polymerase chain reaction test for the virus in the cerebrospinal fluid. In this article, we review the diagnosis, investigations, and management of acute encephalitis. With few exceptions (for example, aciclovir for HSE), no specific therapy is available for most forms of viral encephalitis. Mortality and morbidity may be high and long term sequelae are known among survivors. The emergence of unusual forms of zoonotic encephalitis has posed an important public health problem. Vaccination and vector control measures are useful preventive strategies in certain arboviral and zoonotic encephalitis. However, we need better antiviral therapy to meet the challenge of acute viral encephalitis more effectively. PMID:12415078

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.

Shape transformation of viral capsids and HIV

NASA Astrophysics Data System (ADS)

Nguyen, Toan

2005-03-01

We present a continuum description of the shape transformation of viral capsids. The cone-like HIV virus is shown to be an thermodynamic stable shape, intermediate between icosahedral and sphero-cylinder capsid shapes. A generalized Caspar-Klug classification is introduced to describe spherical, conical and cylinderical shapes of virus.

History and Global Burden of Viral Hepatitis.

PubMed

Blum, Hubert E

Between 1963 and 1989, 5 hepatotropic viruses have been discovered that are the major causes of viral hepatitides worldwide: hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus and hepatitis E virus. Their epidemiology and pathogenesis have been studied in great detail. Furthermore, the structure and genetic organization of their DNA or RNA genome including the viral life cycle have been elucidated and have been successfully translated into important clinical applications, such as the specific diagnosis, therapy and prevention of the associated liver diseases, including liver cirrhosis and hepatocellular carcinoma (HCC). The prevalence of acute and chronic viral hepatitis A-E shows distinct geographic differences. The global burden of disease (prevalence, incidence, death, disability-adjusted life years) has been analyzed in seminal studies that show that the worldwide prevalence of hepatitis A-E has significantly decreased between 1990 and 2013. During the same time, the incidence of HBV-related liver cirrhosis and HCC, respectively, also decreased or increased slightly, the incidence of the HCV-related liver cirrhosis remained stable and the incidence of HCV-related HCC showed a major increase. During the coming years, we expect to improve our ability to prevent and effectively treat viral hepatitis A-E, resulting in the control of these global infections and the elimination of their associated morbidities and mortalities. © 2016 S. Karger AG, Basel.

Chromatin organization regulates viral egress dynamics

SciTech Connect

Aho, Vesa; Myllys, Markko; Ruokolainen, Visa

Various types of DNA viruses are known to elicit the formation of a large nuclear viral replication compartment and marginalization of the cell chromatin. We used three-dimensional soft x-ray tomography, confocal and electron microscopy, combined with numerical modelling of capsid diffusion to analyse the molecular organization of chromatin in herpes simplex virus 1 infection and its effect on the transport of progeny viral capsids to the nuclear envelope. Our data showed that the formation of the viral replication compartment at late infection resulted in the enrichment of heterochromatin in the nuclear periphery accompanied by the compaction of chromatin. Random walkmore » modelling of herpes simplex virus 1–sized particles in a three-dimensional soft x-ray tomography reconstruction of an infected cell nucleus demonstrated that the peripheral, compacted chromatin restricts viral capsid diffusion, but due to interchromatin channels capsids are able to reach the nuclear envelope, the site of their nuclear egress.« less

Chromatin organization regulates viral egress dynamics

DOE PAGES

Aho, Vesa; Myllys, Markko; Ruokolainen, Visa; ...

2017-06-16

Various types of DNA viruses are known to elicit the formation of a large nuclear viral replication compartment and marginalization of the cell chromatin. We used three-dimensional soft x-ray tomography, confocal and electron microscopy, combined with numerical modelling of capsid diffusion to analyse the molecular organization of chromatin in herpes simplex virus 1 infection and its effect on the transport of progeny viral capsids to the nuclear envelope. Our data showed that the formation of the viral replication compartment at late infection resulted in the enrichment of heterochromatin in the nuclear periphery accompanied by the compaction of chromatin. Random walkmore » modelling of herpes simplex virus 1–sized particles in a three-dimensional soft x-ray tomography reconstruction of an infected cell nucleus demonstrated that the peripheral, compacted chromatin restricts viral capsid diffusion, but due to interchromatin channels capsids are able to reach the nuclear envelope, the site of their nuclear egress.« less

Viral skin diseases of the rabbit.

PubMed

Meredith, Anna L

2013-09-01

This article describes the viral skin diseases affecting the domestic rabbit, the most important being myxomatosis. Transmission and pathogenesis, clinical signs, diagnosis, treatment, and control are described and the article will be of interest to veterinary practitioners who treat rabbits. Shope fibroma virus, Shope papilloma virus, and rabbitpox are also discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

The Etiology and Pathogenesis of Viral Gastroenteritis.

DTIC Science & Technology

1984-07-31

with subsequent seroconversion or susceptibility to illness in a naturally occurring outbreak of Norwalk virus gastroenteritis among American teen ... anorexia , myalgia and malaise. It can be severe, indeed fatal, in the elderly, infant, debilitated or malnourished pa- tient. Viral gastroenteritis...community-wide outbreaks of gastroenteritis among older children and adults. The older medical literature gives a variety of descriptive labels to this

Acute Viral Hepatitis in Pediatric Age Groups.

PubMed

Kc, Sudhamshu; Sharma, Dilip; Poudyal, Nandu; Basnet, Bhupendra Kumar

2014-01-01

Our clinical experience showed that there has been no decrease in pediatric cases of acute viral hepatitis in Kathmandu. The objective of the study was to analyze the etiology, clinical features, laboratory parameters, sonological findings and other to determine the probable prognostic factors of Acute Viral Hepatitis in pediatric population. Consecutive patients of suspected Acute Viral Hepatitis, below the age of 15 years, attending the liver clinic between January 2006 and December 2010 were studied. After clinical examination they were subjected to blood tests and ultrasound examination of abdomen. The patients were divided in 3 age groups; 0-5, 5-10 and 5-15 years. Clinical features, laboratory parameters, ultrasound findings were compared in three age groups. Etiology of Acute Viral Hepatitis was Hepatitis A virus 266 (85%), Hepatitis E virus in 24 (8%), Hepatitis B virus in 15 (5%). In 7(2%) patients etiology was unknown. Three patients went to acute liver failure but improved with conservative treatment. There was no statistical difference in most of the parameters studied in different age groups. Ascites was more common in 5-10 years age group. Patients with secondary bacterial infection, ultrasound evidence of prominent biliary tree and ascites were associated with increased duration of illness. Patients with history of herbal medications had prolonged cholestasis. Hepatitis A is most common cause of Acute Viral Hepatitis in pediatric population. Improper use of herbal medications, secondary bacterial infection and faulty dietary intake was associated with prolonged illness. Patients with prominent biliary radicals should be treated with antibiotics even with normal blood counts for earlier recovery.

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

USGS Publications Warehouse

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

2010-01-01

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

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

USGS Publications Warehouse

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

2010-01-01

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

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

MedlinePlus

... Search The CDC Health Disparities in HIV/AIDS, Viral Hepatitis, STDs, and TB Note: Javascript is disabled or ... Other Pacific Islanders MMWR Publications HIV and AIDS Viral Hepatitis STDs Tuberculosis Training and Networking Resources Call for ...

Comparative Viral Metagenomics of Environmental Samples from Korea

PubMed Central

Kim, Min-Soo; Whon, Tae Woong

2013-01-01

The introduction of metagenomics into the field of virology has facilitated the exploration of viral communities in various natural habitats. Understanding the viral ecology of a variety of sample types throughout the biosphere is important per se, but it also has potential applications in clinical and diagnostic virology. However, the procedures used by viral metagenomics may produce technical errors, such as amplification bias, while public viral databases are very limited, which may hamper the determination of the viral diversity in samples. This review considers the current state of viral metagenomics, based on examples from Korean viral metagenomic studies-i.e., rice paddy soil, fermented foods, human gut, seawater, and the near-surface atmosphere. Viral metagenomics has become widespread due to various methodological developments, and much attention has been focused on studies that consider the intrinsic role of viruses that interact with their hosts. PMID:24124407

Viral Perturbations of Host Networks Reflect Disease Etiology

PubMed Central

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

2012-01-01

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

Adenovirus-Mediated Gene Therapy Against Viral Biothreat Agents

DTIC Science & Technology

2016-04-12

economy. Vaccine development is an important strategy to thwart the threat of these viral biothreat agents. There is an urgent need to improve...Alberta, Tl A 8K6. Canada E-mail: josh. wu@drdc-rddc.gc.ca .• 78 JoshQ.H. Wu existing vaccines against these agents and to develop new ones. Gene...of vaccines against viral biothreat agents. Genes encoding protective antigens of viral biothreat agents can be carried by these viral vectors and

Factors affecting the stability of viral vaccines.

PubMed

Peetermans, J

1996-01-01

The stability of viral vaccines is determined by the rate of loss of "integrity" of the viral antigen during storage. For live vaccines, such as measles, mumps, rubella, canine distemper, stability is equivalent to the preservation of the infectious titres. For inactivated and subunit vaccines, the preservation of the antigenic structure and the correct steric presentation of the relevant epitopes are the parameters which determine their stability. In general, the following factors may have a negative effect on stability: temperature, pH outside the physiological limits, organic solvents, repeated freezing and thawing, some antiseptics and inactivating agents, and light. However their negative effect is in most cases specific for the individual viruses. Approaches to stabilisation of most vaccines are based on the elimination or neutralisation of the negative factors. Practical examples for the most relevant existing vaccines are described.

Immunological features underlying viral hemorrhagic fevers.

PubMed

Messaoudi, Ilhem; Basler, Christopher F

2015-10-01

Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF. Copyright © 2015 Elsevier Ltd. All rights reserved.

Broad-spectrum antivirals against viral fusion

PubMed Central

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

2015-01-01

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

[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.

Multiplexing Short Primers for Viral Family PCR

SciTech Connect

Gardner, S N; Hiddessen, A L; Hara, C A

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

Lytic to temperate switching of viral communities

NASA Astrophysics Data System (ADS)

Knowles, B.; Silveira, C. B.; Bailey, B. A.; Barott, K.; Cantu, V. A.; Cobián-Güemes, A. G.; Coutinho, F. H.; Dinsdale, E. A.; Felts, B.; Furby, K. A.; George, E. E.; Green, K. T.; Gregoracci, G. B.; Haas, A. F.; Haggerty, J. M.; Hester, E. R.; Hisakawa, N.; Kelly, L. W.; Lim, Y. W.; Little, M.; Luque, A.; McDole-Somera, T.; McNair, K.; de Oliveira, L. S.; Quistad, S. D.; Robinett, N. L.; Sala, E.; Salamon, P.; Sanchez, S. E.; Sandin, S.; Silva, G. G. Z.; Smith, J.; Sullivan, C.; Thompson, C.; Vermeij, M. J. A.; Youle, M.; Young, C.; Zgliczynski, B.; Brainard, R.; Edwards, R. A.; Nulton, J.; Thompson, F.; Rohwer, F.

2016-03-01

Microbial viruses can control host abundances via density-dependent lytic predator-prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus ‘more microbes, fewer viruses’.

Viral activity in two contrasting lake ecosystems.

PubMed

Bettarel, Yvan; Sime-Ngando, Télesphore; Amblard, Christian; Dolan, John

2004-05-01

For aquatic systems, especially freshwaters, there is little data on the long-term (i.e., >6-month period) and depth-related variability of viruses. In this study, we examined virus-induced mortality of heterotrophic bacteria over a 10-month period and throughout the water column in two lakes of the French Massif Central, the oligomesotrophic Lake Pavin and the eutrophic Lake Aydat. Concurrently, we estimated nonviral mortality through heterotrophic nanoflagellate and ciliate bacterivory. Overall, viral infection parameters were much less variable than bacterial production. We found that the frequency of visibly infected cells (FVIC), estimated using transmission electron microscopy, peaked in both lakes at the end of spring (May to June) and in early autumn (September to October). FVIC values were significantly higher in Lake Pavin (mean [M] = 1.6%) than in Lake Aydat (M = 1.1%), whereas the opposite trend was observed for burst sizes, which averaged 25.7 and 30.2 virus particles bacterium(-1), respectively. We detected no significant depth-related differences in FVIC or burst size. We found that in both lakes the removal of bacterial production by flagellate grazing (M(Pavin) = 37.7%, M(Aydat) = 18.5%) was nearly always more than the production removed by viral lysis (M(Pavin) = 16.2%, M(Aydat) = 19%) or ciliate grazing (M(Pavin) = 2.7%, M(Aydat) = 8.8%). However, at specific times and locations, viral lysis prevailed over protistan grazing, for example, in the anoxic hypolimnion of Lake Aydat. In addition, viral mortality represented a relatively constant mortality source in a bacterial community showing large variations in growth rate and subject to large variations in loss rates from grazers. Finally, although viruses did not represent the main agent of bacterial mortality, our data seem to show that their relative importance was higher in the less productive system.

Vaginal microbiota and viral sexually transmitted diseases.

PubMed

Nardis, C; Mosca, L; Mastromarino, P

2013-01-01

Healthy vaginal microbiota is an important biological barrier to pathogenic microorganisms. When this predominantly Lactobacillus community is disrupted, decreased in abundance and replaced by different anaerobes, bacterial vaginosis (BV) may occur. BV is associated with prevalence and incidence of several sexually transmitted infections. This review provides background on BV, discusses the epidemiologic data to support a role of altered vaginal microbiota for acquisition of sexually transmitted diseases and analyzes mechanisms by which lactobacilli could counteract sexually transmitted viral infections.

Undiagnosed Acute Viral Febrile Illnesses, Sierra Leone

DTIC Science & Technology

2014-07-01

Sierra Leone in West Africa is in a Lassa fever – hyperendemic region that also includes Guinea and Li- beria. Each year...suspected Lassa fever cases result in submission of ≈500–700 samples to the Kenema Govern- ment Hospital Lassa Diagnostic Laboratory in eastern Si- erra...patients have acute diseases of unknown origin. To investigate what other ar- thropod-borne and hemorrhagic fever viral diseases might cause serious

MRI-Guided Delivery of Viral Vectors.

PubMed

Salegio, Ernesto A; Bringas, John; Bankiewicz, Krystof S

2016-01-01

Gene therapy has emerged as a potential avenue of treatment for many neurological disorders. Technological advances in imaging techniques allow for the monitoring of real-time infusions into the brain of rodents, nonhuman primates, and humans. Here, we discuss the use of magnetic resonance imaging (MRI) as a tool in the delivery of adeno-associated viral (AAV) particles into brain of nonhuman primates.

Viral Immunotherapy to Eradicate Subclinical Brain Metastases

DTIC Science & Technology

2014-05-01

host innate and adaptive immune cells in metastases and normal tissues i. Months 6-21 ii. Basse Brain tissue with D2F2/E2 tumors from animals...and viral antigens which could activate memory T- cells in the draining lymphoid organs. Time course studies showed that virus infection produced a 2.6... lymphoid tissues. III. ACTIVATED NK CELLS LOCALIZE EFFICIENTLY AT TUMOR SITES The densities of NK cells found in well-established tumors in most

Maintaining a low viral load with Nevirapine?

PubMed

1998-12-01

A study called INCAS enrolled 150 treatment-naive subjects. Half of the subjects had CD4+ counts of 370 and a viral load of about 32,000 copies. Subjects were divided into groups that received AZT and Nevirapine, ddI and Nevirapine, or AZT with ddI and Nevirapine. Researchers monitored the subjects for 1 year. Results indicated that subjects who received the triple drug combination had fewer complications and infections.

Global issues related to enteric viral infections.

PubMed

Desselberger, Ulrich

2014-01-01

Acute viral gastroenteritis is a major health issue worldwide and is associated with high annual mortality, particularly in children of developing countries. Rotaviruses, caliciviruses and astroviruses are the main causes. Accurate diagnoses are possible by recently developed molecular techniques. In many setups, zoonotic transmission is an important epidemiological factor. Treatment consists of rehydration and is otherwise symptomatic. The worldwide introduction of universal rotavirus vaccination of infants has significantly reduced rotavirus disease and mortality.

Viral antibody dynamics in a chiropteran host

PubMed Central

Baker, Kate S; Suu-Ire, Richard; Barr, Jennifer; Hayman, David T S; Broder, Christopher C; Horton, Daniel L; Durrant, Christopher; Murcia, Pablo R; Cunningham, Andrew A; Wood, James L N

2014-01-01

Bats host many viruses that are significant for human and domestic animal health, but the dynamics of these infections in their natural reservoir hosts remain poorly elucidated. In these, and other, systems, there is evidence that seasonal life-cycle events drive infection dynamics, directly impacting the risk of exposure to spillover hosts. Understanding these dynamics improves our ability to predict zoonotic spillover from the reservoir hosts. To this end, we followed henipavirus antibody levels of >100 individual E. helvum in a closed, captive, breeding population over a 30-month period, using a powerful novel antibody quantitation method. We demonstrate the presence of maternal antibodies in this system and accurately determine their longevity. We also present evidence of population-level persistence of viral infection and demonstrate periods of increased horizontal virus transmission associated with the pregnancy/lactation period. The novel findings of infection persistence and the effect of pregnancy on viral transmission, as well as an accurate quantitation of chiropteran maternal antiviral antibody half-life, provide fundamental baseline data for the continued study of viral infections in these important reservoir hosts. PMID:24111634

TRIM proteins: another class of viral victims.

PubMed

Munir, Muhammad

2010-04-20

TRIM (tripartite motif) proteins are a family of RING (really interesting new gene) domain-containing proteins comprising more than 70 human members, with new members still being described. In addition to their involvement in cell proliferation, differentiation, development, morphogenesis, and apoptosis, roles in immune signaling and antiviral functions are emerging. In response to viral infection, TRIM25 ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I), and this modification is essential for RIG-I to interact with its downstream partner mitochondrial antiviral signaling (MAVS). TRIM25 activity thus leads to activation of the RIG-I signaling pathway, which results in type I interferon production to limit viral replication. Recently, it has been demonstrated that influenza A viruses target TRIM25 and disable its antiviral function, thereby suppressing the host interferon response. This Journal Club article highlights the emerging roles of TRIM proteins in antiviral defense mechanisms and an immune evasion strategy in which influenza viruses target a member of the TRIM family.

Metabolic reprogramming: a hallmark of viral oncogenesis.

PubMed

Lévy, P; Bartosch, B

2016-08-11

More than 1 in 10 cases of cancer in the world are due to chronic viral infections. Viruses induce oncogenesis by targeting the same pathways known to be responsible for neoplasia in tumor cells, such as control of cell cycle progression, cell migration, proliferation and evasion from cell death and the host's immune defense. In addition, metabolic reprogramming has been identified over a century ago as a requirement for growth of transformed cells. Renewed interest in this topic has emerged recently with the discovery that basically all metabolic changes in tumor cells are finely orchestrated by oncogenes and tumor suppressors. Indeed, cancer cells activate biosynthetic pathways in order to provide them with sufficient levels of energy and building blocks to proliferate. Interestingly, viruses introduce into their host cells similar metabolic adaptations, and importantly, it seems that they depend on these changes for their persistence and amplification. The central carbon metabolism, for example, is not only frequently altered in tumor cells but also modulated by human papillomavirus, hepatitis B and C viruses, Epstein-Barr virus and Kaposi's Sarcoma-associated virus. Moreover, adenoviruses (Ad) and human cytomegalovirus, which are not directly oncogenic but present oncomodulatory properties, also divert cellular metabolism in a tumor cell-like mnner. Thus, metabolic reprogramming appears to be a hallmark of viral infection and provides an interesting therapeutic target, in particular, for oncogenic viruses. Therapeutic targeting of metabolic pathways may not only allow to eliminate or control the viral infection but also to prevent virus-induced carcinogenesis.

Biological species in the viral world.

PubMed

Bobay, Louis-Marie; Ochman, Howard

2018-06-05

Due to their dependence on cellular organisms for metabolism and replication, viruses are typically named and assigned to species according to their genome structure and the original host that they infect. But because viruses often infect multiple hosts and the numbers of distinct lineages within a host can be vast, their delineation into species is often dictated by arbitrary sequence thresholds, which are highly inconsistent across lineages. Here we apply an approach to determine the boundaries of viral species based on the detection of gene flow within populations, thereby defining viral species according to the biological species concept (BSC). Despite the potential for gene transfer between highly divergent genomes, viruses, like the cellular organisms they infect, assort into reproductively isolated groups and can be organized into biological species. This approach revealed that BSC-defined viral species are often congruent with the taxonomic partitioning based on shared gene contents and host tropism, and that bacteriophages can similarly be classified in biological species. These results open the possibility to use a single, universal definition of species that is applicable across cellular and acellular lifeforms.

Molecular Determinants of Enterovirus 71 Viral Entry

PubMed Central

Chen, Pan; Song, Zilin; Qi, Yonghe; Feng, Xiaofeng; Xu, Naiqing; Sun, Yinyan; Wu, Xing; Yao, Xin; Mao, Qunyin; Li, Xiuling; Dong, Wenjuan; Wan, Xiaobo; Huang, Niu; Shen, Xinliang; Liang, Zhenglun; Li, Wenhui

2012-01-01

Enterovirus 71 (EV71) is one of the major pathogens that cause hand, foot, and mouth disease outbreaks in young children in the Asia-Pacific region in recent years. Human scavenger receptor class B 2 (SCARB2) is the main cellular receptor for EV71 on target cells. The requirements of the EV71-SCARB2 interaction have not been fully characterized, and it has not been determined whether SCARB2 serves as an uncoating receptor for EV71. Here we compared the efficiency of the receptor from different species including human, horseshoe bat, mouse, and hamster and demonstrated that the residues between 144 and 151 are critical for SCARB2 binding to viral capsid protein VP1 of EV71 and seven residues from the human receptor could convert murine SCARB2, an otherwise inefficient receptor, to an efficient receptor for EV71 viral infection. We also identified that EV71 binds to SCARB2 via a canyon of VP1 around residue Gln-172. Soluble SCARB2 could convert the EV71 virions from 160 S to 135 S particles, indicating that SCARB2 is an uncoating receptor of the virus. The uncoating efficiency of SCARB2 significantly increased in an acidic environment (pH 5.6). These studies elucidated the viral capsid and receptor determinants of enterovirus 71 infection and revealed a possible target for antiviral interventions. PMID:22219187

Viral vectors for therapy of neurologic diseases

PubMed Central

Choudhury, Sourav R.; Hudry, Eloise; Maguire, Casey A.; Sena-Esteves, Miguel; Breakefield, Xandra O.; Grandi, Paola

2018-01-01

Neurological disorders – disorders of the brain, spine and associated nerves – are a leading contributor to global disease burden with a shockingly large associated economic cost. Various treatment approaches – pharmaceutical medication, device-based therapy, physiotherapy, surgical intervention, among others – have been explored to alleviate the resulting extent of human suffering. In recent years, gene therapy using viral vectors – encoding a therapeutic gene or inhibitory RNA into a “gutted” viral capsid and supplying it to the nervous system – has emerged as a clinically viable option for therapy of brain disorders. In this Review, we provide an overview of the current state and advances in the field of viral vector-mediated gene therapy for neurological disorders. Vector tools and delivery methods have evolved considerably over recent years, with the goal of providing greater and safer genetic access to the central nervous system. Better etiological understanding of brain disorders has concurrently led to identification of improved therapeutic targets. We focus on the vector technology, as well as preclinical and clinical progress made thus far for brain cancer and various neurodegenerative and neurometabolic disorders, and point out the challenges and limitations that accompany this new medical modality. Finally, we explore the directions that neurological gene therapy is likely to evolve towards in the future. PMID:26905292

A Viral Pilot for HCMV Navigation?

PubMed

Adler, Barbara

2015-07-15

gH/gL virion envelope glycoprotein complexes of herpesviruses serve as entry complexes and mediate viral cell tropism. By binding additional viral proteins, gH/gL forms multimeric complexes which bind to specific host cell receptors. Both Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) express alternative multimeric gH/gL complexes. Relative amounts of these alternative complexes in the viral envelope determine which host cells are preferentially infected. Host cells of EBV can modulate the gH/gL complex complement of progeny viruses by cell type-dependent degradation of one of the associating proteins. Host cells of HCMV modulate the tropism of their virus progenies by releasing or not releasing virus populations with a specific gH/gL complex complement out of a heterogeneous pool of virions. The group of Jeremy Kamil has recently shown that the HCMV ER-resident protein UL148 controls integration of one of the HCMV gH/gL complexes into virions and thus creates a pool of virions which can be routed by different host cells. This first mechanistic insight into regulation of the gH/gL complex complement of HCMV progenies presents UL148 as a pilot candidate for HCMV navigation in its infected host.

A Viral Pilot for HCMV Navigation?

PubMed Central

Adler, Barbara

2015-01-01

gH/gL virion envelope glycoprotein complexes of herpesviruses serve as entry complexes and mediate viral cell tropism. By binding additional viral proteins, gH/gL forms multimeric complexes which bind to specific host cell receptors. Both Epstein–Barr virus (EBV) and human cytomegalovirus (HCMV) express alternative multimeric gH/gL complexes. Relative amounts of these alternative complexes in the viral envelope determine which host cells are preferentially infected. Host cells of EBV can modulate the gH/gL complex complement of progeny viruses by cell type-dependent degradation of one of the associating proteins. Host cells of HCMV modulate the tropism of their virus progenies by releasing or not releasing virus populations with a specific gH/gL complex complement out of a heterogeneous pool of virions. The group of Jeremy Kamil has recently shown that the HCMV ER-resident protein UL148 controls integration of one of the HCMV gH/gL complexes into virions and thus creates a pool of virions which can be routed by different host cells. This first mechanistic insight into regulation of the gH/gL complex complement of HCMV progenies presents UL148 as a pilot candidate for HCMV navigation in its infected host. PMID:26184287

Role of viral coinfections in asthma development.

PubMed

Garcia-Garcia, Maria Luz; Calvo, Cristina; Ruiz, Sara; Pozo, Francisco; Del Pozo, Victoria; Remedios, Laura; Exposito, Nadia; Tellez, Ana; Casas, Inmaculada

2017-01-01

Viral respiratory infections, especially acute bronchiolitis, play a key role in the development of asthma in childhood. However, most studies have focused on respiratory syncytial virus or rhinovirus infections and none of them have compared the long-term evolution of single versus double or multiple viral infections. Our aim was to compare the frequency of asthma development at 6-8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection. A cross-sectional study was performed in 244 children currently aged 6-8 years, previously admitted due to bronchiolitis between September 2008 and December 2011. A structured clinical interview and the ISAAC questionnaire for asthma symptoms for 6-7-year-old children, were answered by parents by telephone. Specimens of nasopharyngeal aspirate for virological study (polymerase chain reaction) and clinical data were prospectively taken during admission for bronchiolitis. Median current age at follow-up was 7.3 years (IQR: 6.7-8.1). The rate of recurrent wheezing was 82.7% in the coinfection group and 69.7% in the single-infection group, p = 0.06. The number of wheezing-related admissions was twice as high in coinfections than in single infections, p = 0.004. Regarding the ISAAC questionnaire, 30.8% of coinfections versus 15% of single infections, p = 0.01, presented "wheezing in the last 12 months", data that strongly correlate with current prevalence of asthma. "Dry cough at night" was also reported more frequently in coinfections than in single infections, p = 0.02. The strongest independent risk factors for asthma at 6-8 years of age were: age > 9 months at admission for bronchiolitis (OR: 3.484; CI95%: 1.459-8.317, p:0.005), allergic rhinitis (OR: 5.910; 95%CI: 2.622-13.318, p<0.001), and viral coinfection-bronchiolitis (OR: 3.374; CI95%: 1.542-7.386, p:0.01). Asthma at 6-8 years is more frequent and severe in those children previously hospitalized with viral

Viral Vectors for in Vivo Gene Transfer

NASA Astrophysics Data System (ADS)

Thévenot, E.; Dufour, N.; Déglon, N.

The transfer of DNA into the nucleus of a eukaryotic cell (gene transfer) is a central theme of modern biology. The transfer is said to be somatic when it refers to non-germline organs of a developed individual, and germline when it concerns gametes or the fertilised egg of an animal, with the aim of transmitting the relevant genetic modification to its descendents [1]. The efficient introduction of genetic material into a somatic or germline cell and the control of its expression over time have led to major advances in understanding how genes work in vivo, i.e., in living organisms (functional genomics), but also to the development of innovative therapeutic methods (gene therapy). The efficiency of gene transfer is conditioned by the vehicle used, called the vector. Desirable features for a vector are as follows: Easy to produce high titer stocks of the vector in a reproducible way. Absence of toxicity related to transduction (transfer of genetic material into the target cell, and its expression there) and no immune reaction of the organism against the vector and/or therapeutic protein. Stability in the expression of the relevant gene over time, and the possibility of regulation, e.g., to control expression of the therapeutic protein on the physiological level, or to end expression at the end of treatment. Transduction of quiescent cells should be as efficient as transduction of dividing cells. Vectors currently used fall into two categories: non-viral and viral vectors. In non-viral vectors, the DNA is complexed with polymers, lipids, or cationic detergents (described in Chap. 3). These vectors have a low risk of toxicity and immune reaction. However, they are less efficient in vivo than viral vectors when it comes to the number of cells transduced and long-term transgene expression. (Naked DNA transfer or electroporation is rather inefficient in the organism. This type of gene transfer will not be discussed here, and the interested reader is referred to the

Advances in Non-Viral DNA Vectors for Gene Therapy

PubMed Central

Hardee, Cinnamon L.; Arévalo-Soliz, Lirio Milenka; Hornstein, Benjamin D.; Zechiedrich, Lynn

2017-01-01

Uses of viral vectors have thus far eclipsed uses of non-viral vectors for gene therapy delivery in the clinic. Viral vectors, however, have certain issues involving genome integration, the inability to be delivered repeatedly, and possible host rejection. Fortunately, development of non-viral DNA vectors has progressed steadily, especially in plasmid vector length reduction, now allowing these tools to fill in specifically where viral or other non-viral vectors may not be the best options. In this review, we examine the improvements made to non-viral DNA gene therapy vectors, highlight opportunities for their further development, address therapeutic needs for which their use is the logical choice, and discuss their future expansion into the clinic. PMID:28208635

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

PubMed Central

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

2013-01-01

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

Underreporting of viral encephalitis and viral meningitis, Ireland, 2005-2008.

PubMed

Kelly, Tara A; O'Lorcain, Piaras; Moran, Joanne; Garvey, Patricia; McKeown, Paul; Connell, Jeff; Cotter, Suzanne

2013-01-01

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

KSHV encoded ORF59 modulates histone arginine methylation of the viral genome to promote viral reactivation

PubMed Central

McDowell-Sargent, Maria; Uppal, Timsy; Purushothaman, Pravinkumar

2017-01-01

Kaposi’s sarcoma associated herpesvirus (KSHV) persists in a highly-ordered chromatin structure inside latently infected cells with the majority of the viral genome having repressive marks. However, upon reactivation the viral chromatin landscape changes into ‘open’ chromatin through the involvement of lysine demethylases and methyltransferases. Besides methylation of lysine residues of histone H3, arginine methylation of histone H4 plays an important role in controlling the compactness of the chromatin. Symmetric methylation of histone H4 at arginine 3 (H4R3me2s) negatively affects the methylation of histone H3 at lysine 4 (H3K4me3), an active epigenetic mark deposited on the viral chromatin during reactivation. We identified a novel binding partner to KSHV viral DNA processivity factor, ORF59-a protein arginine methyl transferase 5 (PRMT5). PRMT5 is an arginine methyltransferase that dimethylates arginine 3 (R3) of histone H4 in a symmetric manner, one hallmark of condensed chromatin. Our ChIP-seq data of symmetrically methylated H4 arginine 3 showed a significant decrease in H4R3me2s on the viral genome of reactivated cells as compared to the latent cells. Reduction in arginine methylation correlated with the binding of ORF59 on the viral chromatin and disruption of PRMT5 from its adapter protein, COPR5 (cooperator of PRMT5). Binding of PRMT5 through COPR5 is important for symmetric methylation of H4R3 and the expression of ORF59 competitively reduces the association of PRMT5 with COPR5, leading to a reduction in PRMT5 mediated arginine methylation. This ultimately resulted in a reduced level of symmetrically methylated H4R3 and increased levels of H3K4me3 marks, contributing to the formation of an open chromatin for transcription and DNA replication. Depletion of PRMT5 levels led to a decrease in symmetric methylation and increase in viral gene transcription confirming the role of PRMT5 in viral reactivation. In conclusion, ORF59 modulates histone

KSHV encoded ORF59 modulates histone arginine methylation of the viral genome to promote viral reactivation.

PubMed

Strahan, Roxanne C; McDowell-Sargent, Maria; Uppal, Timsy; Purushothaman, Pravinkumar; Verma, Subhash C

2017-07-01

Kaposi's sarcoma associated herpesvirus (KSHV) persists in a highly-ordered chromatin structure inside latently infected cells with the majority of the viral genome having repressive marks. However, upon reactivation the viral chromatin landscape changes into 'open' chromatin through the involvement of lysine demethylases and methyltransferases. Besides methylation of lysine residues of histone H3, arginine methylation of histone H4 plays an important role in controlling the compactness of the chromatin. Symmetric methylation of histone H4 at arginine 3 (H4R3me2s) negatively affects the methylation of histone H3 at lysine 4 (H3K4me3), an active epigenetic mark deposited on the viral chromatin during reactivation. We identified a novel binding partner to KSHV viral DNA processivity factor, ORF59-a protein arginine methyl transferase 5 (PRMT5). PRMT5 is an arginine methyltransferase that dimethylates arginine 3 (R3) of histone H4 in a symmetric manner, one hallmark of condensed chromatin. Our ChIP-seq data of symmetrically methylated H4 arginine 3 showed a significant decrease in H4R3me2s on the viral genome of reactivated cells as compared to the latent cells. Reduction in arginine methylation correlated with the binding of ORF59 on the viral chromatin and disruption of PRMT5 from its adapter protein, COPR5 (cooperator of PRMT5). Binding of PRMT5 through COPR5 is important for symmetric methylation of H4R3 and the expression of ORF59 competitively reduces the association of PRMT5 with COPR5, leading to a reduction in PRMT5 mediated arginine methylation. This ultimately resulted in a reduced level of symmetrically methylated H4R3 and increased levels of H3K4me3 marks, contributing to the formation of an open chromatin for transcription and DNA replication. Depletion of PRMT5 levels led to a decrease in symmetric methylation and increase in viral gene transcription confirming the role of PRMT5 in viral reactivation. In conclusion, ORF59 modulates histone

Viral coinfection in childhood respiratory tract infections.

PubMed

Martínez-Roig, A; Salvadó, M; Caballero-Rabasco, M A; Sánchez-Buenavida, A; López-Segura, N; Bonet-Alcaina, M

2015-01-01

The introduction of molecular techniques has enabled better understanding of the etiology of respiratory tract infections in children. The objective of the study was to analyze viral coinfection and its relationship to clinical severity. Hospitalized pediatric patients with a clinical diagnosis of respiratory infection were studied during the period between 2009-2010. Clinical and epidemiological data, duration of hospitalization, need for oxygen therapy, bacterial coinfection and need for mechanical ventilation were collected. Etiology was studied by multiplex PCR and low-density microarrays for 19 viruses. A total of 385 patients were positive, 44.94% under 12 months. The most frequently detected viruses were RSV-B: 139, rhinovirus: 114, RSV-A: 111, influenza A H1N1-2009: 93 and bocavirus: 77. Coinfection was detected in 61.81%, 36.36% with 2 viruses, 16.10% and 9.35% with 3 to 4 or more. Coinfection was higher in 2009 with 69.79 vs. 53.88% in 2010. Rhinovirus/RSV-B on 10 times and RSV-A/RSV-B on 5 times were the most detected coinfections. Hospitalization decreased with greater number of viruses (P<0,001). Oxygen therapy was required by 26.75% (one virus was detected in 55.34% of cases). A larger number of viruses resulted in less need for oxygen (P<0,001). Ten cases required mechanical ventilation, 4 patients with bacterial coinfection and 5 with viral coinfection (P=0,69). An inverse relationship was found between the number of viruses detected in nasopharyngeal aspirate, the need for oxygen therapy and hospitalization days. More epidemiological studies and improved quantitative detection techniques are needed to define the role of viral coinfections in respiratory disease and its correlation with the clinical severity. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Vaccines for viral diseases with dermatologic manifestations.

PubMed

Brentjens, Mathijs H; Yeung-Yue, Kimberly A; Lee, Patricia C; Tyring, Stephen K

2003-04-01

Vaccines against infectious diseases have been available since the 1800s, when an immunization strategy against smallpox developed by Jenner gained wide acceptance. Until recently, the only vaccination strategies available involved the use of protein-based, whole killed, and attenuated live virus vaccines. These strategies have led to the development of effective vaccines against a variety of diseases with primary or prominent cutaneous manifestations. Effective and safe vaccines now used worldwide include those directed against measles and rubella (now commonly used together with a mumps vaccine as the trivalent MMR), chickenpox, and hepatitis B. The eradication of naturally occurring smallpox remains one of the greatest successes in the history of modern medicine, but stockpiles of live smallpox exist in the United States and Russia. Renewed interest in the smallpox vaccine reflects concerns about a possible bioterrorist threat using this virus. Yellow fever is a hemorrhagic virus endemic to tropical areas of South America and Africa. An effective vaccine for this virus has existed since 1937, and it is used widely in endemic areas of South America, and to a lesser extent in Africa. This vaccine is recommended once every 10 years for people who are traveling to endemic areas. Advances in immunology have led to a greater understanding of immune system function in viral diseases. Progress in genetics and molecular biology has allowed researchers to design vaccines with novel mechanisms of action (eg, DNA, vector, and VLP vaccines). Vaccines have also been designed to specifically target particular viral components, allowing for stimulation of various arms of the immune system as desired. Ongoing research shows promise in prophylactic and therapeutic vaccination for viral infections with cutaneous manifestations. Further studies are necessary before vaccines for HSV, HPV, and HIV become commercially available.

[Decimeter-wave physiotherapy in viral hepatitis].

PubMed

Kents, V V; Mavrodiĭ, V M

1995-01-01

Effectiveness was evaluated of magnetotherapy, inductothermy, UNF electric field and electromagnetic waves of decimetric wave band (460 MHz) on the projection of the liver, adrenals and thyroid gland in controlled trials enrolling a total of 835 patients with viral hepatitis (type A, B, associated forms). A conclusion is reached that optimum effectiveness of decimetric field on the projection of the adrenals and thyroid gland can be achieved through the application of minimum power and everyday alternation of exposures. It has been estimated that as many as 69 percent of the patients derive benefit from the above treatment.

Current status and strategies for viral hepatitis control in Korea.

PubMed

Sinn, Dong Hyun; Cho, Eun Ju; Kim, Ji Hoon; Kim, Do Young; Kim, Yoon Jun; Choi, Moon Seok

2017-09-01

Viral hepatitis is one of major global health challenges with increasing disease burden worldwide. Hepatitis B virus and hepatitis C virus infections are major causes of chronic liver diseases. They can lead to cirrhosis, hepatocellular carcinoma, and death in significant portion of affected people. Transmission of hepatitis B virus can be blocked by vaccination. Progression of hepatitis B virus-related liver diseases can be prevented by long-term viral suppression with effective drugs. Although vaccine for hepatitis C virus is currently unavailable, hepatitis C virus infection can be eradicated by oral direct antiviral agents. To eliminate viral hepatitis, World Health Organization (WHO) has urged countries to develop national goals and targets through reducing 90% of new infections and providing universal access to key treatment services up to 80%. This can lead to 65% reduction of viral hepatitis-related mortality. Here, we discuss some key features of viral hepatitis, strategies to control viral hepatitis suggested by WHO, and current status and strategies for viral hepatitis control in South Korea. To achieve the goal of viral hepatitis elimination by 2030 in South Korea, an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention (CDC) needs to be established to organize and execute comprehensive strategy for the management of viral hepatitis in South Korea.

Broad Surveys of DNA Viral Diversity Obtained through Viral Metagenomics of Mosquitoes

PubMed Central

Ng, Terry Fei Fan; Willner, Dana L.; Lim, Yan Wei; Schmieder, Robert; Chau, Betty; Nilsson, Christina; Anthony, Simon; Ruan, Yijun; Rohwer, Forest; Breitbart, Mya

2011-01-01

Viruses are the most abundant and diverse genetic entities on Earth; however, broad surveys of viral diversity are hindered by the lack of a universal assay for viruses and the inability to sample a sufficient number of individual hosts. This study utilized vector-enabled metagenomics (VEM) to provide a snapshot of the diversity of DNA viruses present in three mosquito samples from San Diego, California. The majority of the sequences were novel, suggesting that the viral community in mosquitoes, as well as the animal and plant hosts they feed on, is highly diverse and largely uncharacterized. Each mosquito sample contained a distinct viral community. The mosquito viromes contained sequences related to a broad range of animal, plant, insect and bacterial viruses. Animal viruses identified included anelloviruses, circoviruses, herpesviruses, poxviruses, and papillomaviruses, which mosquitoes may have obtained from vertebrate hosts during blood feeding. Notably, sequences related to human papillomaviruses were identified in one of the mosquito samples. Sequences similar to plant viruses were identified in all mosquito viromes, which were potentially acquired through feeding on plant nectar. Numerous bacteriophages and insect viruses were also detected, including a novel densovirus likely infecting Culex erythrothorax. Through sampling insect vectors, VEM enables broad survey of viral diversity and has significantly increased our knowledge of the DNA viruses present in mosquitoes. PMID:21674005

Molecular pathogenesis of viral hemorrhagic fever.

PubMed

Basler, Christopher F

2017-07-01

The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation. Among these cell populations, monocytes and macrophages are proposed to produce damaging inflammatory cytokines, while infected dendritic cells fail to undergo proper maturation, potentially impairing adaptive immunity. Uncontrolled virus replication and accompanying inflammatory responses are thought to promote vascular leakage and coagulopathy. However, the specific molecular pathways that underlie these features of VHF remain poorly understood. The arenavirus Lassa virus and the flavivirus yellow fever virus exhibit similar molecular pathogenesis suggesting common underlying mechanisms. Because non-human primate models that closely mimic VHF are available for Ebola, Lassa, and yellow fever viruses, we propose that comparative molecular studies using these models will yield new insights into the molecular underpinnings of VHF and suggest new therapeutic approaches.

Detection of viral hemorrhagic septicemia virus

USGS Publications Warehouse

Winton, James; Kurath, Gael; Batts, William

2007-01-01

Viral hemorrhagic septicemia virus (VHSV) is considered to be one of the most important viral pathogens of finfish and is listed as reportable by many nations and international organizations (Office International des Epizooties 2006). Prior to 1988, VHSV was thought to be limited to Europe (Wolf 1988; Smail 1999). Subsequently, it was shown that the virus is endemic among many marine and anadromous fish species in both the Pacific and Atlantic Oceans (Meyers and Winton 1995; Skall et al. 2005). Genetic analysis reveals that isolates of VHSV can be divided into four genotypes that generally correlate with geographic location with the North American isolates generally falling into VHSV Genotype IV (Snow et al. 2004). In 2005-2006, reports from the Great Lakes region indicated that wild fish had experienced disease or, in some cases, very large die-offs from VHSV (Elsayed et al. 2006, Lumsden et al. 2007). The new strain from the Great Lakes, now identified as VHSV Genotype IVb, appears most closely related to isolates of VHSV from mortalities that occurred during 2000-2004 in rivers and near-shore areas of New Brunswick and Nova Scotia, Canada (Gagne et al. 2007). The type IVb isolate found in the Great Lakes region is the only strain outside of Europe that has been associated with significant mortality in freshwater species.

Branching dynamics of viral information spreading

NASA Astrophysics Data System (ADS)

Iribarren, José Luis; Moro, Esteban

2011-10-01

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

Branching dynamics of viral information spreading.

PubMed

Iribarren, José Luis; Moro, Esteban

2011-10-01

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

Persistent viral infections and immune aging.

PubMed

Brunner, Stefan; Herndler-Brandstetter, Dietmar; Weinberger, Birgit; Grubeck-Loebenstein, Beatrix

2011-07-01

Immunosenescence comprises a set of dynamic changes occurring to both, the innate as well as the adaptive immune system that accompany human aging and result in complex manifestations of still poorly defined deficiencies in the elderly population. One of the most prominent alterations during aging is the continuous involution of the thymus gland which is almost complete by the age of 50. Consequently, the output of naïve T cells is greatly diminished in elderly individuals which puts pressure on homeostatic forces to maintain a steady T cell pool for most of adulthood. In a great proportion of the human population, this fragile balance is challenged by persistent viral infections, especially Cytomegalovirus (CMV), that oblige certain T cell clones to monoclonally expand repeatedly over a lifetime which then occupy space within the T cell pool. Eventually, these inflated memory T cell clones become exhausted and their extensive accumulation accelerates the age-dependent decline of the diversity of the T cell pool. As a consequence, infectious diseases are more frequent and severe in elderly persons and immunological protection following vaccination is reduced. This review therefore aims to shed light on how various types of persistent viral infections, especially CMV, influence the aging of the immune system and highlight potential measures to prevent the age-related decline in immune function. Copyright © 2010 Elsevier B.V. All rights reserved.

Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe.

PubMed

Blanquart, François; Wymant, Chris; Cornelissen, Marion; Gall, Astrid; Bakker, Margreet; Bezemer, Daniela; Hall, Matthew; Hillebregt, Mariska; Ong, Swee Hoe; Albert, Jan; Bannert, Norbert; Fellay, Jacques; Fransen, Katrien; Gourlay, Annabelle J; Grabowski, M Kate; Gunsenheimer-Bartmeyer, Barbara; Günthard, Huldrych F; Kivelä, Pia; Kouyos, Roger; Laeyendecker, Oliver; Liitsola, Kirsi; Meyer, Laurence; Porter, Kholoud; Ristola, Matti; van Sighem, Ard; Vanham, Guido; Berkhout, Ben; Kellam, Paul; Reiss, Peter; Fraser, Christophe

2017-06-01

HIV-1 set-point viral load-the approximately stable value of viraemia in the first years of chronic infection-is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%-43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical "Brownian motion" model and another model ("Ornstein-Uhlenbeck") that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%-43%) is consistent with other studies based on regression of viral load in donor-recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation.

Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe

PubMed Central

Wymant, Chris; Cornelissen, Marion; Gall, Astrid; Bakker, Margreet; Bezemer, Daniela; Hall, Matthew; Hillebregt, Mariska; Ong, Swee Hoe; Albert, Jan; Bannert, Norbert; Fellay, Jacques; Fransen, Katrien; Gourlay, Annabelle J.; Grabowski, M. Kate; Gunsenheimer-Bartmeyer, Barbara; Günthard, Huldrych F.; Kivelä, Pia; Kouyos, Roger; Laeyendecker, Oliver; Liitsola, Kirsi; Meyer, Laurence; Porter, Kholoud; Ristola, Matti; van Sighem, Ard; Vanham, Guido; Berkhout, Ben; Kellam, Paul; Reiss, Peter; Fraser, Christophe

2017-01-01

HIV-1 set-point viral load—the approximately stable value of viraemia in the first years of chronic infection—is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%–43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical “Brownian motion” model and another model (“Ornstein–Uhlenbeck”) that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%–43%) is consistent with other studies based on regression of viral load in donor–recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation. PMID:28604782

Viral Evasion and Manipulation of Host RNA Quality Control Pathways

PubMed Central

2016-01-01

Viruses have evolved diverse strategies to maximize the functional and coding capacities of their genetic material. Individual viral RNAs are often used as substrates for both replication and translation and can contain multiple, sometimes overlapping open reading frames. Further, viral RNAs engage in a wide variety of interactions with both host and viral proteins to modify the activities of important cellular factors and direct their own trafficking, packaging, localization, stability, and translation. However, adaptations increasing the information density of small viral genomes can have unintended consequences. In particular, viral RNAs have developed features that mark them as potential targets of host RNA quality control pathways. This minireview focuses on ways in which viral RNAs run afoul of the cellular mRNA quality control and decay machinery, as well as on strategies developed by viruses to circumvent or exploit cellular mRNA surveillance. PMID:27226372

Viral Evasion and Manipulation of Host RNA Quality Control Pathways.

PubMed

Hogg, J Robert

2016-08-15

Viruses have evolved diverse strategies to maximize the functional and coding capacities of their genetic material. Individual viral RNAs are often used as substrates for both replication and translation and can contain multiple, sometimes overlapping open reading frames. Further, viral RNAs engage in a wide variety of interactions with both host and viral proteins to modify the activities of important cellular factors and direct their own trafficking, packaging, localization, stability, and translation. However, adaptations increasing the information density of small viral genomes can have unintended consequences. In particular, viral RNAs have developed features that mark them as potential targets of host RNA quality control pathways. This minireview focuses on ways in which viral RNAs run afoul of the cellular mRNA quality control and decay machinery, as well as on strategies developed by viruses to circumvent or exploit cellular mRNA surveillance. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Exploring viral infection using single-cell sequencing.

PubMed

Rato, Sylvie; Golumbeanu, Monica; Telenti, Amalio; Ciuffi, Angela

2017-07-15

Single-cell sequencing (SCS) has emerged as a valuable tool to study cellular heterogeneity in diverse fields, including virology. By studying the viral and cellular genome and/or transcriptome, the dynamics of viral infection can be investigated at single cell level. Most studies have explored the impact of cell-to-cell variation on the viral life cycle from the point of view of the virus, by analyzing viral sequences, and from the point of view of the cell, mainly by analyzing the cellular host transcriptome. In this review, we will focus on recent studies that use single-cell sequencing to explore viral diversity and cell variability in response to viral replication. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Inhibitor-Based Therapeutics for Treatment of Viral Hepatitis.

PubMed

Dey, Debajit; Banerjee, Manidipa

2016-09-28

Viral hepatitis remains a significant worldwide threat, in spite of the availability of several successful therapeutic and vaccination strategies. Complications associated with acute and chronic infections, such as liver failure, cirrhosis and hepatocellular carcinoma, are the cause of considerable morbidity and mortality. Given the significant burden on the healthcare system caused by viral hepatitis, it is essential that novel, more effective therapeutics be developed. The present review attempts to summarize the current treatments against viral hepatitis, and provides an outline for upcoming, promising new therapeutics. Development of novel therapeutics requires an understanding of the viral life cycles and viral effectors in molecular detail. As such, this review also discusses virally-encoded effectors, found to be essential for virus survival and replication in the host milieu, which may be utilized as potential candidates for development of alternative therapies in the future.

Silencing and innate immunity in plant defense against viral and non-viral pathogens.

PubMed

Zvereva, Anna S; Pooggin, Mikhail M

2012-10-29

The frontline of plant defense against non-viral pathogens such as bacteria, fungi and oomycetes is provided by transmembrane pattern recognition receptors that detect conserved pathogen-associated molecular patterns (PAMPs), leading to pattern-triggered immunity (PTI). To counteract this innate defense, pathogens deploy effector proteins with a primary function to suppress PTI. In specific cases, plants have evolved intracellular resistance (R) proteins detecting isolate-specific pathogen effectors, leading to effector-triggered immunity (ETI), an amplified version of PTI, often associated with hypersensitive response (HR) and programmed cell death (PCD). In the case of plant viruses, no conserved PAMP was identified so far and the primary plant defense is thought to be based mainly on RNA silencing, an evolutionary conserved, sequence-specific mechanism that regulates gene expression and chromatin states and represses invasive nucleic acids such as transposons. Endogenous silencing pathways generate 21-24 nt small (s)RNAs, miRNAs and short interfering (si)RNAs, that repress genes post-transcriptionally and/or transcriptionally. Four distinct Dicer-like (DCL) proteins, which normally produce endogenous miRNAs and siRNAs, all contribute to the biogenesis of viral siRNAs in infected plants. Growing evidence indicates that RNA silencing also contributes to plant defense against non-viral pathogens. Conversely, PTI-based innate responses may contribute to antiviral defense. Intracellular R proteins of the same NB-LRR family are able to recognize both non-viral effectors and avirulence (Avr) proteins of RNA viruses, and, as a result, trigger HR and PCD in virus-resistant hosts. In some cases, viral Avr proteins also function as silencing suppressors. We hypothesize that RNA silencing and innate immunity (PTI and ETI) function in concert to fight plant viruses. Viruses counteract this dual defense by effectors that suppress both PTI-/ETI-based innate responses and RNA

Viral load of patients with hantavirus pulmonary syndrome in Argentina.

PubMed

Bellomo, Carla María; Pires-Marczeski, Fanny Clara; Padula, Paula Julieta

2015-11-01

Hantavirus causes severe illness including pneumonia, which leads to hospitalization and often death. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely both virus-mediated and host-mediated mechanisms, are involved. The aim of this study was to correlate viral load in samples of hantavirus pulmonary syndrome cases and hantavirus infected individuals, with clinical epidemiological parameters and disease outcome. The variables that could potentially be related with viral load were analyzed. The retrospective study included 73 cases or household contacts, with different clinical evolution. Viral load was measured by reverse-transcription and real time polymerase chain reaction. There was no statistically significant association between blood viral RNA levels and severity of disease. However, viral load was inversely correlated with IgG response in a statistically significant manner. The level of viral RNA was significantly higher in patients infected with Andes virus South lineage, and was markedly low in persons infected with Laguna Negra virus. These results suggest that the infecting viral genotype is associated with disease severity, and that high viral load is associated with a low specific IgG response. Sex, age and disease severity were not related with viral load. Further investigations increasing strikingly the number of cases and also limiting the variables to be studied are necessary. © 2015 Wiley Periodicals, Inc.

Viral loads of cerebrospinal fluid in infants with enterovirus meningitis.

PubMed

Kawashima, Hisashi; Ioi, Hiroaki; Ishii, Chiako; Hasegawa, Yuka; Amaha, Masahiro; Kashiwagi, Yasuyo; Takekuma, Kouji; Hoshika, Akinori; Watanabe, Yasuo

2008-01-01

For a better understanding of the role of the viral load, free radicals, and cytokines in viral meningitis, we surveyed cerebrospinal fluid (CSF) obtained from patients below 1 year of age who showed positive for enterovirus. In their first examinations interleukin (IL)-6 and free radicals increased whereas pleocytosis was rarely observed. IL-6 decreased within the short period. Viral loads and free radicals increased simultaneously. IL-6 and free radicals of CSF are helpful for diagnosis and treatment of viral meningitis at an early stage. (c) 2008 Wiley-Liss, Inc.

Coarse-grained Simulations of Viral Assembly

NASA Astrophysics Data System (ADS)

Elrad, Oren M.

2011-12-01

The formation of viral capsids is a marvel of natural engineering and design. A large number (from 60 to thousands) of protein subunits assemble into complete, reproducible structures under a variety of conditions while avoiding kinetic and thermodynamic traps. Small single-stranded RNA viruses not only assemble their coat proteins in this fashion but also package their genome during the self-assembly process. Recent experiments have shown that the coat proteins are competent to assemble not merely around their own genomes but heterologous RNA, synthetic polyanions and even functionalized gold nanoparticles. Remarkably these viruses can even assemble around cargo not commensurate with their native state by adopting different morphologies. Understanding the properties that confer such exquisite precision and flexibility to the assembly process could aid biomedical research in the search for novel antiviral remedies, drug-delivery vehicles and contrast agents used in bioimaging. At the same time, viral assembly provides an excellent model system for the development of a statistical mechanical understanding of biological self-assembly, in the hopes of that we will identify some universal principles that underly such processes. This work consists of computational studies using coarse-grained representations of viral coat proteins and their cargoes. We find the relative strength of protein-cargo and protein-protein interactions has a profound effect on the assembly pathway, in some cases leading to assembly mechanisms that are markedly different from those found in previous work on the assembly of empty capsids. In the case of polymeric cargo, we find the first evidence for a previously theorized mechanism in which the polymer actively participates in recruiting free subunits to the assembly process through cooperative polymer-protein motions. We find that successful assembly is non-monotonic in protein-cargo affinity, such affinity can be detrimental to assembly if it

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

Viral Oncology: Molecular Biology and Pathogenesis

PubMed Central

Mui, Uyen Ngoc; Haley, Christopher T.; Tyring, Stephen K.

2017-01-01

Oncoviruses are implicated in approximately 12% of all human cancers. A large number of the world’s population harbors at least one of these oncoviruses, but only a small proportion of these individuals go on to develop cancer. The interplay between host and viral factors is a complex process that works together to create a microenvironment conducive to oncogenesis. In this review, the molecular biology and oncogenic pathways of established human oncoviruses will be discussed. Currently, there are seven recognized human oncoviruses, which include Epstein-Barr Virus (EBV), Human Papillomavirus (HPV), Hepatitis B and C viruses (HBV and HCV), Human T-cell lymphotropic virus-1 (HTLV-1), Human Herpesvirus-8 (HHV-8), and Merkel Cell Polyomavirus (MCPyV). Available and emerging therapies for these oncoviruses will be mentioned. PMID:29186062

Nuclear import of viral DNA genomes.

PubMed

Greber, Urs F; Fassati, Ariberto

2003-03-01

The genomes of many viruses traffic into the nucleus, where they are either integrated into host chromosomes or maintained as episomal DNA and then transcriptionally activated or silenced. Here, we discuss the existing evidence on how the lentiviruses, adenoviruses, herpesviruses, hepadnaviruses and autonomous parvoviruses enter the nucleus. Depending on the size of the capsid enclosing the genome, three principles of viral nucleic acids import are discussed. The first principle is that the capsid disassembles in the cytosol or in a docked state at the nuclear pore complex and a subviral genomic complex is trafficked through the pore. Second, the genome is injected from a capsid that is docked to the pore complex, and third, import factors are recruited to cytosolic capsids to increase capsid affinity to the pore complex, mediate translocation and allow disassembly in the nucleoplasm.

Hepatoerythropoietic porphyria precipitated by viral hepatitis.

PubMed Central

Hift, R J; Meissner, P N; Todd, G

1993-01-01

Porphyria cutanea tarda (PCT), the condition resulting from a deficiency of hepatic uroporphyrinogen decarboxylase activity, is the commonest form of porphyria. Both acquired and familial form exist and are commonly associated in adults with liver disease and hepatic iron overload. The condition is extremely rare in children; most cases of childhood PCT are familial and some particularly severe cases have been shown to have a hepatoerythropoietic porphyria or homozygous uroporphyrinogen decarboxylase deficiency. A case is described of hepatoerythropoietic porphyria in which the disease was first precipitated at the age of two by a coincidental hepatitis A infection and improved as the hepatitis cleared. This paper reviews the evidence that viral hepatitis may precipitate overt PCT in children in a manner analogous to the precipitation of PCT in adults by alcohol associated liver disease. PMID:7902313

Antiviral Lectins: Selective Inhibitors of Viral Entry

PubMed Central

Mitchell, Carter A.; Ramessar, Koreen; O’Keefe, Barry R.

2017-01-01

Many natural lectins have been reported to have antiviral activity. As some of these have been put forward as potential development candidates for preventing or treating viral infections, we have set out in this review to survey the literature on antiviral lectins. The review groups lectins by structural class and class of source organism we also detail their carbohydrate specificity and their reported antiviral activities. The review concludes with a brief discussion of several of the pertinent hurdles that heterologous proteins must clear to be useful clinical candidates and cites examples where such studies have been reported for antiviral lectins. Though the clearest path currently being followed is the use of antiviral lectins as anti-HIV microbicides via topical mucosal administration, some investigators have also found systemic efficacy against acute infections following subcutaneous administration. PMID:28322922

Confirmed viral meningitis with normal CSF findings.

PubMed

Dawood, Naghum; Desjobert, Edouard; Lumley, Janine; Webster, Daniel; Jacobs, Michael

2014-07-17

An 18-year-old woman presented with a progressively worsening headache, photophobia feverishness and vomiting. Three weeks previously she had returned to the UK from a trip to Peru. At presentation, she had clinical signs of meningism. On admission, blood tests showed a mild lymphopenia, with a normal C reactive protein and white cell count. Chest X-ray and CT of the head were normal. Cerebrospinal fluid (CSF) microscopy was normal. CSF protein and glucose were in the normal range. MRI of the head and cerebral angiography were also normal. Subsequent molecular testing of CSF detected enterovirus RNA by reverse transcriptase PCR. The patient's clinical syndrome correlated with her virological diagnosis and no other cause of her symptoms was found. Her symptoms were self-limiting and improved with supportive management. This case illustrates an important example of viral central nervous system infection presenting clinically as meningitis but with normal CSF microscopy. 2014 BMJ Publishing Group Ltd.

Subacute sclerosing panencephalitis and chronic viral encephalitis.

PubMed

Anlar, Banu

2013-01-01

Subacute sclerosing panencephalitis (SSPE) is a chronic infection of the central nervous system associated with the presence of mutant measles virus in the brain. It presents as a progressive, usually fatal disease. The diagnosis is based on clinical criteria and an elevated titer of measles antibodies in the cerebrospinal fluid (CSF). Electroencephalography and imaging studies provide supportive laboratory data. A brain biopsy is indicated only when CSF serology is negative or equivocal in a suspected case to assess the presence of inclusion bodies, measles virus antigens, or viral RNA. Among many drugs and methods tried in the treatment, the highest rate of stabilization or improvement was obtained with intraventricular human lymphoblastoid interferon-α and oral inosiplex. Further research for more available and efficient therapeutic regimens is warranted. Measles and SSPE are preventable by maintenance of high rates of immunization in the population. Copyright © 2013 Elsevier B.V. All rights reserved.

Papillomaviruses: Viral evolution, cancer and evolutionary medicine.

PubMed

Bravo, Ignacio G; Félez-Sánchez, Marta

2015-01-28

Papillomaviruses (PVs) are a numerous family of small dsDNA viruses infecting virtually all mammals. PVs cause infections without triggering a strong immune response, and natural infection provides only limited protection against reinfection. Most PVs are part and parcel of the skin microbiota. In some cases, infections by certain PVs take diverse clinical presentations from highly productive self-limited warts to invasive cancers. We propose PVs as an excellent model system to study the evolutionary interactions between the immune system and pathogens causing chronic infections: genotypically, PVs are very diverse, with hundreds of different genotypes infecting skin and mucosa; phenotypically, they display extremely broad gradients and trade-offs between key phenotypic traits, namely productivity, immunogenicity, prevalence, oncogenicity and clinical presentation. Public health interventions have been launched to decrease the burden of PV-associated cancers, including massive vaccination against the most oncogenic human PVs, as well as systematic screening for PV chronic anogenital infections. Anti-PVs vaccines elicit protection against infection, induce cross-protection against closely related viruses and result in herd immunity. However, our knowledge on the ecological and intrapatient dynamics of PV infections remains fragmentary. We still need to understand how the novel anthropogenic selection pressures posed by vaccination and screening will affect viral circulation and epidemiology. We present here an overview of PV evolution and the connection between PV genotypes and the phenotypic, clinical manifestations of the diseases they cause. This differential link between viral evolution and the gradient cancer-warts-asymptomatic infections makes PVs a privileged playground for evolutionary medicine research. © The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

Superresolution imaging of viral protein trafficking

PubMed Central

Salka, Kyle; Bhuvanendran, Shivaprasad; Yang, David

2015-01-01

The endoplasmic reticulum (ER) membrane is closely apposed to the outer mitochondrial membrane (OMM), which facilitates communication between these organelles. These contacts, known as mitochondria-associated membranes (MAM), facilitate calcium signaling, lipid transfer, as well as antiviral and stress responses. How cellular proteins traffic to the MAM, are distributed therein, and interact with ER and mitochondrial proteins are subject of great interest. The human cytomegalovirus UL37 exon 1 protein or viral mitochondria-localized inhibitor of apoptosis (vMIA) is crucial for viral growth. Upon synthesis at the ER, vMIA traffics to the MAM and OMM, where it reprograms the organization and function of these compartments. vMIA significantly changes the abundance of cellular proteins at the MAM and OMM, including proteins that regulate calcium homeostasis and cell death. Through the use of superresolution imaging, we have shown that vMIA is distributed at the OMM in nanometer scale clusters. This is similar to the clusters reported for the mitochondrial calcium channel, VDAC, as well as electron transport chain, translocase of the OMM complex, and mitochondrial inner membrane organizing system components. Thus, aside from addressing how vMIA targets the MAM and regulates survival of infected cells, biochemical studies and superresolution imaging of vMIA offer insights into the formation, organization, and functioning of MAM. Here, we discuss these insights into trafficking, function, and organization of vMIA at the MAM and OMM and discuss how the use of superresolution imaging is contributing to the study of the formation and trafficking of viruses. PMID:25724304

Progress and challenges in viral vector manufacturing

PubMed Central

van der Loo, Johannes C.M.; Wright, J. Fraser

2016-01-01

Promising results in several clinical studies have emphasized the potential of gene therapy to address important medical needs and initiated a surge of investments in drug development and commercialization. This enthusiasm is driven by positive data in clinical trials including gene replacement for Hemophilia B, X-linked Severe Combined Immunodeficiency, Leber's Congenital Amaurosis Type 2 and in cancer immunotherapy trials for hematological malignancies using chimeric antigen receptor T cells. These results build on the recent licensure of the European gene therapy product Glybera for the treatment of lipoprotein lipase deficiency. The progress from clinical development towards product licensure of several programs presents challenges to gene therapy product manufacturing. These include challenges in viral vector-manufacturing capacity, where an estimated 1–2 orders of magnitude increase will likely be needed to support eventual commercial supply requirements for many of the promising disease indications. In addition, the expanding potential commercial product pipeline and the continuously advancing development of recombinant viral vectors for gene therapy require that products are well characterized and consistently manufactured to rigorous tolerances of purity, potency and safety. Finally, there is an increase in regulatory scrutiny that affects manufacturers of investigational drugs for early-phase clinical trials engaged in industry partnerships. Along with the recent increase in biopharmaceutical funding in gene therapy, industry partners are requiring their academic counterparts to meet higher levels of GMP compliance at earlier stages of clinical development. This chapter provides a brief overview of current progress in the field and discusses challenges in vector manufacturing. PMID:26519140

HIV community viral load trends in South Carolina.

PubMed

Chakraborty, Hrishikesh; Weissman, Sharon; Duffus, Wayne A; Hossain, Akhtar; Varma Samantapudi, Ashok; Iyer, Medha; Albrecht, Helmut

2017-03-01

Community viral load is an aggregate measure of HIV viral load in a particular geographic location, community, or subgroup. Community viral load provides a measure of disease burden in a community and community transmission risk. This study aims to examine community viral load trend in South Carolina and identify differences in community viral load trends between selected population subgroups using a state-wide surveillance dataset that maintains electronic records of all HIV viral load measurements reported to the state health department. Community viral load trends were examined using random mixed effects models, adjusting for age, race, gender, residence, CD4 counts, HIV risk group, and initial antiretroviral regimen during the study period, and time. The community viral load gradually decreased from 2004 to 2013 ( p < 0.0001). The number of new infections also decreased ( p = 0.0001) over time. A faster rate of decrease was seen among men compared to women ( p < 0.0001), men who have sex with men ( p = 0.0001) compared to heterosexuals, patients diagnosed in urban areas compared to that in rural areas ( p = 0.0004), and patients prescribed single-tablet regimen compared to multiple-tablet regimen ( p < 0.0001). While the state-wide community viral load decreased over time, the decline was not uniform among residence at diagnosis, HIV risk group, and single-tablet regimen versus multiple-tablet regimen subgroups. Slower declines in community viral load among females, those in rural areas, and heterosexuals suggest possible disparities in care that require further exploration. The association between using single-tablet regimen and faster community viral load decline is noteworthy.

[Development of viral vectors and the application for viral entry mechanisms].

PubMed

Tani, Hideki

2011-06-01

Virus is identified as one of the obligate intracellular parasites, which only amplify in cells of specific living things. Viral vectors, which are developed by utilizing these properties, are available in the various fields such as basic research of medical biology or application of gene therapy. Our research group has studied development of viral vectors using properties of baculovirus or vesicular stomatitis virus (VSV). Due to the development of new baculoviral vectors for mammalian cells, it is possible to be more efficient transduction of foreign gene in mammalian cells and animals. Furthermore, pseudotype or recombinant VSV possessing the envelope proteins of hepatitis C virus, Japanese encephalitis virus or baculovirus were constructed, and characteristics of the envelope proteins or entry mechanisms of these viruses were analyzed.

Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring

USGS Publications Warehouse

Lovy, Jan; Lewis, N.L.; Hershberger, P.K.; Bennett, W.; Meyers, T.R.; Garver, K.A.

2012-01-01

Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring.

A catalog of viral diseases of insects and mites.

Treesearch

Mauro E. Martignoni; Paul J. Iwai

1975-01-01

This comprehensive catalog of viral diseases of two large groups of arthropods updates the previous surveys of the world's literature published by Hughes in 1957 and by Martignoni and Langston in 1960. This computer-based catalog lists over 600 species of insects and mites, each reported to have one or more of 21 viral diseases or disease groups, for a total of...

Depth-related gradients of viral activity in Lake Pavin.

PubMed

Colombet, J; Sime-Ngando, T; Cauchie, H M; Fonty, G; Hoffmann, L; Demeure, G

2006-06-01

High-resolution vertical sampling and determination of viral and prokaryotic parameters in a deep volcanic lake shows that in the absence of thermal stratification but within light, oxygen, and chlorophyll gradients, host availability empirically is prevalent over the physical and chemical environments and favors lytic over lysogenic "viral life cycles."

Depth-Related Gradients of Viral Activity in Lake Pavin

PubMed Central

Colombet, J.; Sime-Ngando, T.; Cauchie, H. M.; Fonty, G.; Hoffmann, L.; Demeure, G.

2006-01-01

High-resolution vertical sampling and determination of viral and prokaryotic parameters in a deep volcanic lake shows that in the absence of thermal stratification but within light, oxygen, and chlorophyll gradients, host availability empirically is prevalent over the physical and chemical environments and favors lytic over lysogenic “viral life cycles.” PMID:16751565

Dynamics of viral load in Crimean Congo hemorrhagic fever.

PubMed

Hasanoglu, Imran; Guner, Rahmet; Carhan, Ahmet; K Tufan, Zeliha; Y Caglayik, Dilek; Yilmaz, Gul R; Tasyaran, Mehmet A

2018-04-01

Crimean Congo hemorrhagic fever (CCHF) is a viral zoonotic disease with high mortality rate. There are only a few studies on viral load in CCHF. In our study, we revealed the dynamics of viral load and its relationship with mortality in early phase of the disease. A total of 138 serum samples were collected from 23 patients. All patients had positive PCR for CCHF on admission. Serum samples were obtained daily from all patients for the first 6 days of hospitalization and stored at -80°C for viral load measurement. We found statistically significant difference between mean number of viremic serum samples of fatal and non-fatal patients. Furthermore, non-fatal cases' viral loads demonstrated statistically significant decreases over time; however, we could not observe a similar trend in viral loads of fatal cases. Limited number of studies on CCHF indicate that score of the contest between CCHF virus and immune system determines the survival in CCHF and viral load is found to be the most prognostic factor. In our study, we found that there is a notable decrease trend in viral loads of non-fatal patients over time and this clearance of CCHF virus is significantly related with survival. © 2017 Wiley Periodicals, Inc.

Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

PubMed Central

Ruffner, Melanie A.; Sullivan, Kathleen E.; Henrickson, Sarah E.

2017-01-01

Viral infections are commonplace and often innocuous. Nevertheless, within the population of patients with primary immunodeficiencies (PIDDs), viral infections can be the feature that drives a diagnostic evaluation or can be the most significant morbidity for the patient. This review is focused on the viral complications of PIDDs. It will focus on respiratory viruses, the most common type of viral infection in the general population. Children and adults with an increased frequency or severity of respiratory viral infections are often referred for an immunologic evaluation. The classic teaching is to investigate humoral function in people with recurrent sinopulmonary infections, but this is often interpreted to mean recurrent bacterial infections. Recurrent or very severe viral infections may also be a harbinger of a primary immunodeficiency as well. This review will also cover persistent cutaneous viral infections, systemic infections, central nervous system infections, and gastrointestinal infections. In each case, the specific viral infections may drive a diagnostic evaluation that is specific for that type of virus. This review also discusses the management of these infections, which can become problematic in patients with PIDDs. PMID:28674531

Mechanisms of inhibition of viral replication in plants

SciTech Connect

Not Available

1990-01-01

We have made a number of interesting observations of importance to the fields of virology and plant molecular biology. Topics include the genome of cucumber mosaic virus (CMV), recombination of the CMV genome, transgenic plants and viral movement genes, mapping resistance breakage sequences in the tomato mosaic virus (TMV) genome, and mapping pathogeneticity domains and viral RNA heterogeneity. 1 fig., 1 tab.

pelo Is Required for High Efficiency Viral Replication

PubMed Central

Wu, Xiurong; He, Wan-Ting; Tian, Shuye; Meng, Dan; Li, Yuanyue; Chen, Wanze; Li, Lisheng; Tian, Lili; Zhong, Chuan-Qi; Han, Felicia; Chen, Jianming; Han, Jiahuai

2014-01-01

Viruses hijack host factors for their high speed protein synthesis, but information about these factors is largely unknown. In searching for genes that are involved in viral replication, we carried out a forward genetic screen for Drosophila mutants that are more resistant or sensitive to Drosophila C virus (DCV) infection-caused death, and found a virus-resistant line in which the expression of pelo gene was deficient. Our mechanistic studies excluded the viral resistance of pelo deficient flies resulting from the known Drosophila anti-viral pathways, and revealed that pelo deficiency limits the high level synthesis of the DCV capsid proteins but has no or very little effect on the expression of some other viral proteins, bulk cellular proteins, and transfected exogenous genes. The restriction of replication of other types of viruses in pelo deficient flies was also observed, suggesting pelo is required for high level production of capsids of all kinds of viruses. We show that both pelo deficiency and high level DCV protein synthesis increase aberrant 80S ribosomes, and propose that the preferential requirement of pelo for high level synthesis of viral capsids is at least partly due to the role of pelo in dissociation of stalled 80S ribosomes and clearance of aberrant viral RNA and proteins. Our data demonstrated that pelo is a host factor that is required for high efficiency translation of viral capsids and targeting pelo could be a strategy for general inhibition of viral infection. PMID:24722736

Advances in viral hepatitis: 50 years of Australian gastroenterology.

PubMed

McCaughan, Geoff

2009-10-01

Viral hepatitis classification, treatments and pathogenesis has been increasingly defined over the past 50 years. Australian researchers have made significant contributions in the areas of viral hepatitis A vaccine development, treatment outcomes for chronic hepatitis B and C, the role of liver transplantation and the pathogenesis of injury and disease progression. This review outlines some of these contributions.

A catalog of viral diseases of insects, mites, and ticks.

Treesearch

Mauro E. Martignoni; Paul J. Iwai

1986-01-01

This comprehensive catalog of viral diseases of three large groups of arthropods updates the previous surveys of the world's literature published by Hughes in 1957, by Martignoni and Langston in 1960, and by Martignoni and Iwai in 1975. This computer-based catalog lists over 1,100 species of insects, mites, and ticks, each reported to have one or more of 22 viral...

Bovine viral diarrhea virus modulation of monocyte derived macrophages

USDA-ARS?s Scientific Manuscript database

Bovine viral diarrhea virus (BVDV) is a single stranded, positive sense RNA virus and is the causative agent of bovine viral diarrhea (BVD). Disease can range from persistently infected (PI) animals displaying no clinical symptoms of disease to an acute, severe disease. Presently, limited studies ha...

In vitro anti-viral effect of β-santalol against influenza viral replication.

PubMed

Paulpandi, Manickam; Kannan, Soundarapandian; Thangam, Ramar; Kaveri, Krishnasamy; Gunasekaran, Palani; Rejeeth, Chandrababu

2012-02-15

The anti-influenza A/HK (H3N2) virus activity of β-santalol was evaluated in MDCK cells and investigated the effect of β-santalol on synthesis of viral mRNAs. β-Santalol was investigated for its antiviral activity against influenza A/HK (H3N2) virus using a cytopathic effect (CPE) reduction method. β-Santalol exhibited anti-influenza A/HK (H3N2) virus activity of 86% with no cytotoxicity at the concentration of 100 μg/ml reducing the formation of a visible CPE. Oseltamivir also showed moderate antiviral activity of about 83% against influenza A/HK (H3N2) virus at the concentration of 100 μg/ml. Furthermore, the mechanism of anti-influenza virus action in the inhibition of viral mRNA synthesis was analyzed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), and the data indicated an inhibitory effect in late viral RNA synthesis compared with oseltamivir in the presence of 100 μg/ml of β-santalol. β-Santalol should be further studied for therapeutic and prophylactic potential especially for influenza epidemics and pandemics. Copyright © 2011 Elsevier GmbH. All rights reserved.

Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

USGS Publications Warehouse

Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

2012-01-01

Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

Synthetic approaches to construct viral capsid-like spherical nanomaterials.

PubMed

Matsuura, Kazunori

2018-06-06

This feature article describes recent progress in synthetic strategies to construct viral capsid-like spherical nanomaterials using the self-assembly of peptides and/or proteins. By mimicking the self-assembly of spherical viral capsids and clathrin, trigonal peptide conjugates bearing β-sheet-forming peptides, glutathiones, or coiled-coil-forming peptides were developed to construct viral capsid-like particles. β-Annulus peptides from tomato bushy stunt virus self-assembled into viral capsid-like nanocapsules with a size of 30-50 nm, which could encapsulate various guest molecules and be decorated with different molecules on their surface. Rationally designed fusion proteins bearing symmetric assembling units afforded precise viral capsid-like polyhedral assemblies. These synthetic approaches to construct artificial viruses could become useful guidelines to develop novel drug carriers, vaccine platforms, nanotemplates and nanoreactors.

Plant Viral Proteases: Beyond the Role of Peptide Cutters

PubMed Central

Rodamilans, Bernardo; Shan, Hongying; Pasin, Fabio; García, Juan Antonio

2018-01-01

Almost half of known plant viral species rely on proteolytic cleavages as key co- and post-translational modifications throughout their infection cycle. Most of these viruses encode their own endopeptidases, proteases with high substrate specificity that internally cleave large polyprotein precursors for the release of functional sub-units. Processing of the polyprotein, however, is not an all-or-nothing process in which endopeptidases act as simple peptide cutters. On the contrary, spatial-temporal modulation of these polyprotein cleavage events is crucial for a successful viral infection. In this way, the processing of the polyprotein coordinates viral replication, assembly and movement, and has significant impact on pathogen fitness and virulence. In this mini-review, we give an overview of plant viral proteases emphasizing their importance during viral infections and the varied functionalities that result from their proteolytic activities.

Viral mimicry of cytokines, chemokines and their receptors.

PubMed

Alcami, Antonio

2003-01-01

Viruses have evolved elegant mechanisms to evade detection and destruction by the host immune system. One of the evasion strategies that have been adopted by large DNA viruses is to encode homologues of cytokines, chemokines and their receptors--molecules that have a crucial role in control of the immune response. Viruses have captured host genes or evolved genes to target specific immune pathways, and so viral genomes can be regarded as repositories of important information about immune processes, offering us a viral view of the host immune system. The study of viral immunomodulatory proteins might help us to uncover new human genes that control immunity, and their characterization will increase our understanding of not only viral pathogenesis, but also normal immune mechanisms. Moreover, viral proteins indicate strategies of immune modulation that might have therapeutic potential.

Analysis of HSV viral reactivation in explants of sensory neurons

PubMed Central

Turner, Anne-Marie W.; Kristie, Thomas M.

2014-01-01

As with all Herpesviruses, Herpes simplex virus (HSV) has both a lytic replication phase and a latency-reactivation cycle. During lytic replication, there is an ordered cascade of viral gene expression that leads to the synthesis of infectious viral progeny. In contrast, latency is characterized by the lack of significant lytic gene expression and the absence of infectious virus. Reactivation from latency is characterized by the re-entry of the virus into the lytic replication cycle and the production of recurrent disease. This unit describes the establishment of the mouse sensory neuron model of HSV-1 latency-reactivation as a useful in vivo system for the analysis of mechanisms involved in latency and reactivation. Assays including the determination of viral yields, immunohistochemical/immunofluorescent detection of viral antigens, and mRNA quantitation are used in experiments designed to investigate the network of cellular and viral proteins regulating HSV-1 lytic infection, latency, and reactivation. PMID:25367271

Integrated Evaluation of Latent Viral Reactivation During Spaceflight

NASA Technical Reports Server (NTRS)

Pierson, Duane L.; Paloski, W. H. (Technical Monitor)

2000-01-01

This application proposes a continuation of our current effort, which has provided the first demonstration of viral reactivation during space flight. We have used the herpesvirus EBV as a model for latent viral reactivation and have shown that increased amounts of EBV DNA were shed by astronauts during space flight. Analysis of the Antarctic space flight analog indicated that the frequency of viral shedding may also increase (along with the increased numbers of virus) during long periods of isolation. However, a number of critical questions remain before the findings may be considered a significant health risk during extended space flight. These include: Are other latent viruses (e.g., other herpesviruses and polyornaviruses) in addition to EBV also reactivated and shed more frequently and/or in higher numbers during space flight? Is the viral reactivation observed in space flight and ground-based analogs mediated through the hypothalamus-pituitary-adrenal (HPA) axis resulting in a decreased cell-mediated immune response? How does detection of viral DNA by PCR analysis correlate with infectious virus? How does the amount of virus found during flight compare with viral levels observed in acute/chronic viral illnesses and in control individuals? This expanded study will examine the phenomenon of viral reactivation from the initiating stress through the HPA axis with the accompanying suppression of the immune system resulting in viral reactivation. This information is essential to determine if latent viral reactivation among crewmembers represents a sufficient medical risk to space travel to require the development of suitable countermeasures.

Epigenetic Treatment of Persistent Viral Infections.

PubMed

Moos, Walter H; Pinkert, Carl A; Irwin, Michael H; Faller, Douglas V; Kodukula, Krishna; Glavas, Ioannis P; Steliou, Kosta

2017-02-01

Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population. Exploring the population diversity of the human microbiome and the effects its compositional variances have on the immune system, health, and disease are the subjects of intense investigational research and study. Among the collection of viruses, bacteria, fungi, and single-cell eukaryotes that comprise the human microbiome, the virome has been grossly understudied relative to the influence it exerts on human pathophysiology, much as mitochondria have until recently failed to receive the attention they deserve, given their critical biomedical importance. Fortunately, cellular epigenetic machinery offers a wealth of druggable targets for therapeutic intervention in numerous disease indications, including those outlined above. With advances in synthetic biology, engineering our body's commensal microorganisms to seek out and destroy pathogenic species is clearly on the horizon. This is especially the case given recent breakthroughs in genetic manipulation with tools such as the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) gene-editing platforms. Tying these concepts together with our previous work on the microbiome and neurodegenerative and neuropsychiatric diseases, we suggest that, because mammalian cells

Thousands of Viral Populations Recovered from Peatland Soil Metagenomes Reveal Viral Impacts on Carbon Cycling in Thawing Permafrost

NASA Astrophysics Data System (ADS)

Emerson, J. B.; Brum, J. R.; Roux, S.; Bolduc, B.; Woodcroft, B. J.; Singleton, C. M.; Boyd, J. A.; Hodgkins, S. B.; Wilson, R.; Trubl, G. G.; Jang, H. B.; Crill, P. M.; Chanton, J.; Saleska, S. R.; Rich, V. I.; Tyson, G. W.; Sullivan, M. B.

2016-12-01

Methane and carbon dioxide emissions, which are under significant microbial control, provide positive feedbacks to climate change in thawing permafrost peatlands. Although viruses in marine systems have been shown to impact microbial ecology and biogeochemical cycling through host cell lysis, horizontal gene transfer, and auxiliary metabolic gene expression, viral ecology in permafrost and other soils remains virtually unstudied due to methodological challenges. Here, we identified viral sequences in 208 assembled bulk soil metagenomes derived from a permafrost thaw gradient in Stordalen Mire, northern Sweden, from 2010-2012. 2,048 viral populations were recovered, which genome- and network-based classification revealed to be largely novel, increasing known viral genera globally by 40%. Ecologically, viral communities differed significantly across the thaw gradient and by soil depth. Co-occurring microbial community composition, soil moisture, and pH were predictors of viral community composition, indicative of biological and biogeochemical feedbacks as permafrost thaws. Host prediction—achieved through clustered regularly interspaced short palindromic repeats (CRISPRs), tetranucleotide frequency patterns, and other sequence similarities to binned microbial population genomes—was able to link 38% of the viral populations to a microbial host. 5% of the implicated hosts were archaea, predominantly methanogens and ammonia-oxidizing Nitrososphaera, 45% were Acidobacteria or Verrucomicrobia (mostly predicted heterotrophic complex carbon degraders), and 21% were Proteobacteria, including methane oxidizers. Recovered viral genome fragments also contained auxiliary metabolic genes involved in carbon and nitrogen cycling. Together, these data reveal multiple levels of previously unknown viral contributions to biogeochemical cycling, including to carbon gas emissions, in peatland soils undergoing and contributing to climate change. This work represents a significant step

Biological Gene Delivery Vehicles: Beyond Viral Vectors

PubMed Central

Seow, Yiqi; Wood, Matthew J

2009-01-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications. PMID:19277019

Biological gene delivery vehicles: beyond viral vectors.

PubMed

Seow, Yiqi; Wood, Matthew J

2009-05-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications.

Waterborne viral infections and their prevention

PubMed Central

Chang, Shih L.

1968-01-01

Unless special measures are taken, community water supplies are likely to contain enteric viruses which may lead to sporadic cases, or even epidemics, of such diseases as infectious hepatitis or poliomyelitis. After a general discussion of waterborne viral infections, in which it is pointed out that subclinical infections may considerably outnumber clinical cases, the author proposes a method for the concentration and detection of enteric viruses in water by means of membrane filtration and growth on monkey-kidney-cell or other tissue cultures. The various methods of disinfection of water which can reduce the virus concentration to an acceptable level are discussed, and it is concluded that flocculation and filtration followed by chlorination, or ozonation followed by chlorination, are adequate methods where large volumes of water are to be treated. In developing countries where relatively small volumes of water have to be treated, iodination appears to offer certain advantages, allowing the construction of a simple water-treatment plant requiring little supervision. However, until the long-term effects of iodine, in particular on pregnant women and young children, are known iodination plants should be used only on an experimental basis. PMID:5302332

Animal models of viral hemorrhagic fever.

PubMed

Smith, Darci R; Holbrook, Michael R; Gowen, Brian B

2014-12-01

The term "viral hemorrhagic fever" (VHF) designates a syndrome of acute febrile illness, increased vascular permeability and coagulation defects which often progresses to bleeding and shock and may be fatal in a significant percentage of cases. The causative agents are some 20 different RNA viruses in the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae, which are maintained in a variety of animal species and are transferred to humans through direct or indirect contact or by an arthropod vector. Except for dengue, which is transmitted among humans by mosquitoes, the geographic distribution of each type of VHF is determined by the range of its animal reservoir. Treatments are available for Argentine HF and Lassa fever, but no approved countermeasures have been developed against other types of VHF. The development of effective interventions is hindered by the sporadic nature of most infections and their occurrence in geographic regions with limited medical resources. Laboratory animal models that faithfully reproduce human disease are therefore essential for the evaluation of potential vaccines and therapeutics. The goal of this review is to highlight the current status of animal models that can be used to study the pathogenesis of VHF and test new countermeasures. Copyright © 2014 Elsevier B.V. All rights reserved.

Undiagnosed Acute Viral Febrile Illnesses, Sierra Leone

PubMed Central

Rossi, Cynthia A.; Khan, Sheik H.; Goba, Augustine; Fair, Joseph N.

2014-01-01

Sierra Leone in West Africa is in a Lassa fever–hyperendemic region that also includes Guinea and Liberia. Each year, suspected Lassa fever cases result in submission of ≈500–700 samples to the Kenema Government Hospital Lassa Diagnostic Laboratory in eastern Sierra Leone. Generally only 30%–40% of samples tested are positive for Lassa virus (LASV) antigen and/or LASV-specific IgM; thus, 60%–70% of these patients have acute diseases of unknown origin. To investigate what other arthropod-borne and hemorrhagic fever viral diseases might cause serious illness in this region and mimic Lassa fever, we tested patient serum samples that were negative for malaria parasites and LASV. Using IgM-capture ELISAs, we evaluated samples for antibodies to arthropod-borne and other hemorrhagic fever viruses. Approximately 25% of LASV-negative patients had IgM to dengue, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola, and Marburg viruses but not to Crimean-Congo hemorrhagic fever virus. PMID:24959946

Good manufacturing practice and viral safety.

PubMed

Kerner, B

1995-07-01

The concept of virus inactivation during the manufacture of blood products raises questions about possible recontamination of the product by the environment. A strict regime of good manufacturing practice (GMP) is mandatory. The guidelines originally issued by the World Health Organization (WHO), and now law in most countries, are an excellent basis for the operation of a production plant. The following elements of GMP require special concern: (i) All functions shall be defined in a clear organization chart. (ii) Personnel shall be appropriately trained for the job and to perfect hygiene. (iii) Buildings and facilities, as well as supply systems, shall exclude the possibility of recontamination of already virus-inactivated materials. (iv) Equipment shall be easy to clean and fully sterilizable. (v) Production shall follow appropriate written procedures. (vi) The Quality Control Organization shall monitor the process by in-process controls and review the records for possible deviations. All GMP issues are coordinated by a Quality Assurance Organization that also reviews the overall performance of the operation. The maintenance of viral safety of the products basically depends upon the full commitment of all bodies involved to proper and non-negotiable GMP.

Evolution of viral virulence: empirical studies

USGS Publications Warehouse

Kurath, Gael; Wargo, Andrew R.

2016-01-01

The concept of virulence as a pathogen trait that can evolve in response to selection has led to a large body of virulence evolution theory developed in the 1980-1990s. Various aspects of this theory predict increased or decreased virulence in response to a complex array of selection pressures including mode of transmission, changes in host, mixed infection, vector-borne transmission, environmental changes, host vaccination, host resistance, and co-evolution of virus and host. A fundamental concept is prediction of trade-offs between the costs and benefits associated with higher virulence, leading to selection of optimal virulence levels. Through a combination of observational and experimental studies, including experimental evolution of viruses during serial passage, many of these predictions have now been explored in systems ranging from bacteriophage to viruses of plants, invertebrates, and vertebrate hosts. This chapter summarizes empirical studies of viral virulence evolution in numerous diverse systems, including the classic models myxomavirus in rabbits, Marek's disease virus in chickens, and HIV in humans. Collectively these studies support some aspects of virulence evolution theory, suggest modifications for other aspects, and show that predictions may apply in some virus:host interactions but not in others. Finally, we consider how virulence evolution theory applies to disease management in the field.

The three lives of viral fusion peptides

PubMed Central

Apellániz, Beatriz; Huarte, Nerea; Largo, Eneko; Nieva, José L.

2014-01-01

Fusion peptides comprise conserved hydrophobic domains absolutely required for the fusogenic activity of glycoproteins from divergent virus families. After 30 years of intensive research efforts, the structures and functions underlying their high degree of sequence conservation are not fully elucidated. The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis. Firstly, the VFP sequence must fulfill the set of native interactions required for (meta) stable folding within the globular ectodomains of glycoprotein complexes. Secondly, at the onset of the fusion process, they get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Here we review different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions, and discuss briefly their potential as targets for clinical intervention. PMID:24704587

Packaging DNA Origami into Viral Protein Cages.

PubMed

Linko, Veikko; Mikkilä, Joona; Kostiainen, Mauri A

2018-01-01

The DNA origami technique is a widely used method to create customized, complex, spatially well-defined two-dimensional (2D) and three-dimensional (3D) DNA nanostructures. These structures have huge potential to serve as smart drug-delivery vehicles and molecular devices in various nanomedical and biotechnological applications. However, so far only little is known about the behavior of these novel structures in living organisms or in cell culture/tissue models. Moreover, enhancing pharmacokinetic bioavailability and transfection properties of such structures still remains a challenge. One intriguing approach to overcome these issues is to coat DNA origami nanostructures with proteins or lipid membranes. Here, we show how cowpea chlorotic mottle virus (CCMV) capsid proteins (CPs) can be used for coating DNA origami nanostructures. We present a method for disassembling native CCMV particles and isolating the pure CP dimers, which can further bind and encapsulate a rectangular DNA origami shape. Owing to the highly programmable nature of DNA origami, packaging of DNA nanostructures into viral protein cages could find imminent uses in enhanced targeting and cellular delivery of various active nano-objects, such as enzymes and drug molecules.

