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Viruses with large genomes encode numerous proteins that do not directly participate in virus biogenesis but rather modify key functional systems of infected cells. We report that a distinct group of giantvirusesinfecting unicellular eukaryotes that includes Organic Lake Phycodnaviruses and Phaeocystis globosa virus encode predicted proteorhodopsins that have not been previously detected in viruses. Search of metagenomic sequence data shows that putative viral proteorhodopsins are extremely abundant in marine environments. Phylogenetic analysis suggests that giantviruses acquired proteorhodopsins via horizontal gene transfer from proteorhodopsin-encoding protists although the actual donor(s) could not be presently identified. The pattern of conservation of the predicted functionally important amino acid residues suggests that viral proteorhodopsin homologs function as sensory rhodopsins. We hypothesize that viral rhodopsins modulate light-dependent signaling, in particular phototaxis, in infected protists. PMID:23036091
Viruses with large genomes encode numerous proteins that do not directly participate in virus biogenesis but rather modify key functional systems of infected cells. We report that a distinct group of giantvirusesinfecting unicellular eukaryotes that includes Organic Lake Phycodnaviruses and Phaeocystis globosa virus encode predicted proteorhodopsins that have not been previously detected in viruses. Search of metagenomic sequence data shows that putative viral proteorhodopsins are extremely abundant in marine environments. Phylogenetic analysis suggests that giantviruses acquired proteorhodopsins via horizontal gene transfer from proteorhodopsin-encoding protists although the actual donor(s) could not be presently identified. The pattern of conservation of the predicted functionally important amino acid residues suggests that viral proteorhodopsin homologs function as sensory rhodopsins. We hypothesize that viral rhodopsins modulate light-dependent signaling, in particular phototaxis, in infected protists. This article was reviewed by Igor B. Zhulin and Laksminarayan M. Iyer. For the full reviews, see the Reviewers reports section.
"Giant Condylomas" of the cervix are very uncommon, and have not been fully characterized in the English literature. We report 4 cases of cervical giant condyloma seen in our practice. Patients were predominantly young and presented with a cervical lesion producing bleeding or a mass effect. Biopsy/excision revealed a uniformly bland, exophytic squamous epithelial proliferation with viral cytopathic changes and absence of stromal invasion. Human papilloma virus types 6 and 11 were detected in all cases. Follow-up was uneventful without recurrence or spread. Giant condylomas of the cervix as defined in this report signify a benign albeit extensive variant of low-risk human papilloma virusinfection. This term is proposed as a specific descriptor for such lesions and should be considered in the setting of any large well-differentiated exophytic cervical squamous lesion in young or immunosuppressed women. The term "giant condyloma of Buschke and Loewenstein" should be discontinued given the lack of specificity. PMID:23282973
Parra-Herran, Carlos; Herfs, Michael; Doria, Manuel; Crum, Christopher P; Nucci, Marisa R
Giantviruses contain large genomes, encode many proteins atypical for viruses, replicate in large viral factories, and tend to infect protists. The giantvirus replication factories can in turn be infected by so called virophages, which are smaller viruses that negatively impact giantvirus replication. An example is Mimiviruses that infect the protist Acanthamoeba and that are themselves infected by the virophage Sputnik. This study examines the evolutionary dynamics of this system, using mathematical models. While the models suggest that the virophage population will evolve to increasing degrees of giantvirus inhibition, it further suggests that this renders the virophage population prone to extinction due to dynamic instabilities over wide parameter ranges. Implications and conditions required to avoid extinction are discussed. Another interesting result is that virophage presence can fundamentally alter the evolutionary course of the giantvirus. While the giantvirus is predicted to evolve toward increasing its basic reproductive ratio in the absence of the virophage, the opposite is true in its presence. Therefore, virophages can not only benefit the host population directly by inhibiting the giantviruses but also indirectly by causing giantviruses to evolve toward weaker phenotypes. Experimental tests for this model are suggested.
In 1998, an outbreak of acute encephalitis with high mortality rates among pig handlers in Malaysia led to the discovery of a novel paramyxovirus named Nipah virus. A multidisciplinary investigation that included epidemiology, microbiology, molecular biology, and pathology was pivotal in the discovery of this new human infection. Clinical and autopsy findings were derived from a series of 32 fatal human cases of Nipah virusinfection. Diagnosis was established in all cases by a combination of immunohistochemistry (IHC) and serology. Routine histological stains, IHC, and electron microscopy were used to examine autopsy tissues. The main histopathological findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system. Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels. Characteristic viral inclusions were seen by light and electron microscopy. IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels. Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons. Infection of endothelial cells and neurons as well as vasculitis and thrombosis seem to be critical to the pathogenesis of this new human disease.
Background A recent work has provided strong arguments in favor of a fourth domain of Life composed of nucleo-cytoplasmic large DNA viruses (NCLDVs). This hypothesis was supported by phylogenetic and phyletic analyses based on a common set of proteins conserved in Eukarya, Archaea, Bacteria, and viruses, and implicated in the functions of information storage and processing. Recently, the genome of a new NCLDV, Cafeteria roenbergensis virus (CroV), was released. The present work aimed to determine if CroV supports the fourth domain of Life hypothesis. Methods A consensus phylogenetic tree of NCLDVs including CroV was generated from a concatenated alignment of four universal proteins of NCLDVs. Some features of the gene complement of CroV and its distribution along the genome were further analyzed. Phylogenetic and phyletic analyses were performed using the previously identified common set of informational genes present in Eukarya, Archaea, Bacteria, and NCLDVs, including CroV. Findings Phylogenetic reconstructions indicated that CroV is clearly related to the Mimiviridae family. The comparison between the gene repertoires of CroV and Mimivirus showed similarities regarding the gene contents and genome organization. In addition, the phyletic clustering based on the comparison of informational gene repertoire between Eukarya, Archaea, Bacteria, and NCLDVs unambiguously classified CroV with other NCLDVs and clearly included it in a fourth domain of Life. Taken together, these data suggest that Mimiviridae, including CroV, may have inherited a common gene content probably acquired from a common Mimiviridae ancestor. Conclusions This further analysis of the gene repertoire of CroV consolidated the fourth domain of Life hypothesis and contributed to outline a functional pan-genome for giantvirusesinfecting phagocytic protistan grazers.
Serum samples from 92 giant pandas in three captive facilities were tested for antibodies against five viruses of carnivores. Antibody titers against canine distemper virus (CDV) in two facilities in which giant pandas were vaccinated were variable. The canine adenovirus (CAV-1) and canine parvovirus (CPV) titers in vaccinated group were both positive, but titers were not high and varied among individual except one vaccinated panda had extremely high CAV-1 titer, indicating infection with the field virus following vaccination. Our results suggest that the vaccines used for these giant pandas do not elicit consistent antibody titers. Antibody titers against CDV, CPV and CAV-1 in unvaccinated giant pandas were highly variable, especially CPV titer. Almost half of sera were CPV antibody positive, and CPV titers were high enough to suggest infection with the virus. Canine coronavirus (CCV) and canine parainfluenza virus (CPIV) titers were not detected in all serum samples. The results of this study emphasize the need for research on infectious diseases of giant pandas and development of suitable vaccines for the species. PMID:19913371
Molluscum contagiosum virus is an important human skin pathogen: it can cause disfigurement and suffering in children, in adults it is less common and often sexually transmitted. Extensive and persistent skin infection with the virus can indicate underlying immunodeficiency. Traditional ablative therapies have not been compared directly with newer immune-modulating and specific antiviral therapies. Advances in research raise the prospect of new approaches to treatment informed by the biology of the virus; in human skin, the infection is localised in the epidermal layers, where it induces a typical, complex hyperproliferative lesion with an abundance of virus particles but a conspicuous absence of immune effectors. Functional studies of the viral genome have revealed effects on cellular pathways involved in the cell cycle, innate immunity, inflammation, and cell death. Extensive lesions caused by molluscum contagiosum can occur in patients with DOCK8 deficiency-a genetic disorder affecting migration of dendritic and specialised T cells in skin. Sudden disappearance of lesions is the consequence of a vigorous immune response in healthy people. Further study of the unique features of infection with molluscum contagiosum virus could give fundamental insight into the nature of skin immunity. PMID:23972567
In the last twenty years, numerous giant, dsDNA, icosahedral viruses have been discovered and assigned to the nucleocytoplasmic large dsDNA virus (NCLDV) clade. The major capsid proteins of these viruses consist of two consecutive jelly-roll domains, assembled into trimers, with pseudo 6-fold symmetry. The capsomers are assembled into arrays that have either p6 (as in Paramecium bursaria Chlorella virus-1) or p3 symmetry (as in Mimivirus). Most of the NCLDV viruses have a membrane that separates the nucleocapsid from the external capsid.
Isoflavones and their related flavonoid compounds exert antiviral properties in vitro and in vivo against a wide range of viruses. Genistein is, by far, the most studied soy isoflavone in this regard, and it has been shown to inhibit the infectivity of enveloped or nonenveloped viruses, as well as single-stranded or double-stranded RNA or DNA viruses. At concentrations ranging from
Aline Andres; Sharon M. Donovan; Mark S. Kuhlenschmidt
Amoebae are unicellular phagocytes that feed on microorganisms in their environment. Some amoebae have the largest genome size currently known on earth. They phagocytose any inert particle larger than 0.5 ?m. Phagocytic amoebae can harbor different bacteria, fungi and giantviruses within the same cell. There is evidence of lateral gene transfer between the amoeba and its microbiological hosts. There
Dengue virusinfection causes dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), whose pathogeneses are not clearly understood. Current hypotheses of antibody-dependent enhancement, virus virulence, and IFN-?\\/TNF?-mediated immunopathogenesis are insufficient to explain clinical manifestations of DHF\\/DSS such as thrombocytopenia and hemoconcentration. Dengue virusinfection induces transient immune aberrant activation of CD4\\/CD8 ratio inversion and cytokine overproduction,
Neonatal herpes simplex virusinfections are uncommon, but because of the morbidity and mortality associated with the infection they are often considered in the differential diagnosis of ill neonates. The use of polymerase chain reaction for diagnosis of central nervous system infections and the development of safe and effective antiviral therapy has revolutionized the diagnosis and management of these infants. Initiation of long-term antiviral suppressive therapy in these infants has led to significant improvement in morbidity. This article summarizes the epidemiology of neonatal herpes simplex virusinfections and discusses clinical presentation, diagnosis, management, and follow up of infants with neonatal herpes disease. PMID:23481105
The current paradigm on the nature of viruses is based on early work of the phage group (the pro-phage concept) and molecular biologists working on tumour viruses (the proto-oncogene concept). It posits that viruses evolved from either prokaryotic or eukaryotic cellular genes that became infectious via their association with capsid genes. In this view, after their emergence viruses continued to
Giant double-stranded DNA viruses (such as record breaking Acanthamoeba polyphaga Mimivirus), with particle sizes of 0.2 to 0.6 microm, genomes of 300 kbp to 1.200 kbp, and commensurate complex gene contents, constitute an evolutionary mystery. They challenge the common vision of viruses, traditionally seen as highly streamlined genomes optimally fitted to the smallest possible--filterable--package. Such giantviruses are now discovered in increasing numbers through the systematic sampling of ocean waters as well as freshwater aquatic environments, where they play a significant role in controlling phyto- and bacterio- plankton populations. The 4th Algal Virus Workshop showed that the study of these ecologically important viruses is now massively entering the genomic era, promising a better understanding of their diversity and, hopefully, some insights on their origin and the evolutionary forces that shaped their genomes. PMID:15967028
Many studies have shown that hepatitis B virusinfection may also occur in hepatitis B surface antigen-negative patients. This occult infection has been identified both in patients with cryptogenic liver disease and in patients with hepatitis C virus-related chronic hepatitis, and much evidence suggests that it may be a risk factor of hepatocellular carcinoma development. However several aspects of this occult infection remain unclear such as its prevalence and the factor(s) involved in the lack of circulating hepatitis B surface antigen. Moreover, it is uncertain whether the occult hepatitis B virusinfection may contribute to chronic liver damage, considering that it is usually associated with a suppressed viral replication. Evidence and hypotheses concerning this fascinating field of bio-medical research are reviewed. PMID:11215565
Raimondo, G; Balsano, C; Craxì, A; Farinati, F; Levrero, M; Mondelli, M; Pollicino, T; Squadrito, G; Tiribelli, C
Genital warts are believed to be caused by human papilloma viruses and to be sexually transmitted. The viruses are classified by DNA types, which appear to cause different types of disease. The choice of treatment, and usually its success rate, vary according to the type of disease and its location.
... or visit us online at: www.OTISpregnancy.org . West Nile VirusInfection and Pregnancy This sheet talks about ... advice from your health care provider. What is West Nile Virus (WNV)? WNV is a virus that can ...
Respiratory syncytial virusinfection is the leading cause of lower respiratory tract infections in young children. Palivizumab, a respiratory syncytial virus-specific monoclonal antibody, reduces the hospitalization rate of high-risk children but it is very costly. This statement replaces three previous position statements from the Canadian Paediatric Society about this topic, and was updated primarily to discuss recent changes in the American Academy of Pediatrics guidelines in the Canadian context. It reviews the published literature and provides recommendations regarding palivizumab use in high-risk children.
Objective: Metagenomic studies have revealed that Acanthamoeba polyphaga Mimivirus relatives are common in the environment; however, only three Acanthamoeba-growing giantviruses have been isolated from hundreds of environmental samples. We attempted herein to isolate new Acanthamoeba-growing giantviruses from environmental samples. Methods: We inoculated 105 environmental samples by our usual procedure but with the addition of selected antibiotics to inhibit
Bernard La Scola; Angélique Campocasso; Rolande NDong; Ghislain Fournous; Lina Barrassi; Christophe Flaudrops; Didier Raoult
The simian immunodeficiency viruses (SIVs) are a diverse group of viruses that naturally infect a wide range of African primates, including African green monkeys (AGMs) and sooty mangabey monkeys (SMs). Although natural infection is widespread in feral populations of AGMs and SMs, this infection generally does not result in immunodeficiency. However, experimental inoculation of Asian macaques results in an immunodeficiency syndrome remarkably similar to human AIDS. Thus, natural nonprogressive SIV infections appear to represent an evolutionary adaptation between these animals and their primate lentiviruses. Curiously, these animals maintain robust virus replication but have evolved strategies to avoid disease progression. Adaptations observed in these primates include phenotypic changes to CD4+ T cells, limited chronic immune activation, and altered mucosal immunity. It is probable that these animals have achieved a unique balance between T-cell renewal and proliferation and loss through activation-induced apoptosis, and virus-induced cell death. A clearer understanding of the mechanisms underlying the lack of disease progression in natural hosts for SIV infection should therefore yield insights into the pathogenesis of AIDS and may inform vaccine design.
A preliminary survey of parasitic and infectious hypodermal and haematopoietic necrosis virus (IHHNV) infections in giant freshwater prawn from the Damak Sea of Rejang River, Kuching, Sarawak was conducted. Symptoms of black spots/patches on the rostrum, carapace, pleopods or telson were observed in most of the 107 samples collected. Parasitic examination revealed sessiline peritrichs such as (Zoothamnium sp.), nematode larvae, gregarine stage and cocoon of leech with prevalences of 1.2%, 1.2%, 5% and 17% respectively. Under histopathological examination, changes like accumulation of hemocytes around hepatopancreatic tubules due to vibriosis, basophilic intranuclear inclusions in the epithelium and E-cell of hepatopancreatic tubules as a result of HPV were seen through the section. No positive infection of IHHNV was detected in 78 samples. As such, the wild giant freshwater prawns in Damak Sea of Rejang River in Kuching are IHHNV-free though infections of parvo-like virus and bacteria were seen in histopathology. PMID:21602773
Kua, Beng Chu; Choong, F C; Hazreen Nita, M K; Muhd Faizul H, A H; Bhassu, S; Imelda, R R; Mohammed, M
Dengue haemorrhagic fever (DHF) is a complicated disease associated with viral and immune pathogenesis. There is still no effective vaccine to prevent the progression of DHF because of its undefined pathogenic mechanisms. The generation of autoimmunity in dengue virus (DEN) infection has been implicated in dengue pathogenesis. Based on our previous studies showing antibodies (Abs) against DEN nonstructural protein 1
Reported incidence of dengue has increased worldwide in recent decades, but little is known about its incidence in Africa. During 19602010, a total of 22 countries in Africa reported sporadic cases or outbreaks of dengue; 12 other countries in Africa reported dengue only in travelers. The presence of disease and high prevalence of antibody to dengue virus in limited serologic surveys suggest endemic dengue virusinfection in all or many parts of Africa. Dengue is likely underrecognized and underreported in Africa because of low awareness by health care providers, other prevalent febrile illnesses, and lack of diagnostic testing and systematic surveillance. Other hypotheses to explain low reported numbers of cases include cross-protection from other endemic flavivirus infections, genetic host factors protecting against infection or disease, and low vector competence and transmission efficiency. Population-based studies of febrile illness are needed to determine the epidemiology and true incidence of dengue in Africa.