Coarse-grained mechanics of viral shells

NASA Astrophysics Data System (ADS)

Klug, William S.; Gibbons, Melissa M.

2008-03-01

We present an approach for creating three-dimensional finite element models of viral capsids from atomic-level structural data (X-ray or cryo-EM). The models capture heterogeneous geometric features and are used in conjunction with three-dimensional nonlinear continuum elasticity to simulate nanoindentation experiments as performed using atomic force microscopy. The method is extremely flexible; able to capture varying levels of detail in the three-dimensional structure. Nanoindentation simulations are presented for several viruses: Hepatitis B, CCMV, HK97, and φ29. In addition to purely continuum elastic models a multiscale technique is developed that combines finite-element kinematics with MD energetics such that large-scale deformations are facilitated by a reduction in degrees of freedom. Simulations of these capsid deformation experiments provide a testing ground for the techniques, as well as insight into the strength-determining mechanisms of capsid deformation. These methods can be extended as a framework for modeling other proteins and macromolecular structures in cell biology.

Leucopenia associated with abalone viral ganglioneuritis.

PubMed

Hooper, C; Slocombe, R; Day, R; Crawford, S

2012-01-01

To compare microscopic lesion severity with circulating total haemocyte counts (THC) in abalone affected by abalone viral ganglioneuritis (AVG). A herpes-like virus led to severe mortality in a number of Australian abalone farms in 2006. The infection was associated with severe necrotising ganglioneuritis. The microscopic lesions were well demarcated, affecting the neural tissue almost exclusively and were characterised by necrosis and increased cellularity in affected ganglia and nerves. On two farms, the presence or absence of typical AVG pathology was compared with THC. Those abalone with microscopic lesions of AVG had significantly lower haemocyte counts. The mean THC in abalone with no evidence of AVG from both farms was 4.6 × 10(6)/mL (±0.3 SE). The THC in AVG-affected abalone in farm 1 was 2.8 × 10(6)/mL (±0.5 SE) and farm 2 was 0.98 × 10(6)/mL (±0.4 SE). Severe AVG is associated with leucopenia in affected abalone. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

A viral peptide for intracellular delivery

NASA Astrophysics Data System (ADS)

Falanga, Annarita; Tarallo, Rossella; Cantisani, Marco; Della Pepa, Maria Elena; Galdiero, Massimiliano; Galdiero, Stefania

2012-10-01

Biological membranes represent a critical hindrance for administering active molecules which are often unable to reach their designated intracellular target sites. In order to overcome this barrier-like behavior not easily circumvented by many pharmacologically-active molecules, synthetic transporters have been exploited to promote cellular uptake. Linking or complexing therapeutic molecules to peptides that can translocate through the cellular membranes could enhance their internal delivery, and consequently, a higher amount of active compound would reach the site of action. Use of cell penetrating peptides (CPPs) is one of the most promising strategy to efficiently translocate macromolecules through the plasma membrane, and have attracted a lot of attention. New translocating peptides are continuously described and in the present review, we will focus on viral derived peptides, and in particular a peptide (gH625) derived from the herpes simplex virus type 1 (HSV-1) glycoprotein H (gH) that has proved to be a useful delivery vehicle due to its intrinsic properties of inducing membrane perturbation.

Immunization with viral antigens: Infectious haematopoietic necrosis

USGS Publications Warehouse

Winton, J.R.; Midtlyng, Paul J.; Brown, F.

1997-01-01

Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease.

Viral factors in influenza pandemic risk assessment

PubMed Central

Lipsitch, Marc; Barclay, Wendy; Raman, Rahul; Russell, Charles J; Belser, Jessica A; Cobey, Sarah; Kasson, Peter M; Lloyd-Smith, James O; Maurer-Stroh, Sebastian; Riley, Steven; Beauchemin, Catherine AA; Bedford, Trevor; Friedrich, Thomas C; Handel, Andreas; Herfst, Sander; Murcia, Pablo R; Roche, Benjamin; Wilke, Claus O; Russell, Colin A

2016-01-01

The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk. DOI: http://dx.doi.org/10.7554/eLife.18491.001 PMID:27834632

Emerging viral diseases of fish and shrimp

USGS Publications Warehouse

Winton, James R.; Walker, Peter J.

2010-01-01

The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change.

Viral and Synthetic RNA Vector Technologies and Applications

PubMed Central

Schott, Juliane W; Morgan, Michael; Galla, Melanie; Schambach, Axel

2016-01-01

Use of RNA is an increasingly popular method to transiently deliver genetic information for cell manipulation in basic research and clinical therapy. In these settings, viral and nonviral RNA platforms are employed for delivery of small interfering RNA and protein-coding mRNA. Technological advances allowing RNA modification for increased stability, improved translation and reduced immunogenicity have led to increased use of nonviral synthetic RNA, which is delivered in naked form or upon formulation. Alternatively, highly efficient viral entry pathways are exploited to transfer genes of interest as RNA incorporated into viral particles. Current viral RNA transfer technologies are derived from Retroviruses, nonsegmented negative-strand RNA viruses or positive-stranded Alpha- and Flaviviruses. In retroviral particles, the genes of interest can either be incorporated directly into the viral RNA genome or as nonviral RNA. Nonsegmented negative-strand virus-, Alpha- and Flavivirus-derived vectors support prolonged expression windows through replication of viral RNA encoding genes of interest. Mixed technologies combining viral and nonviral components are also available. RNA transfer is ideal for all settings that do not require permanent transgene expression and excludes potentially detrimental DNA integration into the target cell genome. Thus, RNA-based technologies are successfully applied for reprogramming, transdifferentiation, gene editing, vaccination, tumor therapy, and gene therapy. PMID:27377044

A comprehensive and quantitative exploration of thousands of viral genomes

PubMed Central

Mahmoudabadi, Gita

2018-01-01

The complete assembly of viral genomes from metagenomic datasets (short genomic sequences gathered from environmental samples) has proven to be challenging, so there are significant blind spots when we view viral genomes through the lens of metagenomics. One approach to overcoming this problem is to leverage the thousands of complete viral genomes that are publicly available. Here we describe our efforts to assemble a comprehensive resource that provides a quantitative snapshot of viral genomic trends – such as gene density, noncoding percentage, and abundances of functional gene categories – across thousands of viral genomes. We have also developed a coarse-grained method for visualizing viral genome organization for hundreds of genomes at once, and have explored the extent of the overlap between bacterial and bacteriophage gene pools. Existing viral classification systems were developed prior to the sequencing era, so we present our analysis in a way that allows us to assess the utility of the different classification systems for capturing genomic trends. PMID:29624169

A comparison of methods for determining HIV viral set point.

PubMed

Mei, Y; Wang, L; Holte, S E

2008-01-15

During a course of human immunodeficiency virus (HIV-1) infection, the viral load usually increases sharply to a peak following infection and then drops rapidly to a steady state, where it remains until progression to AIDS. This steady state is often referred to as the viral set point. It is believed that the HIV viral set point results from an equilibrium between the HIV virus and immune response and is an important indicator of AIDS disease progression. In this paper, we analyze a real data set of viral loads measured before antiretroviral therapy is initiated, and propose two-phase regression models to utilize all available data to estimate the viral set point. The advantages of the proposed methods are illustrated by comparing them with two empirical methods, and the reason behind the improvement is also studied. Our results illustrate that for our data set, the viral load data are highly correlated and it is cost effective to estimate the viral set point based on one or two measurements obtained between 5 and 12 months after HIV infection. The utility and limitations of this recommendation will be discussed. Copyright (c) 2007 John Wiley & Sons, Ltd.

A comprehensive and quantitative exploration of thousands of viral genomes.

PubMed

Mahmoudabadi, Gita; Phillips, Rob

2018-04-19

The complete assembly of viral genomes from metagenomic datasets (short genomic sequences gathered from environmental samples) has proven to be challenging, so there are significant blind spots when we view viral genomes through the lens of metagenomics. One approach to overcoming this problem is to leverage the thousands of complete viral genomes that are publicly available. Here we describe our efforts to assemble a comprehensive resource that provides a quantitative snapshot of viral genomic trends - such as gene density, noncoding percentage, and abundances of functional gene categories - across thousands of viral genomes. We have also developed a coarse-grained method for visualizing viral genome organization for hundreds of genomes at once, and have explored the extent of the overlap between bacterial and bacteriophage gene pools. Existing viral classification systems were developed prior to the sequencing era, so we present our analysis in a way that allows us to assess the utility of the different classification systems for capturing genomic trends. © 2018, Mahmoudabadi et al.

Molecular indices of viral disease development in wild migrating salmon†.

PubMed

Miller, Kristina M; Günther, Oliver P; Li, Shaorong; Kaukinen, Karia H; Ming, Tobi J

2017-01-01

Infectious diseases can impact the physiological performance of individuals, including their mobility, visual acuity, behavior and tolerance and ability to effectively respond to additional stressors. These physiological effects can influence competitiveness, social hierarchy, habitat usage, migratory behavior and risk to predation, and in some circumstances, viability of populations. While there are multiple means of detecting infectious agents (microscopy, culture, molecular assays), the detection of infectious diseases in wild populations in circumstances where mortality is not observable can be difficult. Moreover, if infection-related physiological compromise leaves individuals vulnerable to predation, it may be rare to observe wildlife in a late stage of disease. Diagnostic technologies designed to diagnose cause of death are not always sensitive enough to detect early stages of disease development in live-sampled organisms. Sensitive technologies that can differentiate agent carrier states from active disease states are required to demonstrate impacts of infectious diseases in wild populations. We present the discovery and validation of salmon host transcriptional biomarkers capable of distinguishing fish in an active viral disease state [viral disease development (VDD)] from those carrying a latent viral infection, and viral versus bacterial disease states. Biomarker discovery was conducted through meta-analysis of published and in-house microarray data, and validation performed on independent datasets including disease challenge studies and farmed salmon diagnosed with various viral, bacterial and parasitic diseases. We demonstrate that the VDD biomarker panel is predictive of disease development across RNA-viral species, salmon species and salmon tissues, and can recognize a viral disease state in wild-migrating salmon. Moreover, we show that there is considerable overlap in the biomarkers resolved in our study in salmon with those based on similar human

Molecular indices of viral disease development in wild migrating salmon†

PubMed Central

Günther, Oliver P.; Li, Shaorong; Kaukinen, Karia H.; Ming, Tobi J.

2017-01-01

Abstract Infectious diseases can impact the physiological performance of individuals, including their mobility, visual acuity, behavior and tolerance and ability to effectively respond to additional stressors. These physiological effects can influence competitiveness, social hierarchy, habitat usage, migratory behavior and risk to predation, and in some circumstances, viability of populations. While there are multiple means of detecting infectious agents (microscopy, culture, molecular assays), the detection of infectious diseases in wild populations in circumstances where mortality is not observable can be difficult. Moreover, if infection-related physiological compromise leaves individuals vulnerable to predation, it may be rare to observe wildlife in a late stage of disease. Diagnostic technologies designed to diagnose cause of death are not always sensitive enough to detect early stages of disease development in live-sampled organisms. Sensitive technologies that can differentiate agent carrier states from active disease states are required to demonstrate impacts of infectious diseases in wild populations. We present the discovery and validation of salmon host transcriptional biomarkers capable of distinguishing fish in an active viral disease state [viral disease development (VDD)] from those carrying a latent viral infection, and viral versus bacterial disease states. Biomarker discovery was conducted through meta-analysis of published and in-house microarray data, and validation performed on independent datasets including disease challenge studies and farmed salmon diagnosed with various viral, bacterial and parasitic diseases. We demonstrate that the VDD biomarker panel is predictive of disease development across RNA-viral species, salmon species and salmon tissues, and can recognize a viral disease state in wild-migrating salmon. Moreover, we show that there is considerable overlap in the biomarkers resolved in our study in salmon with those based on

[Atomic force microscopy: a tool to analyze the viral cycle].

PubMed

Bernaud, Julien; Castelnovo, Martin; Muriaux, Delphine; Faivre-Moskalenko, Cendrine

2015-05-01

Each step of the HIV-1 life cycle frequently involves a change in the morphology and/or mechanical properties of the viral particle or core. The atomic force microscope (AFM) constitutes a powerful tool for characterizing these physical changes at the scale of a single virus. Indeed, AFM enables the visualization of viral capsids in a controlled physiological environment and to probe their mechanical properties by nano-indentation. Finally, AFM force spectroscopy allows to characterize the affinities between viral envelope proteins and cell receptors at the single molecule level. © 2015 médecine/sciences – Inserm.

An unexpected twist in viral capsid maturation

SciTech Connect

Gertsman, Ilya; Gan, Lu; Guttman, Miklos

2009-04-14

Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsidmore » structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 {angstrom} resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 {angstrom}. A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and -sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol{sup -1} of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an

Emerging viral diseases of fish and shrimp

PubMed Central

Walker, Peter J.; Winton, James R.

2010-01-01

The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change. PMID:20409453

Intercellular Transfer of a Soluble Viral Superantigen

PubMed Central

Reilly, Melissa; Mix, Denise; Reilly, Andrew A.; Yang Ye, Xiang; Winslow, Gary M.

2000-01-01

Mouse mammary tumor virus (MMTV) superantigens (vSAgs) can undergo intercellular transfer in vivo and in vitro such that a vSAg can be presented to T cells by major histocompatibility complex (MHC) class II proteins on antigen-presenting cells (APCs) that do not express the superantigen. This process may allow T-cell activation to occur prior to viral infection. Consistent with these findings, vSAg produced by Chinese hamster ovary (CHO) cells was readily transferred to class II IE and IA (H-2k and H-2d) proteins on a B-cell lymphoma or mouse splenocytes. Fixed class II-expressing acceptor cells were used to demonstrate that the vSAg, but not the class II proteins, underwent intercellular transfer, indicating that vSAg binding to class II MHC could occur directly at the cell surface. Intercellular transfer also occurred efficiently to splenocytes from endogenous retrovirus-free mice, indicating that other proviral proteins were not involved. Presentation of vSAg7 produced by a class II-negative, furin protease-deficient CHO variant (FD11) was unsuccessful, indicating that proteolytic processing was a requisite event and that proteolytic activity could not be provided by an endoprotease on the acceptor APC. Furthermore, vSAg presentation was effected using cell-free supernatant from class II-negative, vSAg-positive cells, indicating that a soluble molecule, most likely produced by proteolytic processing, was sufficient to stimulate T cells. Because the membrane-proximal endoproteolytic cleavage site in the vSAg (residues 68 to 71) was not necessary for intercellular transfer, the data support the notion that the carboxy-terminal endoproteolytic cleavage product is an active vSAg moiety. PMID:10954523

Ribavirin has a Demonstrable Effect on Crimean-Congo Hemorrhagic Fever Viral Populations and Viral Load during Patient Treatment.

PubMed

Espy, Nicole; Pérez-Sautu, Unai; Ramírez de Arellano, Eva; Negredo, Anabel; Wiley, Michael R; Bavari, Sina; Díaz Menendez, Marta; Paz Sánchez-Seco, María; Palacios, Gustavo

2018-03-23

The use of ribavirin to treat infections of Crimean-Congo Hemorrhagic Fever virus (CCHFV) has been controversial based on uncertainties on its antiviral efficacy in clinical case studies. We studied the effect of ribavirin treatment on viral populations in a recent case by deep sequencing plasma samples taken from a CCHFV-infected patient before, during, and after a five-day regimen of ribavirin. CCHFV viral load dropped during ribavirin treatment and subclonal diversity (transitions) and indels increased in viral genomes during treatment. Although the results are based on a single case, these data demonstrate the mutagenic effect of ribavirin on CCHFV in vivo. (Word Count: 100).

[Innate immune responses against viral infection and its suppression by viral proteins].

PubMed

Oshiumi, Hiroyuki; Matsumoto, Misako; Seya, Tsukasa

2013-01-01

Retinoic acid-inducible gene-I(RIG-I) is a cytoplasmic RNA helicase and a viral RNA sensor. RIG-I recognizes 5' triphosphate double-stranded RNA (dsRNA) and activates the IPS-1 adaptor molecule. The association of IPS-1 with RIG-I causes the formation of the prion-like structure of IPS-1. This structure is essential for activation of the signaling required for the induction of type I interferon (IFN), which possesses strong antiviral activity. Recent studies have revealed the novel factors involved in the RIG-I-dependent pathway. DDX3 and DDX60 RNA helicases associate with RIG-I and promote its binding to viral RNA. Riplet and TRIM25 ubiquitin ligase deliver Lys63-linked polyubiquitin moiety to RIG-I and result in signal activation. Several pathogenic viruses have evolved excellent systems to suppress type I IFN production. For example, NS3-4A of hepatitis C virus (HCV) cleaves IPS-1, which is the adaptor molecule of RIG-I, while the HCV core protein abrogates DDX3 function to suppress RIG-I-dependent IPS-1 activation, and the NS-1 of flu inhibits TRIM25 function to suppress RIG-I activation.

Dampened antiviral immunity to intravaginal exposure to RNA viral pathogens allows enhanced viral replication

PubMed Central

Woodruff, Erik M.; Trapecar, Martin; Fontaine, Krystal A.; Ezaki, Ashley; Ott, Melanie

2016-01-01

Understanding the host immune response to vaginal exposure to RNA viruses is required to combat sexual transmission of this class of pathogens. In this study, using lymphocytic choriomeningitis virus (LCMV) and Zika virus (ZIKV) in wild-type mice, we show that these viruses replicate in the vaginal mucosa with minimal induction of antiviral interferon and inflammatory response, causing dampened innate-mediated control of viral replication and a failure to mature local antigen-presenting cells (APCs). Enhancement of innate-mediated inflammation in the vaginal mucosa rescues this phenotype and completely inhibits ZIKV replication. To gain a better understanding of how this dampened innate immune activation in the lower female reproductive tract may also affect adaptive immunity, we modeled CD8 T cell responses using vaginal LCMV infection. We show that the lack of APC maturation in the vaginal mucosa leads to a delay in CD8 T cell activation in the draining lymph node and hinders the timely appearance of effector CD8 T cells in vaginal mucosa, thus further delaying viral control in this tissue. Our study demonstrates that vaginal tissue is exceptionally vulnerable to infection by RNA viruses and provides a conceptual framework for the male to female sexual transmission observed during ZIKV infection. PMID:27852793

Prophage-mediated defense against viral attack and viral counter-defense

PubMed Central

Dedrick, Rebekah M.; Jacobs-Sera, Deborah; Guerrero Bustamante, Carlos A.; Garlena, Rebecca A.; Mavrich, Travis N.; Pope, Welkin H.; Reyes, Juan C Cervantes; Russell, Daniel A.; Adair, Tamarah; Alvey, Richard; Bonilla, J. Alfred; Bricker, Jerald S.; Brown, Bryony R.; Byrnes, Deanna; Cresawn, Steven G.; Davis, William B.; Dickson, Leon A.; Edgington, Nicholas P.; Findley, Ann M.; Golebiewska, Urszula; Grose, Julianne H.; Hayes, Cory F.; Hughes, Lee E.; Hutchison, Keith W.; Isern, Sharon; Johnson, Allison A.; Kenna, Margaret A.; Klyczek, Karen K.; Mageeney, Catherine M.; Michael, Scott F.; Molloy, Sally D.; Montgomery, Matthew T.; Neitzel, James; Page, Shallee T.; Pizzorno, Marie C.; Poxleitner, Marianne K.; Rinehart, Claire A.; Robinson, Courtney J.; Rubin, Michael R.; Teyim, Joseph N.; Vazquez, Edwin; Ware, Vassie C.; Washington, Jacqueline; Hatfull, Graham F.

2017-01-01

Temperate phages are common and prophages are abundant residents of sequenced bacterial genomes. Mycobacteriophages are viruses infecting mycobacterial hosts including Mycobacterium tuberculosis and Mycobacterium smegmatis, encompass substantial genetic diversity, and are commonly temperate. Characterization of ten Cluster N temperate mycobacteriophages reveals at least five distinct prophage-expressed viral defense systems that interfere with infection of lytic and temperate phages that are either closely-related (homotypic defense) or unrelated (heterotypic defense). Target specificity is unpredictable, ranging from a single target phage to one-third of those tested. The defense systems include a single-subunit restriction system, a heterotypic exclusion system, and a predicted (p)ppGpp synthetase, which blocks lytic phage growth, promotes bacterial survival, and enables efficient lysogeny. The predicted (p)ppGpp synthetase coded by the Phrann prophage defends against phage Tweety infection, but Tweety codes for a tetrapeptide repeat protein, gp54, that acts as a highly effective counter-defense system. Prophage-mediated viral defense offers an efficient mechanism for bacterial success in host-virus dynamics, and counter-defense promotes phage co-evolution. PMID:28067906

Viral entry pathways: the example of common cold viruses.

PubMed

Blaas, Dieter

2016-05-01

For infection, viruses deliver their genomes into the host cell. These nucleic acids are usually tightly packed within the viral capsid, which, in turn, is often further enveloped within a lipid membrane. Both protect them against the hostile environment. Proteins and/or lipids on the viral particle promote attachment to the cell surface and internalization. They are likewise often involved in release of the genome inside the cell for its use as a blueprint for production of new viruses. In the following, I shall cursorily discuss the early more general steps of viral infection that include receptor recognition, uptake into the cell, and uncoating of the viral genome. The later sections will concentrate on human rhinoviruses, the main cause of the common cold, with respect to the above processes. Much of what is known on the underlying mechanisms has been worked out by Renate Fuchs at the Medical University of Vienna.

Expanding the histological findings in postvaccinial non-viral folliculitis

PubMed Central

Bunick, Christopher G.; Mariwalla, Kavita; Ibrahim, Omer; Modi, Badri; Imaeda, Suguru; McNiff, Jennifer

2014-01-01

Postvaccinial non-viral folliculitis has been recognized in the past decade as a new adverse cutaneous reaction to the smallpox vaccination. Contrary to more serious smallpox vaccine reactions, postvaccinial non-viral folliculitis has a benign course resolving spontaneously within approximately seven days. We describe additional histopathological findings associated with postvaccinial non-viral folliculitis, which has only been described once previously. New findings include the presence of neutrophilic or lymphohistiocytic infiltrates that concentrate around the hair follicles. We compare our findings to the follicular nature of varicella and herpes zoster infections, generating the hypothesis of deposition of vaccinia protein within folliculosebaceous units as a potential pathophysiologic mechanism behind postvaccinial non-viral folliculitis. PMID:23278890

Global trends in emerging viral diseases of wildlife origin

USGS Publications Warehouse

Sleeman, Jonathan M.; Ip, Hon S.

2015-01-01

The following article provides examples of recently emerged viral diseases of wildlife origin. The examples have been selected to illustrate the drivers of emerging viral diseases, both novel pathogens and previously known diseases, the impacts of these diseases, as well as the role of wildlife both as “villains” or reservoirs as well as “victims” of these viral diseases. The article also discusses potential management strategies for emerging viral diseases in wildlife populations and future science directions in wildlife health to prevent, prepare, respond to, and recover from these disease events. Finally, the concept of One Health and its potential role in developing solutions to these issues of mutual concern is discussed.

Nucleic Acid-Based Approaches for Detection of Viral Hepatitis

PubMed Central

Behzadi, Payam; Ranjbar, Reza; Alavian, Seyed Moayed

2014-01-01

Context: To determining suitable nucleic acid diagnostics for individual viral hepatitis agent, an extensive search using related keywords was done in major medical library and data were collected, categorized, and summarized in different sections. Results: Various types of molecular biology tools can be used to detect and quantify viral genomic elements and analyze the sequences. These molecular assays are proper technologies for rapidly detecting viral agents with high accuracy, high sensitivity, and high specificity. Nonetheless, the application of each diagnostic method is completely dependent on viral agent. Conclusions: Despite rapidity, automation, accuracy, cost-effectiveness, high sensitivity, and high specificity of molecular techniques, each type of molecular technology has its own advantages and disadvantages. PMID:25789132

RNA Recombination In Vivo in the Absence of Viral Replication

PubMed Central

Gallei, Andreas; Pankraz, Alexander; Thiel, Heinz-Jürgen; Becher, Paul

2004-01-01

To study fundamental aspects of RNA recombination, an in vivo RNA recombination system was established. This system allowed the efficient generation of recombinant cytopathogenic pestiviruses after transfection of synthetic, nonreplicatable, subgenomic transcripts in cells infected with a replicating noncytopathogenic virus. Studies addressing the interplay between RNA recombination and replication revealed that cotransfection of noninfected cells with various pairs of nonreplicatable RNA derivatives also led to the emergence of recombinant viral genomes. Remarkably, homologous and nonhomologous recombination occurred between two overlapping transcripts, each lacking different essential parts of the viral RNA-dependent RNA polymerase (RdRp) gene. Apart from the generally accepted viral replicative copy choice recombination, our results prove the existence of a viral RdRp-independent mechanism of RNA recombination that occurs in vivo. It appears likely that such a mechanism not only contributes to the evolution of RNA viruses but also leads to the generation of recombinant cellular RNAs. PMID:15163720

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

Physical non-viral gene delivery methods for tissue engineering.

PubMed

Mellott, Adam J; Forrest, M Laird; Detamore, Michael S

2013-03-01

The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that "fits-all" cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications.

Physical non-viral gene delivery methods for tissue engineering

PubMed Central

Mellott, Adam J.; Forrest, M. Laird; Detamore, Michael S.

2016-01-01

The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that “fits-all” cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications. PMID:23099792

Dry eye disease caused by viral infection: review.

PubMed

Alves, Monica; Angerami, Rodrigo Nogueira; Rocha, Eduardo Melani

2013-01-01

Dry eye disease and ocular surface disorders may be caused or worsened by viral agents. There are several known and suspected virus associated to ocular surface diseases. The possible pathogenic mechanisms for virus-related dry eye disease are presented herein. This review serves to reinforce the importance of ophthalmologists as one of the healthcare professional able to diagnose a potentially large number of infected patients with high prevalent viral agents.

Impact of xynthia tempest on viral contamination of shellfish.

PubMed

Grodzki, Marco; Ollivier, Joanna; Le Saux, Jean-Claude; Piquet, Jean-Côme; Noyer, Mathilde; Le Guyader, Françoise S

2012-05-01

Viral contamination in oyster and mussel samples was evaluated after a massive storm with hurricane wind named "Xynthia tempest" destroyed a number of sewage treatment plants in an area harboring many shellfish farms. Although up to 90% of samples were found to be contaminated 2 days after the disaster, detected viral concentrations were low. A 1-month follow-up showed a rapid decrease in the number of positive samples, even for norovirus.

Zika viral dynamics and shedding in rhesus and cynomolgus macaques

DOE PAGES

Osuna, Christa E.; Lim, So -Yon; Deleage, Claire; ...

2016-10-03

Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection wasmore » cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Finally, early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans.« less

Rituximab-related viral infections in lymphoma patients.

PubMed

Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Dede, Didem Sener; Dizdar, Omer; Altundag, Kadri; Barista, Ibrahim

2007-07-01

Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkin's lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 - 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 - 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.

Viral Infections in Pregnancy: A Focus on Ebola Virus.

PubMed

Olgun, Nicole S

2018-01-30

During gestation, the immune response of the placenta to viruses and other pathogens plays an important role in determining a pregnant woman's vulnerability toward infectious diseases. Located at the maternal- fetal interface, trophoblast cells serve to minimize the spread of viruses between the host and developing fetus through an intricate system of innate antiviral immune signaling. Adverse pregnancy outcomes, ranging from learning disabilities to preterm birth and fetal death, are all documented results of a viral breach in the placental barrier. Viral infections during pregnancy can also be spread through blood and vaginal secretions, and during the post-natal period, via breast milk. Thus, even in the absence of vertical transmission of viral infection to the fetus, maternal health can still be compromised and threaten the pregnancy. The most common viral DNA isolates found in gestation are adenovirus, cytomegalovirus, and enterovirus. However, with the recent pandemic of Ebola virus, and the first documented case of a neonate to survive due to experimental therapies in 2017, it is becoming increasingly apparent that the changing roles and impacts of viral infection during pregnancy needs to be better understood, while strategies to minimize adverse pregnancy outcomes need to be identified. This review focuses on the adverse impacts of viral infection during gestation, with an emphasis on Ebola virus. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Translational Control of Viral Gene Expression in Eukaryotes

PubMed Central

Gale, Michael; Tan, Seng-Lai; Katze, Michael G.

2000-01-01

As obligate intracellular parasites, viruses rely exclusively on the translational machinery of the host cell for the synthesis of viral proteins. This relationship has imposed numerous challenges on both the infecting virus and the host cell. Importantly, viruses must compete with the endogenous transcripts of the host cell for the translation of viral mRNA. Eukaryotic viruses have thus evolved diverse mechanisms to ensure translational efficiency of viral mRNA above and beyond that of cellular mRNA. Mechanisms that facilitate the efficient and selective translation of viral mRNA may be inherent in the structure of the viral nucleic acid itself and can involve the recruitment and/or modification of specific host factors. These processes serve to redirect the translation apparatus to favor viral transcripts, and they often come at the expense of the host cell. Accordingly, eukaryotic cells have developed antiviral countermeasures to target the translational machinery and disrupt protein synthesis during the course of virus infection. Not to be outdone, many viruses have answered these countermeasures with their own mechanisms to disrupt cellular antiviral pathways, thereby ensuring the uncompromised translation of virion proteins. Here we review the varied and complex translational programs employed by eukaryotic viruses. We discuss how these translational strategies have been incorporated into the virus life cycle and examine how such programming contributes to the pathogenesis of the host cell. PMID:10839817

Nanotip analysis for dielectrophoretic concentration of nanosized viral particles.

PubMed

Yeo, Woon-Hong; Lee, Hyun-Boo; Kim, Jong-Hoon; Lee, Kyong-Hoon; Chung, Jae-Hyun

2013-05-10

Rapid and sensitive detection of low-abundance viral particles is strongly demanded in health care, environmental control, military defense, and homeland security. Current detection methods, however, lack either assay speed or sensitivity, mainly due to the nanosized viral particles. In this paper, we compare a dendritic, multi-terminal nanotip ('dendritic nanotip') with a single terminal nanotip ('single nanotip') for dielectrophoretic (DEP) concentration of viral particles. The numerical computation studies the concentration efficiency of viral particles ranging from 25 to 100 nm in radius for both nanotips. With DEP and Brownian motion considered, when the particle radius decreases by two times, the concentration time for both nanotips increases by 4-5 times. In the computational study, a dendritic nanotip shows about 1.5 times faster concentration than a single nanotip for the viral particles because the dendritic structure increases the DEP-effective area to overcome the Brownian motion. For the qualitative support of the numerical results, the comparison experiment of a dendritic nanotip and a single nanotip is conducted. Under 1 min of concentration time, a dendritic nanotip shows a higher sensitivity than a single nanotip. When the concentration time is 5 min, the sensitivity of a dendritic nanotip for T7 phage is 10(4) particles ml(-1). The dendritic nanotip-based concentrator has the potential for rapid identification of viral particles.

The role of viral persistence in flavivirus biology

PubMed Central

Mlera, Luwanika; Melik, Wessam; Bloom, Marshall E.

2014-01-01

In nature, vector-borne flaviviruses are persistently cycled between either the tick or mosquito vector and small mammals such as rodents, skunks, and swine. These viruses account for considerable human morbidity and mortality worldwide. Increasing and substantial evidence of viral persistence in humans, which includes the isolation of RNA by RT-PCR and infectious virus by culture, continues to be reported. Viral persistence can also be established in vitro in various human, animal, arachnid and insect cell lines in culture. Although some research has focused on the potential roles of defective virus particles, evasion of the immune response through the manipulation of autophagy and/or apoptosis, the precise mechanism of flavivirus persistence is still not well understood. We propose additional research for further understanding of how viral persistence is established in different systems. Avenues for additional studies include determining if the multifunctional flavivirus protein NS5 has a role in viral persistence, the development of relevant animal models of viral persistence as well as investigating the host responses that allow vector borne flavivirus replication without detrimental effects on infected cells. Such studies might shed more light on the viral-host relationships, and could be used to unravel the mechanisms for establishment of persistence. PMID:24737600

Autoimmune disease: A role for new anti-viral therapies?

PubMed

Dreyfus, David H

2011-12-01

Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism. Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk. Copyright © 2011 Elsevier B.V. All rights reserved.

The Role of Graphlets in Viral Processes on Networks

NASA Astrophysics Data System (ADS)

Khorshidi, Samira; Al Hasan, Mohammad; Mohler, George; Short, Martin B.

2018-05-01

Predicting the evolution of viral processes on networks is an important problem with applications arising in biology, the social sciences, and the study of the Internet. In existing works, mean-field analysis based upon degree distribution is used for the prediction of viral spreading across networks of different types. However, it has been shown that degree distribution alone fails to predict the behavior of viruses on some real-world networks and recent attempts have been made to use assortativity to address this shortcoming. In this paper, we show that adding assortativity does not fully explain the variance in the spread of viruses for a number of real-world networks. We propose using the graphlet frequency distribution in combination with assortativity to explain variations in the evolution of viral processes across networks with identical degree distribution. Using a data-driven approach by coupling predictive modeling with viral process simulation on real-world networks, we show that simple regression models based on graphlet frequency distribution can explain over 95% of the variance in virality on networks with the same degree distribution but different network topologies. Our results not only highlight the importance of graphlets but also identify a small collection of graphlets which may have the highest influence over the viral processes on a network.

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

Insect symbiotic bacteria harbour viral pathogens for transovarial transmission.

PubMed

Jia, Dongsheng; Mao, Qianzhuo; Chen, Yong; Liu, Yuyan; Chen, Qian; Wu, Wei; Zhang, Xiaofeng; Chen, Hongyan; Li, Yi; Wei, Taiyun

2017-03-06

Many insects, including mosquitoes, planthoppers, aphids and leafhoppers, are the hosts of bacterial symbionts and the vectors for transmitting viral pathogens 1-3 . In general, symbiotic bacteria can indirectly affect viral transmission by enhancing immunity and resistance to viruses in insects 3-5 . Whether symbiotic bacteria can directly interact with the virus and mediate its transmission has been unknown. Here, we show that an insect symbiotic bacterium directly harbours a viral pathogen and mediates its transovarial transmission to offspring. We observe rice dwarf virus (a plant reovirus) binding to the envelopes of the bacterium Sulcia, a common obligate symbiont of leafhoppers 6-8 , allowing the virus to exploit the ancient oocyte entry path of Sulcia in rice leafhopper vectors. Such virus-bacterium binding is mediated by the specific interaction of the viral capsid protein and the Sulcia outer membrane protein. Treatment with antibiotics or antibodies against Sulcia outer membrane protein interferes with this interaction and strongly prevents viral transmission to insect offspring. This newly discovered virus-bacterium interaction represents the first evidence that a viral pathogen can directly exploit a symbiotic bacterium for its transmission. We believe that such a model of virus-bacterium communication is a common phenomenon in nature.

Zika viral dynamics and shedding in rhesus and cynomolgus macaques

SciTech Connect

Osuna, Christa E.; Lim, So -Yon; Deleage, Claire

Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection wasmore » cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Finally, early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans.« less

Viral meningitis: current issues in diagnosis and treatment.

PubMed

McGill, Fiona; Griffiths, Michael J; Solomon, Tom

2017-04-01

The purpose of this review is to give an overview of viral meningitis and then focus in on some of the areas of uncertainty in diagnostics, treatment and outcome. Bacterial meningitis has been declining in incidence over recent years. Over a similar time period molecular diagnostics have increasingly been used. Because of both of these developments viral meningitis is becoming relatively more important. However, there are still many unanswered questions. Despite improvements in diagnostics many laboratories do not use molecular methods and even when they are used many cases still remain without a proven viral aetiology identified. There are also no established treatments for viral meningitis and the one potential treatment, aciclovir, which is effective in vitro for herpes simplex virus, has never been subjected to a clinical trial. Viruses are in increasingly important cause of meningitis in the era of declining bacterial disease. The exact viral aetiology varies according to age and country. Molecular diagnostics can not only improve the rate of pathogen detection but also reduce unnecessary antibiotics use and length of hospitalization. Further research is required into treatments for viral meningitis and the impact in terms of longer term sequelae.

Dual role of commensal bacteria in viral infections

PubMed Central

Wilks, Jessica; Beilinson, Helen; Golovkina, Tatyana V.

2013-01-01

Summary With our capabilities to culture and sequence the commensal bacteria that dwell on and within a host, we can now study the host in its entirety, as a supraorganism that must be navigated by the pathogen invader. At present, the majority of studies have focused on the interaction between the host’s microbiota and bacterial pathogens. This is not unwarranted, given that bacterial pathogens must compete with commensal organisms for the limited territory afforded by the host. However, viral pathogens also enter the host through surfaces coated with microbial life and encounter an immune system shaped by this symbiotic community. Therefore, we believe the microbiota cannot be ignored when examining the interplay between the host and viral pathogens. Here we review work that details mechanisms by which the microbiota either promotes or inhibits viral replication and virally-induced pathogenesis. The impact of the microbitota on viral infection promises to be a new and exciting avenue of investigation, which will ultimately lead to better treatments and preventions of virally-induced diseases. PMID:23947358

Nanotip analysis for dielectrophoretic concentration of nanosized viral particles

NASA Astrophysics Data System (ADS)

Yeo, Woon-Hong; Lee, Hyun-Boo; Kim, Jong-Hoon; Lee, Kyong-Hoon; Chung, Jae-Hyun

2013-05-01

Rapid and sensitive detection of low-abundance viral particles is strongly demanded in health care, environmental control, military defense, and homeland security. Current detection methods, however, lack either assay speed or sensitivity, mainly due to the nanosized viral particles. In this paper, we compare a dendritic, multi-terminal nanotip (‘dendritic nanotip’) with a single terminal nanotip (‘single nanotip’) for dielectrophoretic (DEP) concentration of viral particles. The numerical computation studies the concentration efficiency of viral particles ranging from 25 to 100 nm in radius for both nanotips. With DEP and Brownian motion considered, when the particle radius decreases by two times, the concentration time for both nanotips increases by 4-5 times. In the computational study, a dendritic nanotip shows about 1.5 times faster concentration than a single nanotip for the viral particles because the dendritic structure increases the DEP-effective area to overcome the Brownian motion. For the qualitative support of the numerical results, the comparison experiment of a dendritic nanotip and a single nanotip is conducted. Under 1 min of concentration time, a dendritic nanotip shows a higher sensitivity than a single nanotip. When the concentration time is 5 min, the sensitivity of a dendritic nanotip for T7 phage is 104 particles ml-1. The dendritic nanotip-based concentrator has the potential for rapid identification of viral particles.

Viral-induced Modulation of Multiple Checkpoint Proteins in Cancers.

PubMed

Nuovo, Gerard J; Folcik, Virginia A; Magro, Cynthia

2017-07-01

Therapy with checkpoint inhibitors represents a major advance in cancer treatment. The purpose of this study was to examine the expression patterns of the checkpoint proteins programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3-dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4) in cancers including those associated with viral infections. Normal, noninflamed tissues rarely express checkpoint proteins with exceptions including the placenta and stomach. Expression of PD L1 was noted in 30%, PD L2 in 18%, IDO1 in 13%, and CTLA4 in 14% of 333 nonviral malignancies including endometrial, ovarian, lung, and breast cancers. The expression of each checkpoint protein was significantly higher among 166 cases of viral-related (mostly human papillomavirus) cancers where expression of PD L1 was noted in 84%, PD L2 in 67%, IDO1 in 61%, and CTLA4 in 37% (each P value <0.001); 97% of the viral-related cancers showed expression of at least 1 checkpoint protein. In addition, over 90% of the CD8 cells in the viral-associated cancers were quiescent based on low coexpression of Ki-67 as well as pSTAT1. It is concluded that viral infection in cancers is associated with the increased expression of key checkpoint proteins. This indicates that cancers with productive viral infection may be better targets for checkpoint inhibitor therapy.

Viral evasion of intracellular DNA and RNA sensing

PubMed Central

Chan, Ying Kai; Gack, Michaela U.

2016-01-01

The co-evolution of viruses with their hosts has led to the emergence of viral pathogens that are adept at evading or actively suppressing host immunity. Pattern recognition receptors (PRRs) are key components of antiviral immunity that detect conserved molecular features of viral pathogens and initiate signalling that results in the expression of antiviral genes. In this Review, we discuss the strategies that viruses use to escape immune surveillance by key intracellular sensors of viral RNA or DNA, with a focus on RIG-I-like receptors (RLRs), cyclic GMP–AMP synthase (cGAS) and interferon-γ (IFNγ)-inducible protein 16 (IFI16). Such viral strategies include the sequestration or modification of viral nucleic acids, interference with specific post-translational modifications of PRRs or their adaptor proteins, the degradation or cleavage of PRRs or their adaptors, and the sequestration or relocalization of PRRs. An understanding of viral immune-evasion mechanisms at the molecular level may guide the development of vaccines and antivirals. PMID:27174148

Plasmonic Techniques for Viral Membrane Characterization

NASA Astrophysics Data System (ADS)

Feizpour, Amin

The lipid bilayer membrane of enveloped viruses, such as human immunodeficiency virus type 1 (HIV-1), plays an important role in key steps of the infection, including cell binding and uptake. Phosphatidylserine (PS) and monosialotetrahexosylganglioside (GM1) are examples of two host-derived lipids in the membrane of enveloped virus particles that are known to contribute to virus attachment, uptake, and ultimately dissemination. A quantitative characterization of their contribution to the functionality of the virus requires information about their relative concentrations in the viral membrane. In this dissertation, a gold nanoparticle (NP) binding assay for probing relative PS and GM1 lipid concentrations in the outer leaflet of different virus-like particles (VLPs) using small sample sizes is introduced. The assay evaluates both scattering intensity and resonance wavelength and determines relative NP densities through plasmon coupling as a measure for the target lipid concentrations in the NP-labeled VLP membrane. The performed studies reveal significant differences in the membrane of HIV-1 and Ebola VLPs that assemble at different intracellular sites and pave the way to an optical quantification of lipid concentration in virus particles at physiological titers. In addition, this technique was used in another application to improve the understanding of the relationship between the membrane PS lipid and the infectivity of HIV-2 and murine leukemia virus (MLV). The composition of the membrane, in particular the cholesterol (chol) content, determines its fluidity. As differences in the membrane composition of individual virus particles can lead to different intracellular fates, biophysical tools capable of probing the membrane fluidity on the single-virus level are required. In this dissertation, we demonstrate that fluctuations in the polarization of light scattered off gold or silver nanoparticle (NP)-labeled virus-like-particles (VLPs) encode information about the

Strong viral associations with SLE among Filipinos

PubMed Central

Vista, Evan S; Weisman, Michael H; Ishimori, Mariko L; Chen, Hua; Bourn, Rebecka L; Bruner, Ben F; Hamijoyo, Laniyati; Tanangunan, Robelle D; Gal, Noga J; Robertson, Julie M; Harley, John B; Guthridge, Joel M; Navarra, Sandra V; James, Judith A

2017-01-01

Objectives Epstein-Barr virus (EBV) is considered an important environmental factor in SLE aetiology, but the relationship between SLE and EBV in the Filipino population is unknown. We tested associations between SLE, lupus-associated autoantibodies and seropositivity for EBV and other herpes viruses in the Filipino population. Methods Sera from Filipino patients with SLE (n=233), unaffected first-degree relatives (FDRs, n=543) and unrelated controls (n=221) were tested for antibodies against EBV, cytomegalovirus (CMV) and herpes simplex viruses (HSV-1 and HSV-2) by standardised ELISAs. Humoral specificity against EBV nuclear antigen (EBNA)-1 was compared by solid-phase epitope mapping. Autoantibodies were detected by a bead-based multiplex assay. Results were analysed by Fisher's exact test, Student's t-test, χ2 test and one-way analysis of variance, as appropriate for the question. Results Filipino patients with SLE had increased seroprevalence and elevated antibody concentrations against EBV viral capsid antigen (EBV-VCA), CMV, HSV-1 and HSV-2 compared with unrelated controls (p<0.05). Seropositivity for anti-EBV early antigen (EA), a marker of EBV reactivation, was dramatically increased in patients with SLE compared with unrelated controls (92.3% vs 40.4%; OR 17.15(95% CI 10.10, 30.66), p<0.0001) or unaffected FDRs (49.4%; OR 12.04(7.42, 20.74), p<0.0001), despite similar seroprevalence of EBV-VCA in patients and FDRs. In patients with SLE, EBV-EA seropositivity correlated with lupus-associated autoantibodies (p<0.001), most notably with autoantibodies against dsDNA, chromatin, Sm, SmRNP and RNP A (p<0.01). Patient and unrelated control sera reacted to the highly repetitive glycine and alanine domain of EBNA-1. An epitope spanning EBNA-1410-420 was identified in sera of patients with SLE and showed limited binding by FDR and control sera. Conclusions Filipino patients with SLE have elevated prevalence and concentrations of antibodies against EBV, CMV, HSV-1

Viral hemorrhagic septicemia virus in North America

USGS Publications Warehouse

Meyers, Theodore R.; Winton, James R.