Kuritsky, Joel N.; Letson, G. William; Margolis, Harold S.
Reported incidence of dengue has increased worldwide in recent decades, but little is known about its incidence in Africa. During 1960-2010, a total of 22 countries in Africa reported sporadic cases or outbreaks of dengue; 12 other countries in Africa reported dengue only in travelers. The presence of disease and high prevalence of antibody to dengue virus in limited serologic surveys suggest endemic dengue virusinfection in all or many parts of Africa. Dengue is likely underrecognized and underreported in Africa because of low awareness by health care providers, other prevalent febrile illnesses, and lack of diagnostic testing and systematic surveillance. Other hypotheses to explain low reported numbers of cases include cross-protection from other endemic flavivirus infections, genetic host factors protecting against infection or disease, and low vector competence and transmission efficiency. Population-based studies of febrile illness are needed to determine the epidemiology and true incidence of dengue in Africa. PMID:21801609
Amarasinghe, Ananda; Kuritsk, Joel N; Letson, G William; Margolis, Harold S
Background The family Mimiviridae belongs to the large monophyletic group of Nucleo-Cytoplasmic Large DNA Viruses (NCLDV; proposed order Megavirales) and encompasses giantvirusesinfecting amoeba and probably other unicellular eukaryotes. The recent discovery of the Cafeteria roenbergensis virus (CroV), a distant relative of the prototype mimiviruses, led to a substantial expansion of the genetic variance within the family Mimiviridae. In the light of these findings, a reassessment of the relationships between the mimiviruses and other NCLDV and reconstruction of the evolution of giantvirus genomes emerge as interesting and timely goals. Results Database searches for the protein sequences encoded in the genomes of several viruses originally classified as members of the family Phycodnaviridae, in particular Organic Lake phycodnaviruses and Phaeocystis globosa viruses (OLPG), revealed a greater number of highly similar homologs in members of the Mimiviridae than in phycodnaviruses. We constructed a collection of 898 Clusters of Orthologous Genes for the putative expanded family Mimiviridae (MimiCOGs) and used these clusters for a comprehensive phylogenetic analysis of the genes that are conserved in most of the NCLDV. The topologies of the phylogenetic trees for these conserved viral genes strongly support the monophyly of the OLPG and the mimiviruses. The same tree topology was obtained by analysis of the phyletic patterns of conserved viral genes. We further employed the mimiCOGs to obtain a maximum likelihood reconstruction of the history of genes losses and gains among the giantviruses. The results reveal massive gene gain in the mimivirus branch and modest gene gain in the OLPG branch. Conclusions These phylogenomic results reported here suggest a substantial expansion of the family Mimiviridae. The proposed expanded family encompasses a greater diversity of viruses including a group of viruses with much smaller genomes than those of the original members of the Mimiviridae. If the OLPG group is included in an expanded family Mimiviridae, it becomes the only family of giantviruses currently shown to host virophages. The mimiCOGs are expected to become a key resource for phylogenomics of giantviruses.
Summary Several strains of rubella virus were able to establish a persistent or carrier-type infection in adult hamsters and suckling rabbits. No evidence of rubella virus persistence for prolonged periods was detected in suckling and adult ferrets or in adult rabbits, although serological studies suggested that these animals had been infected with rubella virus.
Summary The hepatitis B virus (HBV) infection is the most prevalent chronic infectious disease in the world. Perinatal acquisition is the major cause of infection in infants and children. Without vaccine during infancy, 90 % of infants born to women positive for the virus will go on to become lifelong carriers. There are significant sequelae associated with HBV infection, ranging
In order to explain the speed of Vesicular Stomatitis Virus (VSV) infections, we develop a simple model that improves previous approaches to the propagation of virusinfections. For VSV infections, we find that the delay time elapsed between the adsorption of a viral particle into a cell and the release of its progeny has a very important effect. Moreover, this
In a survey of virus cross-infection in paediatric wards there were 15 cross-infections due to respiratory syncytial (R.S.) virus and 16 due to influenza A, both during a four-month period, and 19 due to parainfluenza viruses over two years. The illnesses produced by these infections acquired in hospital ranged from a slight cold to severe pneumonia: in 17 of the
P. S. Gardner; S. D. M. Court; J. T. Brocklebank; M. A. P. S. Downham; D. Weightman
Virusinfections usually begin in peripheral tissues and can invade the mammalian nervous system (NS), spreading into the peripheral (PNS) and more rarely the central (CNS) nervous systems. The CNS is protected from most virusinfections by effective immune responses and multilayer barriers. However, some viruses enter the NS with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. Most viruses in the NS are opportunistic or accidental pathogens, but a few, most notably the alpha herpesviruses and rabies virus, have evolved to enter the NS efficiently and exploit neuronal cell biology. Remarkably, the alpha herpesviruses can establish quiescent infections in the PNS, with rare but often fatal CNS pathology. Here we review how viruses gain access to and spread in the well-protected CNS, with particular emphasis on alpha herpesviruses, which establish and maintain persistent NS infections. PMID:23601101
More than 500 million people worldwide are persistently infected with the hepatitis B virus (HBV) and\\/or hepatitis C virus (HCV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite many common features in the pathogenesis of HBV- and HCV-related liver disease, these viruses markedly differ in their virological properties and in their immune escape and
A 33-year-old male patient was admitted to our nephrology department with rapidly deteriorating general health, fever, respiratory difficulties, and acute renal failure. Computed tomography of the thorax revealed interstitial edema with thickening of the interlobular septa, peribronchial cuffing, ground-glass opacities, and small pleural and pericardial effusions. Polymerase chain reaction tests verified Puumala virusinfection. The patient recovered with supportive treatment. Hantavirus infection should be considered in the differential diagnosis of young patients who present with acute renal failure of an unknown origin and the nonspecific radiologic finding of noncardiogenic interstitial edema, which in combination with typical clinical symptoms and laboratory parameters, can be indicative of this disease. PMID:20736852
Fakhrai, Negar; Mueller-Mang, Christina; El-Rabadi, Karem; Böhmig, Georg A; Herold, Christian J
In reviewing the clinical features, diagnostic evaluations and therapies of the most common ocular viral infections we attempt to whet your appetite for attacking the numerous challenges in diagnosis and treatment of viral eye disease. The herpes viruses, HSV, VZV and CMV are the cause of significant ocular morbidity. HSV most commonly affects the cornea producing keratitis that can be recurrent and may lead to corneal clouding and neovascularisation. Manifestations can be purely infectious or immunological and treatment options must be tailored to the underlying pathophysiology. Herpes zoster ophthalmicus, caused by VZV infection of the first branch of the trigeminal nerve, produces a characteristic rash and can progress to keratitis and uveitis. HSV and VZV can cause retinitis in both immunocompetent and immunocompromised individuals. There has been a significant increase in the incidence of CMV retinitis since the beginning of the AIDS epidemic. We review the numerous new treatments, diagnostic tests and treatment strategies which have been developed in response to this potentially blinding retinal infection. Adenovirus produces an epidemic conjunctivitis and epidemic keratoconjunctivitis which are severe and extremely contagious conjunctival infections. HIV, molluscum contagiosum, EBV and rubeola also cause ocular diseases which are described.Copyright 1998 John Wiley & Sons, Ltd. PMID:10398508
Currently, the mechanisms involved in the pathogenesis of DHF\\/DSS remain poorly understood and there is no effective vaccine available to prevent infection with DEN virus. The lack of a reliable small animal model that mimics dengue disease is a major obstacle. In this paper, the development of small animal models such as mice for dengue virusinfections is reviewed.
We report eight recent cases of Chikungunya virusinfection in travellers to Australia. Patients presented with fevers, rigors, headaches, arthralgia, and rash. The current Indian Ocean epidemic and Italian outbreak have featured prominently on Internet infectious disease bulletins, and Chikungunya virusinfection had been anticipated in travellers from the outbreak areas. Diagnosis was by a generic alphavirus reverse transcriptase polymerase chain reaction with confirmatory sequencing. Prompt diagnosis of Chikungunya virusinfections is of public health significance as the mosquito vectors for transmission exist in Australia. There is potential for this infection to spread in the largely naïve Australian population. PMID:18205563
Johnson, Douglas F; Druce, Julian D; Chapman, Scott; Swaminathan, Ashwin; Wolf, Josh; Richards, Jack S; Korman, Tony; Birch, Chris; Richards, Michael J
Syncytia or multinucleated giant-cell formation is one of the major cytopathic effects induced by human immunodeficiency virus (HIV) infection. Cell fusion results from the strong interaction of CD4 molecules on the surface of the uninfected T cells and gp120, an external envelope glycoprotein of HIV on the infected T cells. We studied the production of HIV in fusion cells between
Preventing and treating influenza virusinfection remain a challenge because of incomplete understanding of the hostpathogen interactions, limited therapeutics and lack of a universal vaccine. So far, methods for monitoring the course of infection with influenza virus in real time in living animals are lacking. Here we report the visualization of influenza viral infection in living mice using an engineered replication-competent influenza A virus carrying luciferase reporter gene. After intranasal inoculation, bioluminescence can be detected in the chest and nasopharyngeal passage of living mice. The intensity of bioluminescence in the chest correlates with the dosage of infection and the viral load in the lung. Bioluminescence in the chest of infected mice diminishes on antiviral treatment. This work provides a novel approach that enables real-time study of influenza virusinfection and effects of antiviral therapeutics in living animals.
During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. Identification of aggregates has become a useful diagnostic tool for certain viral infections. There is wide variety of viral aggregates, which differ by their location, size, content and putative function. The role of aggregation in the context of a specific virus is often poorly understood, especially in the case of plant viruses. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intra- and intercellular transportation. Aggregated structures may protect viral functional complexes from the cellular degradation machinery. Alternatively, the activation of host defense mechanisms may involve sequestration of virus components in aggregates, followed by their neutralization as toxic for the host cell. The diversity of virus-induced aggregates in mammalian and plant cells is the subject of this review.
During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. Identification of aggregates has become a useful diagnostic tool for certain viral infections. There is wide variety of viral aggregates, which differ by their location, size, content and putative function. The role of aggregation in the context of a specific virus is often poorly understood, especially in the case of plant viruses. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intra- and intercellular transportation. Aggregated structures may protect viral functional complexes from the cellular degradation machinery. Alternatively, the activation of host defense mechanisms may involve sequestration of virus components in aggregates, followed by their neutralization as toxic for the host cell. The diversity of virus-induced aggregates in mammalian and plant cells is the subject of this review. PMID:23202461
In order to explain the speed of Vesicular Stomatitis Virus (VSV) infections, we develop a simple model that improves previous approaches to the propagation of virusinfections. For VSV infections, we find that the delay time elapsed between the adsorption of a viral particle into a cell and the release of its progeny has a very important effect. Moreover, this delay time makes the adsorption rate essentially irrelevant in order to predict VSV infection speeds. Numerical simulations are in agreement with the analytical results. Our model satisfactorily explains the experimentally measured speeds of VSV infections.
The diagnosis of respiratory virusinfections has evolved substantially in recent years, with the emergence of new pathogens and the development of novel detection methods. While recent advances have improved the sensitivity and turn-around time of diagnostic tests for respiratory viruses, they have also raised important issues such as cost, and the clinical significance of detecting multiple viruses in a single specimen by molecular methods. This article reviews recent advances in specimen collection and detection methods for diagnosis of respiratory virusinfections, and discusses the performance characteristics and limitations of these methods.
Dengue virus causes ?50100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virusinfection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virusinfected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.
Perera, Rushika; Moore, Ronald J.; Weitz, Karl W.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.
Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.
Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.
Studies have been carried out to determine the role of local immunity in influenza virusinfection, and to investigate various parameters related to local immunization. The particle size in aerosol immunization was found to be important. Children respond ...
Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV-specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to 1-3 dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV-specific immunity, the role of apoptosis in VZV-induced cell death, and the development of an animal model provided by simian varicella virusinfection of monkeys.
Gilden, D.; Mahalingam, R.; Nagel, M. A.; Pugazhenthi, S.; Cohrs, R. J.
This unit describes protocols for infecting the mouse respiratory tract, and assaying virus replication and host response in the lung. Respiratory infections are the leading cause of acute illness worldwide, affecting mostly infants and children in developing countries. The purpose of this unit is to provide the readers with a basic strategy and protocols to study the pathogenesis and immunology of respiratory virusinfection using the mouse as an animal model. The procedures include: (i) basic techniques for mouse infection, tissue sampling and preservation, (ii) determination of viral titers, isolation and analysis of lymphocytes and dendritic cells using flow-cytometry, and (iii) lung histology, immunohistochemistry and in situ hybridization.
Flano, Emilio; Jewell, Nancy A.; Durbin, Russell K.; Durbin, Joan E.
It is now estimated that approximately 10 % of worldwide cancers are attributable to viral infection, with the vast majority (>85 %) occurring in the developing world. Oncogenic viruses include various classes of DNA and RNA viruses and induce cancer by a variety of mechanisms. A unifying theme is that cancer develops in a minority of infected individuals and only after chronic infection of many years duration. The viruses associated with the greatest number of cancer cases are the human papillomaviruses (HPVs), which cause cervical cancer and several other epithelial malignancies, and the hepatitis viruses HBV and HCV, which are responsible for the majority of hepatocellular cancer. Other oncoviruses include Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). Identification of the infectious cause has led to several interventions that may reduce the risk of developing these tumors. These include preventive vaccines against HBV and HPV, HPV-based testing for cervical cancer screening, anti-virals for the treatment of chronic HBV and HCV infection, and screening the blood supply for the presence of HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may lead to further insight into etiology and pathogenesis as well as to new approaches for therapeutic and prophylactic intervention. PMID:24008290
Several factors, such as age and nutritional status can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virusinfections in rodent models. Influenza virus primarily infects ...
Summary Viruses are obligate intracellular symbionts. Plant viruses are often discovered and studied as pathogenic parasites that cause diseases in agricultural plants. However, here it is shown that viruses can extend survival of their hosts under conditions of abiotic stress that could benefit hosts if they subsequently recover and reproduce. Various plant species were inoculated with four different
Ping Xu; Fang Chen; Jonathan P. Mannas; Tracy Feldman; Lloyd W. Sumner; Marilyn J. Roossinck
Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs), leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation.