1995-01-01

The first detections of viral hemorrhagic septicemia virus (VHSV) in North America were in Washington State from adult coho (Oncorhynchus kisutch) and chinook (O. tshawytscha) salmon in 1988. Subsequently, VHSV was isolated from adult coho salmon returning to hatcheries in the Pacific Northwest in 1989, 1991 and 1994. These isolates represented a strain of VHSV that was genetically different from European VHSV as determined by DNA sequence analysis and T1 ribonuclease fingerprinting. The North American strain of VHSV was also isolated from skin lesions of Pacific cod (Gadus macrocephalus) taken from Prince William Sound (PWS), Alaska in 1990, 1991 and 1993. In 1993 and 1994, the virus was isolated from Pacific herring (Clupea harengus pallasi) in Alaskan waters of PWS, Kodiak Island, Auke Bay and Port Frederick. During 1993 and 1994 the herring fishery in PWS failed from a probable complex of environmental stressors but VHSV isolates were associated with hemorrhages of the skin and fins in fish that returned to spawn. Also in 1993 and 1994, VHSV was isolated from apparently healthy stocks of herring in British Columbia, Canada and Puget Sound, Washington. Thus, the North American strain of VHSV is enzootic in the Northeastern Pacific Ocean among Pacific herring stocks with Pacific cod serving as a secondary reservoir. Although the North American strain of the virus appears to be moderately pathogenic for herring, causing occasional self-limiting epizootics, it was shown to be relatively avirulent for several species of salmonids. Pacific herring are common prey for cod and salmon and were most probably the source of the VHSV isolates from the adult salmon returning to spawn in rivers or at hatcheries in Washington State. Compelling circumstances involving the European isolates of VHSV suggest that this strain of the virus also is enzootic among marine fish in the Atlantic Oean. The highly pathogenic nature of the European strain of VHSV for salmonid fish may be the

Viruses Roll the Dice: The Stochastic Behavior of Viral Genome Molecules Accelerates Viral Adaptation at the Cell and Tissue Levels

PubMed Central

Miyashita, Shuhei; Ishibashi, Kazuhiro; Kishino, Hirohisa; Ishikawa, Masayuki

2015-01-01

Recent studies on evolutionarily distant viral groups have shown that the number of viral genomes that establish cell infection after cell-to-cell transmission is unexpectedly small (1–20 genomes). This aspect of viral infection appears to be important for the adaptation and survival of viruses. To clarify how the number of viral genomes that establish cell infection is determined, we developed a simulation model of cell infection for tomato mosaic virus (ToMV), a positive-strand RNA virus. The model showed that stochastic processes that govern the replication or degradation of individual genomes result in the infection by a small number of genomes, while a large number of infectious genomes are introduced in the cell. It also predicted two interesting characteristics regarding cell infection patterns: stochastic variation among cells in the number of viral genomes that establish infection and stochastic inequality in the accumulation of their progenies in each cell. Both characteristics were validated experimentally by inoculating tobacco cells with a library of nucleotide sequence–tagged ToMV and analyzing the viral genomes that accumulated in each cell using a high-throughput sequencer. An additional simulation model revealed that these two characteristics enhance selection during tissue infection. The cell infection model also predicted a mechanism that enhances selection at the cellular level: a small difference in the replication abilities of coinfected variants results in a large difference in individual accumulation via the multiple-round formation of the replication complex (i.e., the replication machinery). Importantly, this predicted effect was observed in vivo. The cell infection model was robust to changes in the parameter values, suggesting that other viruses could adopt similar adaptation mechanisms. Taken together, these data reveal a comprehensive picture of viral infection processes including replication, cell-to-cell transmission, and

Linkage and retention in care and the time to HIV viral suppression and viral rebound - New York City.

PubMed

Robertson, McKaylee; Laraque, Fabienne; Mavronicolas, Heather; Braunstein, Sarah; Torian, Lucia

2015-01-01

The success of antiretroviral therapy (ART) as treatment for the individual patient and as prevention requires the achievment and maintenance of human immunodeficiency virus (HIV) viral suppression. Linkage to and retention in care are required for access to ART. We describe the impact of care on viral suppression using routinely reported surveillance data. We included New York City residents ≥13 years of age, diagnosed with HIV/AIDS from 1 July 2005 to 30 June 2009 with a viral load (VL) or CD4 reported within six months of diagnosis and ≥1 VL reported from 1 July 2005 to 30 June 2011. To examine viral rebound, we restricted the analysis to those who achieved viral suppression and had a subsequent VL measure reported by 30 June 2011. Cox proportional hazards models were used to evaluate factors associated with time to viral suppression (VL ≤ 400 copies/mL) and rebound (VL > 1000 copies/mL). Initiation of care within three months of diagnosis (CD4/VL report within three months of diagnosis), female sex, and an initial CD4 < 350 (cells/mm(3)) at diagnosis significantly increased the likelihood of viral suppression. Irregular care (no CD4/VL reported every six months), younger age, non-white race/ethnicity, having an initial CD4 ≥ 350 at diagnosis, and AIDS diagnosis by 2010 increased the likelihood of rebound. These findings lend support to interventions for improving linkage to and maintenance in regular care as a way to achieve and maintain suppression. Surveillance data represent an ideal means for monitoring engagement in care and viral suppression at the population level.

Defining the chemokine basis for leukocyte recruitment during viral encephalitis.

PubMed

Michlmayr, Daniela; McKimmie, Clive S; Pingen, Marieke; Haxton, Ben; Mansfield, Karen; Johnson, Nicholas; Fooks, Anthony R; Graham, Gerard J

2014-09-01

The encephalitic response to viral infection requires local chemokine production and the ensuing recruitment of immune and inflammatory leukocytes. Accordingly, chemokine receptors present themselves as plausible therapeutic targets for drugs aimed at limiting encephalitic responses. However, it remains unclear which chemokines are central to this process and whether leukocyte recruitment is important for limiting viral proliferation and survival in the brain or whether it is predominantly a driver of coincident inflammatory pathogenesis. Here we examine chemokine expression and leukocyte recruitment in the context of avirulent and virulent Semliki Forest virus (SFV) as well as West Nile virus infection and demonstrate rapid and robust expression of a variety of inflammatory CC and CXC chemokines in all models. On this basis, we define a chemokine axis involved in leukocyte recruitment to the encephalitic brain during SFV infection. CXCR3 is the most active; CCR2 is also active but less so, and CCR5 plays only a modest role in leukocyte recruitment. Importantly, inhibition of each of these receptors individually and the resulting suppression of leukocyte recruitment to the infected brain have no effect on viral titer or survival following infection with a virulent SFV strain. In contrast, simultaneous blockade of CXCR3 and CCR2 results in significantly reduced mortality in response to virulent SFV infection. In summary, therefore, our data provide an unprecedented level of insight into chemokine orchestration of leukocyte recruitment in viral encephalitis. Our data also highlight CXCR3 and CCR2 as possible therapeutic targets for limiting inflammatory damage in response to viral infection of the brain. Brain inflammation (encephalitis) in response to viral infection can lead to severe illness and even death. This therefore represents an important clinical problem and one that requires the development of new therapeutic approaches. Central to the pathogenesis of

VirSorter: mining viral signal from microbial genomic data.

PubMed

Roux, Simon; Enault, Francois; Hurwitz, Bonnie L; Sullivan, Matthew B

2015-01-01

Viruses of microbes impact all ecosystems where microbes drive key energy and substrate transformations including the oceans, humans and industrial fermenters. However, despite this recognized importance, our understanding of viral diversity and impacts remains limited by too few model systems and reference genomes. One way to fill these gaps in our knowledge of viral diversity is through the detection of viral signal in microbial genomic data. While multiple approaches have been developed and applied for the detection of prophages (viral genomes integrated in a microbial genome), new types of microbial genomic data are emerging that are more fragmented and larger scale, such as Single-cell Amplified Genomes (SAGs) of uncultivated organisms or genomic fragments assembled from metagenomic sequencing. Here, we present VirSorter, a tool designed to detect viral signal in these different types of microbial sequence data in both a reference-dependent and reference-independent manner, leveraging probabilistic models and extensive virome data to maximize detection of novel viruses. Performance testing shows that VirSorter's prophage prediction capability compares to that of available prophage predictors for complete genomes, but is superior in predicting viral sequences outside of a host genome (i.e., from extrachromosomal prophages, lytic infections, or partially assembled prophages). Furthermore, VirSorter outperforms existing tools for fragmented genomic and metagenomic datasets, and can identify viral signal in assembled sequence (contigs) as short as 3kb, while providing near-perfect identification (>95% Recall and 100% Precision) on contigs of at least 10kb. Because VirSorter scales to large datasets, it can also be used in "reverse" to more confidently identify viral sequence in viral metagenomes by sorting away cellular DNA whether derived from gene transfer agents, generalized transduction or contamination. Finally, VirSorter is made available through the i

Viral impacts on microbial carbon cycling in thawing permafrost soils

NASA Astrophysics Data System (ADS)

Trubl, G. G.; Roux, S.; Bolduc, B.; Jang, H. B.; Emerson, J. B.; Solonenko, N.; Li, F.; Solden, L. M.; Vik, D. R.; Wrighton, K. C.; Saleska, S. R.; Sullivan, M. B.; Rich, V. I.

2017-12-01

Permafrost contains 30-50% of global soil carbon (C) and is rapidly thawing. While the fate of this C is unknown, it will be shaped in part by microbes and their associated viruses, which modulate host activities via mortality and metabolic control. To date, viral research in soils has been outpaced by that in aquatic environments, due to the technical challenges of accessing viruses as well as the dramatic physicochemical heterogeneity in soils. Here, we describe advances in soil viromics from our research on permafrost-associated soils, and their implications for associated terrestrial C cycling. First, we optimized viral resuspension-DNA extraction methods for a range of soil types. Second, we applied cutting-edge viral-specific informatics methods to recover viral populations, define their gene content, connect them to potential hosts, and analyze their relationships to environmental parameters. A total of 781 viral populations were recovered from size-fractionated virus samples of three soils along a permafrost thaw gradient. Ecological analyses revealed endemism as recovered viral populations were largely unique to each habitat and unlike those in aquatic communities. Genome- and network-based classification assigned these viruses into 226 viral clusters (VCs; genus-level taxonomy), 55% of which were novel. This increases the number of VCs by a third and triples the number of soil viral populations in the RefSeq database (currently contains 256 VCs and 316 soil viral populations). Genomic analyses revealed 85% of the genes were functionally unknown, though 5% of the annotatable genes contained C-related auxiliary metabolic genes (AMGs; e.g. glycoside hydrolases). Using sequence-based features and microbial population genomes, we were able to in silico predict hosts for 30% of the viral populations. The identified hosts spanned 3 phyla and 6 genera but suggested these viruses have species-specific host ranges as >80% of hosts for a given virus were in the same

VirSorter: mining viral signal from microbial genomic data

PubMed Central

Roux, Simon; Enault, Francois; Hurwitz, Bonnie L.

2015-01-01

Viruses of microbes impact all ecosystems where microbes drive key energy and substrate transformations including the oceans, humans and industrial fermenters. However, despite this recognized importance, our understanding of viral diversity and impacts remains limited by too few model systems and reference genomes. One way to fill these gaps in our knowledge of viral diversity is through the detection of viral signal in microbial genomic data. While multiple approaches have been developed and applied for the detection of prophages (viral genomes integrated in a microbial genome), new types of microbial genomic data are emerging that are more fragmented and larger scale, such as Single-cell Amplified Genomes (SAGs) of uncultivated organisms or genomic fragments assembled from metagenomic sequencing. Here, we present VirSorter, a tool designed to detect viral signal in these different types of microbial sequence data in both a reference-dependent and reference-independent manner, leveraging probabilistic models and extensive virome data to maximize detection of novel viruses. Performance testing shows that VirSorter’s prophage prediction capability compares to that of available prophage predictors for complete genomes, but is superior in predicting viral sequences outside of a host genome (i.e., from extrachromosomal prophages, lytic infections, or partially assembled prophages). Furthermore, VirSorter outperforms existing tools for fragmented genomic and metagenomic datasets, and can identify viral signal in assembled sequence (contigs) as short as 3kb, while providing near-perfect identification (>95% Recall and 100% Precision) on contigs of at least 10kb. Because VirSorter scales to large datasets, it can also be used in “reverse” to more confidently identify viral sequence in viral metagenomes by sorting away cellular DNA whether derived from gene transfer agents, generalized transduction or contamination. Finally, VirSorter is made available through the i

Viral-specific T-cell transfer from HSCT donor for the treatment of viral infections or diseases after HSCT.

PubMed

Qian, C; Wang, Y; Reppel, L; D'aveni, M; Campidelli, A; Decot, V; Bensoussan, D

2018-02-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for treatment of some malignant and non-malignant hematological diseases. However, post-HSCT patients are severely immunocompromised and susceptible to viral infections, which are a major cause of morbidity and mortality. Although antiviral agents are now available for most types of viral infections, they are not devoid of side effects and their efficacy is limited when there is no concomitant antiviral immune reconstitution. In recent decades, adoptive transfer of viral-specific T cells (VSTs) became an alternative treatment for viral infection after HSCT. However, two major issues are concerned in VST transfer: the risk of GVHD and antiviral efficacy. We report an exhaustive review of the published studies that focus on prophylactic and/or curative therapy by donor VST transfer for post-HSCT common viral infections. A low incidence of GVHD and a good antiviral efficacy was observed after adoptive transfer of VSTs from HSCT donor. Viral-specific T-cell transfer is a promising approach for a broad clinical application. Nevertheless, a randomized controlled study in a large cohort of patients comparing antiviral treatment alone to antiviral treatment combined with VSTs is still needed to demonstrate efficacy and safety.

Kaposi's Sarcoma-Associated Herpesvirus mRNA Accumulation in Nuclear Foci Is Influenced by Viral DNA Replication and Viral Noncoding Polyadenylated Nuclear RNA.

PubMed

Vallery, Tenaya K; Withers, Johanna B; Andoh, Joana A; Steitz, Joan A

2018-07-01

Kaposi's sarcoma-associated herpesvirus (KSHV), like other herpesviruses, replicates within the nuclei of its human cell host and hijacks host machinery for expression of its genes. The activities that culminate in viral DNA synthesis and assembly of viral proteins into capsids physically concentrate in nuclear areas termed viral replication compartments. We sought to better understand the spatiotemporal regulation of viral RNAs during the KSHV lytic phase by examining and quantifying the subcellular localization of select viral transcripts. We found that viral mRNAs, as expected, localized to the cytoplasm throughout the lytic phase. However, dependent on active viral DNA replication, viral transcripts also accumulated in the nucleus, often in foci in and around replication compartments, independent of the host shutoff effect. Our data point to involvement of the viral long noncoding polyadenylated nuclear (PAN) RNA in the localization of an early, intronless viral mRNA encoding ORF59-58 to nuclear foci that are associated with replication compartments. IMPORTANCE Late in the lytic phase, mRNAs from Kaposi's sarcoma-associated herpesvirus accumulate in the host cell nucleus near viral replication compartments, centers of viral DNA synthesis and virion production. This work contributes spatiotemporal data on herpesviral mRNAs within the lytic host cell and suggests a mechanism for viral RNA accumulation. Our findings indicate that the mechanism is independent of the host shutoff effect and splicing but dependent on active viral DNA synthesis and in part on the viral noncoding RNA, PAN RNA. PAN RNA is essential for the viral life cycle, and its contribution to the nuclear accumulation of viral messages may facilitate propagation of the virus. Copyright © 2018 American Society for Microbiology.

Viral Genome DataBase: storing and analyzing genes and proteins from complete viral genomes.

PubMed

Hiscock, D; Upton, C

2000-05-01

The Viral Genome DataBase (VGDB) contains detailed information of the genes and predicted protein sequences from 15 completely sequenced genomes of large (&100 kb) viruses (2847 genes). The data that is stored includes DNA sequence, protein sequence, GenBank and user-entered notes, molecular weight (MW), isoelectric point (pI), amino acid content, A + T%, nucleotide frequency, dinucleotide frequency and codon use. The VGDB is a mySQL database with a user-friendly JAVA GUI. Results of queries can be easily sorted by any of the individual parameters. The software and additional figures and information are available at http://athena.bioc.uvic.ca/genomes/index.html .

21 CFR 866.3980 - Respiratory viral panel multiplex nucleic acid assay.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Respiratory viral panel multiplex nucleic acid... § 866.3980 Respiratory viral panel multiplex nucleic acid assay. (a) Identification. A respiratory viral... simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or...

21 CFR 866.3980 - Respiratory viral panel multiplex nucleic acid assay.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Respiratory viral panel multiplex nucleic acid... § 866.3980 Respiratory viral panel multiplex nucleic acid assay. (a) Identification. A respiratory viral... simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or...

21 CFR 866.3980 - Respiratory viral panel multiplex nucleic acid assay.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Respiratory viral panel multiplex nucleic acid... § 866.3980 Respiratory viral panel multiplex nucleic acid assay. (a) Identification. A respiratory viral... simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or...

21 CFR 866.3980 - Respiratory viral panel multiplex nucleic acid assay.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Respiratory viral panel multiplex nucleic acid... § 866.3980 Respiratory viral panel multiplex nucleic acid assay. (a) Identification. A respiratory viral... simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or...

21 CFR 866.3980 - Respiratory viral panel multiplex nucleic acid assay.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Respiratory viral panel multiplex nucleic acid... § 866.3980 Respiratory viral panel multiplex nucleic acid assay. (a) Identification. A respiratory viral... simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or...

Comparison of reproductive protection against bovine viral diarrhea virus provided by multivalent viral vaccines containing inactivated fractions of bovine viral diarrhea virus 1 and 2

USDA-ARS?s Scientific Manuscript database

The objective of this study was to compare reproductive protection in cattle against the impacts of bovine viral diarrhea virus (BVDV) provided by three different multivalent vaccines containing inactivated BVDV. Beef heifers and cows (n=122), seronegative and virus negative for BVDV, were randomly ...

Metagenomic Analysis of Viral Communities in (Hado)Pelagic Sediments

PubMed Central

Yoshida, Mitsuhiro; Takaki, Yoshihiro; Eitoku, Masamitsu; Nunoura, Takuro; Takai, Ken

2013-01-01

In this study, we analyzed viral metagenomes (viromes) in the sedimentary habitats of three geographically and geologically distinct (hado)pelagic environments in the northwest Pacific; the Izu-Ogasawara Trench (water depth = 9,760 m) (OG), the Challenger Deep in the Mariana Trench (10,325 m) (MA), and the forearc basin off the Shimokita Peninsula (1,181 m) (SH). Virus abundance ranged from 106 to 1011 viruses/cm3 of sediments (down to 30 cm below the seafloor [cmbsf]). We recovered viral DNA assemblages (viromes) from the (hado)pelagic sediment samples and obtained a total of 37,458, 39,882, and 70,882 sequence reads by 454 GS FLX Titanium pyrosequencing from the virome libraries of the OG, MA, and SH (hado)pelagic sediments, respectively. Only 24−30% of the sequence reads from each virome library exhibited significant similarities to the sequences deposited in the public nr protein database (E-value <10−3 in BLAST). Among the sequences identified as potential viral genes based on the BLAST search, 95−99% of the sequence reads in each library were related to genes from single-stranded DNA (ssDNA) viral families, including Microviridae, Circoviridae, and Geminiviridae. A relatively high abundance of sequences related to the genetic markers (major capsid protein [VP1] and replication protein [Rep]) of two ssDNA viral groups were also detected in these libraries, thereby revealing a high genotypic diversity of their viruses (833 genotypes for VP1 and 2,551 genotypes for Rep). A majority of the viral genes predicted from each library were classified into three ssDNA viral protein categories: Rep, VP1, and minor capsid protein. The deep-sea sedimentary viromes were distinct from the viromes obtained from the oceanic and fresh waters and marine eukaryotes, and thus, deep-sea sediments harbor novel viromes, including previously unidentified ssDNA viruses. PMID:23468952

Metagenomic analysis of viral communities in (hado)pelagic sediments.

PubMed

Yoshida, Mitsuhiro; Takaki, Yoshihiro; Eitoku, Masamitsu; Nunoura, Takuro; Takai, Ken

2013-01-01

In this study, we analyzed viral metagenomes (viromes) in the sedimentary habitats of three geographically and geologically distinct (hado)pelagic environments in the northwest Pacific; the Izu-Ogasawara Trench (water depth = 9,760 m) (OG), the Challenger Deep in the Mariana Trench (10,325 m) (MA), and the forearc basin off the Shimokita Peninsula (1,181 m) (SH). Virus abundance ranged from 10(6) to 10(11) viruses/cm(3) of sediments (down to 30 cm below the seafloor [cmbsf]). We recovered viral DNA assemblages (viromes) from the (hado)pelagic sediment samples and obtained a total of 37,458, 39,882, and 70,882 sequence reads by 454 GS FLX Titanium pyrosequencing from the virome libraries of the OG, MA, and SH (hado)pelagic sediments, respectively. Only 24-30% of the sequence reads from each virome library exhibited significant similarities to the sequences deposited in the public nr protein database (E-value <10(-3) in BLAST). Among the sequences identified as potential viral genes based on the BLAST search, 95-99% of the sequence reads in each library were related to genes from single-stranded DNA (ssDNA) viral families, including Microviridae, Circoviridae, and Geminiviridae. A relatively high abundance of sequences related to the genetic markers (major capsid protein [VP1] and replication protein [Rep]) of two ssDNA viral groups were also detected in these libraries, thereby revealing a high genotypic diversity of their viruses (833 genotypes for VP1 and 2,551 genotypes for Rep). A majority of the viral genes predicted from each library were classified into three ssDNA viral protein categories: Rep, VP1, and minor capsid protein. The deep-sea sedimentary viromes were distinct from the viromes obtained from the oceanic and fresh waters and marine eukaryotes, and thus, deep-sea sediments harbor novel viromes, including previously unidentified ssDNA viruses.

Recent Advances in Non-viral Vectors for Gene Delivery

PubMed Central

Guo, Xia; Huang, Leaf

2011-01-01

CONSPECTUS Non-viral vectors, typically based on cationic lipids or polymers, are preferred due to safety concerns with viral vectors. So far, non-viral vectors can proficiently transfect cells in culture, but obtaining efficient nanomedicines is far from evident. To overcome the hurdles associated with non-viral vectors is significant for improving delivery efficiency and therapeutic effect of nucleic acid. The drawbacks include the strong interaction of cationic delivery vehicles with blood components, uptake by the reticuloendothelial system (RES), toxicity, targeting ability of the carriers to the cells of interest, and so on. PEGylation is the predominant method used to reduce the binding of plasma proteins with non-viral vectors and minimize the clearance by RES after intravenous administration. The nanoparticles that are not rapidly cleared from the circulation accumulate in the tumors due to the enhanced permeability and retention effect, and the targeting ligands attached to the distal end of the PEGylated components allow binding to the receptors on the target cell surface. Neutral or anionic liposomes have been also developed for systemic delivery of nucleic acids in experimental animal model. Designing and synthesizing novel cationic lipids and polymers, and binding nucleic acid with peptides, targeting ligands, polymers, or environmentally sensitive moieties also attract many attentions for resolving the problems encountered by non-viral vectors. The application of inorganic nanoparticles in nucleic acid delivery is an emerging field, too. Recently, different classes of non-viral vectors appear to be converging and the features of different classes of non-viral vectors could be combined in one strategy. More hurdles associated with efficient nucleic acid delivery therefore might be expected to be overcome. In this account, we will focus on these novel non-viral vectors, which are classified into multifunctional hybrid nucleic acid vectors, novel

Non-viral nucleic acid containing nanoparticles as cancer therapeutics.

PubMed

Kozielski, Kristen L; Rui, Yuan; Green, Jordan J

2016-10-01

The delivery of nucleic acids such as DNA and short interfering RNA (siRNA) is promising for the treatment of many diseases, including cancer, by enabling novel biological mechanisms of action. Non-viral nanoparticles are a promising class of nucleic acid carriers that can be designed to be safer and more versatile than traditional viral vectors. In this review, recent advances in the intracellular delivery of DNA and siRNA are described with a focus on non-viral nanoparticle-based delivery methods. Material properties that have enabled successful delivery are discussed as well as applications that have directly been applied to cancer therapy. Strategies to co-deliver different nucleic acids are highlighted, as are novel targets for nucleic acid co-delivery. The treatment of complex genetically-based diseases such as cancer can be enabled by safe and effective intracellular delivery of multiple nucleic acids. Non-viral nanoparticles can be fabricated to deliver multiple nucleic acids to the same cell simultaneously to prevent tumor cells from easily compensating for the knockdown or overexpression of one genetic target. The continued innovation of new therapeutic modalities and non-viral nanotechnologies to provide target-specific and personalized forms of gene therapy hold promise for genetic medicine to treat diseases like cancer in the clinic.

Stormwater runoff drives viral community composition changes in inland freshwaters.

PubMed

Williamson, Kurt E; Harris, Jamie V; Green, Jasmin C; Rahman, Faraz; Chambers, Randolph M

2014-01-01

Storm events impact freshwater microbial communities by transporting terrestrial viruses and other microbes to freshwater systems, and by potentially resuspending microbes from bottom sediments. The magnitude of these impacts on freshwater ecosystems is unknown and largely unexplored. Field studies carried out at two discrete sites in coastal Virginia (USA) were used to characterize the viral load carried by runoff and to test the hypothesis that terrestrial viruses introduced through stormwater runoff change the composition of freshwater microbial communities. Field data gathered from an agricultural watershed indicated that primary runoff can contain viral densities approximating those of receiving waters. Furthermore, viruses attached to suspended colloids made up a large fraction of the total load, particularly in early stages of the storm. At a second field site (stormwater retention pond), RAPD-PCR profiling showed that the viral community of the pond changed dramatically over the course of two intense storms while relatively little change was observed over similar time scales in the absence of disturbance. Comparisons of planktonic and particle-associated viral communities revealed two completely distinct communities, suggesting that particle-associated viruses represent a potentially large and overlooked portion of aquatic viral abundance and diversity. Our findings show that stormwater runoff can quickly change the composition of freshwater microbial communities. Based on these findings, increased storms in the coastal mid-Atlantic region predicted by most climate change models will likely have important impacts on the structure and function of local freshwater microbial communities.

Gene delivery with viral vectors for cerebrovascular diseases

PubMed Central

Gan, Yu; Jing, Zheng; Stetler, R. Anne; Cao, Guodong

2017-01-01

Recent achievements in the understanding of molecular events involved in the pathogenesis of central nervous system (CNS) injury have made gene transfer a promising approach for various neurological disorders, including cerebrovascular diseases. However, special obstacles, including the post-mitotic nature of neurons and the blood-brain barrier (BBB), constitute key challenges for gene delivery to the CNS. Despite the various limitations in current gene delivery systems, a spectrum of viral vectors has been successfully used to deliver genes to the CNS. Furthermore, recent advancements in vector engineering have improved the safety and delivery of viral vectors. Numerous viral vector-based clinical trials for neurological disorders have been initiated. This review will summarize the current implementation of viral gene delivery in the context of cerebrovascular diseases including ischemic stroke, hemorrhagic stroke and subarachnoid hemorrhage (SAH). In particular, we will discuss the potentially feasible ways in which viral vectors can be manipulated and exploited for use in neural delivery and therapy. PMID:23276981

Non-viral nucleic acid containing nanoparticles as cancer therapeutics

PubMed Central

Kozielski, Kristen L.; Rui, Yuan

2016-01-01

Introduction The delivery of nucleic acids such as DNA and short interfering RNA (siRNA) is promising for the treatment of many diseases, including cancer, by enabling novel biological mechanisms of action. Non-viral nanoparticles are a promising class of nucleic acid carriers that can be designed to be safer and more versatile than traditional viral vectors. Areas covered In this review, recent advances in the intracellular delivery of DNA and siRNA are described with a focus on non-viral nanoparticle-based delivery methods. Material properties that have enabled successful delivery are discussed as well as applications that have directly been applied to cancer therapy. Strategies to co-deliver different nucleic acids are highlighted, as are novel targets for nucleic acid co-delivery. Expert opinion The treatment of complex genetically-based diseases such as cancer can be enabled by safe and effective intracellular delivery of multiple nucleic acids. Non-viral nanoparticles can be fabricated to deliver multiple nucleic acids to the same cell simultaneously to prevent tumor cells from easily compensating for the knockdown or overexpression of one genetic target. The continued innovation of new therapeutic modalities and non-viral nanotechnologies to provide target-specific and personalized forms of gene therapy hold promise for genetic medicine to treat diseases like cancer in the clinic. PMID:27248202

Vaccination of cattle against bovine viral diarrhea virus.

PubMed

Newcomer, Benjamin W; Chamorro, Manuel F; Walz, Paul H

2017-07-01

Bovine viral diarrhea virus (BVDV) is responsible for significant losses to the cattle industry. Currently, modified-live viral (MLV) and inactivated viral vaccines are available against BVDV, often in combination with other viral and bacterial antigens. Inactivated and MLV vaccines provide cattle producers and veterinarians safe and efficacious options for herd immunization to limit disease associated with BVDV infection. Vaccination of young cattle against BVDV is motivated by prevention of clinical disease and limiting viral spread to susceptible animals. For reproductive-age cattle, vaccination to prevent viremia and birth of persistently infected offspring is considered more important, while also more difficult to achieve than prevention of clinical disease. Recent advances have been made in the understanding of BVDV vaccine efficacy. In terms of preventing clinical disease, current BVDV vaccines have been demonstrated to have a rapid onset of immunity and MLV vaccines can be effectively utilized in calves possessing maternal immunity. For reproductive protection, more recent studies using multivalent MLV vaccines have demonstrated consistent fetal protection rates in the range of 85-100% in experimental studies. Proper timing and administration of BVDV vaccines can be utilized to maximize vaccine efficacy to provide an important contribution to reducing risks associated with BVDV infection. With improvements in vaccine formulations and increased understanding of the protective immune response following vaccination, control of BVDV through vaccination can be enhanced. Copyright © 2017. Published by Elsevier B.V.

Metagenomic characterization of viral communities in Goseong Bay, Korea

NASA Astrophysics Data System (ADS)

Hwang, Jinik; Park, So Yun; Park, Mirye; Lee, Sukchan; Jo, Yeonhwa; Cho, Won Kyong; Lee, Taek-Kyun

2016-12-01

In this study, seawater samples were collected from Goseong Bay, Korea in March 2014 and viral populations were examined by metagenomics assembly. Enrichment of marine viral particles using FeCl3 followed by next-generation sequencing produced numerous sequences. De novo assembly and BLAST search showed that most of the obtained contigs were unknown sequences and only 0.74% of sequences were associated with known viruses. As a result, 138 viruses, including bacteriophages (87%), viruses infecting algae and others (13%) were identified. The identified 138 viruses were divided into 11 orders, 14 families, 34 genera, and 133 species. The dominant viruses were Pelagibacter phage HTVC010P and Roseobacter phage SIO1. The viruses infecting algae, including the Ostreococcus species, accounted for 9.4% of total identified viruses. In addition, we identified pathogenic herpes viruses infecting fishes and giant viruses infecting parasitic acanthamoeba species. This is a comprehensive study to reveal the viral populations in the Goseong Bay using metagenomics. The information associated with the marine viral community in Goseong Bay, Korea will be useful for comparative analysis in other marine viral communities.

The Fecal Viral Flora of California Sea Lions▿†

PubMed Central

Li, Linlin; Shan, Tongling; Wang, Chunlin; Côté, Colette; Kolman, John; Onions, David; Gulland, Frances M. D.; Delwart, Eric

2011-01-01

California sea lions are one of the major marine mammal species along the Pacific coast of North America. Sea lions are susceptible to a wide variety of viruses, some of which can be transmitted to or from terrestrial mammals. Using an unbiased viral metagenomic approach, we surveyed the fecal virome in California sea lions of different ages and health statuses. Averages of 1.6 and 2.5 distinct mammalian viral species were shed by pups and juvenile sea lions, respectively. Previously undescribed mammalian viruses from four RNA virus families (Astroviridae, Picornaviridae, Caliciviridae, and Reoviridae) and one DNA virus family (Parvoviridae) were characterized. The first complete or partial genomes of sapeloviruses, sapoviruses, noroviruses, and bocavirus in marine mammals are reported. Astroviruses and bocaviruses showed the highest prevalence and abundance in California sea lion feces. The diversity of bacteriophages was higher in unweaned sea lion pups than in juveniles and animals in rehabilitation, where the phage community consisted largely of phages related to the family Microviridae. This study increases our understanding of the viral diversity in marine mammals, highlights the high rate of enteric viral infections in these highly social carnivores, and may be used as a baseline viral survey for comparison with samples from California sea lions during unexplained disease outbreaks. PMID:21795334

Human viral pathogens are pervasive in wastewater treatment center aerosols.

PubMed

Brisebois, Evelyne; Veillette, Marc; Dion-Dupont, Vanessa; Lavoie, Jacques; Corbeil, Jacques; Culley, Alexander; Duchaine, Caroline

2018-05-01

Wastewater treatment center (WTC) workers may be vulnerable to diseases caused by viruses, such as the common cold, influenza and gastro-intestinal infections. Although there is a substantial body of literature characterizing the microbial community found in wastewater, only a few studies have characterized the viral component of WTC aerosols, despite the fact that most diseases affecting WTC workers are of viral origin and that some of these viruses are transmitted through the air. In this study, we evaluated in four WTCs the presence of 11 viral pathogens of particular concern in this milieu and used a metagenomic approach to characterize the total viral community in the air of one of those WTCs. The presence of viruses in aerosols in different locations of individual WTCs was evaluated and the results obtained with four commonly used air samplers were compared. We detected four of the eleven viruses tested, including human adenovirus (hAdV), rotavirus, hepatitis A virus (HAV) and Herpes Simplex virus type 1 (HSV1). The results of the metagenomic assay uncovered very few viral RNA sequences in WTC aerosols, however sequences from human DNA viruses were in much greater relative abundance. Copyright © 2017. Published by Elsevier B.V.

Stormwater runoff drives viral community composition changes in inland freshwaters

PubMed Central

Williamson, Kurt E.; Harris, Jamie V.; Green, Jasmin C.; Rahman, Faraz; Chambers, Randolph M.

2014-01-01

Storm events impact freshwater microbial communities by transporting terrestrial viruses and other microbes to freshwater systems, and by potentially resuspending microbes from bottom sediments. The magnitude of these impacts on freshwater ecosystems is unknown and largely unexplored. Field studies carried out at two discrete sites in coastal Virginia (USA) were used to characterize the viral load carried by runoff and to test the hypothesis that terrestrial viruses introduced through stormwater runoff change the composition of freshwater microbial communities. Field data gathered from an agricultural watershed indicated that primary runoff can contain viral densities approximating those of receiving waters. Furthermore, viruses attached to suspended colloids made up a large fraction of the total load, particularly in early stages of the storm. At a second field site (stormwater retention pond), RAPD-PCR profiling showed that the viral community of the pond changed dramatically over the course of two intense storms while relatively little change was observed over similar time scales in the absence of disturbance. Comparisons of planktonic and particle-associated viral communities revealed two completely distinct communities, suggesting that particle-associated viruses represent a potentially large and overlooked portion of aquatic viral abundance and diversity. Our findings show that stormwater runoff can quickly change the composition of freshwater microbial communities. Based on these findings, increased storms in the coastal mid-Atlantic region predicted by most climate change models will likely have important impacts on the structure and function of local freshwater microbial communities. PMID:24672520

Clinical prediction rule for differentiating tuberculous from viral meningitis.

PubMed

Hristea, A; Olaru, I D; Baicus, C; Moroti, R; Arama, V; Ion, M

2012-06-01

The Professor Dr Matei Bals National Institute of Infectious Diseases, Bucharest, Romania. To create a prediction rule to enable clinicians to differentiate patients with tuberculous meningitis (TBM) from those with viral meningitis. We retrospectively analysed patients admitted to a tertiary care facility between 2001 and 2011 with viral meningitis and TBM. Patients were defined as having TBM according to a recently published consensus definition, and as viral meningitis if a viral aetiology was confirmed, or after ruling out bacterial, fungal and non-infectious causes of meningitis. We identified 433 patients with viral meningitis and 101 TBM patients and compared their clinical and laboratory features. Multivariable analysis showed a statistically significant association between TBM and the following variables: duration of symptoms before admission of ≥5 days, presence of neurological impairment (altered consciousness, seizures, mild focal signs, multiple cranial nerve palsies, dense hemiplegia or paraparesis), cerebrospinal fluid/blood glucose ratio < 0.5 and cerebrospinal fluid protein level > 100 mg/dl. We propose a diagnostic score based on the coefficients derived from the logistic regression model with a sensitivity and specificity for TBM of respectively 92% and 94%. Our study suggests that easily available clinical and laboratory data are very useful for differentiating TBM from other causes of meningitis.

Measles virus induces persistent infection by autoregulation of viral replication.

PubMed

Doi, Tomomitsu; Kwon, Hyun-Jeong; Honda, Tomoyuki; Sato, Hiroki; Yoneda, Misako; Kai, Chieko

2016-11-24

Natural infection with measles virus (MV) establishes lifelong immunity. Persistent infection with MV is likely involved in this phenomenon, as non-replicating protein antigens never induce such long-term immunity. Although MV establishes stable persistent infection in vitro and possibly in vivo, the mechanism by which this occurs is largely unknown. Here, we demonstrate that MV changes the infection mode from lytic to non-lytic and evades the innate immune response to establish persistent infection without viral genome mutation. We found that, in the persistent phase, the viral RNA level declined with the termination of interferon production and cell death. Our analysis of viral protein dynamics shows that during the establishment of persistent infection, the nucleoprotein level was sustained while the phosphoprotein and large protein levels declined. The ectopic expression of nucleoprotein suppressed viral replication, indicating that viral replication is self-regulated by nucleoprotein accumulation during persistent infection. The persistently infected cells were able to produce interferon in response to poly I:C stimulation, suggesting that MV does not interfere with host interferon responses in persistent infection. Our results may provide mechanistic insight into the persistent infection of this cytopathic RNA virus that induces lifelong immunity.

Viral activities and life cycles in deep subseafloor sediments.

PubMed

Engelhardt, Tim; Orsi, William D; Jørgensen, Bo Barker

2015-12-01

Viruses are highly abundant in marine subsurface sediments and can even exceed the number of prokaryotes. However, their activity and quantitative impact on microbial populations are still poorly understood. Here, we use gene expression data from published continental margin subseafloor metatranscriptomes to qualitatively assess viral diversity and activity in sediments up to 159 metres below seafloor (mbsf). Mining of the metatranscriptomic data revealed 4651 representative viral homologues (RVHs), representing 2.2% of all metatranscriptome sequence reads, which have close translated homology (average 77%, range 60-97% amino acid identity) to viral proteins. Archaea-infecting RVHs are exclusively detected in the upper 30 mbsf, whereas RVHs for filamentous inoviruses predominate in the deepest sediment layers. RVHs indicative of lysogenic phage-host interactions and lytic activity, notably cell lysis, are detected at all analysed depths and suggest a dynamic virus-host association in the marine deep biosphere studied here. Ongoing lytic viral activity is further indicated by the expression of clustered, regularly interspaced, short palindromic repeat-associated cascade genes involved in cellular defence against viral attacks. The data indicate the activity of viruses in subsurface sediment of the Peruvian margin and suggest that viruses indeed cause cell mortality and may play an important role in the turnover of subseafloor microbial biomass. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Conditions for Viral Influence Spreading through Multiplex Correlated Social Networks

NASA Astrophysics Data System (ADS)

Hu, Yanqing; Havlin, Shlomo; Makse, Hernán A.

2014-04-01

A fundamental problem in network science is to predict how certain individuals are able to initiate new networks to spring up "new ideas." Frequently, these changes in trends are triggered by a few innovators who rapidly impose their ideas through "viral" influence spreading, producing cascades of followers and fragmenting an old network to create a new one. Typical examples include the rise of scientific ideas or abrupt changes in social media, like the rise of Facebook to the detriment of Myspace. How this process arises in practice has not been conclusively demonstrated. Here, we show that a condition for sustaining a viral spreading process is the existence of a multiplex-correlated graph with hidden "influence links." Analytical solutions predict percolation-phase transitions, either abrupt or continuous, where networks are disintegrated through viral cascades of followers, as in empirical data. Our modeling predicts the strict conditions to sustain a large viral spreading via a scaling form of the local correlation function between multilayers, which we also confirm empirically. Ultimately, the theory predicts the conditions for viral cascading in a large class of multiplex networks ranging from social to financial systems and markets.

Viral Diseases in Zebrafish: What Is Known and Unknown

PubMed Central

Crim, Marcus J.; Riley, Lela K.

2013-01-01

Naturally occurring viral infections have the potential to introduce confounding variability that leads to invalid and misinterpreted data. Whereas the viral diseases of research rodents are well characterized and closely monitored, no naturally occurring viral infections have been characterized for the laboratory zebrafish (Danio rerio), an increasingly important biomedical research model. Despite the ignorance about naturally occurring zebrafish viruses, zebrafish models are rapidly expanding in areas of biomedical research where the confounding effects of unknown infectious agents present a serious concern. In addition, many zebrafish research colonies remain linked to the ornamental (pet) zebrafish trade, which can contribute to the introduction of new pathogens into research colonies, whereas mice used for research are purpose bred, with no introduction of new mice from the pet industry. Identification, characterization, and monitoring of naturally occurring viruses in zebrafish are crucial to the improvement of zebrafish health, the reduction of unwanted variability, and the continued development of the zebrafish as a model organism. This article addresses the importance of identifying and characterizing the viral diseases of zebrafish as the scope of zebrafish models expands into new research areas and also briefly addresses zebrafish susceptibility to experimental viral infection and the utility of the zebrafish as an infection and immunology model. PMID:23382345

Hemolin-A lepidopteran anti-viral defense factor?

PubMed

Terenius, Olle

2008-01-01

Immunity in insects has largely focused on responses towards bacteria and fungi, but recently the study of immune responses against viral infections has also received attention. In Lepidoptera, phagocytosis and encapsulation mediated by hemocytes, and apoptosis are part of the response against virus infection; however, many studies also suggest the presence of unknown factors involved in the anti-viral defense. An up-regulation of the lepidopteran-specific pattern recognition protein Hemolin after baculovirus infection in the Chinese oak silkmoth and discovery of putative virus responsive elements in the up-stream regions of Hemolin in the Cecropia moth and the Tobacco horn worm could suggest that Hemolin is involved in virus defense. In this paper, a number of studies investigating baculovirus pathogenesis, and others analyzing Hemolin expression have been revisited leading to the speculation that Hemolin could be engaged in several anti-viral processes.

A bright future for bioluminescent imaging in viral research

PubMed Central

Coleman, Stewart M; McGregor, Alistair

2015-01-01

Summary Bioluminescence imaging (BLI) has emerged as a powerful tool in the study of animal models of viral disease. BLI enables real-time in vivo study of viral infection, host immune response and the efficacy of intervention strategies. Substrate dependent light emitting luciferase enzyme when incorporated into a virus as a reporter gene enables detection of bioluminescence from infected cells using sensitive charge-coupled device (CCD) camera systems. Advantages of BLI include low background, real-time tracking of infection in the same animal and reduction in the requirement for larger animal numbers. Transgenic luciferase-tagged mice enable the use of pre-existing nontagged viruses in BLI studies. Continued development in luciferase reporter genes, substrates, transgenic animals and imaging systems will greatly enhance future BLI strategies in viral research. PMID:26413138

New Methods in Tissue Engineering: Improved Models for Viral Infection.

PubMed

Ramanan, Vyas; Scull, Margaret A; Sheahan, Timothy P; Rice, Charles M; Bhatia, Sangeeta N

2014-11-01

New insights in the study of virus and host biology in the context of viral infection are made possible by the development of model systems that faithfully recapitulate the in vivo viral life cycle. Standard tissue culture models lack critical emergent properties driven by cellular organization and in vivo-like function, whereas animal models suffer from limited susceptibility to relevant human viruses and make it difficult to perform detailed molecular manipulation and analysis. Tissue engineering techniques may enable virologists to create infection models that combine the facile manipulation and readouts of tissue culture with the virus-relevant complexity of animal models. Here, we review the state of the art in tissue engineering and describe how tissue engineering techniques may alleviate some common shortcomings of existing models of viral infection, with a particular emphasis on hepatotropic viruses. We then discuss possible future applications of tissue engineering to virology, including current challenges and potential solutions.

Viral Interference and Persistence in Mosquito-Borne Flaviviruses.

PubMed

Salas-Benito, Juan Santiago; De Nova-Ocampo, Mónica

2015-01-01

Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here.

Going viral: a review of replication-selective oncolytic adenoviruses

PubMed Central

Larson, Christopher; Oronsky, Bryan; Scicinski, Jan; Fanger, Gary R.; Stirn, Meaghan; Oronsky, Arnold; Reid, Tony R.

2015-01-01

Oncolytic viruses have had a tumultuous course, from the initial anecdotal reports of patients having antineoplastic effects after natural viral infections a century ago to the development of current cutting-edge therapies in clinical trials. Adenoviruses have long been the workhorse of virotherapy, and we review both the scientific and the not-so-scientific forces that have shaped the development of these therapeutics from wild-type viral pathogens, turning an old foe into a new friend. After a brief review of the mechanics of viral replication and how it has been modified to engineer tumor selectivity, we give particular attention to ONYX-015, the forerunner of virotherapy with extensive clinical testing that pioneered the field. The findings from those as well as other oncolytic trials have shaped how we now view these viruses, which our immune system has evolved to vigorously attack, as promising immunotherapy agents. PMID:26280277

Pest control through viral disease: mathematical modeling and analysis.

PubMed

Bhattacharyya, S; Bhattacharya, D K

2006-01-07

This paper deals with the mathematical modeling of pest management under viral infection (i.e. using viral pesticide) and analysis of its essential mathematical features. As the viral infection induces host lysis which releases more virus into the environment, on the average 'kappa' viruses per host, kappain(1,infinity), the 'virus replication parameter' is chosen as the main parameter on which the dynamics of the infection depends. We prove that there exists a threshold value kappa(0) beyond which the endemic equilibrium bifurcates from the free disease one. Still for increasing kappa values, the endemic equilibrium bifurcates towards a periodic solution. We further analyse the orbital stability of the periodic orbits arising from bifurcation by applying Poor's condition. A concluding discussion with numerical simulation of the model is then presented.

Viral Hepatitis: Past and Future of HBV and HDV

PubMed Central

Thomas, Emmanuel; Yoneda, Masato; Schiff, Eugene R.

2015-01-01

Viral hepatitis is a significant disease afflicting hundreds of millions of people. Hepatitis-causing viruses initiate significant morbidity and mortality by establishing both acute and chronic infections, and several of these viruses are specifically associated with the development of hepatocellular carcinoma (HCC). Consequently, intense research efforts are focused on increasing our understanding of virus biology and on improving antiviral therapy. Even though viral hepatitis can be caused by several viruses from a range of virus families, the discovery of components of the hepatitis B virus (HBV) became a catalyst for the development of diagnostic assays that differentiate between these viruses as well as strategies for novel methods of vaccine development. Improvements in both the treatment and prevention of viral hepatitis are advancing rapidly. However, HBV, along with the associated infection by the hepatitis D virus, is still among the most common pathogens afflicting humans. PMID:25646383

Struggle for space: viral extinction through competition for cells.

PubMed

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

2011-01-14

The design of protocols to suppress the propagation of viral infections is an enduring enterprise, especially hindered by limited knowledge of the mechanisms leading to viral extinction. Here we report on infection extinction due to intraspecific competition to infect susceptible hosts. Beneficial mutations increase the production of viral progeny, while the host cell may develop defenses against infection. For an unlimited number of host cells, a feedback runaway coevolution between host resistance and progeny production occurs. However, physical space limits the advantage that the virus obtains from increasing offspring numbers; thus, infection clearance may result from an increase in host defenses beyond a finite threshold. Our results might be relevant to devise improved control strategies in environments with mobility constraints or different geometrical properties.

The susceptible-infected-recovered (SIR) model for viral marketing

NASA Astrophysics Data System (ADS)

Ismail, Siti Suhaila; Akil, Ku Azlina Ku; Chulan, Majdah; Sharif, Noorzila

2017-11-01

Viral marketing is a marketing strategy utilizes social media to spread information about a product or services provided. It is the most powerful way to share information in a short amount of time. The objective of this study is to investigate the dynamic of viral marketing within a time duration in the point of view of mathematics. This study used the epidemiological model known as Susceptible-Infected-Recovered (SIR). The model consists of a system of three differential equations with three state variables namely susceptible (S), infected (I) and recovered (R). It considers a case of SIR model with demography. Numerical experiments have been performed. The results show that viral marketing reaches its peak within two days. The online messages shared will become higher if the initial number of the infected individual has been increased.

Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome

PubMed Central

Klase, Zachary A.; Khakhina, Svetlana; Schneider, Adriano De Bernardi; Callahan, Michael V.; Glasspool-Malone, Jill

2016-01-01

The ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain–Barré syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of “TORCH” viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication. PMID:27560129

The great escape: viral strategies to counter BST-2/tetherin.

PubMed

Douglas, Janet L; Gustin, Jean K; Viswanathan, Kasinath; Mansouri, Mandana; Moses, Ashlee V; Früh, Klaus

2010-05-13

The interferon-induced BST-2 protein has the unique ability to restrict the egress of HIV-1, Kaposi's sarcoma-associated herpesvirus (KSHV), Ebola virus, and other enveloped viruses. The observation that virions remain attached to the surface of BST-2-expressing cells led to the renaming of BST-2 as "tetherin". However, viral proteins such as HIV-1 Vpu, simian immunodeficiency virus Nef, and KSHV K5 counteract BST-2, thereby allowing mature virions to readily escape from infected cells. Since the anti-viral function of BST-2 was discovered, there has been an explosion of research into several aspects of this intriguing interplay between host and virus. This review focuses on recent work addressing the molecular mechanisms involved in BST-2 restriction of viral egress and the species-specific countermeasures employed by various viruses.

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).

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

Viral capsid mobility: a dynamic conduit for inactivation.

PubMed

Broo, K; Wei, J; Marshall, D; Brown, F; Smith, T J; Johnson, J E; Schneemann, A; Siuzdak, G

2001-02-27

Mass spectrometry and fluorescent probes have provided direct evidence that alkylating agents permeate the protein capsid of naked viruses and chemically inactivate the nucleic acid. N-acetyl-aziridine and a fluorescent alkylating agent, dansyl sulfonate aziridine, inactivated three different viruses, flock house virus, human rhinovirus-14, and foot and mouth disease virus. Mass spectral studies as well as fluorescent probes showed that alkylation of the genome was the mechanism of inactivation. Because particle integrity was not affected by selective alkylation (as shown by electron microscopy and sucrose gradient experiments), it was reasoned that the dynamic nature of the viral capsid acts as a conduit to the interior of the particle. Potential applications include fluorescent labeling for imaging viral genomes in living cells, the sterilization of blood products, vaccine development, and viral inactivation in vivo.

Emmprin and KSHV: new partners in viral cancer pathogenesis

PubMed Central

Dai, Lu; Bai, Lihua; Lu, Ying; Xu, Zengguang; Reiss, Krys; Valle, Luis Del; Kaleeba, Johnan; Toole, Bryan P.; Parsons, Chris; Qin, Zhiqiang

2013-01-01

Emmprin (CD147; basigin) is a multifunctional glycoprotein expressed at higher levels by cancer cells and stromal cells in the tumor microenvironment. Through direct effects within tumor cells and promotion of tumor-stroma interactions, emmprin participates in induction of tumor cell invasiveness, angiogenesis, metastasis and chemoresistance. Although its contribution to cancer progression has been widely studied, the role of emmprin in viral oncogenesis still remains largely unclear, and only a small body of available literature implicates emmprin-associated mechanisms in viral pathogenesis and tumorigenesis. We summarize these data in this review, focusing on the role of emmprin in pathogenesis associated with the Kaposi sarcoma-associated herpesvirus (KSHV), a common etiology for cancers arising in the setting of immune suppression. We also discuss future directions for mechanistic studies exploring roles for emmprin in viral cancer pathogenesis. PMID:23743354

Emmprin and KSHV: new partners in viral cancer pathogenesis.

PubMed

Dai, Lu; Bai, Lihua; Lu, Ying; Xu, Zengguang; Reiss, Krys; Del Valle, Luis; Kaleeba, Johnan; Toole, Bryan P; Parsons, Chris; Qin, Zhiqiang

2013-09-01

Emmprin (CD147; basigin) is a multifunctional glycoprotein expressed at higher levels by cancer cells and stromal cells in the tumor microenvironment. Through direct effects within tumor cells and promotion of tumor-stroma interactions, emmprin participates in induction of tumor cell invasiveness, angiogenesis, metastasis and chemoresistance. Although its contribution to cancer progression has been widely studied, the role of emmprin in viral oncogenesis still remains largely unclear, and only a small body of available literature implicates emmprin-associated mechanisms in viral pathogenesis and tumorigenesis. We summarize these data in this review, focusing on the role of emmprin in pathogenesis associated with the Kaposi sarcoma-associated herpesvirus (KSHV), a common etiology for cancers arising in the setting of immune suppression. We also discuss future directions for mechanistic studies exploring roles for emmprin in viral cancer pathogenesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The interplay between mechanics and stability of viral cages

NASA Astrophysics Data System (ADS)

Hernando-Pérez, Mercedes; Pascual, Elena; Aznar, María; Ionel, Alina; Castón, José R.; Luque, Antoni; Carrascosa, José L.; Reguera, David; de Pablo, Pedro J.

2014-02-01

The stability and strength of viral nanoparticles are crucial to fulfill the functions required through the viral cycle as well as using capsids for biomedical and nanotechnological applications. The mechanical properties of viral shells obtained through Atomic Force Microscopy (AFM) and continuum elasticity theory, such as stiffness or Young's modulus, have been interpreted very often in terms of stability. However, viruses are normally subjected to chemical rather than to mechanical aggression. Thus, a correct interpretation of mechanics in terms of stability requires an adequate linkage between the ability of viral cages to support chemical and mechanical stresses. Here we study the mechanical fragility and chemical stability of bacteriophage T7 in two different maturation states: the early proheads and the final mature capsids. Using chemical stress experiments we show that proheads are less stable than final mature capsids. Still, both particles present similar anisotropic stiffness, indicating that a continuum elasticity description in terms of Young's modulus is not an adequate measure of viral stability. In combination with a computational coarse-grained model we demonstrate that mechanical anisotropy of T7 emerges out of the discrete nature of the proheads and empty capsids. Even though they present the same stiffness, proheads break earlier and have fractures ten times larger than mature capsids, in agreement with chemical stability, thus demonstrating that fragility rather than stiffness is a better indicator of viral cages' stability.The stability and strength of viral nanoparticles are crucial to fulfill the functions required through the viral cycle as well as using capsids for biomedical and nanotechnological applications. The mechanical properties of viral shells obtained through Atomic Force Microscopy (AFM) and continuum elasticity theory, such as stiffness or Young's modulus, have been interpreted very often in terms of stability. However

Viral hepatitis A, B, and C: grown-up issues.

PubMed

Sharapov, Umid M; Hu, Dale J

2010-08-01

Viral hepatitis is a major global health problem associated with significant morbidity and mortality. Although there are five major and distinct human hepatitis viruses characterized to date--referred to as hepatitis A, B, C, D, and E, respectively--only hepatitis A, B, and C are epidemiologically and clinically relevant for adolescents in North America. The clinical presentation of acute infection with each of these viruses is similar; thus, diagnosis depends on the use of specific serologic markers and viral nucleic acids. This review provides data on the epidemiology, clinical symptoms, diagnosis, treatment, and prevention of each of these three viral infections, along with points that are important or unique to adolescent patients.

Immunological biomarkers predict HIV-1 viral rebound after treatment interruption

PubMed Central

Hurst, Jacob; Hoffmann, Matthias; Pace, Matthew; Williams, James P.; Thornhill, John; Hamlyn, Elizabeth; Meyerowitz, Jodi; Willberg, Chris; Koelsch, Kersten K.; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David A.; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Babiker, Abdel; Weber, Jonathan; Kelleher, Anthony D.; Phillips, Rodney E.; Frater, John

2015-01-01

Treatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of ‘post-treatment control' (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunological biomarkers can predict time to viral rebound after stopping ART by analysing data from a randomized study of primary HIV-1 infection incorporating a treatment interruption (TI) after 48 weeks of ART (the SPARTAC trial). T-cell exhaustion markers PD-1, Tim-3 and Lag-3 measured prior to ART strongly predict time to the return of viraemia. These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription. Our results may open new avenues for understanding the mechanisms underlying PTC, and eventually HIV-1 eradication. PMID:26449164

Metagenomic Analysis of the Ferret Fecal Viral Flora

PubMed Central

Smits, Saskia L.; Raj, V. Stalin; Oduber, Minoushka D.; Schapendonk, Claudia M. E.; Bodewes, Rogier; Provacia, Lisette; Stittelaar, Koert J.; Osterhaus, Albert D. M. E.; Haagmans, Bart L.

2013-01-01

Ferrets are widely used as a small animal model for a number of viral infections, including influenza A virus and SARS coronavirus. To further analyze the microbiological status of ferrets, their fecal viral flora was studied using a metagenomics approach. Novel viruses from the families Picorna-, Papilloma-, and Anelloviridae as well as known viruses from the families Astro-, Corona-, Parvo-, and Hepeviridae were identified in different ferret cohorts. Ferret kobu- and hepatitis E virus were mainly present in human household ferrets, whereas coronaviruses were found both in household as well as farm ferrets. Our studies illuminate the viral diversity found in ferrets and provide tools to prescreen for newly identified viruses that potentially could influence disease outcome of experimental virus infections in ferrets. PMID:23977082

SpaceView (Viral Space Situational Awareness) One Year Update

NASA Astrophysics Data System (ADS)

Gleckler, A.; Butterfield, M.; Copenhaver, R.; Wade, A.; Apponi, A.

2013-09-01

Viral SSA takes advantage of the amateur astronomy community to provide an extremely low-cost and geographically-diverse network of optical SSA sites. In the spirit of programs such as DARPA's Grand Challenge and the National Weather Service's program of providing amateur meteorologists with weather stations linked to a central professional meteorological facility, we form a cooperative bond with a willing community of technicallyminded individuals. We term this program "viral" because we will qualify an initial set of astronomers for SSA operation and then use word of mouth in the astronomy community, as well as an outreach program, to pull in new observers. The use of modern remote controlled telescopes allows the incorporation of certified amateur, university, and commercial telescope systems. The availability of the local Viral SSA member for troubleshooting eliminates most significant costs of operating a large network. In this talk, we discuss the project's first year and the roadmap for the next two years.

Anti-metastatic effects of viral and non-viral mediated Nk4 delivery to tumours.

PubMed

Buhles, Alexandra; Collins, Sara A; van Pijkeren, Jan P; Rajendran, Simon; Miles, Michelle; O'Sullivan, Gerald C; O'Hanlon, Deirdre M; Tangney, Mark

2009-03-09

The most common cause of death of cancer sufferers is through the occurrence of metastases. The metastatic behaviour of tumour cells is regulated by extracellular growth factors such as hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, and aberrant expression/activation of the c-Met receptor is closely associated with metastatic progression. Nk4 (also known as Interleukin (IL)32b) is a competitive antagonist of the HGF c-Met system and inhibits c-Met signalling and tumour metastasis. Nk4 has an additional anti-angiogenic activity independent of its HGF-antagonist function. Angiogenesis-inhibitory as well as cancer-specific apoptosis inducing effects make the Nk4 sequence an attractive candidate for gene therapy of cancer. This study investigates the inhibition of tumour metastasis by gene therapy mediated production of Nk4 by the primary tumour. Optimal delivery of anti-cancer genes is vital in order to achieve the highest therapeutic responses. Non-viral plasmid delivery methods have the advantage of safety and ease of production, providing immediate transgene expression, albeit short-lived in most tumours. Sustained presence of anti-angiogenic molecules is preferable with anti-angiogenic therapies, and the long-term expression mediated by Adeno-associated Virus (AAV) might represent a more appropriate delivery in this respect. However, the incubation time required by AAV vectors to reach appropriate gene expression levels hampers efficacy in many fast-growing murine tumour models. Here, we describe murine trials assessing the effects of Nk4 on the spontaneously metastatic Lewis Lung Carcinoma (LLC) model when delivered to primary tumour via plasmid lipofection or AAV2 vector. Intratumoural AAV-Nk4 administration produced the highest therapeutic response with significant reduction in both primary tumour growth and incidence of lung metastases. Plasmid-mediated therapy also significantly reduced metastatic growth, but with moderate

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

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

IFITM proteins-cellular inhibitors of viral entry.

PubMed

Smith, Se; Weston, S; Kellam, P; Marsh, M

2014-02-01

Interferon inducible transmembrane (IFITM) proteins are a recently discovered family of cellular anti-viral proteins that restrict the replication of a number of enveloped and non-enveloped viruses. IFITM proteins are located in the plasma membrane and endosomal membranes, the main portals of entry for many viruses. Biochemical and membrane fusion studies suggest IFITM proteins have the ability to inhibit viral entry, possibly by modulating the fluidity of cellular membranes. Here we discuss the IFITM proteins, recent work on their mode of action, and future directions for research. Copyright © 2014 Elsevier B.V. All rights reserved.

Diabetes mellitus and renal involvement in chronic viral liver disease.

PubMed

Iovanescu, V F; Streba, C T; Ionescu, M; Constantinescu, A F; Vere, C C; Rogoveanu, I; Moța, E

2015-01-01

Chronic viral liver disease is often associated with other conditions. Diabetes mellitus (DM) is frequently reported in this context and may play a role in the progression of the liver disease to hepatocellular carcinoma (HCC). Renal disease is also an important extrahepatic manifestation of hepatitis viral infection and its presence is associated with poor prognosis and management issues. Our study had multiple purposes: to determine the frequency of the association between chronic viral liver disease and diabetes mellitus, evaluate the potential of diabetes mellitus as a risk factor for HCC and assess an eventual renal involvement. We included in our study a number of 246 patients with chronic liver disease, from whom 136 were diagnosed with chronic viral hepatitis and 110 with viral liver cirrhosis. These patients were assessed by using a clinical examination and a series of tests, including serum transaminase levels, serum bilirubin, serum albumin, markers of cholestasis, fasting plasma glucose levels, serum creatinine, urea, albuminuria, Addis-Hamburger test, electrophoresis of urinary proteins, abdominal ultrasound and, in some cases, CT examination. We obtained the following results: diabetes mellitus is often associated with chronic liver disease of viral etiology, having been identified in 18.29% of the patients in our study. Age above 60 in patients with chronic hepatitis (p=0.013<0.05) and presence of hepatitis C virus were particularly correlated with the presence of diabetes mellitus. Renal disease was present in 13.4% of the patients with chronic liver disease and it was especially associated with liver cirrhosis and hepatitis C virus. The most common form of renal injury was glomerulonephritis. Acute kidney injury was diagnosed only in cirrhotic patients as hepatorenal syndrome, occurring in 7.27% of the subjects, while chronic kidney disease was identified only in two cases of chronic viral hepatitis. Four patients in our study were diagnosed with

New insights into an X-traordinary viral protein

PubMed Central

Schaller, Torsten; Bauby, Hélène; Hué, Stéphane; Malim, Michael H.; Goujon, Caroline

2014-01-01

Vpx is a protein encoded by members of the HIV-2/SIVsmm and SIVrcm/SIVmnd-2 lineages of primate lentiviruses, and is packaged into viral particles. Vpx plays a critical role during the early steps of the viral life cycle and has been shown to counteract SAMHD1, a restriction factor in myeloid and resting T cells. However, it is becoming evident that Vpx is a multifunctional protein in that SAMHD1 antagonism is likely not its sole role. This review summarizes the current knowledge on this X-traordinary protein. PMID:24782834

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. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A strategy to estimate unknown viral diversity in mammals.

PubMed

Anthony, Simon J; Epstein, Jonathan H; Murray, Kris A; Navarrete-Macias, Isamara; Zambrana-Torrelio, Carlos M; Solovyov, Alexander; Ojeda-Flores, Rafael; Arrigo, Nicole C; Islam, Ariful; Ali Khan, Shahneaz; Hosseini, Parviez; Bogich, Tiffany L; Olival, Kevin J; Sanchez-Leon, Maria D; Karesh, William B; Goldstein, Tracey; Luby, Stephen P; Morse, Stephen S; Mazet, Jonna A K; Daszak, Peter; Lipkin, W Ian

2013-09-03

The majority of emerging zoonoses originate in wildlife, and many are caused by viruses. However, there are no rigorous estimates of total viral diversity (here termed "virodiversity") for any wildlife species, despite the utility of this to future surveillance and control of emerging zoonoses. In this case study, we repeatedly sampled a mammalian wildlife host known to harbor emerging zoonotic pathogens (the Indian Flying Fox, Pteropus giganteus) and used PCR with degenerate viral family-level primers to discover and analyze the occurrence patterns of 55 viruses from nine viral families. We then adapted statistical techniques used to estimate biodiversity in vertebrates and plants and estimated the total viral richness of these nine families in P. giganteus to be 58 viruses. Our analyses demonstrate proof-of-concept of a strategy for estimating viral richness and provide the first statistically supported estimate of the number of undiscovered viruses in a mammalian host. We used a simple extrapolation to estimate that there are a minimum of 320,000 mammalian viruses awaiting discovery within these nine families, assuming all species harbor a similar number of viruses, with minimal turnover between host species. We estimate the cost of discovering these viruses to be ~$6.3 billion (or ~$1.4 billion for 85% of the total diversity), which if annualized over a 10-year study time frame would represent a small fraction of the cost of many pandemic zoonoses. Recent years have seen a dramatic increase in viral discovery efforts. However, most lack rigorous systematic design, which limits our ability to understand viral diversity and its ecological drivers and reduces their value to public health intervention. Here, we present a new framework for the discovery of novel viruses in wildlife and use it to make the first-ever estimate of the number of viruses that exist in a mammalian host. As pathogens continue to emerge from wildlife, this estimate allows us to put

Long-Term Resolution of Viral Breakthrough after Changing HIV Viral Load Assay.

PubMed

Obeid, Karam M; Sural, Preethi; Szpunar, Susan; Johnson, Leonard B

2011-01-01

Viral load (VL) measurement assays differ in their sensitivity with polymerase chain reaction assays (PCR) being more sensitive than branched DNA (bDNA) assays. We evaluated virologic outcomes of patients and physicians' response to increased VL after a switch from bDNA to PCR assay. Retrospective, case-control study on 65 HIV+ patients receiving highly active antiretroviral therapy (HAART). Cases included patients with undetectable VL by bDNA that became detectable after the switch; controls were patients that remained undetectable. Records were reviewed up to 1 year after the switch. A total of 58.5% patients had detectable VL after the switch. Repeat VL testing and resistance testing were ordered in 15.4% and 23.1% of these patients, respectively. By 1 year, VL was undetectable in 82.8% of cases and 92% of controls (P = .30), without change in HAART. Transient viremia after changing VL assay reflects the different sensitivity of these assays with no impact on patients' outcomes compared to controls.

Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness.

PubMed

Edwards, Michael R; Strong, Katherine; Cameron, Aoife; Walton, Ross P; Jackson, David J; Johnston, Sebastian L

2017-10-01

Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with T H 2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and T H 2 mediators. With the renewed interest in anti-T H 2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A review of licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines.

PubMed

Huang, David B; Wu, Jashin J; Tyring, Stephen K

2004-10-01

Viral vaccines could be considered among the most important medical achievements of the 20th century. They have prevented much suffering and saved many lives. Although some curative antiviral drugs exist, we desperately depend on efforts by academic, governmental and industrial scientists in the advancement of viral vaccines in the prevention and control of infectious diseases. In the next decade, we hope to see advancement in the development of current and investigational viral vaccines against childhood and adult infections. In this article, we will review the licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines.

Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation

PubMed Central

2013-01-01

Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases. PMID:24341630

ViralEpi v1.0: a high-throughput spectrum of viral epigenomic methylation profiles from diverse diseases.

PubMed

Khan, Mohd Shoaib; Gupta, Amit Kumar; Kumar, Manoj

2016-01-01

To develop a computational resource for viral epigenomic methylation profiles from diverse diseases. Methylation patterns of Epstein-Barr virus and hepatitis B virus genomic regions are provided as web platform developed using open source Linux-Apache-MySQL-PHP (LAMP) bundle: programming and scripting languages, that is, HTML, JavaScript and PERL. A comprehensive and integrated web resource ViralEpi v1.0 is developed providing well-organized compendium of methylation events and statistical analysis associated with several diseases. Additionally, it also facilitates 'Viral EpiGenome Browser' for user-affable browsing experience using JavaScript-based JBrowse. This web resource would be helpful for research community engaged in studying epigenetic biomarkers for appropriate prognosis and diagnosis of diseases and its various stages.

MicroRNA-like viral small RNA from porcine reproductive and respiratory syndrome virus negatively regulates viral replication by targeting the viral nonstructural protein 2.

PubMed

Li, Na; Yan, Yunhuan; Zhang, Angke; Gao, Jiming; Zhang, Chong; Wang, Xue; Hou, Gaopeng; Zhang, Gaiping; Jia, Jinbu; Zhou, En-Min; Xiao, Shuqi

2016-12-13

Many viruses encode microRNAs (miRNAs) that are small non-coding single-stranded RNAs which play critical roles in virus-host interactions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically impactful viruses in the swine industry. The present study sought to determine whether PRRSV encodes miRNAs that could regulate PRRSV replication. Four viral small RNAs (vsRNAs) were mapped to the stem-loop structures in the ORF1a, ORF1b and GP2a regions of the PRRSV genome by bioinformatics prediction and experimental verification. Of these, the structures with the lowest minimum free energy (MFE) values predicted for PRRSV-vsRNA1 corresponded to typical stem-loop, hairpin structures. Inhibition of PRRSV-vsRNA1 function led to significant increases in viral replication. Transfection with PRRSV-vsRNA1 mimics significantly inhibited PRRSV replication in primary porcine alveolar macrophages (PAMs). The time-dependent increase in the abundance of PRRSV-vsRNA1 mirrored the gradual upregulation of PRRSV RNA expression. Knockdown of proteins associated with cellular miRNA biogenesis demonstrated that Drosha and Argonaute (Ago2) are involved in PRRSV-vsRNA1 biogenesis. Moreover, PRRSV-vsRNA1 bound specifically to the nonstructural protein 2 (NSP2)-coding sequence of PRRSV genome RNA. Collectively, the results reveal that PRRSV encodes a functional PRRSV-vsRNA1 which auto-regulates PRRSV replication by directly targeting and suppressing viral NSP2 gene expression. These findings not only provide new insights into the mechanism of the pathogenesis of PRRSV, but also explore a potential avenue for controlling PRRSV infection using viral small RNAs.

Robust real-time cell analysis method for determining viral infectious titers during development of a viral vaccine production process.

PubMed

Charretier, Cédric; Saulnier, Aure; Benair, Loïc; Armanet, Corinne; Bassard, Isabelle; Daulon, Sandra; Bernigaud, Bertrand; Rodrigues de Sousa, Emanuel; Gonthier, Clémence; Zorn, Edouard; Vetter, Emmanuelle; Saintpierre, Claire; Riou, Patrice; Gaillac, David

2018-02-01

The classical cell-culture methods, such as cell culture infectious dose 50% (CCID 50 ) assays, are time-consuming, end-point assays currently used during the development of a viral vaccine production process to measure viral infectious titers. However, they are not suitable for handling the large number of tests required for high-throughput and large-scale screening analyses. Impedance-based bio-sensing techniques used in real-time cell analysis (RTCA) to assess cell layer biological status in vitro, provide real-time data. In this proof-of-concept study, we assessed the correlation between the results from CCID 50 and RTCA assays and compared time and costs using monovalent and tetravalent chimeric yellow fever dengue (CYD) vaccine strains. For the RTCA assay, Vero cells were infected with the CYD sample and real-time impedance was recorded, using the dimensionless cell index (CI). The CI peaked just after infection and decreased as the viral cytopathic effect occurred in a dose-dependent manner. The time to the median CI (CIT med ) was correlated with viral titers determined by CCID 50 over a range of about 4-5log 10 CCID 50 /ml. This in-house RTCA virus-titration assay was shown to be a robust method for determining real-time viral infectious titers, and could be an alternative to the classical CCID 50 assay during the development of viral vaccine production process. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Viral infection and antiviral therapy in the neonatal intensive care unit.

PubMed

Barford, Galina; Rentz, Alison C; Faix, Roger G

2004-01-01

Viral diseases are leading causes of mortality and morbidity among infants requiring care in the neonatal intensive care unit (NICU), with ongoing discoveries of new viral pathology likely to add to the burdens posed. Many viral diseases in NICU infants are undiagnosed or appreciated only late in the course because of subtle or asymptomatic presentation, confusion with bacterial disease, and failure to consider viral disease. We present an overview of viral disease in NICU infants, with emphasis on pharmacologic agents currently employed for prophylaxis and treatment of such diseases. Advances in molecular biology and popular demand to develop antiviral agents for viral diseases (eg, human immunodeficiency virus) offer great promise for the future.

Liver Failure due to Acute Viral Hepatitis (A-E).

PubMed

Manka, Paul; Verheyen, Jens; Gerken, Guido; Canbay, Ali

2016-04-01

Viral hepatitis is still one of the key causes of acute liver failure (ALF) in the world. A selective literature search of the PubMed database was conducted, including current studies, reviews, meta-analyses, and guidelines. We obtained an overview of ALF due to viral hepatitis in terms of epidemiology, course, and treatment options. Most fulminant viral courses are reported after infection with hepatitis A, B, and B/D, but not with hepatitis C. Hepatitis E is also known to cause ALF but has not gained much attention in recent years. However, more and more autochthonous hepatitis E virus infections have been recently observed in Europe. Reactivation of hepatitis B virus (HBV) under immunosuppressive conditions, such as after intensive chemotherapy, is also an increasing problem. For most viral-induced cases of ALF, liver transplantation represented the only therapeutic option in the past. Today, immediate treatment of HBV-induced ALF with nucleotide or nucleoside analogs is well tolerated and beneficially affects the course of the disease. Although numbers in Western European countries are decreasing rapidly, reliable diagnostic screening for hepatitis A-E is necessary to identify the etiology and to determine those most at risk of developing ALF.

Strategies for targeting primate neural circuits with viral vectors

PubMed Central

El-Shamayleh, Yasmine; Ni, Amy M.

2016-01-01

Understanding how the brain works requires understanding how different types of neurons contribute to circuit function and organism behavior. Progress on this front has been accelerated by optogenetics and chemogenetics, which provide an unprecedented level of control over distinct neuronal types in small animals. In primates, however, targeting specific types of neurons with these tools remains challenging. In this review, we discuss existing and emerging strategies for directing genetic manipulations to targeted neurons in the adult primate central nervous system. We review the literature on viral vectors for gene delivery to neurons, focusing on adeno-associated viral vectors and lentiviral vectors, their tropism for different cell types, and prospects for new variants with improved efficacy and selectivity. We discuss two projection targeting approaches for probing neural circuits: anterograde projection targeting and retrograde transport of viral vectors. We conclude with an analysis of cell type-specific promoters and other nucleotide sequences that can be used in viral vectors to target neuronal types at the transcriptional level. PMID:27052579

Inference with viral quasispecies diversity indices: clonal and NGS approaches.

PubMed

Gregori, Josep; Salicrú, Miquel; Domingo, Esteban; Sanchez, Alex; Esteban, Juan I; Rodríguez-Frías, Francisco; Quer, Josep

2014-04-15

Given the inherent dynamics of a viral quasispecies, we are often interested in the comparison of diversity indices of sequential samples of a patient, or in the comparison of diversity indices of virus in groups of patients in a treated versus control design. It is then important to make sure that the diversity measures from each sample may be compared with no bias and within a consistent statistical framework. In the present report, we review some indices often used as measures for viral quasispecies complexity and provide means for statistical inference, applying procedures taken from the ecology field. In particular, we examine the Shannon entropy and the mutation frequency, and we discuss the appropriateness of different normalization methods of the Shannon entropy found in the literature. By taking amplicons ultra-deep pyrosequencing (UDPS) raw data as a surrogate of a real hepatitis C virus viral population, we study through in-silico sampling the statistical properties of these indices under two methods of viral quasispecies sampling, classical cloning followed by Sanger sequencing (CCSS) and next-generation sequencing (NGS) such as UDPS. We propose solutions specific to each of the two sampling methods-CCSS and NGS-to guarantee statistically conforming conclusions as free of bias as possible. josep.gregori@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hepatitis B viral breakthrough associated with inappropriate preservation of entecavir

PubMed Central

Karabay, Oguz; Tuna, Nazan; Yahyaoglu, Mehmet

2012-01-01

If virologic breakthrough is observed during chronic hepatitis B treatment, drug resistance or compliance problem should be considered. But in some cases, breakthrough depends on drug preservation conditions. We report the case of a 30-years-old man, who experienced viral breakthrough due to wrong preservation conditions of the drug. PMID:22345891

Information Overload and Viral Marketing: Countermeasures and Strategies

NASA Astrophysics Data System (ADS)

Cheng, Jiesi; Sun, Aaron; Zeng, Daniel

Studying information diffusion through social networks has become an active research topic with important implications in viral marketing applications. One of the fundamental algorithmic problems related to viral marketing is the Influence Maximization (IM) problem: given an social network, which set of nodes should be considered by the viral marketer as the initial targets, in order to maximize the influence of the advertising message. In this work, we study the IM problem in an information-overloaded online social network. Information overload occurs when individuals receive more information than they can process, which can cause negative impacts on the overall marketing effectiveness. Many practical countermeasures have been proposed for alleviating the load of information on recipients. However, how these approaches can benefit viral marketers is not well understood. In our work, we have adapted the classic Information Cascade Model to incorporate information overload and study its countermeasures. Our results suggest that effective control of information overload has the potential to improve marketing effectiveness, but the targeting strategy should be re-designed in response to these countermeasures.

Illuminating structural proteins in viral "dark matter" with metaproteomics.

PubMed

Brum, Jennifer R; Ignacio-Espinoza, J Cesar; Kim, Eun-Hae; Trubl, Gareth; Jones, Robert M; Roux, Simon; VerBerkmoes, Nathan C; Rich, Virginia I; Sullivan, Matthew B

2016-03-01

Viruses are ecologically important, yet environmental virology is limited by dominance of unannotated genomic sequences representing taxonomic and functional "viral dark matter." Although recent analytical advances are rapidly improving taxonomic annotations, identifying functional dark matter remains problematic. Here, we apply paired metaproteomics and dsDNA-targeted metagenomics to identify 1,875 virion-associated proteins from the ocean. Over one-half of these proteins were newly functionally annotated and represent abundant and widespread viral metagenome-derived protein clusters (PCs). One primarily unannotated PC dominated the dataset, but structural modeling and genomic context identified this PC as a previously unidentified capsid protein from multiple uncultivated tailed virus families. Furthermore, four of the five most abundant PCs in the metaproteome represent capsid proteins containing the HK97-like protein fold previously found in many viruses that infect all three domains of life. The dominance of these proteins within our dataset, as well as their global distribution throughout the world's oceans and seas, supports prior hypotheses that this HK97-like protein fold is the most abundant biological structure on Earth. Together, these culture-independent analyses improve virion-associated protein annotations, facilitate the investigation of proteins within natural viral communities, and offer a high-throughput means of illuminating functional viral dark matter.

Methods of using viral replicase polynucleotides and polypeptides

DOEpatents

Gordon-Kamm, William J.; Lowe, Keith S.; Bailey, Matthew A.; Gregory, Carolyn A.; Hoerster, George J.; Larkins, Brian A.; Dilkes, Brian R.; Burnett, Ronald; Woo, Young Min

2007-12-18

The invention provides novel methods of using viral replicase polypeptides and polynucleotides. Included are methods for increasing transformation frequencies, increasing crop yield, providing a positive growth advantage, modulating cell division, transiently modulating cell division, and for providing a means of positive selection.

DEVELOPMENT OF BIOMARKER OF EXPOSURE TO VIRAL PATHOGENS

EPA Science Inventory

Interferon gamma (IFN-γ) was selected as a biomarker for a viral exposure study. Twelve-week-old BALB/c mice were intraperitoneally injected with 0.2ml of 104 PFU/ml of coxsackievirus B3 or B4 diluted in phosphate-buffered saline (PBS). Control mice were injected with PBS on...

Analysis of hepatitis C viral dynamics using Latin hypercube sampling

NASA Astrophysics Data System (ADS)

Pachpute, Gaurav; Chakrabarty, Siddhartha P.

2012-12-01

We consider a mathematical model comprising four coupled ordinary differential equations (ODEs) to study hepatitis C viral dynamics. The model includes the efficacies of a combination therapy of interferon and ribavirin. There are two main objectives of this paper. The first one is to approximate the percentage of cases in which there is a viral clearance in absence of treatment as well as percentage of response to treatment for various efficacy levels. The other is to better understand and identify the parameters that play a key role in the decline of viral load and can be estimated in a clinical setting. A condition for the stability of the uninfected and the infected steady states is presented. A large number of sample points for the model parameters (which are physiologically feasible) are generated using Latin hypercube sampling. An analysis of the simulated values identifies that, approximately 29.85% cases result in clearance of the virus during the early phase of the infection. Results from the χ2 and the Spearman's tests done on the samples, indicate a distinctly different distribution for certain parameters for the cases exhibiting viral clearance under the combination therapy.

Targeted DNA Mutagenesis for the Cure of Chronic Viral Infections

PubMed Central

Schiffer, Joshua T.; Aubert, Martine; Weber, Nicholas D.; Mintzer, Esther; Stone, Daniel

2012-01-01

Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), and herpes simplex virus (HSV) have been incurable to date because effective antiviral therapies target only replicating viruses and do not eradicate latently integrated or nonreplicating episomal viral genomes. Endonucleases that can target and cleave critical regions within latent viral genomes are currently in development. These enzymes are being engineered with high specificity such that off-target binding of cellular DNA will be absent or minimal. Imprecise nonhomologous-end-joining (NHEJ) DNA repair following repeated cleavage at the same critical site may permanently disrupt translation of essential viral proteins. We discuss the benefits and drawbacks of three types of DNA cleavage enzymes (zinc finger endonucleases, transcription activator-like [TAL] effector nucleases [TALENs], and homing endonucleases [also called meganucleases]), the development of delivery vectors for these enzymes, and potential obstacles for successful treatment of chronic viral infections. We then review issues regarding persistence of HIV-1, HBV, and HSV that are relevant to eradication with genome-altering approaches. PMID:22718830

Illuminating structural proteins in viral "dark matter" with metaproteomics

DOE PAGES

Brum, Jennifer R.; Ignacio-Espinoza, J. Cesar; Kim, Eun -Hae; ...

2016-02-16

Viruses are ecologically important, yet environmental virology is limited by dominance of unannotated genomic sequences representing taxonomic and functional "viral dark matter." Although recent analytical advances are rapidly improving taxonomic annotations, identifying functional darkmatter remains problematic. Here, we apply paired metaproteomics and dsDNA-targeted metagenomics to identify 1,875 virion-associated proteins from the ocean. Over one-half of these proteins were newly functionally annotated and represent abundant and widespread viral metagenome-derived protein clusters (PCs). One primarily unannotated PC dominated the dataset, but structural modeling and genomic context identified this PC as a previously unidentified capsid protein from multiple uncultivated tailed virus families. Furthermore,more » four of the five most abundant PCs in the metaproteome represent capsid proteins containing the HK97-like protein fold previously found in many viruses that infect all three domains of life. The dominance of these proteins within our dataset, as well as their global distribution throughout the world's oceans and seas, supports prior hypotheses that this HK97-like protein fold is the most abundant biological structure on Earth. Altogether, these culture-independent analyses improve virion-associated protein annotations, facilitate the investigation of proteins within natural viral communities, and offer a high-throughput means of illuminating functional viral dark matter.« less

N6-Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection.

PubMed

Gokhale, Nandan S; McIntyre, Alexa B R; McFadden, Michael J; Roder, Allison E; Kennedy, Edward M; Gandara, Jorge A; Hopcraft, Sharon E; Quicke, Kendra M; Vazquez, Christine; Willer, Jason; Ilkayeva, Olga R; Law, Brittany A; Holley, Christopher L; Garcia-Blanco, Mariano A; Evans, Matthew J; Suthar, Mehul S; Bradrick, Shelton S; Mason, Christopher E; Horner, Stacy M

2016-11-09

The RNA modification N6-methyladenosine (m 6 A) post-transcriptionally regulates RNA function. The cellular machinery that controls m 6 A includes methyltransferases and demethylases that add or remove this modification, as well as m 6 A-binding YTHDF proteins that promote the translation or degradation of m 6 A-modified mRNA. We demonstrate that m 6 A modulates infection by hepatitis C virus (HCV). Depletion of m 6 A methyltransferases or an m 6 A demethylase, respectively, increases or decreases infectious HCV particle production. During HCV infection, YTHDF proteins relocalize to lipid droplets, sites of viral assembly, and their depletion increases infectious viral particles. We further mapped m 6 A sites across the HCV genome and determined that inactivating m 6 A in one viral genomic region increases viral titer without affecting RNA replication. Additional mapping of m 6 A on the RNA genomes of other Flaviviridae, including dengue, Zika, yellow fever, and West Nile virus, identifies conserved regions modified by m 6 A. Altogether, this work identifies m 6 A as a conserved regulatory mark across Flaviviridae genomes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

Methods of treating Parkinson's disease using viral vectors

SciTech Connect

Bankiewicz, Krystof; Cunningham, Janet

Methods of delivering viral vectors, particularly recombinant adeno-associated virus (rAAV) virions, to the central nervous system (CNS) using convection enhanced delivery (CED) are provided. The rAAV virions include a nucleic acid sequence encoding a therapeutic polypeptide. The methods can be used for treating CNS disorders such as for treating Parkinson's Disease.

Viral vectors for production of recombinant proteins in plants.

PubMed

Lico, Chiara; Chen, Qiang; Santi, Luca

2008-08-01

Global demand for recombinant proteins has steadily accelerated for the last 20 years. These recombinant proteins have a wide range of important applications, including vaccines and therapeutics for human and animal health, industrial enzymes, new materials and components of novel nano-particles for various applications. The majority of recombinant proteins are produced by traditional biological "factories," that is, predominantly mammalian and microbial cell cultures along with yeast and insect cells. However, these traditional technologies cannot satisfy the increasing market demand due to prohibitive capital investment requirements. During the last two decades, plants have been under intensive investigation to provide an alternative system for cost-effective, highly scalable, and safe production of recombinant proteins. Although the genetic engineering of plant viral vectors for heterologous gene expression can be dated back to the early 1980s, recent understanding of plant virology and technical progress in molecular biology have allowed for significant improvements and fine tuning of these vectors. These breakthroughs enable the flourishing of a variety of new viral-based expression systems and their wide application by academic and industry groups. In this review, we describe the principal plant viral-based production strategies and the latest plant viral expression systems, with a particular focus on the variety of proteins produced and their applications. We will summarize the recent progress in the downstream processing of plant materials for efficient extraction and purification of recombinant proteins. (c) 2008 Wiley-Liss, Inc.

The Association of Viral Hepatitis and Acute Pancreatitis

PubMed Central

Geokas, Michael C.; Olsen, Harvey; Swanson, Virginia; Rinderknecht, Heinrich

1972-01-01

The histological features of 24 pancreases obtained from patients who died of causes other than hepatitis, pancreatitis or pancreatic tumors, included a variable degree of autolysis, rare foci of inflammatory reaction but no hemorrhagic fat necrosis or destruction of elastic tissue in vessel walls (elastolysis). Assays of elastase in extracts of these pancreases showed no free enzyme, but varying amounts of proelastase. A review of autopsy findings in 33 patients with fatal liver necrosis attributed to halothane anesthesia, demonstrated changes of acute pancreatitis only in two. On the other hand, a review of 16 cases of fulminant viral hepatitis revealed changes characteristic of acute pancreatitis in seven – interstitial edema, hemorrhagic fat necrosis, inflammatory reaction and frequently elastolysis in vessel walls. Determination of elastase in extracts of one pancreas showed the bulk of the enzyme in free form. Furthermore, assays of urinary amylase in 44 patients with viral hepatitis showed increased levels of this enzyme (2583 ± 398 mean value ± standard error, Somogyi units per 100 ml in 13, or 29.5 percent). The evidence suggests that acute pancreatitis may at times complicate viral hepatitis. Although direct proof of viral pancreatic involvement is not feasible at present, a rational hypothesis is advanced which underlines similar mechanisms of tissue involvement in both liver and pancreas that may be brought about by the hepatitis viruses. PMID:5070694

Viral nanomechanics with a virtual atomic force microscope

NASA Astrophysics Data System (ADS)

Aznar, María; Roca-Bonet, Sergi; Reguera, David

2018-07-01

One of the most important components of a virus is the protein shell or capsid that encloses its genetic material. The main role of the capsid is to protect the viral genome against external aggressions, facilitating its safe and efficient encapsulation and delivery. As a consequence, viral capsids have developed astonishing mechanical properties that are crucial for viral function. These remarkable properties have started to be unveiled in single-virus nanoindentation experiments, and are opening the door to the use of viral-derived artificial nanocages for promising bio- and nano-technological applications. However, the interpretation of nanoindentation experiments is often difficult, requiring the support of theoretical and simulation analysis. Here we present a ‘Virtual AFM’ (VAFM), a Brownian Dynamics simulation of a coarse-grained model of virus aimed to mimic the standard setup of atomic force microscopy (AFM) nanoindentation experiments. Despite the heavy level of coarse-graining, these simulations provide valuable information which is not accessible in experiments. Rather than focusing on a specific virus, the VAFM will be used to analyze how the mechanical response and breaking of viruses depend on different parameters controlling the effective interactions between capsid’s structural units. In particular, we will discuss the influence of adsorption, the tip radius, and the rigidity and shape of the shell on its mechanical response.

Neutrophil subset responses in infants with severe viral respiratory infection.

PubMed

Cortjens, Bart; Ingelse, Sarah A; Calis, Job C; Vlaar, Alexander P; Koenderman, Leo; Bem, Reinout A; van Woensel, Job B

2017-03-01

Neutrophils are the predominant inflammatory cells recruited to the respiratory tract as part of the innate immune response to viral infections. Recent reports indicate the existence of distinct functional neutrophil subsets in the circulatory compartment of adults, following severe inflammatory conditions. Here, we evaluated the occurrence of neutrophil subsets in blood and broncho-alveolar lavage fluid during severe viral respiratory infection in infants based on CD16/CD62L expression. We show that during the course of severe respiratory infection infants may develop four heterogeneous neutrophil subsets in blood (mature, immature, progenitor, and suppressive neutrophils), each with distinct activation states. However, while isolated viral respiratory infection was characterized by a relative absence of suppressive neutrophils in both blood and lungs, only patients with bacterial co-infection were shown to produce suppressive neutrophils. These data suggest the occurrence of distinct and unique neutrophil subset responses during severe viral and (secondary) bacterial respiratory infection in infants. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

COLIPHAGES AS POTENTIAL VIRAL INDICATORS OF FECAL POLLUTION

EPA Science Inventory

Friedman, Stephanie D. In press. Coliphages as Potential Viral Indicators of Fecal Pollution (Abstract). To be presented at the SWS/GERS Fall Joint Society Meeting: Communication and Collaboration: Coastal Systems of the Gulf of Mexico and Southeastern United States, 6-9 October ...

Toll-like receptor-2 exacerbates murine acute viral hepatitis.

PubMed

Bleau, Christian; Burnette, Mélanie; Filliol, Aveline; Piquet-Pellorce, Claire; Samson, Michel; Lamontagne, Lucie

2016-10-01

Viral replication in the liver is generally detected by cellular endosomal Toll-like receptors (TLRs) and cytosolic helicase sensors that trigger antiviral inflammatory responses. Recent evidence suggests that surface TLR2 may also contribute to viral detection through recognition of viral coat proteins but its role in the outcome of acute viral infection remains elusive. In this study, we examined in vivo the role of TLR2 in acute infections induced by the highly hepatotrophic mouse hepatitis virus (MHV) type 3 and weakly hepatotrophic MHV-A59 serotype. To address this, C57BL/6 (wild-type; WT) and TLR2 knockout (KO) groups of mice were intraperitoneally infected with MHV3 or MHV-A59. MHV3 infection provoked a fulminant hepatitis in WT mice, characterized by early mortality and high alanine and aspartate transaminase levels, histopathological lesions and viral replication whereas infection of TLR2 KO mice was markedly less severe. MHV-A59 provoked a comparable mild and subclinical hepatitis in WT and TLR2 KO mice. MHV3-induced fulminant hepatitis in WT mice correlated with higher hepatic expression of interferon-β, interleukin-6, tumour necrosis factor-α, CXCL1, CCL2, CXCL10 and alarmin (interleukin-33) than in MHV-A59-infected WT mice and in MHV3-infected TLR2 KO mice. Intrahepatic recruited neutrophils, natural killer cells, natural killer T cells or macrophages rapidly decreased in MHV3-infected WT mice whereas they were sustained in MHV-A59-infected WT mice and MHV3-infected TLR2 KO. MHV3 in vitro infection of macrophagic cells induced rapid and higher viral replication and/or interleukin-6 induction in comparison to MHV-A59, and depended on viral activation of TLR2 and p38 mitogen-activated protein kinase. Taken together, these results support a new aggravating inflammatory role for TLR2 in MHV3-induced acute fulminant hepatitis. © 2016 John Wiley & Sons Ltd.