The International Agency for Research on Cancer (IARC) has comprehensively assessed the human carcinogenicity of biological agents. Seven viruses including Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1), and human papillomavirus (HPV) have been classified as Group 1 human carcinogens by IARC. The conclusions are based on the findings of epidemiological and mechanistic studies. EBV, HPV, HTLV-1, and KSHV are direct carcinogens; HBV and HCV are indirect carcinogens through chronic inflammation; HIV-1 is an indirect carcinogen through immune suppression. Some viruses may cause more than one cancer, while some cancers may be caused by more than one virus. However, only a proportion of persons infected by these oncogenic viruses will develop specific cancers. A series of studies have been carried out to assess the viral, host, and environmental cofactors of EBV-associated nasopharyngeal carcinoma, HBV/HCV-associated hepatocellular carcinoma, and HPV-associated cervical carcinoma. Persistent infection and high viral load are important risk predictors of these virus-caused cancers. Risk calculators incorporating host and viral factors have also been developed for the prediction of long-term risk of hepatocellular carcinoma. These risk calculators are useful for the triage and clinical management of infected patients. Both clinical trials and national programs of immunization or antiviral therapy have demonstrated a significant reduction in the incidence of cancers caused by HBV, HCV, and HPV. Future researches on gene-gene and gene-environment interaction of oncogenic viruses and human host are in urgent need. PMID:24008291
The absence of a robust cell culture model of hepatitis C virus (HCV) infection has severely limited analysis of the HCV life cycle and the development of effective antivirals and vaccines. Here we report the establishment of a simple yet robust HCV cell culture infection system based on the HCV JFH-1 molecular clone and Huh-7-derived cell lines that allows the
Jin Zhong; Pablo Gastaminza; Guofeng Cheng; Sharookh Kapadia; Takanobu Kato; Dennis R. Burton; Stefan F. Wieland; Susan L. Uprichard; Takaji Wakita; Francis V. Chisari
Influenza is a paradigm for understanding viral infections. As an opportunistic pathogen exploiting the cellular endocytic machinery for infection, influenza is also a valuable model system for exploring the cell's constitutive endocytic pathway. We have studied the transport, acidification, and fusion of single influenza viruses in living cells by using real-time fluorescence microscopy and have dissected individual stages of the
Melike Lakadamyali; Michael J. Rust; Hazen P. Babcock; Xiaowei Zhuang
West Nile virus (WNV) is a re-emerging pathogen responsible for fatal outbreaks of meningoencephalitis in humans. Recent research using a mouse model of infection has indicated that specific chemokines and chemokine receptors help mediate the host response to WNV acting by at least three mechanisms: control of early neutrophil recruitment to the infection site (Cxcr2), control of monocytosis in blood
It was proved that the protoplasts prepared from mesophyll of Nicotiana tabacum are infected by tobacco mosaic virus. The infection occurred when purified tobacco mosaic virus particles were added to a protoplast suspension in the presence of poly-L-ornithine. The virus multiplied in these protoplasts to a level of 106 virus particles per infected protoplast during 24 hours of incubation. The
Dengue virusinfection causes dengue fever, dengue haemorrhagic fever and dengue shock syndrome. No animal model is available that mimics these clinical manifestations. In this study, the establishment is reported of a murine model for dengue virusinfection that resembles the thrombocytopenia manifestation. Dengue-2 virus (dengue virus type 2) can infect murine cells either in vitro (primary cell culture) or
Kao-Jean Huang; Shu-Yi J. Li; Shiour-Ching Chen; Hsiao-Sheng Liu; Yee-Shin Lin; Trai-Ming Yeh; Ching-Chuan Liu; Huan-Yao Lei
Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virusinfectivity by inhibiting hemagglutination (HA) activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB)-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter) than for the pseudorabies virus (approximately 180 nm) and the vaccinia virus (roughly 335 × 200 × 200 nm). These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses.
Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries.
. The Nipah virus outbreak represented one of several bat-derived paramyxoviruses that has emerged during the last decade to\\u000a cause severe human and animal disease. The pathogenesis of Nipah infection is associated with its ability to infect blood\\u000a vessels and extravascular parenchyma in many organs, particularly in the central nervous system. The clinical manifestations\\u000a of acute Nipah infection range from
Background: Pestiviruses are the veterinary viruses with genome homology to human hepatitis C virus (HCV). This group includes classical swine fever virus (CSFV), border disease virus of sheep (BDV) and bovine virus diarrhoea virus (BVDV). There are some similarities in the pathology of all three virusinfections; in utero transmission to the foetus can cause early embryonic losses, severe congenital
Virusinfection can severely inhibit plant growth and distort development. This article reviews changes in plant growth regulator metabolism caused by infection. In general, virusinfection decreases auxin and gibberellin concentrations and increases abscisic acid concentration. Ethylene production is stimulated in necrotic or chlorotic reactions to infection, but not where the virus spreads systemically without necrosis. While these broad trends
We evaluated 49 swine industry workers and 79 nonexposed controls for antibodies to swine influenza viruses. Multivariate modeling showed that workers who seldom used gloves (odds ratio [OR] 30.3) or who smoked (OR 18.7) most frequently had evidence of previous H1N1 swine virus. These findings may be valuable in planning for pandemic influenza. PMID:16707061
Ramirez, Alejandro; Capuano, Ana W; Wellman, Debbie A; Lesher, Kelly A; Setterquist, Sharon F; Gray, Gregory C
Hepatitis C virus (HCV) infection is the leading cause of cirrhosis and liver transplantation in the United States. It is difficult to assess the prevalence of HCV infection; the asymptomatic nature of acute infection and early chronic infection leaves many infected individuals undiagnosed. Exposure to infected blood is the primary means for HCV transmission, with intravenous drug use the most common source. Genotype 1 HCV infection accounts for approximately 75% of cases. Because of the asymptomatic and slow course of HCV infection, many physicians and healthcare advocates support routine testing at the primary care level, especially in patients 40 to 65 years of age. Approximately 80% of individuals infected with HCV fail to clear the virus, although this varies considerably based on sex, age at infection, immune status, route of infection, race, alcohol use, and presence of steatosis. Long-term outcomes of chronic HCV infection are cirrhosis, end-stage liver disease, and hepatocellular carcinoma. The current standard of care for patients with chronic HCV infection is combination therapy with subcutaneous injections of peginterferon plus oral ribavirin for 48 weeks. A sustained virologic response (SVR) is also considered a virologic "cure." There is a trend toward response-guided therapy, in which treatment duration is shortened or lengthened based on viral genotype, patient characteristics, and viral kinetics. The efficacy and tolerability of peginterferon therapy, however, is limited. Approximately 45% of patients infected with HCV genotype 1 achieve an SVR, whereas 65% of those infected with gentoype 2 or 3 do so. Moreover, retreatment or switching to other interferons provides little benefit. Several new therapies for HCV infection are in development. Protease inhibitors are expected to become the new standard of care for nonresponders, with the potential to become a first-line treatment for chronic HCV infection. PMID:21767067
Acanthamoeba polyphaga mimivirus, Marseillevirus, and Sputnik, a virophage, are intra-amoebal viruses that have been isolated from water collected in cooling towers. They have provided fascinating data and have raised exciting questions about viruses definition and evolution. Mimivirus and Marseillevirus have been classified in the nucleo-cytoplasmic large DNA viruses (NCLDVs) class. Their genomes are the largest and fifth largest viral genomes
The interplay between autophagy and intracellular pathogens is intricate as autophagy is an essential cellular response to fight against infections, whereas numerous microbes have developed strategies to escape this process or even exploit it to their own benefit. The fine tuned timing and/or selective molecular pathways involved in the induction of autophagy upon infections could be the cornerstone allowing cells to either control intracellular pathogens, or be invaded by them. We report here that measles virusinfection induces successive autophagy signallings in permissive cells, via distinct and uncoupled molecular pathways. Immediately upon infection, attenuated measles virus induces a first transient wave of autophagy, via a pathway involving its cellular receptor CD46 and the scaffold protein GOPC. Soon after infection, a new autophagy signalling is initiated which requires viral replication and the expression of the non-structural measles virus protein C. Strikingly, this second autophagy signalling can be sustained overtime within infected cells, independently of the expression of C, but via a third autophagy input resulting from cell-cell fusion and the formation of syncytia. Whereas this sustained autophagy signalling leads to the autophagy degradation of cellular contents, viral proteins escape from degradation. Furthermore, this autophagy flux is ultimately exploited by measles virus to limit the death of infected cells and to improve viral particle formation. Whereas CD150 dependent virulent strains of measles virus are unable to induce the early CD46/GOPC dependent autophagy wave, they induce and exploit the late and sustained autophagy. Overall, our work describes distinct molecular pathways for an induction of self-beneficial sustained autophagy by measles virus. PMID:24086130
The interplay between autophagy and intracellular pathogens is intricate as autophagy is an essential cellular response to fight against infections, whereas numerous microbes have developed strategies to escape this process or even exploit it to their own benefit. The fine tuned timing and/or selective molecular pathways involved in the induction of autophagy upon infections could be the cornerstone allowing cells to either control intracellular pathogens, or be invaded by them. We report here that measles virusinfection induces successive autophagy signallings in permissive cells, via distinct and uncoupled molecular pathways. Immediately upon infection, attenuated measles virus induces a first transient wave of autophagy, via a pathway involving its cellular receptor CD46 and the scaffold protein GOPC. Soon after infection, a new autophagy signalling is initiated which requires viral replication and the expression of the non-structural measles virus protein C. Strikingly, this second autophagy signalling can be sustained overtime within infected cells, independently of the expression of C, but via a third autophagy input resulting from cell-cell fusion and the formation of syncytia. Whereas this sustained autophagy signalling leads to the autophagy degradation of cellular contents, viral proteins escape from degradation. Furthermore, this autophagy flux is ultimately exploited by measles virus to limit the death of infected cells and to improve viral particle formation. Whereas CD150 dependent virulent strains of measles virus are unable to induce the early CD46/GOPC dependent autophagy wave, they induce and exploit the late and sustained autophagy. Overall, our work describes distinct molecular pathways for an induction of self-beneficial sustained autophagy by measles virus.