Impact of Chloroquine on Viral Load in Breast Milk

PubMed Central

Semrau, Katherine; Kuhn, Louise; Kasonde, Prisca; Sinkala, Moses; Kankasa, Chipepo; Shutes, Erin; Vwalika, Cheswa; Ghosh, Mrinal; Aldrovandi, Grace; Thea, Donald M.

2006-01-01

Summary The anti-malarial agent chloroquine has activity against HIV. We compared the effect of chloroquine (n = 18) to an anti-malarial agent without known anti-HIV-activity, sulfadoxine-pyrimethamine (n = 12), on breast milk HIV RNA levels among HIV-infected breastfeeding women in Zambia. After adjusting for CD4 count and plasma viral load, chloroquine was associated with a trend towards lower levels of HIV RNA in breast milk compared with sulfadoxine-pyrimethamine (P 0.05). Higher breastmilk viral load was also observed among women receiving presumptive treatment = for symptomatic malaria compared with asymptomatic controls and among controls reporting fever in the prior week. Further research is needed to determine the potential role of chloroquine in prevention of HIV transmission through breastfeeding. Impacte de la chloroquine sur la charge virale dans le lait maternelle La chloroquine, agent antimalarique, a une activité contre le VIH. Nous avons comparé l’effet de la chloroquine à celui d’un autre agent antimalarique, la sulfadoxine-pyrimethamine, dont l’activité sur le VIH n’est pas connue, en mesurant les taux d’ARN de VIH dans le lait maternel de femmes allaitantes infectées par le VIH en Zambie. Après ajustement pour les taux de CD4 et la charge virale dans le plasma, la chloroquine comparée à la sulfadoxine pyrimethamine était associée à une tendance vers des teneurs plus bas en ARN de VIH dans le lait maternel (P = 0,05). Des charges virales plus élevées dans le lait maternel étaient aussi observées chez des femmes recevant un traitement présomptif pour des symptômes de malaria par rapport aux contrôles asymptomatiques et par rapport à des contrôles rapportant de la fièvre durant la première semaine. Des études supplémentaires sont nécessaires pour déterminer le rôle potentiel de la chloroquine dans la prévention de la transmission du VIH par l’allaitement maternel. mots clésVIH, malaria, allaitement maternel

Viral-bacterial associations in acute apical abscesses.

PubMed

Ferreira, Dennis C; Rôças, Isabela N; Paiva, Simone S M; Carmo, Flávia L; Cavalcante, Fernanda S; Rosado, Alexandre S; Santos, Kátia R N; Siqueira, José F

2011-08-01

Viral-bacterial and bacterial synergism have been suggested to contribute to the pathogenesis of several human diseases. This study sought to investigate the possible associations between 9 candidate endodontic bacterial pathogens and 9 human viruses in samples from acute apical abscesses. DNA extracts from purulent exudate aspirates of 33 cases of acute apical abscess were surveyed for the presence of 9 selected bacterial species using a 16S ribosomal RNA gene-based nested polymerase chain reaction (PCR) approach. Single or nested PCR assays were used for detection of the human papillomavirus (HPV) and herpesviruses types 1 to 8. Two-thirds of the abscess samples were positive for at least one of the target viruses. Specifically, the most frequently detected viruses were HHV-8 (54.5%); HPV (9%); and varicella zoster virus (VZV), Epstein-Barr virus (EBV), and HHV-6 (6%). Bacterial DNA was present in all cases and the most prevalent bacterial species were Treponema denticola (70%), Tannerella forsythia (67%), Porphyromonas endodontalis (67%), Dialister invisus (61%), and Dialister pneumosintes (57.5%). HHV-8 was positively associated with 7 of the target bacterial species and HPV with 4, but all these associations were weak. Several bacterial pairs showed a moderate positive association. Viral coinfection was found in 6 abscess cases, but no significant viral association could be determined. Findings demonstrated that bacterial and viral DNA occurred concomitantly in two-thirds of the samples from endodontic abscesses. Although this may suggest a role for viruses in the etiology of apical abscesses, the possibility also exists that the presence of viruses in abscess samples is merely a consequence of the bacterially induced disease process. Further studies are necessary to clarify the role of these viral-bacterial interactions, if any, in the pathogenesis of acute apical abscesses. Copyright © 2011 Mosby, Inc. All rights reserved.

Virally mediated gene manipulation in the adult CNS

PubMed Central

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

2011-01-01

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

Neurological diseases associated with viral and Mycoplasma pneumoniae infections

PubMed Central

Assaad, F.; Gispen, R.; Kleemola, M.; Syrůček, L.; Esteves, K.

1980-01-01

In 1963 the World Health Organization established a system for the collection and dissemination of information on viral infections and by 1976, laboratories in 49 countries were participating in this scheme. The present study is in two parts: part 1 is an analysis of almost 60 000 reports on neurological disease associated with viral and Mycoplasma pneumoniae infections reported during the 10-year period 1967-76. This analysis showed a steady increase in the yearly number of reports of viral neurological diseases, which closely followed the general increase in the overall reporting of virus diseases. Likewise, the seasonal pattern was similar to that seen in general for any given virus. Over 75% of the cases were in children. Over half of all viral neurological diseases were associated with enteroviruses, while the myxoviruses accounted for almost 30%. Among the myxoviruses, mumps virus was by far the most frequently reported. The polioviruses were the agents most commonly detected in cases of paralytic disease. The other enteroviruses, mumps virus, and the herpesviruses were the most frequently reported viruses in cases of aseptic meningitis or encephalitis. On the other hand, one-third to over one-half of the reports on the myxoviruses (excluding mumps and measles) related to ill-defined clinical conditions. Part 2 of the study deals in particular with viruses whose role in neurological disease is less well documented. One laboratory reported an outbreak of adenoviral aseptic meningitis in Czechoslovakia, while another described neurological disease associated with M. pneumoniae infection in Finland. Part 2 also includes a detailed appraisal of viral infections diagnosed in the Netherlands during the period 1973-76. The results are very similar to those routinely reported. PMID:6249511

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 andmore » 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.« less

Viral-Associated GN: Hepatitis C and HIV.

PubMed

Kupin, Warren L

2017-08-07

Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage. Copyright © 2017 by the American Society of Nephrology.

Viral Diversity Threshold for Adaptive Immunity in Prokaryotes

PubMed Central

Weinberger, Ariel D.; Wolf, Yuri I.; Lobkovsky, Alexander E.; Gilmore, Michael S.; Koonin, Eugene V.

2012-01-01

ABSTRACT Bacteria and archaea face continual onslaughts of rapidly diversifying viruses and plasmids. Many prokaryotes maintain adaptive immune systems known as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (Cas). CRISPR-Cas systems are genomic sensors that serially acquire viral and plasmid DNA fragments (spacers) that are utilized to target and cleave matching viral and plasmid DNA in subsequent genomic invasions, offering critical immunological memory. Only 50% of sequenced bacteria possess CRISPR-Cas immunity, in contrast to over 90% of sequenced archaea. To probe why half of bacteria lack CRISPR-Cas immunity, we combined comparative genomics and mathematical modeling. Analysis of hundreds of diverse prokaryotic genomes shows that CRISPR-Cas systems are substantially more prevalent in thermophiles than in mesophiles. With sequenced bacteria disproportionately mesophilic and sequenced archaea mostly thermophilic, the presence of CRISPR-Cas appears to depend more on environmental temperature than on bacterial-archaeal taxonomy. Mutation rates are typically severalfold higher in mesophilic prokaryotes than in thermophilic prokaryotes. To quantitatively test whether accelerated viral mutation leads microbes to lose CRISPR-Cas systems, we developed a stochastic model of virus-CRISPR coevolution. The model competes CRISPR-Cas-positive (CRISPR-Cas+) prokaryotes against CRISPR-Cas-negative (CRISPR-Cas−) prokaryotes, continually weighing the antiviral benefits conferred by CRISPR-Cas immunity against its fitness costs. Tracking this cost-benefit analysis across parameter space reveals viral mutation rate thresholds beyond which CRISPR-Cas cannot provide sufficient immunity and is purged from host populations. These results offer a simple, testable viral diversity hypothesis to explain why mesophilic bacteria disproportionately lack CRISPR-Cas immunity. More generally, fundamental limits on the adaptability of biological

T cell responses in experimental viral retinitis: mechanisms, peculiarities and implications for gene therapy with viral vectors.

PubMed

Zinkernagel, Martin S; McMenamin, Paul G; Forrester, John V; Degli-Esposti, Mariapia A

2011-07-01

T lymphocytes play a decisive role in the course and clinical outcome of viral retinal infection. This review focuses on aspects of the adaptive cellular immune response against viral pathogens in the retina. Two distinct models to study adaptive cell mediated immune responses in viral retinitis are presented: (i) experimental retinitis induced by murine cytomegalovirus (MCMV), where the immune system prevents necrotizing damage to the retina and (ii) retinitis induced by the non-cytopathic lymphocytic choriomeningitis virus (LCMV), where the retinal microanatomy is compromised not by the virus, but by the immune response itself. From these studies it is clear that, in the context of viral infections, the cytotoxic T cell response against a pathogen in the retina does not differ from that seen in other organs, and that once such a response has been initiated, clearing of virus from retinal tissue has priority over preservation of retinal architecture and function. Furthermore, implications drawn from these models for gene therapy in retinal diseases are discussed. Copyright © 2011. Published by Elsevier Ltd.

Passive immunization against highly pathogenic Avian Influenza Virus (AIV) strain H7N3 with antiserum generated from viral polypeptides protect poultry birds from lethal viral infection

PubMed Central

Shahzad, Mirza Imran; Naeem, Khalid; Mukhtar, Muhammad; Khanum, Azra

2008-01-01

Our studies were aimed at developing a vaccination strategy that could provide protection against highly pathogenic avian influenza virus (AIV), H7N3 or its variants outbreaks. A purified viral stock of highly pathogenic H7N3 isolate was lysed to isolate viral proteins by electrophresing on 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by their elution from gel through trituration in phosphate buffered saline (PBS). Overall, five isolated viral polypeptides/proteins upon characterization were used to prepare hyperimmune monovalent serum against respective polypeptides independently and a mixture of all five in poultry birds, and specificity confirmation of each antiserum through dot blot and Western blotting. Antiserum generated from various group birds was pooled and evaluated in 2-week old broiler chicken, for its protection against viral challenge. To evaluate in-vivo protection of each antiserum against viral challenges, six groups of 2-week old broiler chicken were injected with antiserum and a seventh control group received normal saline. Each group was exposed to purified highly pathogenic AIV H7N3 strain at a dose 105 embryo lethal dose (ELD50). We observed that nucleoprotein (NP) antiserum significantly protected birds from viral infection induced morbidity, mortality and lowered viral shedding compared with antiserum from individual viral proteins or mixed polypeptides/proteins inclusive of NP component. The capability of individual viral polypeptide specific antisera to protect against viral challenges in decreasing order was nucleoprotein (NP) > hemagglutinin (HA) > neuraminidase (NA) > viral proteins mix > viral polymerase (PM) > non-structural proteins (NS). Our data provide proof of concept for potential utilization of passive immunization in protecting poultry industry during infection outbreaks. Furthermore conserved nature of avian NP makes it an ideal candidate to produce antiserum protective against viral

Pregnant and breastfeeding women: A priority population for HIV viral load monitoring.

PubMed

Myer, Landon; Essajee, Shaffiq; Broyles, Laura N; Watts, D Heather; Lesosky, Maia; El-Sadr, Wafaa M; Abrams, Elaine J

2017-08-01

Landon Myer and colleagues discuss viral load monitoring for pregnant HIV-positive women and those breastfeeding; ART treatments can suppress viral load and are key to preventing transmission to the child.

Reducing inherent biases introduced during DNA viral metagenome analyses of municipal wastewater

EPA Science Inventory

Metagenomics is a powerful tool for characterizing viral composition within environmental samples, but sample and molecular processing steps can bias the estimation of viral community structure. The objective of this study is to understand the inherent variability introduced when...

Occupational viral hepatitis in the Slovak and the Czech Republic.

PubMed

Buchancová, Jana; Svihrová, Viera; Legáth, L'ubomir; Osina, Oto; Urban, Pavel; Fenclová, Zdenka; Zibolenová, Jana; Rosková, Dana; Murajda, Lukás; Hudecková, Henrieta

2013-06-01

The proportion of occupational infectious diseases (ID) in the total number of occupational diseases reported in the Slovak Republic (SR) and the Czech Republic (CR) was decreasing from 1973 to 2010. Our study presents a longitudinal analysis of the occurrence of occupational infectious diseases in the Slovak Republic and the Czech Republic in the period from 1973-2010 with special focus on viral hepatitis. The sources of data were national health statistics of Czechoslovakia, the Czech Republic and the Slovak Republic. Descriptive statistical methods were used for data analysis. Incidence rate of reported diseases was calculated per 100,000 general population or per 100,000 people insured. During the studied period, a total of 2,931 and 8,318 cases of occupational viral hepatitis (VH) were reported in the Slovak Republic and the Czech Republic, respectively. The incidence culminated in the late 1970s when hepatitis represented almost 50% of all reported occupational infectious diseases. Most cases of occupational hepatitis occurred in health and social services. Since the early 1980s, a steep decrease in the incidence of hepatitis has been observed due to the gradual implementation of mandatory vaccination against hepatitis A and B in risk groups. In SR in 1973, the incidence rate of occupational infectious diseases and that of occupational viral hepatitis was 10.85/100,000 and 1.86/100,000, respectively. In 2010, these rates decreased to 0.74/100,000 and 0.20/100,000, respectively. In CR, the incidence rates of occupational infectious diseases and that of occupational viral hepatitis reported in 1973 were 11.75/100,000 and 3.69/100,000. In 2010, reported incidence rates were 1.71/100,000 and 0.10/100,000, respectively. Although the incidence of occupational viral hepatitis has dramatically decreased in the Slovak and the Czech Republic as well as in other Visegrad group countries during the studied period, we emphasize the necessity of continuing epidemiological

Viral tRNA Mimicry from a Biocommunicative Perspective

PubMed Central

Ariza-Mateos, Ascensión; Gómez, Jordi

2017-01-01

RNA viruses have very small genomes which limits the functions they can encode. One of the strategies employed by these viruses is to mimic key factors of the host cell so they can take advantage of the interactions and activities these factors typically participate in. The viral RNA genome itself was first observed to mimic cellular tRNA over 40 years ago. Since then researchers have confirmed that distinct families of RNA viruses are accessible to a battery of cellular factors involved in tRNA-related activities. Recently, potential tRNA-like structures have been detected within the sequences of a 100 mRNAs taken from human cells, one of these being the host defense interferon-alpha mRNA; these are then additional to the examples found in bacterial and yeast mRNAs. The mimetic relationship between tRNA, cellular mRNA, and viral RNA is the central focus of two considerations described below. These are subsequently used as a preface for a final hypothesis drawing on concepts relating to mimicry from the social sciences and humanities, such as power relations and creativity. Firstly, the presence of tRNA-like structures in mRNAs indicates that the viral tRNA-like signal could be mimicking tRNA-like elements that are contextualized by the specific carrier mRNAs, rather than, or in addition to, the tRNA itself, which would significantly increase the number of potential semiotic relations mediated by the viral signals. Secondly, and in particular, mimicking a host defense mRNA could be considered a potential new viral strategy for survival. Finally, we propose that mRNA’s mimicry of tRNA could be indicative of an ancestral intracellular conflict in which species of mRNAs invaded the cell, but from within. As the meaning of the mimetic signal depends on the context, in this case, the conflict that arises when the viral signal enters the cell can change the meaning of the mRNAs’ internal tRNA-like signals, from their current significance to that they had in the

Ribavirin, Interferon, and Antibody Approaches to Prophylaxis and Therapy for Viral Hemorrhagic Fevers

DTIC Science & Technology

1990-01-01

competitively inhibits intracellular pools of tive in preventing nosocomial infections (MMWR 1988, guanosine triphosphate required for viral nucleic...separation of cytotoxic and viral inhibitory activ- serious viral infections , they assume another dimension ities (Smith and Kirkpatrick, eds., Ribavirin, A...individuals or those exposed to clinical trials conducted since 1977, ribavirin has been self-limited viral infections must also take into account administered

Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study.

PubMed

Ai, Junhong; Xie, Zhengde; Liu, Gang; Chen, Zongbo; Yang, Yong; Li, Yuning; Chen, Jing; Zheng, Guo; Shen, Kunling

2017-07-14

In China, there were few studies about the pathogens of acute viral encephalitis and meningitis in children in recent years. The aims of this study were to characterize the etiology and prognosis of acute viral encephalitis and meningitis in Chinese children. This was a multicentre prospective study. Two hundred and sixty one viral encephalitis patients and 285 viral meningitis patients were enrolled. The mean age of viral encephalitis and meningitis were 5.88 ± 3.60 years and 6.39 ± 3.57 years, respectively. Real-time reverse transcription PCR and multiplex PCR were used to detect human enteroviruses and herpes viruses in cerebrospinal fluid (CSF) of patients with encephalitis or meningitis. The enzyme-linked immune absorbent assay (ELISA) was used for detecting IgM antibody against Japanese encephalitis virus (JEV) in CSF and against mumps virus, tick-borne encephalitis virus (TBEV), dengue virus and rubella virus in acute serum. The clinical and outcome data were collected during patients' hospitalization. The etiology of viral encephalitis was confirmed in 52.5% patients. The primary pathogen was human enteroviruses (27.7%) in viral encephalitis. The incidence of sequelae and the fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The etiology of viral meningitis was identified in 42.8% cases. The leading pathogen was also human enteroviruses (37.7%) in viral meningitis. The prognosis of viral meningitis was favorable with only 0.7% patients had neurological sequelae. Human enteroviruses were the leading cause both in acute viral encephalitis and viral meningitis in children. The incidence of sequelae and fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The prognosis of viral meningitis was favorable compared to viral encephalitis.

Homoisoflavonoids from Caesalpinia sappan displaying viral neuraminidases inhibition.

PubMed

Jeong, Hyung Jae; Kim, Young Min; Kim, Jang Hoon; Kim, Ji Young; Park, Ji-Young; Park, Su-Jin; Ryu, Young Bae; Lee, Woo Song

2012-01-01

In this study, twelve neuraminidase (NA) inhibitory compounds 1-12 were isolated from heartwood of Caesalpinia sappan on the basis of their biological activities against three types of viral NAs. Of isolated homoisoflavonoids, sappanone A (2) showed the most potent NAs inhibitory activities with IC(50) values of 0.7 µM [H1N1], 1.1 µM [H3N2], and 1.0 µM [H9N2], respectively, whereas saturated homoisoflavonoid (3) did not show significantly inhibition. This result revealed that α,β-unsaturated carbonyl group in A-ring was the key requirements for viral NAs inhibitory activity. In our enzyme kinetic study, all NA inhibitors screened were found to be reversible noncompetitive types.

Bioreactor concepts for cell culture-based viral vaccine production.

PubMed

Gallo-Ramírez, Lilí Esmeralda; Nikolay, Alexander; Genzel, Yvonne; Reichl, Udo

2015-01-01

Vaccine manufacturing processes are designed to meet present and upcoming challenges associated with a growing vaccine market and to include multi-use facilities offering a broad portfolio and faster reaction times in case of pandemics and emerging diseases. The final products, from whole viruses to recombinant viral proteins, are very diverse, making standard process strategies hardly universally applicable. Numerous factors such as cell substrate, virus strain or expression system, medium, cultivation system, cultivation method, and scale need consideration. Reviewing options for efficient and economical production of human vaccines, this paper discusses basic factors relevant for viral antigen production in mammalian cells, avian cells and insect cells. In addition, bioreactor concepts, including static systems, single-use systems, stirred tanks and packed-beds are addressed. On this basis, methods towards process intensification, in particular operational strategies, the use of perfusion systems for high product yields, and steps to establish continuous processes are introduced.

Latency reversal and viral clearance to cure HIV-1

PubMed Central

Margolis, David M.; Garcia, J. Victor; Hazuda, Daria J.; Haynes, Barton F.

2016-01-01

Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication—a cure for AIDS. Paired testing of latency reversal and clearance strategies has begun, but additional obstacles to HIV eradication may emerge. Nevertheless, there is reason for optimism that advances in long-acting antiretroviral therapy and HIV prevention strategies will contribute to efforts in HIV cure research and that the implementation of these efforts will synergize to markedly blunt the effect of the HIV pandemic on society. PMID:27463679

Latency reversal and viral clearance to cure HIV-1.

PubMed

Margolis, David M; Garcia, J Victor; Hazuda, Daria J; Haynes, Barton F

2016-07-22

Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication--a cure for AIDS. Paired testing of latency reversal and clearance strategies has begun, but additional obstacles to HIV eradication may emerge. Nevertheless, there is reason for optimism that advances in long-acting antiretroviral therapy and HIV prevention strategies will contribute to efforts in HIV cure research and that the implementation of these efforts will synergize to markedly blunt the effect of the HIV pandemic on society. Copyright © 2016, American Association for the Advancement of Science.

Investigating the thermal dissociation of viral capsid by lattice model

NASA Astrophysics Data System (ADS)

Chen, Jingzhi; Chevreuil, Maelenn; Combet, Sophie; Lansac, Yves; Tresset, Guillaume

2017-11-01

The dissociation of icosahedral viral capsids was investigated by a homogeneous and a heterogeneous lattice model. In thermal dissociation experiments with cowpea chlorotic mottle virus and probed by small-angle neutron scattering, we observed a slight shrinkage of viral capsids, which can be related to the strengthening of the hydrophobic interaction between subunits at increasing temperature. By considering the temperature dependence of hydrophobic interaction in the homogeneous lattice model, we were able to give a better estimate of the effective charge. In the heterogeneous lattice model, two sets of lattice sites represented different capsid subunits with asymmetric interaction strengths. In that case, the dissociation of capsids was found to shift from a sharp one-step transition to a gradual two-step transition by weakening the hydrophobic interaction between AB and CC subunits. We anticipate that such lattice models will shed further light on the statistical mechanics underlying virus assembly and disassembly.

The emerging role of nuclear viral DNA sensors.

PubMed

Diner, Benjamin A; Lum, Krystal K; Cristea, Ileana M

2015-10-30

Detecting pathogenic DNA by intracellular receptors termed "sensors" is critical toward galvanizing host immune responses and eliminating microbial infections. Emerging evidence has challenged the dogma that sensing of viral DNA occurs exclusively in sub-cellular compartments normally devoid of cellular DNA. The interferon-inducible protein IFI16 was shown to bind nuclear viral DNA and initiate immune signaling, culminating in antiviral cytokine secretion. Here, we review the newly characterized nucleus-originating immune signaling pathways, their links to other crucial host defenses, and unique mechanisms by which viruses suppress their functions. We frame these findings in the context of human pathologies associated with nuclear replicating DNA viruses. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Pathophysiology of viral-induced exacerbations of COPD

PubMed Central

Alfredo, Potena; Gaetano, Caramori; Paolo, Casolari; Marco, Contoli; Johnston, Sebastian L; Alberto, Papi

2007-01-01

Inflammation of the lower airways is a central feature of chronic obstructive pulmonary disease (COPD). Inflammatory responses are associated with an increased expression of a cascade of proteins including cytokines, chemokines, growth factors, enzymes, adhesion molecules and receptors. In most cases the increased expression of these proteins is the result of enhanced gene transcription: many of these genes are not expressed in normal cells under resting conditions but they are induced in the inflammatory process in a cell-specific manner. Transcription factors regulate the expression of many pro-inflammatory genes and play a key role in the pathogenesis of airway inflammation. Many studies have suggested a role for viral infections as a causative agent of COPD exacerbations. In this review we will focus our attention on the relationship between common respiratory viral infections and the molecular and inflammatory mechanisms that lead to COPD exacerbation. PMID:18268922

Vaccines against viral hemorrhagic fevers: non-human primate models.

PubMed

Carrion, Ricardo; Patterson, Jean L

2011-06-01

Viral hemorrhagic fevers are a group of disease syndromes caused by infection with certain RNA viruses. The disease is marked by a febrile response, malaise, coagulopathy and vascular permeability culminating in death. Case fatality rates can reach 90% depending on the etiologic agent. Currently, there is no approved antiviral treatment. Because of the high case fatality, risk of importation and the potential to use these agents as biological weapons, development of countermeasures to these agents is a high priority. The sporadic nature of disease outbreaks and the ethical issues associated with conducting a human trial for such diseases make human studies impractical; therefore, development of countermeasures must occur in relevant animal models. Non-human primates are superior models to study infectious disease because their immune system is similar to humans and they are good predictors of efficacy in vaccine development and other intervention strategies. This review article summarizes viral hemorrhagic fever non-human primate models.

Interrogating viral capsid assembly with ion mobility-mass spectrometry

NASA Astrophysics Data System (ADS)

Uetrecht, Charlotte; Barbu, Ioana M.; Shoemaker, Glen K.; van Duijn, Esther; Heck, Albert J. R.

2011-02-01

Most proteins fulfil their function as part of large protein complexes. Surprisingly, little is known about the pathways and regulation of protein assembly. Several viral coat proteins can spontaneously assemble into capsids in vitro with morphologies identical to the native virion and thus resemble ideal model systems for studying protein complex formation. Even for these systems, the mechanism for self-assembly is still poorly understood, although it is generally thought that smaller oligomeric structures form key intermediates. This assembly nucleus and larger viral assembly intermediates are typically low abundant and difficult to monitor. Here, we characterised small oligomers of Hepatitis B virus (HBV) and norovirus under equilibrium conditions using native ion mobility mass spectrometry. This data in conjunction with computational modelling enabled us to elucidate structural features of these oligomers. Instead of more globular shapes, the intermediates exhibit sheet-like structures suggesting that they are assembly competent. We propose pathways for the formation of both capsids.

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

Virality Prediction and Community Structure in Social Networks

NASA Astrophysics Data System (ADS)

Weng, Lilian; Menczer, Filippo; Ahn, Yong-Yeol

2013-08-01

How does network structure affect diffusion? Recent studies suggest that the answer depends on the type of contagion. Complex contagions, unlike infectious diseases (simple contagions), are affected by social reinforcement and homophily. Hence, the spread within highly clustered communities is enhanced, while diffusion across communities is hampered. A common hypothesis is that memes and behaviors are complex contagions. We show that, while most memes indeed spread like complex contagions, a few viral memes spread across many communities, like diseases. We demonstrate that the future popularity of a meme can be predicted by quantifying its early spreading pattern in terms of community concentration. The more communities a meme permeates, the more viral it is. We present a practical method to translate data about community structure into predictive knowledge about what information will spread widely. This connection contributes to our understanding in computational social science, social media analytics, and marketing applications.

Virality Prediction and Community Structure in Social Networks

PubMed Central

Weng, Lilian; Menczer, Filippo; Ahn, Yong-Yeol

2013-01-01

How does network structure affect diffusion? Recent studies suggest that the answer depends on the type of contagion. Complex contagions, unlike infectious diseases (simple contagions), are affected by social reinforcement and homophily. Hence, the spread within highly clustered communities is enhanced, while diffusion across communities is hampered. A common hypothesis is that memes and behaviors are complex contagions. We show that, while most memes indeed spread like complex contagions, a few viral memes spread across many communities, like diseases. We demonstrate that the future popularity of a meme can be predicted by quantifying its early spreading pattern in terms of community concentration. The more communities a meme permeates, the more viral it is. We present a practical method to translate data about community structure into predictive knowledge about what information will spread widely. This connection contributes to our understanding in computational social science, social media analytics, and marketing applications. PMID:23982106

Virality prediction and community structure in social networks.

PubMed

Weng, Lilian; Menczer, Filippo; Ahn, Yong-Yeol

2013-01-01

How does network structure affect diffusion? Recent studies suggest that the answer depends on the type of contagion. Complex contagions, unlike infectious diseases (simple contagions), are affected by social reinforcement and homophily. Hence, the spread within highly clustered communities is enhanced, while diffusion across communities is hampered. A common hypothesis is that memes and behaviors are complex contagions. We show that, while most memes indeed spread like complex contagions, a few viral memes spread across many communities, like diseases. We demonstrate that the future popularity of a meme can be predicted by quantifying its early spreading pattern in terms of community concentration. The more communities a meme permeates, the more viral it is. We present a practical method to translate data about community structure into predictive knowledge about what information will spread widely. This connection contributes to our understanding in computational social science, social media analytics, and marketing applications.

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

Atypical viral dynamics from transport through popular places

NASA Astrophysics Data System (ADS)

Manrique, Pedro D.; Xu, Chen; Hui, Pak Ming; Johnson, Neil F.

2016-08-01

The flux of visitors through popular places undoubtedly influences viral spreading—from H1N1 and Zika viruses spreading through physical spaces such as airports, to rumors and ideas spreading through online spaces such as chat rooms and social media. However, there is a lack of understanding of the types of viral dynamics that can result. Here we present a minimal dynamical model that focuses on the time-dependent interplay between the mobility through and the occupancy of such spaces. Our generic model permits analytic analysis while producing a rich diversity of infection profiles in terms of their shapes, durations, and intensities. The general features of these theoretical profiles compare well to real-world data of recent social contagion phenomena.

Paraneoplastic limbic encephalitis presenting as acute viral encephalitis.

PubMed

Kararizou, E; Markou, I; Zalonis, I; Gkiatas, K; Triantafyllou, N; Kararizos, G; Likomanos, D; Zambelis, T; Vassilopoulos, D

2005-11-01

To describe a case of limbic encephalitis which initially presented as viral limbic encephalitis and during the clinical evaluation a renal carcinoma was diagnosed. Patient with history of peripheral paresis of right facial nerve, 1 month after symptoms appearance and treatment, developed fever, vomiting, grand mal seizure, decreased level of consciousness, confusion, hallucinations and agitation. The patient initially presented a clinical picture of viral LE. which confirmed by CSF. MRI brain showed areas with pathological intensity signal in the region of limbic system unilateral. During the clinical evaluation a renal carcinoma was discovered and a nephrectomy has been performed. Although PLE typically presents as a chronic or subacute disease, it may be fulminant and clinically indistinguishable from an acute HSVE. This association pose the problem of a possible relation between this two syndromes and the correct diagnosis is very important, because there are effective treatments.

Viral hepatitis in Hawai'i--differing perspectives.

PubMed

Tice, Alan D; Bannan, Michael; Bauman, Kay; Collis, Tarquin; Hall, Alba; Haning, William; Hannemann, Shoshana; Hare, C Bradley; Humphry, Joseph; Jao, Robert; Leevy, Carroll; Lusk, Heather; Ochoa, Edward; Palafox, Neal; Withers, Nancy; Akinaka, Kenneth

2010-04-01

This publication contains information from a conference titled "Individual Perspectives on the Silent Epidemic of Viral Hepatitis in Hawai'i" held in October of 2007 with updates and additional contributions from annual conferences in 2008 and 2009. These conferences were sponsored by the Hepatitis Support Network of Hawai'i and held in Honolulu, Hawai'i at the Queen's Conference Center. The primary objectives of the conferences have been to heighten awareness of viral hepatitis in Hawai'i and to bring together health care professionals to learn about these infections and to help them respond to the challenges they bring to the people of Hawai'i. The initial conference was oriented to present the unique and individual perspectives of patients, physicians, and other healthcare providers specific to the complex issues of hepatitis in an effort to help them understand their role in the context of others and to develop a team approach in responding to this epidemic.

Subversion of cytokine networks by virally encoded decoy receptors

PubMed Central

Epperson, Megan L.; Lee, Chung A.; Fremont, Daved H.

2012-01-01

Summary During the course of evolution, viruses have captured or created a diverse array of open reading frames that encode for proteins that serve to evade and sabotage the host innate and adaptive immune responses, which would otherwise lead to their elimination. These viral genomes are some of the best textbooks of immunology ever written. The established arsenal of immunomodulatory proteins encoded by viruses is large and growing and includes specificities for virtually all known inflammatory pathways and targets. The focus of this review is on herpes and poxvirus-encoded cytokine and chemokine binding proteins that serve to undermine the coordination of host immune surveillance. Structural and mechanistic studies of these decoy receptors have provided a wealth of information, not only about viral pathogenesis but also about the inner workings of cytokine signaling networks. PMID:23046131

Cerebrospinal fluid monocytes in bacterial meningitis, viral meningitis, and neuroborreliosis.

PubMed

Martinot, M; Greigert, V; Souply, L; Rosolen, B; De Briel, D; Mohseni Zadeh, M; Kaiser, J-D

2018-04-05

Cerebrospinal fluid (CSF) leukocytes analysis is commonly used to diagnose meningitis and to differentiate bacterial from viral meningitis. Interpreting CSF monocytes can be difficult for physicians, especially in France where lymphocytes and monocytes results are sometimes pooled. We assessed SF monocytes in patients presenting with microbiologically confirmed meningitis (CSF leukocyte count>10/mm 3 for adults or >30/mm 3 for children<2 months), i.e. bacterial meningitis (BM), viral meningitis (VM), and neuroborreliosis (NB). Two-hundred patients (82 BM, 86 VM, and 32 NB) were included. The proportions of monocytes were higher in VM (median 8%; range 0-57%) than in BM (median 5%; range 0-60%, P=0.03) or NB (median 5%; range 0-53%, P=0.46), with a high value overlap between conditions. CSF monocytes should not be used to discriminate BM from VM and NB because of value overlaps. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Strategies to induce broadly protective antibody responses to viral glycoproteins.

PubMed

Krammer, F

2017-05-01

Currently, several universal/broadly protective influenza virus vaccine candidates are under development. Many of these vaccines are based on strategies to induce protective antibody responses against the surface glycoproteins of antigenically and genetically diverse influenza viruses. These strategies might also be applicable to surface glycoproteins of a broad range of other important viral pathogens. Areas covered: Common strategies include sequential vaccination with divergent antigens, multivalent approaches, vaccination with glycan-modified antigens, vaccination with minimal antigens and vaccination with antigens that have centralized/optimized sequences. Here we review these strategies and the underlying concepts. Furthermore, challenges, feasibility and applicability to other viral pathogens are discussed. Expert commentary: Several broadly protective/universal influenza virus vaccine strategies will be tested in humans in the coming years. If successful in terms of safety and immunological readouts, they will move forward into efficacy trials. In the meantime, successful vaccine strategies might also be applied to other antigenically diverse viruses of concern.

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.

Reproductive losses caused by bovine viral diarrhea virus and leptospirosis.

PubMed

Grooms, Daniel L

2006-08-01

Bovine viral diarrhea virus and Leptospira spp. are two of the common pathogenic organisms responsible for reproductive losses in cattle worldwide. Both can be come endemic in herds resulting in chronic low-grade reproductive losses or they can be introduced into relatively naïve herds, resulting in substantial reproductive losses over a short period of time. Both organisms are a differential diagnoses for common reproductive losses that veterinarians investigate, including low conception rates and abortions.

[The viral hepatitis and its economic significance and prevention].

PubMed

Petruchuk, O E; Shchenin, V O; Bedrin, A V; Leshcheva, G A

2008-01-01

The reference of only part of diseases having contagious nature to the infectious pathology is closely related to the tradition of considering the infections as highly contagious diseases inclined to epidemic propagation. The data is presented related to the morbidity of viral hepatitis among the population of the City of Krasnodar. The corresponding economic losses and the achievements of medical preventive activities considering the social economic and other characteristics of the specific socium are considered.

Quality of Human Immunodeficiency Virus Viral Load Testing in Australia

PubMed Central

Best, Susan J.; Gust, Anthony P.; Johnson, Elizabeth I. M.; McGavin, Catherine H.; Dax, Elizabeth M.

2000-01-01

This study determined the proficiencies of laboratories measuring human immunodeficiency virus type 1 (HIV-1) viral loads and the accuracies of two assays used for HIV-1 viral load measurement in Australia and investigated the variability of the new versions of these assays. Quality assessment program panels containing (i) dilutions of HIV-1 subtype B, (ii) replicates of identical samples of HIV-1 subtype B, and (iii) samples of subtype E and B were tested by laboratories. Total variability (within and between laboratories) was tested with quality control samples. The coefficients of variation (CVs) for the Roche AMPLICOR HIV-1 MONITOR version (v) 1.0 and Chiron Quantiplex bDNA 2.0 assays ranged from 53 to 87% and 22 to 31%, respectively. The widespread occurrence of invalid runs with the AMPLICOR HIV-1 MONITOR 1.0 assay was identified. The CVs of the new versions of the assays were 82 to 86% for the AMPLICOR HIV-1 MONITOR v 1.5 assay and 16 to 23% for the Quantiplex bDNA 3.0 assay. For virus dilution samples, all but 5 of 19 laboratories obtained results within 2 standard deviations of the mean. The Quantiplex bDNA 2.0 assay reported values lower than those reported by the AMPLICOR HIV-1 MONITOR version 1.0 assay for samples containing HIV-1 subtype B, whereas the reverse was true for subtype E. Identification and resolution of the problem of invalid runs markedly improved the quality of HIV-1 viral load testing. The variability observed between laboratories and between assays, even the most recent versions, dictates that monitoring of viral load in an individual should always be by the same laboratory and by the same assay. Results for an individual which differ by less than 0.5 log10 HIV-1 RNA copy number/ml should not be considered clinically significant. PMID:11060062

Potency control of modified live viral vaccines for veterinary use.

PubMed

Terpstra, C; Kroese, A H

1996-04-01

This paper reviews various aspects of efficacy, and methods for assaying the potency of modified live viral vaccines. The pros and cons of parametric versus non-parametric methods for analysis of potency assays are discussed and critical levels of protection, as determined by the target(s) of vaccination, are exemplified. Recommendations are presented for designing potency assays on master virus seeds and vaccine batches.

Potency control of modified live viral vaccines for veterinary use.

PubMed

Terpstra, C; Kroese, A H

1996-01-01

This paper reviews various aspects of efficacy, and methods for assaying the potency of modified live viral vaccines. The pros and cons of parametric versus non-parametric methods for analysis of potency assays are discussed and critical levels of protection, as determined by the target(s) of vaccination, are exemplified. Recommendations are presented for designing potency assays on master virus seeds and vaccine batches.

Mechanism of Membranous Tunnelling Nanotube Formation in Viral Genome Delivery

PubMed Central

Peralta, Bibiana; Gil-Carton, David; Castaño-Díez, Daniel; Bertin, Aurelie; Boulogne, Claire; Oksanen, Hanna M.; Bamford, Dennis H.; Abrescia, Nicola G. A.

2013-01-01

In internal membrane-containing viruses, a lipid vesicle enclosed by the icosahedral capsid protects the genome. It has been postulated that this internal membrane is the genome delivery device of the virus. Viruses built with this architectural principle infect hosts in all three domains of cellular life. Here, using a combination of electron microscopy techniques, we investigate bacteriophage PRD1, the best understood model for such viruses, to unveil the mechanism behind the genome translocation across the cell envelope. To deliver its double-stranded DNA, the icosahedral protein-rich virus membrane transforms into a tubular structure protruding from one of the 12 vertices of the capsid. We suggest that this viral nanotube exits from the same vertex used for DNA packaging, which is biochemically distinct from the other 11. The tube crosses the capsid through an aperture corresponding to the loss of the peripentonal P3 major capsid protein trimers, penton protein P31 and membrane protein P16. The remodeling of the internal viral membrane is nucleated by changes in osmolarity and loss of capsid-membrane interactions as consequence of the de-capping of the vertices. This engages the polymerization of the tail tube, which is structured by membrane-associated proteins. We have observed that the proteo-lipidic tube in vivo can pierce the gram-negative bacterial cell envelope allowing the viral genome to be shuttled to the host cell. The internal diameter of the tube allows one double-stranded DNA chain to be translocated. We conclude that the assembly principles of the viral tunneling nanotube take advantage of proteo-lipid interactions that confer to the tail tube elastic, mechanical and functional properties employed also in other protein-membrane systems. PMID:24086111

Alternative autophagy, brefeldin A and viral trafficking pathways.

PubMed

Grose, Charles; Klionsky, Daniel J

2016-09-01

Two topics that have attracted recent attention in the field of autophagy concern the source of the membrane that is used to form the autophagosome during macroautophagy and the role of noncanonical autophagic pathways. The 2 topics may converge when considering the intersection of autophagy with viral infection. We suggest that noncanonical autophagy, which is sensitive to treatment with brefeldin A, may converge with the infectious cycles of certain DNA and RNA viruses that utilize membrane from the ER and cis-Golgi.

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.

Etiology and Rapid Diagnosis of Human Viral Gastroenteritis.

DTIC Science & Technology

1987-05-01

illness typically produces severe diarrhea that commonly lasts for five to eight days and is usually accompanied by fever and vomiting. Rotavirus , which...major target of rotavirus is the very young, itcan produce surprisingly severe clinical disease in adults (1,2). Despite the frequency of viral...pathogen, rotavirus , has been identified by electron microscopy in stool filtrates derived from ill individuals. Serologic assay techniques have been

Does atopy affect the course of viral pneumonia?

PubMed

Erdem, S B; Can, D; Girit, S; Çatal, F; Şen, V; Pekcan, S; Yüksel, H; Bingöl, A; Bostancı, I; Erge, D; Ersu, R

The presence of atopy is considered as a risk factor for severe respiratory symptoms in children. The objective of this study was to examine the effect of atopy on the course of disease in children hospitalised with viral pneumonia. Children between the ages of 1 and 6 years hospitalised due to viral pneumonia between the years of 2013 and 2016 were included to this multicentre study. Patients were classified into two groups as mild-moderate and severe according to the course of pneumonia. Presence of atopy was evaluated with skin prick tests. Groups were compared to evaluate the risk factors associated with severe viral pneumonia. A total of 280 patients from nine centres were included in the study. Of these patients, 163 (58.2%) were male. Respiratory syncytial virus (29.7%), Influenza A (20.5%), rhinovirus (18.9%), adenovirus (10%), human metapneumovirus (8%), parainfluenza (5.2%), coronavirus (6%), and bocavirus (1.6%) were isolated from respiratory samples. Eighty-five (30.4%) children had severe pneumonia. Atopic sensitisation was found in 21.4% of the patients. Ever wheezing (RR: 1.6, 95% CI: 1.1-2.4), parental asthma (RR: 1.5, 95% CI: 1.1-2.2), other allergic diseases in the family (RR: 1.8, 95% CI: 1.2-2.9) and environmental tobacco smoke (RR: 1.6, 95% CI: 1.1-3.5) were more common in the severe pneumonia group. When patients with mild-moderate pneumonia were compared to patients with severe pneumonia, frequency of atopy was not different between the two groups. However, parental asthma, ever wheezing and environmental tobacco smoke exposure are risk factors for severe viral pneumonia in children. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Efficacy of a homeopathic complex on acute viral tonsillitis.

PubMed

Malapane, Eunice; Solomon, Elizabeth M; Pellow, Janice

2014-11-01

Acute viral tonsillitis is an upper respiratory tract infection prevalent in school-aged children. Because this condition is self-limiting, conventional treatment options are usually palliative. Homeopathic remedies are a useful alternative to conventional medications in acute uncomplicated upper respiratory tract infections in children, offering earlier symptom resolution, cost-effectiveness, and fewer adverse effects. This study aimed to determine the efficacy of a homeopathic complex on the symptoms of acute viral tonsillitis in African children in South Africa. This was a randomized, double-blind, placebo-controlled, 6-day pilot study. Thirty children, age 6 to 12 years, with acute viral tonsillitis were recruited from a primary school in Gauteng, South Africa. Participants took two tablets of the medication four times daily. The treatment group received lactose tablets medicated with the homeopathic complex (Atropa belladonna D4, Calcarea phosphoricum D4, Hepar sulphuris D4, Kalium bichromat D4, Kalium muriaticum D4, Mercurius protoiodid D10, and Mercurius biniodid D10). The placebo consisted of the unmedicated vehicle only. The Wong-Baker FACES Pain Rating Scale measured pain intensity, and a Symptom Grading Scale assessed changes in tonsillitis signs and symptoms. The treatment group had a statistically significant improvement in the following symptoms compared with the placebo group: pain associated with tonsillitis, pain on swallowing, erythema and inflammation of the pharynx, and tonsil size. The homeopathic complex used in this study exhibited significant anti-inflammatory and pain-relieving qualities in children with acute viral tonsillitis. No patients reported any adverse effects. These preliminary findings are promising; however, the sample size was small and therefore a definitive conclusion cannot be reached. A larger, more inclusive research study should be undertaken to verify the findings of this study.

A better regulation is required in viral hepatitis smartphone applications.

PubMed

Cantudo-Cuenca, Ma R; Robustillo-Cortés, Ma A; Cantudo-Cuenca, Ma D; Morillo-Verdugo, R

2014-04-01

To describe the characteristics and content of the available viral hepatitis mobile applications, as well as assess the level of participation of medical professionals in their development. A descriptive observational study was carried out in September 2013. We searched smartphone apps specifically relating to the viral hepatitis for using a keyword search with the following terms; «hepatitis», «hepatology», «hbv» and «hcv» in the Google Play Store (Android) and the Apple App Store (iOS). Data recorded included: name, platform, category, cost, user star rating, number of downloads, date the app was updated by the developer and target audience. We analysed the content of the applications, and these were then categorised based on the viral hepatitis type into three groups. We conducted an analysis in which we specifically examined the authorship in order to assess the prevalence of health professional participation in their development. A total of 33 apps were included (from 232 that were identified), among which there were 10 duplicates. Most of these apps were uploaded under the medical category. Three had ratings less than 3.9 stars (out of 5). Only 6 apps had exceeded 1000 downloads. A total of 12 apps were aimed at health professionals, while 4 focused on patients (7 for both of them). The participation of health professionals in the development of apps was 56.6%. Viral hepatitis apps are available for both professionals and patients; however, much of the information contained within them is often not validated. They should be certificated. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Respiratory viral diseases: access to RNA interference therapy

PubMed Central

Bitko, Vira; Barik, Sailen

2008-01-01

This review summarizes recent experimental achievements in the area of the development of new RNA interference (RNAi) therapeutics for the treatment of viral respiratory diseases. Delivery of siRNA to their intended target tissue remains the biggest problem for most therapeutic applications of these compounds. Appropriate formulations and chemical modifications for improved stability will boost the probability of utilization of RNAi drugs in the clinical applications. PMID:19081824

Innate resistance of New Zealand paua to abalone viral ganglioneuritis.