The 331-kbp chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) genome was resequenced and annotated to correct errors in the original 15-year-old sequence; 40 codons was considered the minimum protein size of an open reading frame. PBCV-1 has 416 predicted protein-encoding sequences and 11 tRNAs. A proteome analysis was also conducted on highly purified PBCV-1 virions using two mass spectrometry-based protocols. The mass spectrometry-derived data were compared to PBCV-1 and its host Chlorella variabilis NC64A predicted proteomes. Combined, these analyses revealed 148 unique virus-encoded proteins associated with the virion (about 35% of the coding capacity of the virus) and 1 host protein. Some of these proteins appear to be structural/architectural, whereas others have enzymatic, chromatin modification, and signal transduction functions. Most (106) of the proteins have no known function or homologs in the existing gene databases except as orthologs with proteins of other chloroviruses, phycodnaviruses, and nuclear-cytoplasmic large DNA viruses. The genes encoding these proteins are dispersed throughout the virus genome, and most are transcribed late or early-late in the infection cycle, which is consistent with virion morphogenesis.
Cerny, Ronald L.; Bauman, Andrew T.; Roach, Jared C.; Lane, Leslie C.; Agarkova, Irina V.; Wulser, Kurt; Yanai-Balser, Giane M.; Gurnon, James R.; Vitek, Jason C.; Kronschnabel, Bernard J.; Jeanniard, Adrien; Blanc, Guillaume; Upton, Chris; Duncan, Garry A.; McClung, O. William; Ma, Fangrui
The 331-kbp chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) genome was resequenced and annotated to correct errors in the original 15-year-old sequence; 40 codons was considered the minimum protein size of an open reading frame. PBCV-1 has 416 predicted protein-encoding sequences and 11 tRNAs. A proteome analysis was also conducted on highly purified PBCV-1 virions using two mass spectrometry-based protocols. The mass spectrometry-derived data were compared to PBCV-1 and its host Chlorella variabilis NC64A predicted proteomes. Combined, these analyses revealed 148 unique virus-encoded proteins associated with the virion (about 35% of the coding capacity of the virus) and 1 host protein. Some of these proteins appear to be structural/architectural, whereas others have enzymatic, chromatin modification, and signal transduction functions. Most (106) of the proteins have no known function or homologs in the existing gene databases except as orthologs with proteins of other chloroviruses, phycodnaviruses, and nuclear-cytoplasmic large DNA viruses. The genes encoding these proteins are dispersed throughout the virus genome, and most are transcribed late or early-late in the infection cycle, which is consistent with virion morphogenesis. PMID:22696644
Dunigan, David D; Cerny, Ronald L; Bauman, Andrew T; Roach, Jared C; Lane, Leslie C; Agarkova, Irina V; Wulser, Kurt; Yanai-Balser, Giane M; Gurnon, James R; Vitek, Jason C; Kronschnabel, Bernard J; Jeanniard, Adrien; Blanc, Guillaume; Upton, Chris; Duncan, Garry A; McClung, O William; Ma, Fangrui; Van Etten, James L
Respiratory syncytial virus (RSV) is a common winter time respiratory virus that affects persons of all ages and is the major cause of serious lower respiratory tract infections in young children. However, RSV is also an important pathogen in adults, particularly in the elderly, patients with chronic lung disease, or those with impaired immunity. Clinical features of RSV infections overlap with other respiratory viruses, so laboratory tests are required to establish the diagnosis. Reverse transcriptase polymerase chain reaction (RT-PCR) of samples from nasal swabs, sputum, or bronchoalveolar lavage is a sensitive test to substantiate the diagnosis. Serologies are useful in epidemiological surveys. The clinical course of RSV infections is variable. In infants, RSV presents as bronchiolitis. In adults, mild to moderate upper respiratory tract illness is characteristic. However, severe pneumonia can occur, particularly in the elderly with comorbidities or compromised immune status. Humoral antibodies confer partial immunity to RSV infection and disease severity; cellular immunity is important to eradicate RSV in established infections. Treatment of RSV infections is often supportive. Aerosolized ribavirin is approved for RSV infections in infants; its role in adults is controversial. Infection control measures are critical to limit spread of RSV. Currently, RSV vaccines are not available, but candidate vaccines are being developed. PMID:17458771
The precise etiology of type 1 diabetes (T1D) is still unknown, but viruses have long been suggested as a potential environmental trigger for the disease. However, despite decades of research, the body of evidence supporting a relationship between viral infections and initiation or acceleration of islet autoimmunity remains largely circumstantial. The most robust association with viruses and T1D involves enterovirus species, of which some strains have the ability to induce or accelerate disease in animal models. Several hypotheses have been formulated to mechanistically explain how viruses may affect islet autoimmunity and ?-cell decay. The recent observation that certain viral infections, when encountered at the right time and infectious dose, can prevent autoimmune diabetes illustrates that potential relationships may be more complex than previously thought. Here, we provide a concise summary of data obtained in mouse models and humans, and identify future avenues toward a better characterization of the association between viruses and T1D.
Coppieters, Ken T.; Boettler, Tobias; von Herrath, Matthias
The precise etiology of type 1 diabetes (T1D) is still unknown, but viruses have long been suggested as a potential environmental trigger for the disease. However, despite decades of research, the body of evidence supporting a relationship between viral infections and initiation or acceleration of islet autoimmunity remains largely circumstantial. The most robust association with viruses and T1D involves enterovirus species, of which some strains have the ability to induce or accelerate disease in animal models. Several hypotheses have been formulated to mechanistically explain how viruses may affect islet autoimmunity and ?-cell decay. The recent observation that certain viral infections, when encountered at the right time and infectious dose, can prevent autoimmune diabetes illustrates that potential relationships may be more complex than previously thought. Here, we provide a concise summary of data obtained in mouse models and humans, and identify future avenues toward a better characterization of the association between viruses and T1D. PMID:22315719
Coppieters, Ken T; Boettler, Tobias; von Herrath, Matthias
Measles is a highly contagious disease, which was responsible for high infant mortality before the advent of an effective\\u000a vaccine in 1963. In immuno-competent individuals, measles virus (MV) infection triggers an effective immune response that\\u000a starts with innate responses and then leads to successful adaptive immunity, including cell-mediated immunity and humoral\\u000a immunity. The virus is cleared and lifelong protection is
Congenital varicella syndrome, maternal varicella zoster virus pneumonia and neonatal varicella infection are associated with serious feto-maternal morbidity and not infrequently with mortality. Vaccination against Varicella zoster virus can prevent the disease and outbreak control limits the exposure of pregnant women to the infectious agent. Maternal varicella zoster immune globulin (VZIG) administration before rash development, with or without antivirals medications can modify progression of the disease.
Lamont, Ronald F.; Sobel, Jack D; Carrington, D; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Vaisbuch, Edi; Romero, Roberto
Nipah virus has recently emerged as a zoonotic agent that is highly pathogenic in humans. Outbreaks have occurred regularly over the last two decades in South and Southeast Asia, where mortality rates reach as high as 100 %. The natural reservoir of Nipah virus has been identified as bats from the Pteropus family, where infection is largely asymptomatic. Human disease is characterized by both respiratory and encephalitic components, and thus far, no effective vaccine or intervention strategies are available. Little is know about how the immune response of either the reservoir host or incidental hosts responds to infection, and how this immune response is either inadequate or might contribute to disease in the dead-end host. Experimental vaccines strategies have given us some insight into the immunological requirements for protection. This review summarizes our current understanding of the immune response to Nipah virusinfection and emphasizes the need for further research. PMID:22669317
Prescott, Joseph; de Wit, Emmie; Feldmann, Heinz; Munster, Vincent J
The incidence of respiratory virusinfection after hematopoietic cell transplantation (HCT) has probably been underestimated with conventional testing methods in symptomatic patients. This prospective study assessed viral infection episodes by testing weekly respiratory samples collected from HCT recipients, with and without symptoms reported by questionnaire, for 100 days after HCT. Samples were tested by culture and direct fluorescent antibody testing for respiratory syncytial virus (RSV), parainfluenza virus (PIV), and influenza A and B, and by quantitative reverse transcriptionpolymerase chain reaction for RSV, PIV, influenza A and B, and metapneumovirus (MPV). Of 122 patients, 30 (25%) had 32 infection episodes caused by RSV (5), PIV (17), MPV (6), influenza (3), RSV, or influenza (1). PIV, with a cumulative incidence estimate of 17.9%, was the only virus for which asymptomatic infection was detected. Lower virus copy number in patients with no or one symptom compared with 2 or more symptoms was found for all viruses in all patients (P < .001), with PIV infection having a similar virus-specific comparison (P = .004). Subclinical infection with PIV may help explain why infection-control programs that emphasize symptoms are effective against RSV and influenza but often not against PIV.