PubMed

Corbeil, Serge; McColl, Kenneth A; Williams, Lynette M; Slater, Joanne; Crane, Mark St J

2017-06-01

The susceptibility of New Zealand paua (Haliotis iris) to infection by abalone herpesvirus (Haliotid herpesvirus 1; HaHV) and to the disease abalone viral ganglioneuritis (AVG) was determined. Infection challenges performed by intra-muscular injection and by immersion in infectious water containing HaHV demonstrated that New Zealand paua were highly resistant to infection by Haliotid herpesvirus 1 and were fully resistant to the disease AVG. Copyright © 2017 Elsevier Inc. All rights reserved.

Anticipating Viral Species Jumps: Bioinformatics and Data Needs

DTIC Science & Technology

2011-06-01

FIELD SAMPLING PLAN There are historical examples of viral species jumps that have profoundly affected human society, the most recent being the...Henipaviruses are an important group of emerging zoonotic RNA viruses whose primary hosts are large fruit bats of the genus Pteropus. Henipaviruses...2008). Hendra viruses from Australian fruit bats have caused small, isolated fatal disease outbreaks among horses and fatal spillover cases among

Methods of treating Parkinson's disease using viral vectors

DOEpatents

Bankiewicz, Krys; Cunningham, Janet

2012-11-13

Methods of delivering viral vectors, particularly recombinant AAV virions, to the central nervous system (CNS) are provided for the treatment of CNS disorders, particularly those disorders which involve the neurotransmitter dopamine. The methods entail providing rAAV virions that comprise a transgene encoding aromatic amino acid decarboxylase (AADC) and administering the virions to the brain of a mammal using a non-manual pump.

Magnetotherapy in the treatment of viral conjunctivitis and keratitis.

PubMed

Pasek, Jarosław; Pasek, Tomasz; Herba, Ewa; Misiak, Anna; Sieroń-Stołtny, Karolina; Sieroń, Aleksander

2008-01-01

Ocular infections are one of the most frequent causes of ailments among the patients coming to ophthalmologic offices. This article presents one of the physical medicine's methods--magnetotherapy--which uses the alternating low frequency magnetic fields in the therapy of viral conjunctivitis and keratitis in a 49-year-old female patient. Basing on the obtained results it was stated that this method broadens the treatment possibilities becoming a precious supplement and support treatment method in ophthalmology.

A Scalable Heuristic for Viral Marketing Under the Tipping Model

DTIC Science & Technology

2013-09-01

removal of high-degree nodes. The rest of the paper is organized as follows. In Section 2, we provide formal definitions of the tipping model. This is...that must be activated for it to become activate as well. A Scalable Heuristic for Viral Marketing Under the Tipping Model 3 Definition 1 (Threshold...returns a set of active nodes after one time step. Definition 2 (Activation Function) Given a threshold function, θ, an ac- tivation function Aθ maps

Phosphatidylserine Exposure Controls Viral Innate Immune Responses by Microglia.

PubMed

Tufail, Yusuf; Cook, Daniela; Fourgeaud, Lawrence; Powers, Colin J; Merten, Katharina; Clark, Charles L; Hoffman, Elizabeth; Ngo, Alexander; Sekiguchi, Kohei J; O'Shea, Clodagh C; Lemke, Greg; Nimmerjahn, Axel

2017-02-08

Microglia are the intrinsic immune sentinels of the central nervous system. Their activation restricts tissue injury and pathogen spread, but in some settings, including viral infection, this response can contribute to cell death and disease. Identifying mechanisms that control microglial responses is therefore an important objective. Using replication-incompetent adenovirus 5 (Ad5)-based vectors as a model, we investigated the mechanisms through which microglia recognize and respond to viral uptake. Transgenic, immunohistochemical, molecular-genetic, and fluorescence imaging approaches revealed that phosphatidylserine (PtdSer) exposure on the outer leaflet of transduced cells triggers their engulfment by microglia through TAM receptor-dependent mechanisms. We show that inhibition of phospholipid scramblase 1 (PLSCR1) activity reduces intracellular calcium dysregulation, prevents PtdSer externalization, and enables months-long protection of vector-transduced, transgene-expressing cells from microglial phagocytosis. Our study identifies PLSCR1 as a potent target through which the innate immune response to viral vectors, and potentially other stimuli, may be controlled. Copyright © 2017 Elsevier Inc. All rights reserved.

Identifying predictors of time-inhomogeneous viral evolutionary processes.

PubMed

Bielejec, Filip; Baele, Guy; Rodrigo, Allen G; Suchard, Marc A; Lemey, Philippe

2016-07-01

Various factors determine the rate at which mutations are generated and fixed in viral genomes. Viral evolutionary rates may vary over the course of a single persistent infection and can reflect changes in replication rates and selective dynamics. Dedicated statistical inference approaches are required to understand how the complex interplay of these processes shapes the genetic diversity and divergence in viral populations. Although evolutionary models accommodating a high degree of complexity can now be formalized, adequately informing these models by potentially sparse data, and assessing the association of the resulting estimates with external predictors, remains a major challenge. In this article, we present a novel Bayesian evolutionary inference method, which integrates multiple potential predictors and tests their association with variation in the absolute rates of synonymous and non-synonymous substitutions along the evolutionary history. We consider clinical and virological measures as predictors, but also changes in population size trajectories that are simultaneously inferred using coalescent modelling. We demonstrate the potential of our method in an application to within-host HIV-1 sequence data sampled throughout the infection of multiple patients. While analyses of individual patient populations lack statistical power, we detect significant evidence for an abrupt drop in non-synonymous rates in late stage infection and a more gradual increase in synonymous rates over the course of infection in a joint analysis across all patients. The former is predicted by the immune relaxation hypothesis while the latter may be in line with increasing replicative fitness during the asymptomatic stage.

Classification of viral zoonosis through receptor pattern analysis.

PubMed

Bae, Se-Eun; Son, Hyeon Seok

2011-04-13

Viral zoonosis, the transmission of a virus from its primary vertebrate reservoir species to humans, requires ubiquitous cellular proteins known as receptor proteins. Zoonosis can occur not only through direct transmission from vertebrates to humans, but also through intermediate reservoirs or other environmental factors. Viruses can be categorized according to genotype (ssDNA, dsDNA, ssRNA and dsRNA viruses). Among them, the RNA viruses exhibit particularly high mutation rates and are especially problematic for this reason. Most zoonotic viruses are RNA viruses that change their envelope proteins to facilitate binding to various receptors of host species. In this study, we sought to predict zoonotic propensity through the analysis of receptor characteristics. We hypothesized that the major barrier to interspecies virus transmission is that receptor sequences vary among species--in other words, that the specific amino acid sequence of the receptor determines the ability of the viral envelope protein to attach to the cell. We analysed host-cell receptor sequences for their hydrophobicity/hydrophilicity characteristics. We then analysed these properties for similarities among receptors of different species and used a statistical discriminant analysis to predict the likelihood of transmission among species. This study is an attempt to predict zoonosis through simple computational analysis of receptor sequence differences. Our method may be useful in predicting the zoonotic potential of newly discovered viral strains.

Viral causes of feline lymphoma: retroviruses and beyond.

PubMed

Beatty, Julia

2014-08-01

The most widely recognised cause of feline lymphoma is the gammaretrovirus feline leukaemia virus (FeLV). Research into the mechanisms of cellular transformation employed by FeLV and other oncogenic retroviruses has provided as much information on the regulation of eukaryotic cell growth and differentiation as it has about cancer. The recognition that a cancer has a viral cause opens up the possibility of novel treatments that spare the host from cytotoxic side-effects by specifically targeting the virus, or the host's immune response to it. The ultimate prize for viral-associated cancers is their prevention. Vaccination and changes in management practices have seen the global prevalence of FeLV infection fall and, with it, the incidence of FeLV-related cancers. Remarkably, in the face of this success, the prevalence of feline lymphoma remains high. At least one other virus, the lentivirus feline immunodeficiency virus (FIV), accounts for some of these cases. Transformation by FIV involves incompletely understood mechanisms that are distinct from those employed by FeLV. This review will focus on the current understanding of FeLV-associated and FIV-associated lymphoma and consider whether yet more viral aetiologies could be waiting to be discovered. Copyright © 2014 Elsevier Ltd. All rights reserved.

Encapsidation of Linear Polyelectrolyte in a Viral Nanocontainer

NASA Astrophysics Data System (ADS)

Hu, Yufang

2005-03-01

We present the results from a combined experimental and theoretical study on the self-assembly of a model icosahedral virus, Cowpea Chlorotic Mottle Virus (CCMV). The formation of native CCMV capsids is believed to be driven primarily by the electrostatic interactions between the viral RNA and the positively charged capsid interior, as well as by the hydrophobic interactions between capsid protein subunits. To probe these molecular interactions, in vitro self-assembly reactions are carried out using the CCMV capsid protein and a synthetic linear polyelectrolyte, sodium polystyrene sulfonate (NaPSS), which functions as the analog of viral RNA. Under appropriate solutions conditions, NaPSS is encapsidated by the viral capsid. The molecular weight of NaPSS is systematically varied and the resulting average capsid size, size distribution, and particle morphology are measured by transmission electron microscopy. The correlation between capsid size and packaged cargo size, as well as the upper limit of capsid packaging capacity, are characterized. To elucidate the physical role played by the encapsidated polyelectrolyte in determining the preferred size of spherical viruses, we have used a mean-field approach to calculate the free energy of the virus-like particle as a function of chain length (and of the strength of chain/capsid attractive interaction). We find good agreement with our analytical calculations and experimental results.

Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis.

PubMed

Zakhari, Samir

2013-08-01

Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end-stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Viral infections and breast cancer - A current perspective.

PubMed

Gannon, O M; Antonsson, A; Bennett, I C; Saunders, N A

2018-04-28

Sporadic human breast cancer is the most common cancer to afflict women. Since the discovery, decades ago, of the oncogenic mouse mammary tumour virus, there has been significant interest in the potential aetiologic role of infectious agents in sporadic human breast cancer. To address this, many studies have examined the presence of viruses (e.g. papillomaviruses, herpes viruses and retroviruses), endogenous retroviruses and more recently, microbes, as a means of implicating them in the aetiology of human breast cancer. Such studies have generated conflicting experimental and clinical reports of the role of infection in breast cancer. This review evaluates the current evidence for a productive oncogenic viral infection in human breast cancer, with a focus on the integration of sensitive and specific next generation sequencing technologies with pathogen discovery. Collectively, the majority of the recent literature using the more powerful next generation sequencing technologies fail to support an oncogenic viral infection being involved in disease causality in breast cancer. In balance, the weight of the current experimental evidence supports the conclusion that viral infection is unlikely to play a significant role in the aetiology of breast cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

Understanding viral video dynamics through an epidemic modelling approach

NASA Astrophysics Data System (ADS)

Sachak-Patwa, Rahil; Fadai, Nabil T.; Van Gorder, Robert A.

2018-07-01

Motivated by the hypothesis that the spread of viral videos is analogous to the spread of a disease epidemic, we formulate a novel susceptible-exposed-infected-recovered-susceptible (SEIRS) delay differential equation epidemic model to describe the popularity evolution of viral videos. Our models incorporate time-delay, in order to accurately describe the virtual contact process between individuals and the temporary immunity of individuals to videos after they have grown tired of watching them. We validate our models by fitting model parameters to viewing data from YouTube music videos, in order to demonstrate that the model solutions accurately reproduce real behaviour seen in this data. We use an SEIR model to describe the initial growth and decline of daily views, and an SEIRS model to describe the long term behaviour of the popularity of music videos. We also analyse the decay rates in the daily views of videos, determining whether they follow a power law or exponential distribution. Although we focus on viral videos, the modelling approach may be used to understand dynamics emergent from other areas of science which aim to describe consumer behaviour.

Respiratory viral infections in infants with clinically suspected pertussis.

PubMed

Ferronato, Angela E; Gilio, Alfredo E; Vieira, Sandra E

2013-01-01

to evaluate the frequency of respiratory viral infections in hospitalized infants with clinical suspicion of pertussis, and to analyze their characteristics at hospital admission and clinical outcomes. a historical cohort study was performed in a reference service for pertussis, in which the research of respiratory viruses was also a routine for infants hospitalized with respiratory problems. All infants reported as suspected cases of pertussis were included. Tests for Bordetella pertussis (BP) (polymerase chain reaction/culture) and for respiratory viruses (RVs) (immunofluorescence) were performed. Patients who received macrolides before hospitalization were excluded. Clinical data were obtained from medical records. Among the 67 patients studied, BP tests were positive in 44%, and 26% were positive for RV. There was no etiological identification in 35%, and RV combined with BP was identified in 5%. All patients had similar demographic characteristics. Cough followed by inspiratory stridor or cyanosis was a strong predictor of pertussis, as well as prominent leukocytosis and lymphocytosis. Rhinorrhea and dyspnea were more frequent in viral infections. Macrolides were discontinued in 40% of patients who tested positive for RV and negative for BP. the results suggest that viral infection can be present in hospitalized infants with clinical suspicion of pertussis, and etiological tests may enable a reduction in the use of macrolides in some cases. However, the etiological diagnosis of respiratory virus infection, by itself, does not exclude the possibility of infection with BP. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Viral Aggregation: Impact on Virus Behavior in the Environment.

PubMed

Gerba, Charles P; Betancourt, Walter Q

2017-07-05

Aggregates of viruses can have a significant impact on quantification and behavior of viruses in the environment. Viral aggregates may be formed in numerous ways. Viruses may form crystal like structures and aggregates in the host cell during replication or may form due to changes in environmental conditions after virus particles are released from the host cells. Aggregates tend to form near the isoelectric point of the virus, under the influence of certain salts and salt concentrations in solution, cationic polymers, and suspended organic matter. The given conditions under which aggregates form in the environment are highly dependent on the type of virus, type of salts in solution (cation, anion. monovalent, divalent) and pH. However, virus type greatly influences the conditions when aggregation/disaggregation will occur, making predictions difficult under any given set of water quality conditions. Most studies have shown that viral aggregates increase the survival of viruses in the environment and resistance to disinfectants, especially with more reactive disinfectants. The presence of viral aggregates may also result in overestimation of removal by filtration processes. Virus aggregation-disaggregation is a complex process and predicting the behavior of any individual virus is difficult under a given set of environmental circumstances without actual experimental data.

Initiation of viral RNA-dependent RNA polymerization.

PubMed

van Dijk, Alberdina A; Makeyev, Eugene V; Bamford, Dennis H

2004-05-01

This review summarizes the combined insights from recent structural and functional studies of viral RNA-dependent RNA polymerases (RdRPs) with the primary focus on the mechanisms of initiation of RNA synthesis. Replication of RNA viruses has traditionally been approached using a combination of biochemical and genetic methods. Recently, high-resolution structures of six viral RdRPs have been determined. For three RdRPs, enzyme complexes with metal ions, single-stranded RNA and/or nucleoside triphosphates have also been solved. These advances have expanded our understanding of the molecular mechanisms of viral RNA synthesis and facilitated further RdRP studies by informed site-directed mutagenesis. What transpires is that the basic polymerase right hand shape provides the correct geometrical arrangement of substrate molecules and metal ions at the active site for the nucleotidyl transfer catalysis, while distinct structural elements have evolved in the different systems to ensure efficient initiation of RNA synthesis. These elements feed the template, NTPs and ions into the catalytic cavity, correctly position the template 3' terminus, transfer the products out of the catalytic site and orchestrate the transition from initiation to elongation.

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.

Host and viral ecology determine bat rabies seasonality and maintenance

USGS Publications Warehouse

George, D.B.; Webb, C.T.; Farnsworth, Matthew L.; O'Shea, T.J.; Bowen, R.A.; Smith, D.L.; Stanley, T.R.; Ellison, L.E.; Rupprecht, C.E.

2011-01-01

Rabies is an acute viral infection that is typically fatal. Most rabies modeling has focused on disease dynamics and control within terrestrial mammals (e.g., raccoons and foxes). As such, rabies in bats has been largely neglected until recently. Because bats have been implicated as natural reservoirs for several emerging zoonotic viruses, including SARS-like corona viruses, henipaviruses, and lyssaviruses, understanding how pathogens are maintained within a population becomes vital. Unfortunately, little is known about maintenance mechanisms for any pathogen in bat populations. We present a mathematical model parameterized with unique data from an extensive study of rabies in a Colorado population of big brown bats (Eptesicus fuscus) to elucidate general maintenance mechanisms. We propose that life history patterns of many species of temperate-zone bats, coupled with sufficiently long incubation periods, allows for rabies virus maintenance. Seasonal variability in bat mortality rates, specifically low mortality during hibernation, allows long-term bat population viability. Within viable bat populations, sufficiently long incubation periods allow enough infected individuals to enter hibernation and survive until the following year, and hence avoid an epizootic fadeout of rabies virus. We hypothesize that the slowing effects of hibernation on metabolic and viral activity maintains infected individuals and their pathogens until susceptibles from the annual birth pulse become infected and continue the cycle. This research provides a context to explore similar host ecology and viral dynamics that may explain seasonal patterns and maintenance of other bat-borne diseases.

Persistent bovine viral diarrhea virus (BVDV) infection in cattle herds

PubMed Central

Khodakaram-Tafti, A.; Farjanikish, GH.

2017-01-01

Bovine viral diarrhea virus (BVDV) is a significant pathogen associated with gastrointestinal, respiratory, and reproductive diseases of cattle worldwide. It causes continuous economic losses to the cattle industry primarily due to decreased reproductive performance. The ability of virus to cross the placenta during early pregnancy can result in the birth of persistently infected (PI) calves. Persistently infected animals are generally much more efficient transmitters of BVDV than transiently or acutely infected animals because they are capable of shedding large quantities of virus throughout their lives and are considered the primary reservoirs for BVDV. Due to the nature of viral infections, there is no treatment to fully cure an animal of a viral infection. All control programs which are in use in many countries of the world, mainly depend upon the detection of PI animals, eliminating them and preventing their return into the herds. Detection of PI animals at early stage, particularly soon after birth is of significant benefit to implement BVDV control programs. Available diagnostic tests such as virus isolation (VI), immunohistochemistry (IHC), Antigen-Capture ELISA (ACE), and reverse transcriptase polymerase chain reaction (RT-PCR) are used for detection of PI cattle. Each method to detect BVDV has advantages, disadvantages, and applicability for different diagnostic situations. The reliability of diagnostic tests is optimized by choosing the appropriate sampling strategy on the basis of animal age. PMID:29163643

Massive activation of archaeal defense genes during viral infection.

PubMed

Quax, Tessa E F; Voet, Marleen; Sismeiro, Odile; Dillies, Marie-Agnes; Jagla, Bernd; Coppée, Jean-Yves; Sezonov, Guennadi; Forterre, Patrick; van der Oost, John; Lavigne, Rob; Prangishvili, David

2013-08-01

Archaeal viruses display unusually high genetic and morphological diversity. Studies of these viruses proved to be instrumental for the expansion of knowledge on viral diversity and evolution. The Sulfolobus islandicus rod-shaped virus 2 (SIRV2) is a model to study virus-host interactions in Archaea. It is a lytic virus that exploits a unique egress mechanism based on the formation of remarkable pyramidal structures on the host cell envelope. Using whole-transcriptome sequencing, we present here a global map defining host and viral gene expression during the infection cycle of SIRV2 in its hyperthermophilic host S. islandicus LAL14/1. This information was used, in combination with a yeast two-hybrid analysis of SIRV2 protein interactions, to advance current understanding of viral gene functions. As a consequence of SIRV2 infection, transcription of more than one-third of S. islandicus genes was differentially regulated. While expression of genes involved in cell division decreased, those genes playing a role in antiviral defense were activated on a large scale. Expression of genes belonging to toxin-antitoxin and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems was specifically pronounced. The observed different degree of activation of various CRISPR-Cas systems highlights the specialized functions they perform. The information on individual gene expression and activation of antiviral defense systems is expected to aid future studies aimed at detailed understanding of the functions and interplay of these systems in vivo.

In vitro models of viral-induced congenital deafness.

PubMed

Davis, G L

1981-10-01

Cytomegalovirus (CMV) infects 1 to 2 percent of liveborn infants in the United States and causes varying degrees of perceptive hearing loss. There are eight reported pathologic studies of temporal bones in CMV-infected neonates. Viral replication occurs in nonsensory endolabyrinthine epithelium, but viral antigen is also found in the organ of Corti and spiral ganglion neurons, and CMV has been cultured from perilymph. Further clinicopathologic correlation is frustrated, since the inner ear cannot be biopsied during life, and the number of temporal bones available for study is limited, owing to the decrease in the number of autopsies being performed. Inoculation of CMV into newborn mice, and extracorporeal preparations of mouse and guinea pig fetal inner ears, either in organ culture or as grafts on chick chorioallantoic membranes, yields viral perilabyrinthitis. The different ultrastructural appearances of CMV replicating in epithelial and mesenchymal cells show that animal CMV replicates in mesenchymal cells and human CMV replicates in epithelial cells of the inner ear. These different ultrastructural patterns indicate that the chromophobe (transitional) cells of the stria vascularis of the guinea pig are of mesenchymal origin.

[Countermeasure against viral hemorrhagic fever at the border in Japan].

PubMed

Iwasaki, Emiko

2005-12-01

Human have struggled against many infectious diseases such as cholera, plague, dysentery and yellow fever for a long time. And we have spent a lot of energy to control these infectious diseases and developed various tool for them. One of these efforts was Quarantine system that was established in 14th century in Europe. But during recent days, we are suffering from newly emerged diseases. These new infectious diseases are zoonosis and most of them are serious and highly infectious. Viral hemorrhagic fever such as Ebola hemorrhagic fever, Marburg hemorrhagic fever and Lassa fever are typical these emerging serious diseases, and these outbreak always have occurred in Africa and neighboring countries. Fortunately we have never experienced any case, but as these diseases are so serious, we are so nervous diseases entering in Japan. Against these serious diseases, in Japan, Quarantine Station are doing screening examination at airport and port by questionnaire and measuring body temperature, because these viral hemorrhagic fever patients show high fever. If people were suspected viral hemorrhagic fever at Quarantine Station at the border, they will be leaded to hospital for further examination and treatment as soon as possible.

A Role for Neutrophils in Viral Respiratory Disease.

PubMed

Camp, Jeremy V; Jonsson, Colleen B

2017-01-01

Neutrophils are immune cells that are well known to be present during many types of lung diseases associated with acute respiratory distress syndrome (ARDS) and may contribute to acute lung injury. Neutrophils are poorly studied with respect to viral infection, and specifically to respiratory viral disease. Influenza A virus (IAV) infection is the cause of a respiratory disease that poses a significant global public health concern. Influenza disease presents as a relatively mild and self-limiting although highly pathogenic forms exist. Neutrophils increase in the respiratory tract during infection with mild seasonal IAV, moderate and severe epidemic IAV infection, and emerging highly pathogenic avian influenza (HPAI). During severe influenza pneumonia and HPAI infection, the number of neutrophils in the lower respiratory tract is correlated with disease severity. Thus, comparative analyses of the relationship between IAV infection and neutrophils provide insights into the relative contribution of host and viral factors that contribute to disease severity. Herein, we review the contribution of neutrophils to IAV disease pathogenesis and to other respiratory virus infections.

A minimal kinetic model for a viral DNA packaging machine.

PubMed

Yang, Qin; Catalano, Carlos Enrique

2004-01-20

Terminase enzymes are common to both eukaryotic and prokaryotic double-stranded DNA viruses. These enzymes possess ATPase and nuclease activities that work in concert to "package" a viral genome into an empty procapsid, and it is likely that terminase enzymes from disparate viruses utilize a common packaging mechanism. Bacteriophage lambda terminase possesses a site-specific nuclease activity, a so-called helicase activity, a DNA translocase activity, and multiple ATPase catalytic sites that function to package viral DNA. Allosteric interactions between the multiple catalytic sites have been reported. This study probes these catalytic interactions using enzyme kinetic, photoaffinity labeling, and vanadate inhibition studies. The ensemble of data forms the basis for a minimal kinetic model for lambda terminase. The model incorporates an ADP-driven conformational reorganization of the terminase subunits assembled on viral DNA, which is central to the activation of a catalytically competent packaging machine. The proposed model provides a unifying mechanism for allosteric interaction between the multiple catalytic sites of the holoenzyme and explains much of the kinetic data in the literature. Given that similar packaging mechanisms have been proposed for viruses as dissimilar as lambda and the herpes viruses, the model may find general utility in our global understanding of the enzymology of virus assembly.

Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways

PubMed Central

Wimmer, Peter; Schreiner, Sabrina

2015-01-01

Posttranslational modifications (PTMs) of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub) and small ubiquitin-like modifier (SUMO) moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways. PMID:26343706

Viral Communities Associated with Human Pericardial Fluids in Idiopathic Pericarditis

PubMed Central

Fancello, Laura; Monteil, Sonia; Popgeorgiev, Nikolay; Rivet, Romain; Gouriet, Frédérique; Fournier, Pierre-Edouard; Raoult, Didier; Desnues, Christelle

2014-01-01

Pericarditis is a common human disease defined by inflammation of the pericardium. Currently, 40% to 85% of pericarditis cases have no identified etiology. Most of these cases are thought to be caused by an infection of undetected, unsuspected or unknown viruses. In this work, we used a culture- and sequence-independent approach to investigate the viral DNA communities present in human pericardial fluids. Seven viral metagenomes were generated from the pericardial fluid of patients affected by pericarditis of unknown etiology and one metagenome was generated from the pericardial fluid of a sudden infant death case. As a positive control we generated one metagenome from the pericardial fluid of a patient affected by pericarditis caused by herpesvirus type 3. Furthermore, we used as negative controls a total of 6 pericardial fluids from 6 different individuals affected by pericarditis of non-infectious origin: 5 of them were sequenced as a unique pool and the remaining one was sequenced separately. The results showed a significant presence of torque teno viruses especially in one patient, while herpesviruses and papillomaviruses were present in the positive control. Co-infections by different genotypes of the same viral type (torque teno viruses) or different viruses (herpesviruses and papillomaviruses) were observed. Sequences related to bacteriophages infecting Staphylococcus, Enterobacteria, Streptococcus, Burkholderia and Pseudomonas were also detected in three patients. This study detected torque teno viruses and papillomaviruses, for the first time, in human pericardial fluids. PMID:24690743

Viral Vectors for Gene Delivery to the Central Nervous System

PubMed Central

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

2011-01-01

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

Questing for an optimal, universal viral agent for oncolytic virotherapy

NASA Astrophysics Data System (ADS)

Paiva, L. R.; Martins, M. L.; Ferreira, S. C.

2011-10-01

One of the most promising strategies to treat cancer is attacking it with viruses designed to exploit specific altered pathways. Here, the effects of oncolytic virotherapy on tumors having compact, papillary, and disconnected morphologies are investigated through computer simulations of a multiscale model coupling macroscopic reaction-diffusion equations for the nutrients with microscopic stochastic rules for the actions of individual cells and viruses. The interaction among viruses and tumor cells involves cell infection, intracellular virus replication, and the release of new viruses in the tissue after cell lysis. The evolution over time of both the viral load and cancer cell population, as well as the probabilities for tumor eradication, were evaluated for a range of multiplicities of infection, viral entries, and burst sizes. It was found that in immunosuppressed hosts, the antitumor efficacy of a virus is primarily determined by its entry efficiency, its replicative capacity within the tumor, and its ability to spread over the tissue. However, the optimal traits for oncolytic viruses depend critically on the tumor growth dynamics and do not necessarily include rapid replication, cytolysis, or spreading, currently assumed as necessary conditions for a successful therapeutic outcome. Our findings have potential implications on the design of new vectors for the viral therapy of cancer.

Viral etiology of aseptic meningitis among children in southern Iran.

PubMed

Hosseininasab, Ali; Alborzi, Abdolvahab; Ziyaeyan, Mazyar; Jamalidoust, Marzieh; Moeini, Mahsa; Pouladfar, Gholamreza; Abbasian, Amin; Kadivar, Mohamad Rahim

2011-05-01

Aseptic meningitis refers to a clinical syndrome of meningeal inflammation in which bacteria cannot be identified in the cerebrospinal fluid (CSF). The viral etiology and the epidemiological, clinical, and laboratory characteristics of aseptic meningitis among children aged 2 months to 15 years in Shiraz, southern Iran were determined. From May 2007 to April 2008, 65 patients were admitted to the hospital with aseptic meningitis. Seven viruses, non-polio human enteroviruses, mumps virus, herpes simplex virus (HSV), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), human herpes virus type 6 (HHV-6), and Epstein-Barr virus (EBV) were investigated by polymerase chain reaction (PCR) method. Viruses were detected in 30 (46.2%) patients in whom non-polio human enterovirus and mumps virus were detected in 13 (43.3%) and 11 (36.7%), respectively. The remaining 6 (20%) of the cases were caused by HSV, VZV, HCMV, and HHV-6. Haemophilus influenzae and non-polio human enterovirus were detected in one patient simultaneously. Viral meningitis was found to be more frequent during spring and summer. The majority (66.6%) of the patients were treated in the hospital for 10 days and had received antibiotics in the case of bacterial meningitis. Rapid diagnosis of viral meningitis using PCR testing of CSF can help shorten hospitalization, and avoid the unnecessary use of antibiotics. Copyright © 2011 Wiley-Liss, Inc.

Host and viral ecology determine bat rabies seasonality and maintenance.

PubMed

George, Dylan B; Webb, Colleen T; Farnsworth, Matthew L; O'Shea, Thomas J; Bowen, Richard A; Smith, David L; Stanley, Thomas R; Ellison, Laura E; Rupprecht, Charles E

2011-06-21

Rabies is an acute viral infection that is typically fatal. Most rabies modeling has focused on disease dynamics and control within terrestrial mammals (e.g., raccoons and foxes). As such, rabies in bats has been largely neglected until recently. Because bats have been implicated as natural reservoirs for several emerging zoonotic viruses, including SARS-like corona viruses, henipaviruses, and lyssaviruses, understanding how pathogens are maintained within a population becomes vital. Unfortunately, little is known about maintenance mechanisms for any pathogen in bat populations. We present a mathematical model parameterized with unique data from an extensive study of rabies in a Colorado population of big brown bats (Eptesicus fuscus) to elucidate general maintenance mechanisms. We propose that life history patterns of many species of temperate-zone bats, coupled with sufficiently long incubation periods, allows for rabies virus maintenance. Seasonal variability in bat mortality rates, specifically low mortality during hibernation, allows long-term bat population viability. Within viable bat populations, sufficiently long incubation periods allow enough infected individuals to enter hibernation and survive until the following year, and hence avoid an epizootic fadeout of rabies virus. We hypothesize that the slowing effects of hibernation on metabolic and viral activity maintains infected individuals and their pathogens until susceptibles from the annual birth pulse become infected and continue the cycle. This research provides a context to explore similar host ecology and viral dynamics that may explain seasonal patterns and maintenance of other bat-borne diseases.

Viral video: Live imaging of virus-host encounters

NASA Astrophysics Data System (ADS)

Son, Kwangmin; Guasto, Jeffrey S.; Cubillos-Ruiz, Andres; Chisholm, Sallie W.; Sullivan, Matthew B.; Stocker, Roman

2014-11-01

Viruses are non-motile infectious agents that rely on Brownian motion to encounter and subsequently adsorb to their hosts. Paradoxically, the viral adsorption rate is often reported to be larger than the theoretical limit imposed by the virus-host encounter rate, highlighting a major gap in the experimental quantification of virus-host interactions. Here we present the first direct quantification of the viral adsorption rate, obtained using live imaging of individual host cells and viruses for thousands of encounter events. The host-virus pair consisted of Prochlorococcus MED4, a 800 nm small non-motile bacterium that dominates photosynthesis in the oceans, and its virus PHM-2, a myovirus that has a 80 nm icosahedral capsid and a 200 nm long rigid tail. We simultaneously imaged hosts and viruses moving by Brownian motion using two-channel epifluorescent microscopy in a microfluidic device. This detailed quantification of viral transport yielded a 20-fold smaller adsorption efficiency than previously reported, indicating the need for a major revision in infection models for marine and likely other ecosystems.

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

Host and Viral Factors in HIV-Mediated Bystander Apoptosis

PubMed Central

Garg, Himanshu; Joshi, Anjali

2017-01-01

Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis. PMID:28829402

DNA vaccines against viral diseases of farmed fish.

PubMed

Evensen, Øystein; Leong, Jo-Ann C

2013-12-01

Immunization by an antigen-encoding DNA was approved for commercial sale in Canada against a Novirhabdovirus infection in fish. DNA vaccines have been particularly successful against the Novirhabdoviruses while there are reports on the efficacy against viral pathogens like infectious pancreatic necrosis virus, infectious salmon anemia virus, and lymphocystis disease virus and these are inferior to what has been attained for the novirhabdoviruses. Most recently, DNA vaccination of Penaeus monodon against white spot syndrome virus was reported. Research efforts are now focused on the development of more effective vectors for DNA vaccines, improvement of vaccine efficacy against various viral diseases of fish for which there is currently no vaccines available and provision of co-expression of viral antigen and immunomodulatory compounds. Scientists are also in the process of developing new delivery methods. While a DNA vaccine has been approved for commercial use in farmed salmon in Canada, it is foreseen that it is still a long way to go before a DNA vaccine is approved for use in farmed fish in Europe. Copyright © 2013 Elsevier Ltd. All rights reserved.

Geochemical Interactions and Viral-Prokaryote Relationships in Freshwater Environments

NASA Astrophysics Data System (ADS)

Kyle, J. E.; Ferris, G.

2009-05-01

Viral and prokaryotic abundances were surveyed throughout southern Ontario aquatic habitats to determine relationships with geochemical parameters in the natural environment. Surface water samples were collected from acid mine drainage in summer of 2007 and 2008 and from circum-neutral pH environments in October to November 2008. Site determination was based on collecting samples from various aquatic habitats (acid mine drainage, lakes, rivers, tributaries, wetlands) with differing bedrock geology (limestone and shale dominated vs granitic Canadian Shield) to obtain a range of geochemical conditions. At each site, measurements of temperature, pH, and Eh were conducted. Samples collected for microbial counts and electron imaging were preserved to a final concentration of 2.5 % (v/v) glutaraldehyde. Additional sample were filtered into 60 mL nalgene bottles and amber EPA certified 40 mL glass vials to determine chemical constituents and dissolved organic carbon (DOC), respectively. Water was also collected to determine additional physiochemical parameters (dissolved total iron, ferric iron, nitrate, sulfate, phosphate, alkalinity, and turbidity). All samples were stored at 4 °C until analysis. Viral and prokaryotic abundance was determined by staining samples with SYBR Green I and examining with a epifluorescence microscope under blue excitation. Multiple regression analysis using stepwise backwards regression and general linear models revealed that viral abundance was the most influential predictor of prokaryotic abundance. Additional predictors include pH, sulfate, phosphate, and magnesium. The strength of the model was very strong with 90 % of the variability explained (R2 = 0.90, p < 0.007). This is the first report, to our knowledge, of viruses exhibiting such strong controls over prokaryotic abundance in the natural environment. All relationships are positively correlated with the exception of Mg, which is negatively correlated. Iron was also noted as a

Diverse Array of New Viral Sequences Identified in Worldwide Populations of the Asian Citrus Psyllid (Diaphorina citri) Using Viral Metagenomics

PubMed Central

Nouri, Shahideh; Salem, Nidá; Nigg, Jared C.

2015-01-01

ABSTRACT The Asian citrus psyllid, Diaphorina citri, is the natural vector of the causal agent of Huanglongbing (HLB), or citrus greening disease. Together; HLB and D. citri represent a major threat to world citrus production. As there is no cure for HLB, insect vector management is considered one strategy to help control the disease, and D. citri viruses might be useful. In this study, we used a metagenomic approach to analyze viral sequences associated with the global population of D. citri. By sequencing small RNAs and the transcriptome coupled with bioinformatics analysis, we showed that the virus-like sequences of D. citri are diverse. We identified novel viral sequences belonging to the picornavirus superfamily, the Reoviridae, Parvoviridae, and Bunyaviridae families, and an unclassified positive-sense single-stranded RNA virus. Moreover, a Wolbachia prophage-related sequence was identified. This is the first comprehensive survey to assess the viral community from worldwide populations of an agricultural insect pest. Our results provide valuable information on new putative viruses, some of which may have the potential to be used as biocontrol agents. IMPORTANCE Insects have the most species of all animals, and are hosts to, and vectors of, a great variety of known and unknown viruses. Some of these most likely have the potential to be important fundamental and/or practical resources. In this study, we used high-throughput next-generation sequencing (NGS) technology and bioinformatics analysis to identify putative viruses associated with Diaphorina citri, the Asian citrus psyllid. D. citri is the vector of the bacterium causing Huanglongbing (HLB), currently the most serious threat to citrus worldwide. Here, we report several novel viral sequences associated with D. citri. PMID:26676774

Diverse Array of New Viral Sequences Identified in Worldwide Populations of the Asian Citrus Psyllid (Diaphorina citri) Using Viral Metagenomics.

PubMed

Nouri, Shahideh; Salem, Nidá; Nigg, Jared C; Falk, Bryce W

2015-12-16

The Asian citrus psyllid, Diaphorina citri, is the natural vector of the causal agent of Huanglongbing (HLB), or citrus greening disease. Together; HLB and D. citri represent a major threat to world citrus production. As there is no cure for HLB, insect vector management is considered one strategy to help control the disease, and D. citri viruses might be useful. In this study, we used a metagenomic approach to analyze viral sequences associated with the global population of D. citri. By sequencing small RNAs and the transcriptome coupled with bioinformatics analysis, we showed that the virus-like sequences of D. citri are diverse. We identified novel viral sequences belonging to the picornavirus superfamily, the Reoviridae, Parvoviridae, and Bunyaviridae families, and an unclassified positive-sense single-stranded RNA virus. Moreover, a Wolbachia prophage-related sequence was identified. This is the first comprehensive survey to assess the viral community from worldwide populations of an agricultural insect pest. Our results provide valuable information on new putative viruses, some of which may have the potential to be used as biocontrol agents. Insects have the most species of all animals, and are hosts to, and vectors of, a great variety of known and unknown viruses. Some of these most likely have the potential to be important fundamental and/or practical resources. In this study, we used high-throughput next-generation sequencing (NGS) technology and bioinformatics analysis to identify putative viruses associated with Diaphorina citri, the Asian citrus psyllid. D. citri is the vector of the bacterium causing Huanglongbing (HLB), currently the most serious threat to citrus worldwide. Here, we report several novel viral sequences associated with D. citri. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Viral and bacterial contamination in a sedimentary aquifer in Uruguay: evaluation of coliforms as regional indicators of viral contamination.

NASA Astrophysics Data System (ADS)

Gamazo, Pablo; Colina, Rodney; Victoria, Matias; Alvareda, Elena; Burutatran, Luciana; Ramos, Julian; Olivera, María; Soler, Joan

2015-04-01

In many areas of Uruguay groundwater is the only source of water for human consumption and for industrial-agricultural economic activities. Traditionally considered as a safe source, groundwater is commonly used without any treatment. The Uruguayan law requires bacteriological (fecal) analysis for most water uses, but virological analyses are not mentioned in the legislation. In the Salto district, where groundwater is used for human consumption and for agricultural activities, bacterial contamination has been detected in several wells but no viruses analysis have been performed. The Republic University (UDELAR), with the support of the National Agency for Research and Innovation (ANII), is studying the incidence of virus and fecal bacteria in groundwater on an intensive agriculture area of the Salto district. An initial screening campaign of 44 wells was performed in which, besides total and fecal coliforms, rotavirus and adenovirus were detected. A subgroup of the screening wells (15) where selected for bimonthly sampling during a year. In accordance with literature results, single well data analysis shows that coliform and viral contamination can be considered as independent variables. However, when spatial data is integrated, coliform and viral contamination show linear correlation. In this work we present the survey results, we analyse the temporal incidence of variables like precipitation, temperature and chemical composition in well contamination and we discuss the value of coliforms as global indicator of viral contamination for the Salto aquifer.

Dynamics of viral hemorrhagic septicemia, viral erythrocytic necrosis and ichthyophoniasis in confined juvenile Pacific herring Clupea pallasii

USGS Publications Warehouse

Hershberger, P.; Hart, A.; Gregg, J.; Elder, N.; Winton, J.

2006-01-01

Capture of wild, juvenile herring Clupea pallasii from Puget Sound (Washington, USA) and confinement in laboratory tanks resulted in outbreaks of viral hemorrhagic septicemia (VHS), viral erythrocytic necrosis (VEN) and ichthyophoniasis; however, the timing and progression of the 3 diseases differed. The VHS epidemic occurred first, characterized by an initially low infection prevalence that increased quickly with confinement time, peaking at 93 to 98% after confinement for 6 d, then decreasing to negligible levels after 20 d. The VHS outbreak was followed by a VEN epidemic that, within 12 d of confinement, progressed from undetectable levels to 100% infection prevalence with >90% of erythrocytes demonstrating inclusions. The VEN epidemic persisted for 54 d, after which the study was terminated, and was characterized by severe blood dyscrasias including reduction of mean hematocrit from 42 to 6% and replacement of mature erythrocytes with circulating erythroblasts and ghost cells. All fish with ichthyophoniasis at capture died within the first 3 wk of confinement, probably as a result of the multiple stressors associated with capture, transport, confinement, and progression of concomitant viral diseases. The results illustrate the differences in disease ecology and possible synergistic effects of pathogens affecting marine fish and highlight the difficulty in ascribing a single causation to outbreaks of disease among populations of wild fishes. ?? Inter-Research 2006.

HPV-16 viral load in oropharyngeal squamous cell carcinoma using digital PCR.

PubMed

Antonsson, Annika; Knight, Lani; Panizza, Benedict J; Porceddu, Sandro V; Emmett, Sarah; Whiteman, David C

2018-05-09

We did not identify any strong associations between HPV-16 viral load and any of the clinical or lifestyle factors. The epidemiology of oropharyngeal SCC is changing, with an increasing proportion of HPV-positive cases seen in the last decade. It is known that a high viral load is linked to the development of cervical cancer, the relation between viral load and oropharyngeal SCC is less clear. We sought to determine HPV-16 viral load in HPV-positive oropharyngeal SCCs using highly sensitive digital PCR and to identify clinical and lifestyle factors associated with viral load. We analysed 45 HPV-16 positive oropharyngeal SCCs diagnosed between 2013 and 2015. All patients completed a lifestyle questionnaire and clinical data were extracted from medical charts. Viral load was determined using digital PCR assays for HPV-L1 and RNAseP. We found large variations in HPV-16 viral load from 1 to 930 copies per cell (median 34 copies per cell).

Comparison of reproductive protection against bovine viral diarrhea virus provided by multivalent viral vaccines containing inactivated fractions of bovine viral diarrhea virus 1 and 2.

PubMed

Walz, Paul H; Riddell, Kay P; Newcomer, Benjamin W; Neill, John D; Falkenberg, Shollie M; Cortese, Victor S; Scruggs, Daniel W; Short, Thomas H

2018-04-23

Bovine viral diarrhea virus (BVDV) is an important viral cause of reproductive disease, immune suppression and clinical disease in cattle. The objective of this study was to compare reproductive protection in cattle against the impacts of bovine viral diarrhea virus (BVDV) provided by three different multivalent vaccines containing inactivated BVDV. BVDV negative beef heifers and cows (n = 122) were randomly assigned to one of four groups. Groups A-C (n = 34/group) received two pre-breeding doses of one of three commercially available multivalent vaccines containing inactivated fractions of BVDV 1 and BVDV 2, and Group D (n = 20) served as negative control and received two doses of saline prior to breeding. Animals were bred, and following pregnancy diagnosis, 110 cattle [Group A (n = 31); Group B (n = 32); Group C (n = 31); Group D (n = 16)] were subjected to a 28-day exposure to cattle persistently infected (PI) with BVDV (1a, 1b and 2a). Of the 110 pregnancies, 6 pregnancies resulted in fetal resorption with no material for testing. From the resultant 104 pregnancies, BVDV transplacental infections were demonstrated in 73 pregnancies. The BVDV fetal infection rate (FI) was calculated at 13/30 (43%) for Group A cows, 27/29 (93%) for Group B cows, 18/30 (60%) for Group C cows, and 15/15 (100%) for Group D cows. Statistical differences were observed between groups with respect to post-vaccination antibody titers, presence and duration of viremia in pregnant cattle, and fetal infection rates in offspring from BVDV-exposed cows. Group A vaccination resulted in significant protection against BVDV infection as compared to all other groups based upon outcome measurements, while Group B vaccination did not differ in protection against BVDV infection from control Group D. Ability of inactivated BVDV vaccines to provide protection against BVDV fetal infection varies significantly among commercially available products; however, in this challenge

Multilaboratory comparison of hepatitis C virus viral load assays.

PubMed

Caliendo, A M; Valsamakis, A; Zhou, Y; Yen-Lieberman, B; Andersen, J; Young, S; Ferreira-Gonzalez, A; Tsongalis, G J; Pyles, R; Bremer, J W; Lurain, N S

2006-05-01

We report a multilaboratory evaluation of hepatitis C virus (HCV) viral load assays to determine their linear range, reproducibility, subtype detection, and agreement. A panel of HCV RNA samples ranging in nominal concentration from 1.0 to 7.0 log10 IU/ml was constructed by diluting a clinical specimen (genotype 1b). Replicates of the panel were tested in multiple laboratories using the Abbott TaqMan analyte-specific reagent (Abbott reverse transcription-PCR [RT-PCR]), Roche TaqMan RUO (Roche RT-PCR), Roche Amplicor Monitor HCV 2.0 (Roche Monitor), and Bayer VERSANT HCV RNA 3.0 (Bayer bDNA) assays. Bayer bDNA-negative specimens were tested reflexively using the Bayer VERSANT HCV RNA qualitative assay (Bayer TMA). Abbott RT-PCR and Roche RT-PCR detected all 28 replicates with a concentration of 1.0 log10 IU/ml and were linear to 7.0 log10 IU/ml. Roche Monitor and Bayer bDNA detected 27 out of 28 and 13 out of 28 replicates, respectively, of 3.0 log10 IU/ml. Bayer TMA detected all seven replicates with 1.0 log10 IU/ml. Bayer bDNA was the most reproducible of the four assays. The mean viral load values for panel members in the linear ranges of the assays were within 0.5 log10 for the different tests. Eighty-nine clinical specimens of various genotypes (1 through 4) were tested in the Bayer bDNA, Abbott RT-PCR, and Roche RT-PCR assays. For Abbott RT-PCR, mean viral load values were 0.61 to 0.96 log10 greater than the values for Bayer bDNA assay for samples with genotype 1, 2, or 3 samples and 0.08 log10 greater for genotype 4 specimens. The Roche RT-PCR assay gave mean viral load values that were 0.28 to 0.82 log10 greater than those obtained with the Bayer bDNA assay for genotype 1, 2, and 3 samples. However, for genotype 4 samples the mean viral load value obtained with the Roche RT-PCR assay was, on average, 0.15 log10 lower than that of the Bayer bDNA. Based on these data, we conclude that the sensitivity and linear range of the Abbott and Roche RT-PCR assays

Viral genome methylation as an epigenetic defense against geminiviruses.

PubMed

Raja, Priya; Sanville, Bradley C; Buchmann, R Cody; Bisaro, David M

2008-09-01

Geminiviruses encapsidate single-stranded DNA genomes that replicate in plant cell nuclei through double-stranded DNA intermediates that associate with cellular histone proteins to form minichromosomes. Like most plant viruses, geminiviruses are targeted by RNA silencing and encode suppressor proteins such as AL2 and L2 to counter this defense. These related proteins can suppress silencing by multiple mechanisms, one of which involves interacting with and inhibiting adenosine kinase (ADK), a cellular enzyme associated with the methyl cycle that generates S-adenosyl-methionine, an essential methyltransferase cofactor. Thus, we hypothesized that the viral genome is targeted by small-RNA-directed methylation. Here, we show that Arabidopsis plants with mutations in genes encoding cytosine or histone H3 lysine 9 (H3K9) methyltransferases, RNA-directed methylation pathway components, or ADK are hypersensitive to geminivirus infection. We also demonstrate that viral DNA and associated histone H3 are methylated in infected plants and that cytosine methylation levels are significantly reduced in viral DNA isolated from methylation-deficient mutants. Finally, we demonstrate that Beet curly top virus L2- mutant DNA present in tissues that have recovered from infection is hypermethylated and that host recovery requires AGO4, a component of the RNA-directed methylation pathway. We propose that plants use chromatin methylation as a defense against DNA viruses, which geminiviruses counter by inhibiting global methylation. In addition, our results establish that geminiviruses can be useful models for genome methylation in plants and suggest that there are redundant pathways leading to cytosine methylation.

Porcine semen as a vector for transmission of viral pathogens.

PubMed

Maes, Dominiek; Van Soom, Ann; Appeltant, Ruth; Arsenakis, Ioannis; Nauwynck, Hans

2016-01-01

Different viruses have been detected in porcine semen. Some of them are on the list of the World Organization for Animal Health (OIE), and consequently, these pathogens are of socioeconomic and/or public health importance and are of major importance in the international trade of animals and animal products. Artificial insemination (AI) is one of the most commonly used assisted reproductive technologies in pig production worldwide. This extensive use has enabled pig producers to benefit from superior genetics at a lower cost compared to natural breeding. However, the broad distribution of processed semen doses for field AI has increased the risk of widespread transmission of swine viral pathogens. Contamination of semen can be due to infections of the boar or can occur during semen collection, processing, and storage. It can result in reduced semen quality, embryonic mortality, endometritis, and systemic infection and/or disease in the recipient female. The presence of viral pathogens in semen can be assessed by demonstration of viable virus, nucleic acid of virus, or indirectly by measuring serum antibodies in the boar. The best way to prevent disease transmission via the semen is to assure that the boars in AI centers are free from the disease, to enforce very strict biosecurity protocols, and to perform routine health monitoring of boars. Prevention of viral semen contamination should be the primary focus because it is easier to prevent contamination than to eliminate viruses once present in semen. Nevertheless, research and development of novel semen processing treatments such as single-layer centrifugation is ongoing and may allow in the future to decontaminate semen. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of reproductive protection against bovine viral diarrhea virus and bovine herpesvirus-1 afforded by annual revaccination with modified-live viral or combination modified-live/killed viral vaccines after primary vaccination with modified-live viral vaccine.

PubMed

Walz, Paul H; Givens, M Daniel; Rodning, Soren P; Riddell, Kay P; Brodersen, Bruce W; Scruggs, Daniel; Short, Thomas; Grotelueschen, Dale

2017-02-15

The objective of this study was to compare reproductive protection in cattle against bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BoHV-1) provided by annual revaccination with multivalent modified-live viral (MLV) vaccine or multivalent combination viral (CV) vaccine containing temperature-sensitive modified-live BoHV-1 and killed BVDV when MLV vaccines were given pre-breeding to nulliparous heifers. Seventy-five beef heifers were allocated into treatment groups A (n=30; two MLV doses pre-breeding, annual revaccination with MLV vaccine), B (n=30; two MLV doses pre-breeding, annual revaccination with CV vaccine) and C (n=15; saline in lieu of vaccine). Heifers were administered treatments on days 0 (weaning), 183 (pre-breeding), 366 (first gestation), and 738 (second gestation). After first calving, primiparous cows were bred, with pregnancy assessment on day 715. At that time, 24 group A heifers (23 pregnancies), 23 group B heifers (22 pregnancies), and 15 group C heifers (15 pregnancies) were commingled with six persistently infected (PI) cattle for 16days. Ninety-nine days after PI removal, cows were intravenously inoculated with BoHV-1. All fetuses and live offspring were assessed for BVDV and BoHV-1. Abortions occurred in 3/23 group A cows, 1/22 group B cows, and 11/15 group C cows. Fetal infection with BVDV or BoHV-1 occurred in 4/23 group A offspring, 0/22 group B offspring, and 15/15 group C offspring. This research demonstrates efficacy of administering two pre-breeding doses of MLV vaccine with annual revaccination using CV vaccine to prevent fetal loss due to exposure to BVDV and BoHV-1. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Viral cause and management of necrotizing herpetic retinopathies].

PubMed

Tran, T H C; Bodaghi, B; Rozenberg, F; Cassoux, N; Fardeau, C; LeHoang, P

2004-03-01

To study the viral cause and present the management of necrotizing herpetic retinopathies. Charts of patients presenting with acute retinal necrosis (ARN) or progressive outer retinal necrosis (PORN) diagnosed between March 1997 and June 2001 were retrospectively reviewed. Intraocular specimens were obtained in 33 cases to determine the viral cause using polymerase chain reaction-based assays and/or detection of intraocular antibody production. The mean age was 43.4 Years. Herpesvirus genome was identified in 29 patients (80.5%). In the ARN group (32 patients, 38 eyes), herpes simplex virus (HSV) DNA was found in 11 patients (34.4%), varicella-zoster virus (VZV) in nine patients (28.1%), and cytomegalovirus (CMV) in four patients (12.5%). One patient (3.1%) presented an Epstein-Barr virus (EBV) infection. ARN was bilateral at initial examination in six patients and secondary bilateralization was observed in four patients. In the PORN group (four patients, eight eyes), the retinitis was bilateral and VZV DNA was detected in all cases. Two patients were treated with intravenous acyclovir, six with foscarnet alone, ten with intravenous foscarnet + acyclovir, 18 with intravenous foscarnet and intravitreous ganciclovir injections. Complications of necrotizing herpetic retinitis were cataract (26%), optic nerve atrophy (23.9%), and retinal detachment (17.4%). Final visual acuity was less or equal to 20/200 in 47.8% of cases. It is important to determine the specific viral etiology since progression and prognosis may be different in herpetic necrotizing retinitis caused by HSV, VZV, or CMV. Visual prognosis is improved by intensive antiviral therapy, but remains poor if complications occur.

Respiratory viral RNA on toys in pediatric office waiting rooms.

PubMed

Pappas, Diane E; Hendley, J Owen; Schwartz, Richard H

2010-02-01

Toys in pediatric office waiting rooms may be fomites for transmission of viruses. Eighteen samples were taken from office objects on 3 occasions. Samples were tested for presence of picornavirus (either rhinovirus or enterovirus) on all 3 sample days; in addition, January samples were tested for respiratory syncytial virus and March samples were tested for influenza A and B. In addition, 15 samples were obtained from the sick waiting room before and after cleaning. Polymerase chain reaction was used to detect picornavirus, respiratory syncytial virus, and influenza A or B virus. Finally, 20 samples were obtained from the fingers of a researcher after handling different toys in the sick waiting room, and samples were then obtained from all the same toys; all samples were tested for picornavirus by polymerase chain reaction. Viral RNA was detected on 11 of 52 (21%) of toys sampled. Ten of the positives were picornavirus; 1 was influenza B virus. Three (30%) of 10 toys from the new toy bag, 6 of 30 (20%) in the sick child waiting room, and 2 of 12 (17%) in the well child waiting room were positive. Six (40%) of 15 toys in the sick waiting room were positive for picornaviral RNA before cleaning; after cleaning, 4 (27%) of 15 were positive in spite of the fact that RNA was removed from 4 of 6 of the original positives. Three (15%) of 20 toys in the sick waiting room were positive for picornaviral RNA, but RNA was not transferred to the fingers of the investigator who handled these toys. About 20% of the objects in a pediatric office may be contaminated with respiratory viral RNA, most commonly picornavirus RNA. Cleaning with a disinfectant cloth was only modestly effective in removing the viral RNA from the surfaces of toys, but transfer of picornaviral RNA from toys to fingers was inefficient.

Autophagy regulates UBC9 levels during viral-mediated tumorigenesis

PubMed Central

Mattoscio, Domenico; Casadio, Chiara; Miccolo, Claudia; Maffini, Fausto; Raimondi, Andrea; Tacchetti, Carlo; Gheit, Tarik; Tagliabue, Marta; Galimberti, Viviana E.; De Lorenzi, Francesca; Chiesa, Fausto; Ansarin, Mohssen; Tommasino, Massimo

2017-01-01

UBC9, the sole E2-conjugating enzyme required for SUMOylation, is a key regulator of essential cellular functions and, as such, is frequently altered in cancers. Along these lines, we recently reported that its expression gradually increases during early stages of human papillomavirus (HPV)-mediated cervical lesions transformation. However, a better understanding of how UBC9 is exploited by transforming viral oncoproteins is still needed. In the present study, we show that in human samples HPV drives UBC9 up-regulation also in very early steps of head and neck tumorigenesis, pointing to the important role for UBC9 in the HPV-mediated carcinogenic program. Moreover, using HPV-infected pre-cancerous tissues and primary human keratinocytes as the natural host of the virus, we investigate the pathological meaning and the cellular mechanisms responsible for UBC9 de-regulation in an oncoviral context. Our results show that UBC9 overexpression is promoted by transforming viral proteins to increase host cells’ resistance to apoptosis. In addition, ultrastuctural, pharmacological and genetic approaches crucially unveil that UBC9 is physiologically targeted by autophagy in human cells. However, the presence of HPV E6/E7 oncoproteins negatively impacts the autophagic process through selective inhibition of autophagosome-lysosome fusion, finally leading to p53 dependent UBC9 accumulation during viral-induced cellular transformation. Therefore, our study elucidates how UBC9 is manipulated by HPV oncoproteins, details the physiological mechanism by which UBC9 is degraded in cells, and identifies how HPV E6/E7 impact on autophagy. These findings point to UBC9 and autophagy as novel hallmarks of HPV oncogenesis, and open innovative avenues towards the treatment of HPV-related malignancies. PMID:28253371

Duck viral enteritis in domestic muscovy ducks in Pennsylvania

USGS Publications Warehouse

Davison, S.; Converse, K.A.; Hamir, A.N.; Eckroade, R.J.

1993-01-01

Duck viral enteritis (DVE) outbreaks occurred at two different locations in Pennsylvania in 1991 and 1992. In the first outbreak, four ducks died out of a group of 30 domestic ducks; in the second outbreak, 65 ducks died out of a group of 114 domestic ducks, and 15 domestic geese died as well. A variety of species of ducks were present on both premises, but only muscovy ducks (Cairina moschata) died from the disease. On necropsy, gross lesions included hepatomegaly with petechial hemorrhages, petechial hemorrhages in the abdominal fat, petechial hemorrhages on the epicardial surface of the heart, and multifocal to coalescing areas of fibrinonecrotic material over the mucosal surface of the trachea, esophagus, intestine, and cloaca. Histologically, the liver had random multifocal areas of necrosis and eosinophilic intranuclear inclusion bodies in hepatocytes. DVE virus was isolated and identified using muscovy duck embryo fibroblast inoculation and virus neutralization. /// En dos sitios diferentes se presentaron brotes de enteritis viral de los patos en el estados de Pensilvania en los a??os 1991 y 1992. En el primer brote, cuatro de un lote de 30 patos murieron mientras que en el segundo brote murieron 65 patos de un lote de 114 patos y 15 gansos. En ambas localidades exist?-a una variedad de especies de patos, sin embargo, s??lamente los patos almizcleros (Cairina moschata) murieron. A la necropsia, las lesiones macrosc??picas incluyeron hepatomegalia con hemorragias petequiales, hemorragias petequiales en la grasa abdominal y en la superficie del epicardio, y ?!reas multifocales o coalescentes de material fibrinonecr??tico sobre la superficie de la mucosa de la tr?!quea, es??fago, intestino y cloaca. Histol??gicamente, el h?-gado mostraba ?!reas multifocales de necrosis y cuerpos de inclusi??n intranucleares eosinof?-licos en los hepatocitos. El virus de la enteritis viral de los patos fue aislado e identificado usando fibroblasto de embriones de pato almizclero

Cerebrospinal fluid ferritin in children with viral and bacterial meningitis.

PubMed

Rezaei, M; Mamishi, S; Mahmoudi, S; Pourakbari, B; Khotaei, G; Daneshjou, K; Hashemi, N

2013-01-01

Despite the fact that the prognosis of bacterial meningitis has been improved by the influence of antibiotics, this disease is still one of the significant causes of morbidity and mortality in children. Rapid differentiation between bacterial and aseptic meningitis, and the need for immediate antibiotic treatment in the former, is crucial in the prognosis of these patients. Ferritin is one of the most sensitive biochemical markers investigated in cerebrospinal fluid (CSF) for the early diagnosis of bacterial meningitis. The present study aims to evaluate the diagnostic capability of CSF ferritin in differentiating bacterial and viral meningitis in the paediatric setting. A cross-sectional study was carried out in the referral Children's Medical Center Hospital, Tehran, during 2008 and 2009. According to the inclusion criteria, CSF samples from 42 patients with suspected meningitis were obtained and divided into two meningitis groups, bacterial (n = 18) and viral (n = 24). Ferritin and other routine determinants (i.e., leucocytes, protein and glucose) were compared between the two groups. Ferritin concentration in the bacterial meningitis group was 106.39 +/- 86.96 ng/dL, which was considerably higher than in the viral meningitis group (10.17 +/- 14.09, P < 0.001). Mean CSF protein concentration and cell count were significantly higher in the bacterial meningitis group and showed a positive correlation with CSF ferritin. In conclusion, this study suggests that CSF ferritin concentration is an accurate test for the early differentiation of bacterial and aseptic meningitis; however, further investigation on a larger cohort of patients is required to confirm this finding.

Clinical Utility of Urinary Cytology to Detect BK Viral Nephropathy.

PubMed

Nankivell, Brian J; Renthawa, Jasveen; Jeoffreys, Neisha; Kable, Kathy; O'Connell, Philip J; Chapman, Jeremy R; Wong, Germaine; Sharma, Raghwa N

2015-08-01

Reactivation of BK polyoma virus can result in destructive viral allograft nephropathy (BKVAN) with limited treatment options. Screening programs using surrogate markers of viral replication are important preventive strategies, guiding immunosuppression reduction. We prospectively evaluated the diagnostic test performance of urinary decoy cells and urinary SV40T immunochemistry of exfoliated cells, to screen for BKVAN, (defined by reference histology with SV40 immunohistochemistry, n = 704 samples), compared with quantitative viremia, from 211 kidney and 141 kidney-pancreas transplant recipients. The disease prevalence of BKVAN was 2.6%. Decoy cells occurred in 95 of 704 (13.5%) samples, with a sensitivity of 66.7%, specificity of 88.6%, positive predictive value (PPV) of 11.7%, and negative predictive value of 98.5% to predict histologically proven BKVAN. Quantification of decoy cells improved the PPV to 32.1% (10 ≥ cells threshold). Immunohistochemical staining of urinary exfoliated cells for SV40T improved sensitivity to 85.7%, detecting atypical or degenerate infected cells (specificity of 92.3% and PPV of 33.3%), but was hampered by technical failures. Viremia occurred in 90 of 704 (12.8%) with sensitivity of 96.3%, specificity of 90.3%, PPV of 31.5%, and negative predictive value of 99.8%. The receiver-operator curve performance of quantitative viremia surpassed decoy cells (area under the curve of 0.95 and 0.79, respectively, P = 0.0018 for differences). Combining decoy cell and BK viremia in a diagnostic matrix improved prediction of BKVAN and diagnostic risk stratification, especially for high-level positive results. Although quantified decoy cells are acceptable surrogate markers of BK viral replication with unexceptional test performances, quantitative viremia displayed superior test characteristics and is suggested as the screening test of choice.

An HIV Epidemic Model Based on Viral Load Dynamics: Value in Assessing Empirical Trends in HIV Virulence and Community Viral Load

PubMed Central

Herbeck, Joshua T.; Mittler, John E.; Gottlieb, Geoffrey S.; Mullins, James I.

2014-01-01

Trends in HIV virulence have been monitored since the start of the AIDS pandemic, as studying HIV virulence informs our understanding of HIV epidemiology and pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary process, using set point viral load (SPVL) as a proxy, to make inferences about empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based epidemic model based on HIV viral load dynamics. The model contains functions for viral load and transmission, SPVL and disease progression, viral load trajectories in multiple stages of infection, and the heritability of SPVL across transmissions. We find that HIV virulence evolves to an intermediate level that balances infectiousness with longer infected lifespans, resulting in an optimal SPVL∼4.75 log10 viral RNA copies/mL. Adaptive viral evolution may explain observed HIV virulence trends: our model produces SPVL trends with magnitudes that are broadly similar to empirical trends. With regard to variation among studies in empirical SPVL trends, results from our model suggest that variation may be explained by the specific epidemic context, e.g. the mean SPVL of the founding lineage or the age of the epidemic; or improvements in HIV screening and diagnosis that results in sampling biases. We also use our model to examine trends in community viral load, a population-level measure of HIV viral load that is thought to reflect a population's overall transmission potential. We find that community viral load evolves in association with SPVL, in the absence of prevention programs such as antiretroviral therapy, and that the mean community viral load is not necessarily a strong predictor of HIV incidence. PMID:24945322

Diagnostics and Discovery in Viral Central Nervous System Infections.

PubMed

Lipkin, Walter Ian; Hornig, Mady

2015-09-01

The range of viruses implicated in central nervous system disease continues to grow with globalization of travel and trade, emergence and reemergence of zoonoses and investments in discovery science. Diagnosis of viral central nervous system infections is challenging in that brain tissue, where the pathogen concentration is likely to be highest, is not readily obtained and sensitive methods for molecular and serological detection of infection are not available in most clinical microbiology laboratories. Here we review these challenges and discuss how they may be addressed using advances in molecular, proteomic and immunological methods. © 2015 International Society of Neuropathology.

Dengue virus life cycle: viral and host factors modulating infectivity.

PubMed

Rodenhuis-Zybert, Izabela A; Wilschut, Jan; Smit, Jolanda M

2010-08-01

Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited dengue fever, an increasing number of patients present more severe manifestations, such as dengue hemorrhagic fever and dengue shock syndrome. In this review we will give an overview of the infectious life cycle of DENV and will discuss the viral and host factors that are important in controlling DENV infection.

An outbreak of viral gastroenteritis associated with adequately prepared oysters.

PubMed Central

Chalmers, J. W.; McMillan, J. H.

1995-01-01

Over Christmas 1993, an outbreak of food poisoning occurred among guests in a hotel in South West Scotland. Evidence from a cohort study strongly suggested that raw oysters were the vehicle for infection, probably due to a Small Round Structured Virus (SRSV). Detailed enquiry about the source and preparation of the oysters revealed no evidence of any unsafe handling at any stage in the food chain, nor any evidence of bacterial contamination. It is suggested that the present standards of preparation and monitoring are inadequate to protect the consumer, and that bacteriophage monitoring may be a useful method of screening for viral contamination in future. PMID:7641830

Stochastical modeling for Viral Disease: Statistical Mechanics and Network Theory

NASA Astrophysics Data System (ADS)

Zhou, Hao; Deem, Michael

2007-04-01

Theoretical methods of statistical mechanics are developed and applied to study the immunological response against viral disease, such as dengue. We use this theory to show how the immune response to four different dengue serotypes may be sculpted. It is the ability of avian influenza, to change and to mix, that has given rise to the fear of a new human flu pandemic. Here we propose to utilize a scale free network based stochastic model to investigate the mitigation strategies and analyze the risk.

Matrix and Backstage: Cellular Substrates for Viral Vaccines

PubMed Central

Jordan, Ingo; Sandig, Volker

2014-01-01

Vaccines are complex products that are manufactured in highly dynamic processes. Cellular substrates are one critical component that can have an enormous impact on reactogenicity of the final preparation, level of attenuation of a live virus, yield of infectious units or antigens, and cost per vaccine dose. Such parameters contribute to feasibility and affordability of vaccine programs both in industrialized countries and developing regions. This review summarizes the diversity of cellular substrates for propagation of viral vaccines from primary tissue explants and embryonated chicken eggs to designed continuous cell lines of human and avian origin. PMID:24732259

Nucleic Acid-Induced Resistance to Viral Infection

PubMed Central

Takano, Kouichi; Warren, Joel; Jensen, Keith E.; Neal, Alan L.

1965-01-01

Takano, Kouichi (Chas. Pfizer & Co., Inc., Terre Haute, Ind.), Joel Warren, Keith E. Jensen, and Alan L. Neal. Nucleic acid resistance to viral infection. J. Bacteriol. 90:1542–1547. 1965.—Administration of nonviral nucleic acids to mice increased their resistance to a subsequent infection with influenza or encephalomyocarditis viruses. Injection of ribonucleic acid or deoxyribonucleic acid by peripheral routes did not modify susceptibility to intranasal infection. Lung tissue extracts from animals previously treated with yeast nucleic acid inhibited the growth of vaccinia and influenza viruses. The protective effect of exogenous nucleic acids persisted in mice for several days, but gradually diminished to undetectable levels. PMID:4285332

Microbial and viral chitinases: Attractive biopesticides for integrated pest management.

PubMed

Berini, Francesca; Katz, Chen; Gruzdev, Nady; Casartelli, Morena; Tettamanti, Gianluca; Marinelli, Flavia

The negative impact of the massive use of synthetic pesticides on the environment and on human health has stimulated the search for environment-friendly practices for controlling plant diseases and pests. Among them, biocontrol, which relies on using beneficial organisms or their products (bioactive molecules and/or hydrolytic enzymes), holds the greatest promise and is considered a pillar of integrated pest management. Chitinases are particularly attractive to this purpose since they have fungicidal, insecticidal, and nematicidal activities. Here, current knowledge on the biopesticidal action of microbial and viral chitinases is reviewed, together with a critical analysis of their future development as biopesticides. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis of the Subunit Stoichiometries in Viral Entry

PubMed Central

Magnus, Carsten; Regoes, Roland R.

2012-01-01

Virions of the Human Immunodeficiency Virus (HIV) infect cells by first attaching with their surface spikes to the CD4 receptor on target cells. This leads to conformational changes in the viral spikes, enabling the virus to engage a coreceptor, commonly CCR5 or CXCR4, and consecutively to insert the fusion peptide into the cellular membrane. Finally, the viral and the cellular membranes fuse. The HIV spike is a trimer consisting of three identical heterodimers composed of the gp120 and gp41 envelope proteins. Each of the gp120 proteins in the trimer is capable of attaching to the CD4 receptor and the coreceptor, and each of the three gp41 units harbors a fusion domain. It is still under debate how many of the envelope subunits within a given trimer have to bind to the CD4 receptors and to the coreceptors, and how many gp41 protein fusion domains are required for fusion. These numbers are referred to as subunit stoichiometries. We present a mathematical framework for estimating these parameters individually by analyzing infectivity assays with pseudotyped viruses. We find that the number of spikes that are engaged in mediating cell entry and the distribution of the spike number play important roles for the estimation of the subunit stoichiometries. Our model framework also shows why it is important to subdivide the question of the number of functional subunits within one trimer into the three different subunit stoichiometries. In a second step, we extend our models to study whether the subunits within one trimer cooperate during receptor binding and fusion. As an example for how our models can be applied, we reanalyze a data set on subunit stoichiometries. We find that two envelope proteins have to engage with CD4-receptors and coreceptors and that two fusion proteins must be revealed within one trimer for viral entry. Our study is motivated by the mechanism of HIV entry but the experimental technique and the model framework can be extended to other viral systems

Structural basis of viral invasion: lessons from paramyxovirus F

PubMed Central

Lamb, Robert A.; Jardetzky, Theodore S.

2007-01-01

Summary The structures of glycoproteins that mediate enveloped virus entry into cells have revealed dramatic structural changes that accompany membrane fusion and provided mechanistic insights into this process. The group of class I viral fusion proteins includes the influenza hemagglutinin, paramyxovirus F, HIV env and other mechanistically related fusogens, but these proteins are unrelated in sequence and exhibit clearly distinct structural features. Recently determined crystal structures of the paramyxovirus F protein in two conformations, representing prefusion and postfusion states, reveal a novel protein architecture that undergoes large-scale, irreversible refolding during membrane fusion, extending our understanding of this diverse group of membrane fusion machines. PMID:17870467

Viral entry mechanisms: the increasing diversity of paramyxovirus entry

PubMed Central

Smith, Everett Clinton; Popa, Andreea; Chang, Andres; Masante, Cyril; Dutch, Rebecca Ellis

2009-01-01

The paramyxovirus family contains established human pathogens such as measles virus and human respiratory syncytial virus, and emerging pathogens including the Hendra and Nipah viruses and the recently identified human metapneumovirus. Two major envelope glycoproteins, the attachment protein and the fusion protein, promote the processes of viral attachment and virus-cell membrane fusion required for entry. While common mechanisms of fusion protein proteolytic activation and the mechanism of membrane fusion promotion have been shown in recent years, considerable diversity exists in the family related to receptor binding and the potential mechanisms of fusion triggering. PMID:19878307

Antibody Maturation and Viral Diversification in HIV-Infected Women

PubMed Central

James, Maria M.; Laeyendecker, Oliver; Sun, Jin; Hoover, Donald R.; Mullis, Caroline E.; Cousins, Matthew M.; Coates, Thomas; Moore, Richard D.; Kelen, Gabor D.; Fowler, Mary Glenn; Kumwenda, Johnstone J.; Mofenson, Lynne M.; Kumwenda, Newton I.; Taha, Taha E.; Eshleman, Susan H.

2013-01-01

Introduction The Post-exposure Prophylaxis in Infants (PEPI)-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA) that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488); a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54). Antibody maturation and viral diversification were examined in these women. Methods Samples collected at enrollment (N = 2,561) and 12–24 months later (N = 1,306) were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM) diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples) and the known non-recent group (43 enrollment samples, 22 follow-up samples). Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US) with known recent infection (N = 102) and known non-recent infection (N = 67). Results In PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non-recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non-recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection. Conclusions Antibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection. PMID:23460842

[Viral hepatitis A - possible diagnostic and therapeutic problems].

PubMed

Husa, Petr; Husa, Petr

Viral hepatitis A (VHA) is the disease which has an ancient history. Reports of epidemic jaundice were described by Hippocrates in Greece during the 5th century B.C. Incidence of VHA in developed countries is dropping in last decades. What was once common disease is now very rare, usually emerging in local epidemies. With decreasing incidence of hepatitis A clinicians losing practical experiences with disease. Authors present possible diagnostic and therapeutic problems based on their experience with large epidemic of hepatitis A, which occurred in 2016-2017 in Brno area.Key words: hepatitis A (VHA) - hepatitis A virus (HAV).

Viral blips during suppressive antiretroviral treatment are associated with high baseline HIV-1 RNA levels.

PubMed

Sörstedt, Erik; Nilsson, Staffan; Blaxhult, Anders; Gisslén, Magnus; Flamholc, Leo; Sönnerborg, Anders; Yilmaz, Aylin

2016-06-21

Many HIV-1-infected patients on suppressive antiretroviral therapy (ART) have transiently elevated HIV RNA levels. The clinical significance of these viral blips is uncertain. We have determined the incidence of blips and investigated important associations in the Swedish HIV-cohort. HIV-1-infected ART naïve adults who commenced ART 2007-2013 were retrospectively included. Viral blips were defined as a transient viral load between 50 and 500 copies/mL Subjects not suppressed after six months on ART were excluded. Viral blips were found in 76/735 included subjects (10.3 %) and in 90/4449 samples (2.0 %). Median blip viral load was 76 copies/mL (range 56-138). Median follow-up time was 170 weeks (range 97-240). Baseline viral load was higher in subjects with viral blips (median log10 4.85 copies/mL) compared with subjects without blips (median log10 4.55 copies/mL) (p < 0.01). There was a significant association between viral blips and risk for subsequent virological failure (p < 0.001). The Swedish national HIV-cohort has a low incidence of viral blips (10 %). Blips were associated with high baseline viral load and an increased risk of subsequent virological failure.

Rapid Multiplex PCR Assay To Identify Respiratory Viral Pathogens: Moving Forward Diagnosing The Common Cold

PubMed Central

Gordon, Sarah M; Elegino-Steffens, Diane U; Agee, Willie; Barnhill, Jason; Hsue, Gunther

2013-01-01

Upper respiratory tract infections (URIs) can be a serious burden to the healthcare system. The majority of URIs are viral in etiology, but definitive diagnosis can prove difficult due to frequently overlapping clinical presentations of viral and bacterial infections, and the variable sensitivity, and lengthy turn-around time of viral culture. We tested new automated nested multiplex PCR technology, the FilmArray® system, in the TAMC department of clinical investigations, to determine the feasibility of replacing the standard viral culture with a rapid turn-around system. We conducted a feasibility study using a single-blinded comparison study, comparing PCR results with archived viral culture results from a convenience sample of cryopreserved archived nasopharyngeal swabs from acutely ill ED patients who presented with complaints of URI symptoms. A total of 61 archived samples were processed. Viral culture had previously identified 31 positive specimens from these samples. The automated nested multiplex PCR detected 38 positive samples. In total, PCR was 94.5% concordant with the previously positive viral culture results. However, PCR was only 63.4% concordant with the negative viral culture results, owing to PCR detection of 11 additional viral pathogens not recovered on viral culture. The average time to process a sample was 75 minutes. We determined that an automated nested multiplex PCR is a feasible alternative to viral culture in an acute clinical setting. We were able to detect at least 94.5% as many viral pathogens as viral culture is able to identify, with a faster turn-around time. PMID:24052914

Viral Capsid DNA Aptamer Conjugates as Multivalent Cell Targeting Vehicles

PubMed Central

Tong, Gary J.; Hsiao, Sonny C.; Carrico, Zachary M.; Francis, Matthew B.

2009-01-01

Nucleic acid aptamers offer significant potential as convenient and evolvable targeting groups for drug delivery. To attach them to the surface of a genome-free viral capsid carrier, an efficient oxidative coupling strategy has been developed. The method involves the periodate-mediated reaction of phenylene diamine substituted oligonucleotides with aniline groups installed on the outer surface of the capsid shells. Up to 60 DNA strands can be attached to each viral capsid with no apparent loss of base-pairing capabilities or protein stability. The ability of the capsids to bind specific cellular targets was demonstrated through the attachment of a 41-nucleotide sequence that targets a tyrosine kinase receptor on Jurkat T cells. After the installation of a fluorescent dye on the capsid interior, capsids bearing the cell-targeting sequence showed significant levels of binding to the cells relative to control samples. Colocalization experiments using confocal microscopy indicated that the capsids were endocytosed and trafficked to lysosomes for degradation. These observations suggest that aptamer-labeled capsids could be used for the targeted drug delivery of acid-labile prodrugs that would be preferentially released upon lysosomal acidification. PMID:19603808

Clinical signs of dysphagia in infants with acute viral bronchiolitis☆

PubMed Central

Barbosa, Lisiane De Rosa; Gomes, Erissandra; Fischer, Gilberto Bueno

2014-01-01

Objective: To determine the occurrence of clinical signs of dysphagia in infants with acute viral bronchiolitis, to compare the respiratory parameters during deglutition, and to ensure the intra- and inter- examiners agreement, as well as to accomplish intra and interexaminators concordance of the clinical evaluation of the deglutition. Methods: This was a cross-sectional study of 42 infants aged 0-12 months. The clinical evaluation was accompanied by measurements of respiratory rate and pulse oximetry. A score of swallowing disorders was designed to establish associations with other studied variables and to ensure the intra- and interrater agreement of clinical feeding assessments. Caregivers also completed a questionnaire about feeding difficulties. Significance was set at p<0.05. Results: Changes in the oral phase (prolonged pauses) and pharyngeal phase (wheezing, coughing and gagging) of swallowing were found. A significant increase in respiratory rate between pre- and post-feeding times was found, and it was determined that almost half of the infants had tachypnea. An association was observed between the swallowing disorder scores and a decrease in oxygen saturation. Infants whose caregivers reported feeding difficulties during hospitalization stated a significantly greater number of changes in the swallowing evaluation. The intra-rater agreement was considered to be very good. Conclusions: Infants with acute viral bronchiolitis displayed swallowing disorders in addition to changes in respiratory rate and measures of oxygen saturation. It is suggested, therefore, that infants displaying these risk factors have a higher probability of dysphagia. PMID:25479843

Host phylogeny determines viral persistence and replication in novel hosts.

PubMed

Longdon, Ben; Hadfield, Jarrod D; Webster, Claire L; Obbard, Darren J; Jiggins, Francis M

2011-09-01

Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

Host and viral traits predict zoonotic spillover from mammals

PubMed Central

Olival, Kevin J.; Hosseini, Parviez R.; Zambrana-Torrelio, Carlos; Ross, Noam; Bogich, Tiffany L.; Daszak, Peter

2017-01-01

The majority of human emerging infectious diseases (EIDs) are zoonotic, with viruses originating in wild mammals of particular concern (e.g. HIV, Ebola, SARS)1–3. Understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs4. However, few analytical tools exist to identify which host species likely harbor the next human virus, or which viruses can cross species boundaries5–7. Here we conduct the most comprehensive analysis yet of mammalian host-virus relationships and show that both the total number of viruses that infect a given species, and the proportion likely to be zoonotic are predictable. After controlling for research effort, the proportion of zoonotic viruses per species is predicted by phylogenetic relatedness to humans, host taxonomy, and human population within a species range – which may reflect human-wildlife contact. We demonstrate for the first time that bats harbor a significantly higher proportion of zoonotic viruses than all other mammalian orders. We identify the taxa and geographic regions with the largest estimated number of ‘missing viruses’ and ‘missing zoonoses’ and therefore of highest value for future surveillance. We then show that phylogenetic host breadth and other viral traits are significant predictors of zoonotic potential, providing a novel framework to assess if a newly discovered mammalian virus could infect people. PMID:28636590

Shrimp viral diseases, import risk assessment and international trade.

PubMed

Karunasagar, Iddya; Ababouch, Lahsen

2012-09-01

Shrimp is an important commodity in international trade accounting for 15 % in terms of value of internationally traded seafood products which reached $102.00 billion in 2008. Aquaculture contributes to over 50 % of global shrimp production. One of the major constraints faced by shrimp aquaculture is the loss due to viral diseases like white spot syndrome, yellow head disease, and Taura syndrome. There are several examples of global spread of shrimp diseases due to importation of live shrimp for aquaculture. Though millions of tonnes of frozen or processed shrimp have been traded internationally during the last two decades despite prevalence of viral diseases in shrimp producing areas in Asia and the Americas, there is no evidence of diseases having been transmitted through shrimp imported for human consumption. The guidelines developed by the World Animal Health Organisation for movement of live animals for aquaculture, frozen crustaceans for human consumption, and the regulations implemented by some shrimp importing regions in the world are reviewed.

HIV-1 low copy viral sequencing-A prototype assay.

PubMed

Mellberg, Tomas; Krabbe, Jon; Gisslén, Magnus; Svennerholm, Bo

2016-01-01

In HIV-1 patients with low viral burden, sequencing is often problematic, yet important. This study presents a sensitive, sub-type independent system for sequencing of low level viremia. Sequencing data from 32 HIV-1 infected patients with low level viremia were collected longitudinally. A combination of ViroSeq® HIV-1 Genotyping System and an in-house nesting protocol was used. Eight sub-types were represented. The success-rate of amplification of both PR and RT in the same sample was 100% in samples with viral loads above 100 copies/ml. Below 100 copies/ml, this study managed to amplify both regions in 7/13 (54%) samples. The assays were able to amplify either PR or RT in all sub-types included but one sub-type A specimen. In conclusion, this study presents a promising, simple assay to increase the ability to perform HIV-1 resistance testing at low level viremia. This is a prototype assay and the method needs further testing to evaluate clinical performance.

The status of live viral vaccination in early life.

PubMed

Gans, Hayley A

2013-05-17

The need for neonatal vaccines is supported by the high disease burden during the first year of life particularly in the first month. Two-thirds of childhood deaths are attributable to infectious diseases of which viruses represent key pathogens. Many infectious diseases have the highest incidence, severity and mortality in the first months of life, and therefore early life vaccination would provide significant protection and life savings. For some childhood viral diseases successful vaccines exist, such as against measles, mumps, rubella, varicella, influenza poliovirus, and rotavirus, but their use in the first year particularly at birth is not yet practiced. Vaccines against other key pathogens continue to elude scientists such as against respiratory syncytial virus. The obstacles for early and neonatal vaccination are complex and include host factors, such as a developing immune system and the interference of passively acquired antibodies, as well vaccine-specific issues, such as optimal route of administration, titer and dosing requirements. Importantly, additional host and infrastructure barriers also present obstacles to neonatal vaccination in the developing world where morbidity and mortality rates are highest. This review will highlight the current live viral vaccines and their use in the first year of life, focusing on efficacy and entertaining the barriers that exist. It is important to understand the successes of current vaccines and use this knowledge to determine strategies that are successful in young infants and for the development of new vaccines for use in early life. Copyright © 2012 Elsevier Ltd. All rights reserved.

Material properties of viral nanocages explored by atomic force microscopy.

PubMed

van Rosmalen, Mariska G M; Roos, Wouter H; Wuite, Gijs J L

2015-01-01

Single-particle nanoindentation by atomic force microscopy (AFM) is an emergent technique to characterize the material properties of nano-sized proteinaceous systems. AFM uses a very small tip attached to a cantilever to scan the surface of the substrate. As a result of the sensitive feedback loop of AFM, the force applied by the tip on the substrate during scanning can be controlled and monitored. By accurately controlling this scanning force, topographical maps of fragile substrates can be acquired to study the morphology of the substrate. In addition, mechanical properties of the substrate like stiffness and breaking point can be determined by using the force spectroscopy capability of AFM. Here we discuss basics of AFM operation and how this technique is used to determine the structure and mechanical properties of protein nanocages, in particular viral particles. Knowledge of morphology as well as mechanical properties is essential for understanding viral life cycles, including genome packaging, capsid maturation, and uncoating, but also contributes to the development of diagnostics, vaccines, imaging modalities, and targeted therapeutic devices based on viruslike particles.

Viral Hepatitis in Hawai‘i - Differing Perspectives

PubMed Central

Bannan, Michael; Bauman, Kay; Collis, Tarquin; Hall, Alba; Haning, William; Hannemann, Shoshana; Hare, C Bradley; Humphry, Joseph; Jao, Robert; Leevy, Carroll; Lusk, Heather; Ochoa, Edward; Palafox, Neal; Withers, Nancy; Akinaka, Kenneth

2010-01-01

This publication contains information from a conference titled “Individual Perspectives on the Silent Epidemic of Viral Hepatitis in Hawai‘i” held in October of 2007 with updates and additional contributions from annual conferences in 2008 and 2009. These conferences were sponsored by the Hepatitis Support Network of Hawai‘i and held in Honolulu, Hawai‘i at the Queen's Conference Center. The primary objectives of the conferences have been to heighten awareness of viral hepatitis in Hawai‘i and to bring together health care professionals to learn about these infections and to help them respond to the challenges they bring to the people of Hawai‘i. The initial conference was oriented to present the unique and individual perspectives of patients, physicians, and other healthcare providers specific to the complex issues of hepatitis in an effort to help them understand their role in the context of others and to develop a team approach in responding to this epidemic. PMID:20533191

Viral Infection-Homograft Interactions in a Murine Model

PubMed Central

Hamilton, John D.; Fitzwilliam, James F.; Cheung, K. S.; Shelburne, John; Lang, David J.; Amos, D. B.

1978-01-01

The effects on some host defenses of murine cytomegalovirus (MCMV) and(or) EL4, a mouse ascites homograft, were studied in mice. Assays of cellular and humoral immunity in response to either or both of these perturbations were carried out by quantitation of various immune activities. Limited studies demonstrated no effect of EL4 inoculation on the host response to MCMV by organ viral titer, duration of viral persistence, or anti MCMV complement-fixing antibody titer. Prior infection with MCMV, however, resulted in greatly reduced numbers of splenocytes, the source in this study of immune effector cells. Residual splenocytes demonstrated less response to both phyto-hemagglutinin and lipopolysaccharide, particularly in the 2-3-wk interval after infection. Similarly, responder cells in mixed lymphocyte cultures were less reactive when derived from infected animals. Lymphocyte-mediated cytolysis of EL4 was significantly less in mice infected on the day of and 7, 14, and 21 days before the tumor homograft with a return to control levels by 28 days. 90% of the cell-mediated cytolysis could be eliminated by treatment with anti-theta serum. Serum-mediated cytolysis of EL4 was also reduced in infected animals. No suppressor cells or serum inhibitory factors could be identified in infected animals. Although alternative explanations exist, this study suggests that in infected animals there is a significant reduction in both the number and function of bone marrow-derived and thymus-derived cells directed against the alloantigens in EL4. PMID:219027

Passive immunization of Pacific herring against viral hemorrhagic septicemia.

USGS Publications Warehouse

Hershberger, P.K.; Gregg, J.L.; Grady, C.A.; LaPatra, S.E.; Winton, J.R.

2011-01-01

The plasma of Pacific herring Clupea pallasii that survived laboratory-induced viral hemorrhagic septicemia (VHS) epizootics contained humoral substances that, when injected into naive animals, conferred passive immunity against the disease. Among groups exposed to viral hemorrhagic septicemia virus (VHSV), injection of donor plasma from VHS survivors resulted in significantly greater survival (50%) and significantly lower tissue titers (1.5 x 10(5) plaque-forming units [PFU]/g) than the injection of plasma from VHSV-naive donors (6% survival; 3.7 x 10(6) PFU/g). Additionally, the magnitude of the protective immune response increased during the postexposure period; plasma that was collected from survivors at 123 d postexposure (931 degree-days) provided greater protection than plasma collected from survivors at 60 d postexposure (409 degree-days). These results provide proof of concept that the VHSV exposure history of Pacific herring populations can be determined post hoc; furthermore, the results can be used as the foundation for developing additional high-throughput diagnostic techniques that may be effective at quantifying herd immunity and forecasting the potential for future VHS epizootics in populations of wild Pacific herring.

Congenital Cytomegalovirus Infection: Molecular Mechanisms Mediating Viral Pathogenesis

PubMed Central

Schleiss, Mark R.

2013-01-01

Human cytomegalovirus (CMV) is responsible for approximately 40,000 congenital infections in the United States each year. Congenital CMV disease frequently produces serious neurodevelopmental disability, as well as vision impairment and sensorineural hearing loss. Development of a CMV vaccine is therefore considered to be a major public health priority. The mechanisms by which CMV injures the fetus are complex and likely include a combination of direct fetal injury induced by pathologic virally-encoded gene products, an inability of the maternal immune response to control infection, and the direct impact of infection on placental function. CMV encodes gene products that function, both at the RNA and the protein level, to interfere with many cellular processes. These include gene products that modify the cell cycle; interfere with apoptosis; induce an inflammatory response; mediate vascular injury; induce site-specific breakage of chromosomes; promote oncogenesis; dysregulate cellular proliferation; and facilitate evasion of host immune responses. This minireview summarizes current concepts regarding these aspects of the molecular virology of CMV and the potential pathogenic impact of viral gene expression on the developing fetus. Areas for potential development of novel therapeutic intervention are suggested for improving the outcome of this disabling congenital infection. PMID:21827434

Regulatory T Cells in Autoimmune and Viral Chronic Hepatitis

PubMed Central

Lapierre, Pascal; Lamarre, Alain

2015-01-01

In both autoimmune liver disease and chronic viral hepatitis, the injury results from an immune-mediated cytotoxic T cell response to liver cells. As such, it is not surprising that CD4+ regulatory T cells, a key regulatory population of T cells able to curb immune responses, could be involved in both autoimmune hepatitis and chronic viral hepatitis. The liver can induce the conversion of naïve CD4+ T cells to CD4+ regulatory T cells and induce tolerance to locally expressed antigens. This tolerance mechanism is carefully regulated in physiological conditions but any imbalance could be pathological. An overly tolerant immune response can lead to chronic infections while an overreactive and unbridled immune response can lead to autoimmune hepatitis. With the recent advent of monoclonal antibodies able to target regulatory T cells (daclizumab) and improve immune responses and several ongoing clinical trials analysing the impact of regulatory T cell infusion on autoimmune liver disease or liver transplant tolerance, modulation of immunological tolerance through CD4+ regulatory T cells could be a key element of future immunotherapies for several liver diseases allowing restoring the balance between proper immune responses and tolerance.   PMID:26106627