Peck, Angela J.; Englund, Janet A.; Kuypers, Jane; Guthrie, Katherine A.; Corey, Lawrence; Morrow, Rhoda; Hackman, Robert C.; Cent, Anne
Diseases of man caused by the virus of herpes simplex fall into two broad categories. The primary disease occurs only once in any individual's life and is caused by transmission of virus from an already infected human. Thereafter, the individual may be subject to recurrent herpetic disease, the manifestations of which are different from the primary disease. Recurrent disease varies in severity from trivial, to incapacitating and frankly lethal (as in diseases resulting from the virus's neurotropic and oncogenic properties). The source of the virus in recurrent herpetic disease has never been conclusively resolved, but is almost certainly endogenous to the patient. Theories, case reports and experiments exist to show that endogenous virus may, in periods of clinical quiescence, be latent (or persistent) at the site of the recurrent lesions itself, or more remotely in nerve tissues related to the site of recurrence. Images Fig. 1
Background Canine distemper virus (CDV) infects a variety of carnivores, including wild and domestic Canidae. In this study, we sequenced and phylogenetic analyses of the hemagglutinin (H) genes from eight canine distemper virus (CDV) isolates obtained from seven raccoon dogs (Nyctereutes procyonoides) and a giant panda (Ailuropoda melanoleuca) in China. Results Phylogenetic analysis of the partial hemagglutinin gene sequences showed close clustering for geographic lineages, clearly distinct from vaccine strains and other wild-type foreign CDV strains, all the CDV strains were characterized as Asia-1 genotype and were highly similar to each other (91.5-99.8% nt and 94.4-99.8% aa). The giant panda and raccoon dogs all were 549Y on the HA protein in this study, irrespective of the host species. Conclusions These findings enhance our knowledge of the genetic characteristics of Chinese CDV isolates, and may facilitate the development of effective strategies for monitoring and controlling CDV for wild canids and non-cainds in China.
Lassa fever is a hemorrhagic fever endemic to West Africa and caused by Lassa virus, an Old World arenavirus. It may be fatal, but most patients recover from acute disease and some experience asymptomatic infection. The immune mechanisms associated with these different outcomes have not yet been fully elucidated, but considerable progress has recently been made, through the use of in vitro human models and nonhuman primates, the only relevant animal model that mimics the pathophysiology and immune responses induced in patients. We discuss here the roles of the various components of the innate and adaptive immune systems in Lassa virusinfection and in the control of viral replication and pathogenesis.
The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virusinfection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic. Images
Previous reports on the spread of bovine virus diarrhoea virus (BVDV) from animals primarily infected with the agent are contradictory. In this study, the possibility of transmission of BVDV from calves simultaneously subjected to acute BVDV and bovine coronavirus (BCV) infection was investigated. Ten calves were inoculated intranasally with BVDV Type 1. Each of the 10 calves was then randomly
Infection of mice with pneumonia virus of mice (PVM) is used as a natural host experimental model for studying the pathogenesis of infection with the closely related human respiratory syncytial virus. We analyzed the contribution of T cells to virus control and pathology after PVM infection. Control of a sublethal infection with PVM strain 15 in C57BL\\/6 mice was accompanied
Stefanie Frey; Christine D. Krempl; Annette Schmitt-Graff; Stephan Ehl
Vaccinia virus (VACV) was used as a surrogate of Variola virus (genus Orthopoxvirus), the causative agent of smallpox, to study orthopoxvirus infection via the respiratory airway. Lung surfactant, a physiological barrier to infection encountered by the virus, is predominantly composed of phospholipids whose role during orthopoxvirus infection has not been investigated. An attenuated Lister strain, derived from the traditional smallpox
Julien Perino; David Crouzier; Danièle Spehner; Jean-Claude Debouzy; Daniel Garin; Jean-Marc Crance; Anne-Laure Favier
This article models the immune system and the virus dynamics of acute influenza infection mathematically. We use the model to study the virus dynamics of some well-known and severe and mild types of viruses. Linkages to well-known models in the literature are illustrated. Simulations are compared with experimental results in vivo by comparing with results from infected ferrets where infection
Infection with herpes simplex is one of the most common sexually transmitted infections. Because the infection is common in women of reproductive age it can be contracted and transmitted to the fetus during pregnancy and the newborn. Herpes simplex virus is an important cause of neonatal infection, which can lead to death or long-term disabilities. Rarely in the uterus, it occurs frequently during the transmission delivery. The greatest risk of transmission to the fetus and the newborn occurs in case of an initial maternal infection contracted in the second half of pregnancy. The risk of transmission of maternal-fetal-neonatal herpes simplex can be decreased by performing a treatment with antiviral drugs or resorting to a caesarean section in some specific cases. The purpose of this paper is to provide recommendations on management of herpes simplex infections in pregnancy and strategies to prevent transmission from mother to fetus.
Straface, Gianluca; Selmin, Alessia; Zanardo, Vincenzo; De Santis, Marco; Ercoli, Alfredo; Scambia, Giovanni
Infection with herpes simplex is one of the most common sexually transmitted infections. Because the infection is common in women of reproductive age it can be contracted and transmitted to the fetus during pregnancy and the newborn. Herpes simplex virus is an important cause of neonatal infection, which can lead to death or long-term disabilities. Rarely in the uterus, it occurs frequently during the transmission delivery. The greatest risk of transmission to the fetus and the newborn occurs in case of an initial maternal infection contracted in the second half of pregnancy. The risk of transmission of maternal-fetal-neonatal herpes simplex can be decreased by performing a treatment with antiviral drugs or resorting to a caesarean section in some specific cases. The purpose of this paper is to provide recommendations on management of herpes simplex infections in pregnancy and strategies to prevent transmission from mother to fetus. PMID:22566740
Straface, Gianluca; Selmin, Alessia; Zanardo, Vincenzo; De Santis, Marco; Ercoli, Alfredo; Scambia, Giovanni
In industrialized countries, hepatitis C virus (HCV) is the most common cause of chronic liver disease in children. Perinatal transmission is the leading cause of infection. Perinatal transmission is confined almost always to women with detectable HCV ribonucleic acid (RNA) in the peripheral blood by the polymerase chain reaction but all children born to women with anti-HCV antibodies should be tested for HCV. Some but not all studies found that a high concentration of serum HCV RNA is associated with a higher risk of transmission. Maternal peripheral blood mononuclear cell infection by HCV, membrane rupture of longer than 6 hr before delivery, and procedures exposing the infant to maternal blood infected with HCV during vaginal delivery are associated with an increased risk of transmission. Maternal coinfection with HCV and human immunodeficiency virus, maternal history of intravenous drug use and of HCV infection of the sexual partner of the mother predict the risk of perinatal transmission and are dependent on the peripheral blood mononuclear cell infection by HCV. Delivery by Cesarean section is not recommended in pregnant women infected with HCV. Infected mothers can breast feed safely their infants if the nipples are not damaged. A previous delivery of a child infected perinatally with HCV does not increase the risk of transmission in subsequent pregnancies. Immunogenetic factors and HCV genotypes are not related to HCV perinatal transmission. Despite an increased understanding of the risk factors involved in perinatal transmission of HCV, to date little is known about the transmission mechanisms and timing. PMID:19319981
Infection with human immunodeficiency virus (HIV) is associated with marked disturbance of metabolism affecting the metabolism of carbohydrates, fats and proteins. In the first decade of clinical experience of HIV, the primary clinical manifestation of such disturbed metabolism was wasting. Such wasting was often severe and contributed significantly to the morbidity and mortality of AIDS. Mechanistic studies demonstrated that in
Respiratory syncytial virus (RSV) is a significant cause of respiratory disease leading to hospitalization in young infants. Preterm infants are especially susceptible and are likely to develop severe disease. Relevant preterm animal models of RSV infection are lacking. The purpose of this study was...
Mouse mammary tumor virus (MMTV) has long been speculated to be involved in human breast cancer and more recently in human primary biliary cirrhosis. Despite complete proviral sequences markedly homologous to MMTV being identified in human breast cancer tissue, no convincing evidence has been presented to date that MMTV can infect human cells. Using both wild-type and a genetically marked
Stanislav Indik; Walter H. Gunzburg; Brian Salmons; Francoise Rouault
An unexpected and large outbreak of Puumala virusinfection in Sweden resulted in 313 nephropathia epidemica patients/100,000 persons in Västerbotten County during 2007. An increase in the rodent population, milder weather, and less snow cover probably contributed to the outbreak. PMID:18439368
Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virusinfection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virusinfection. PMID:22232645
Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa; Kim, Okjin
Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virusinfection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virusinfection.
Immunodominance is a fundamental property of CD8(+) T cell responses to viruses and vaccines. It had been observed that route of administration alters immunodominance after vaccinia virus (VACV) infection, but only a few epitopes were examined and no mechanism was provided. We re-visited this issue, examining a panel of 15 VACV epitopes and four routes, namely intradermal (i.d.), subcutaneous (s.c.), intraperitoneal (i.p.) and intravenous (i.v.) injection. We found that immunodominance is sharpened following peripheral routes of infection (i.d. and s.c.) compared with those that allow systemic virus dissemination (i.p. and i.v.). This increased immunodominance was demonstrated with native epitopes of VACV and with herpes simplex virus glycoprotein B when expressed from VACV. Responses to some subdominant epitopes were altered by as much as fourfold. Tracking of virus, examination of priming sites, and experiments restricting virus spread showed that priming of CD8(+) T cells in the spleen was necessary, but not sufficient to broaden responses. Further, we directly demonstrated that immunodomination occurs more readily when priming is mainly in lymph nodes. Finally, we were able to reduce immunodominance after i.d., but not i.p. infection, using a VACV expressing the costimulators CD80 (B7-1) and CD86 (B7-2), which is notable because VACV-based vaccines incorporating these molecules are in clinical trials. Taken together, our data indicate that resources for CD8(+) T cell priming are limiting in local draining lymph nodes, leading to greater immunodomination. Further, we provide evidence that costimulation can be a limiting factor that contributes to immunodomination. These results shed light on a possible mechanism of immunodomination and highlight the need to consider multiple epitopes across the spectrum of immunogenicities in studies aimed at understanding CD8(+) T cell immunity to viruses. PMID:23633956
Lin, Leon C W; Flesch, Inge E A; Tscharke, David C
A study of influenza virusinfection in the hamster has yielded the following results: 1. Two influenza A strains (Ga. 47 and PR8) multiplied readily in the hamster lung, although no lung lesions were produced during six serial passages. On further passage both viruses abruptly acquired the capacity to produce pulmonary consolidation and death of the animals. 2. Extracts of the lungs during the early passages contained complement-fixing antigen and infectious virus, as revealed by titration in mice and embryonated eggs. Agglutinins for chicken, human, and guinea pig red cells, however, were not demonstrable at this time. With further passage a close correlation was observed between the capacity of the virus to produce lung lesions in the hamster and to agglutinate mammalian types of red cells. In addition, quantitative changes in the virus population were demonstrated in the lung extracts by complement fixation tests and titrations in mice and eggs. 3. Incubation at 37°C. was effective in bringing out agglutinins in high titer for chicken red cells in lung extracts, which originally failed to agglutinate chicken cells but agglutinated mammalian red cells. This method did not increase the titers of mammalian cell agglutinins. 4. The body temperature of the hamster was found to decrease within 1 to 4 days after inoculation of influenza virus. In the early passages the temperature returned to normal within 24 hours, but with the development of the pathogenic strain of virus the temperature remained at subnormal levels until death. 5. The Lee strain of influenza B virus produced pulmonary lesions in the hamster on the first passage and no increase in pathogenicity of the virus occurred during eleven serial passages. Virus was demonstrable in extracts of the lungs by all the methods used and no difference was observed in its capacity to agglutinate fowl and mammalian types of red cells. The implications of these findings are considered briefly in the discussion.
Hepatitis C virus (HCV) infection remains a large-scale and significant health concern. The combination of subcutaneously administered pegylated interferon and oral ribavirin is the FDA-approved regimen for the treatment of chronic HCV infection. Combination therapy may result in a sustained virologic response leading to HCV eradication, with a reduction in risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma. However, the combination of PEG-IFN and ribavirin does not universally result in cure in all patients who undergo treatment. In this article, the authors discuss immunomodulatory therapies and clinical trials in the treatment of HCV infection. PMID:19628156
Occult hepatitis B virus (HBV) infection (OBI) is characterized by the persistence of HBV DNA in the liver tissue in individuals negative for the HBV surface antigen. The prevalence of OBI is quite variable depending on the level of endemic disease in different parts of the world, the different assays utilized in the studies, and the different populations studied. Many studies have been carried out on OBI prevalence in different areas of the world and categories of individuals. The studies show that OBI prevalence seems to be higher among subjects at high risk for HBV infection and with liver disease than among individuals at low risk of infection and without liver disease.
Gutierrez-Garcia, Maria Luisa; Fernandez-Rodriguez, Conrado M; Lledo-Navarro, Jose Luis; Buhigas-Garcia, Ingrid
The epidemic of West Nile virus (WNV) in the USA in 2002 represents the largest outbreak of meningoencephalitis in the Western Hemisphere ever reported. Besides natural transmission by mosquitoes, five new modes of WNV transmission to humans have been reported: blood transfusion, organ transplantation, transplacental transmission, breastfeeding and laboratory-acquired infection. The recognition of these new transmission routes has made the development of rapid and accurate serological diagnosis of WNV infection a public health priority. In this article, the current serologic assays for WNV diagnosis are reviewed, including immunoglobulin M antibody-capture ELISA, immunoglobulin G ELISA, indirect fluorescent antibody tests, hemagglutination inhibition tests and plaque reduction neutralization tests. The recently developed immunoassays that use purified recombinant envelope and nonstructural protein 5 of WNV as antigens are also reviewed. The nonstructural protein 5 protein-based assay can reliably discriminate between WNV and dengue or St. Louis encephalitis virus, as well as between natural WNV infection and flavivirus vaccination. PMID:14628901
West Nile virus (WNV) is a re-emerging pathogen responsible for fatal outbreaks of meningoencephalitis in humans. Recent research using a mouse model of infection has indicated that specific chemokines and chemokine receptors help mediate the host response to WNV acting by at least three mechanisms: control of early neutrophil recruitment to the infection site (Cxcr2), control of monocytosis in blood (Ccr2) and control of leukocyte movement from blood to brain (Cxcr4, Cxcr3, Cxcl10 and possibly Ccr5). CCR5 also appears to be important in human infection, since individuals genetically deficient in this receptor have increased risk of symptomatic disease once infected. These findings provide detailed insight into non-redundant chemokine roles in organ-specific leukocyte recruitment during infection, and emphasize the importance of the balance between pathogen control and immunopathology in determining overall clinical outcome. PMID:21376172
Free-living amoebae serve as hosts for a variety of amoebae-resisting microorganisms, including giantviruses and certain bacteria. The latter include symbiotic bacteria as well as bacteria exhibiting a pathogenic phenotype towards amoebae. Amoebae-resisting bacteria have been shown to be widespread in water and to use the amoebae as a reservoir, a replication niche, a protective armour as well as a training ground to select virulence traits allowing survival in the face of microbicidal effects of macrophages, the first line of defense against invading pathogens. More importantly, amoebae play a significant role as a melting pot for genetic exchanges. These ecological and evolutionary roles of amoebae might also be at play for giantviruses and knowledge derived from the study of amoebae-resisting bacteria is useful for the study and understanding of interactions between amoebae and giantviruses. This is especially important since some genes have spread in all domains of life and the exponential availability of eukaryotic genomes and metagenomic sequences will allow researchers to explore these genetic exchanges in a more comprehensive way, thus completely changing our perception of the evolutionary history of organisms. Thus, a large part of this review is dedicated to report current known gene exchanges between the different amoebae-resisting organisms and between amoebae and the internalized bacteria. PMID:20551677
Dengue virusinfections are an emerging global threat. Severe dengue infection is manifested as dengue hemorrhagic fever and dengue shock syndrome, both of which can be fatal complications. Factors predisposing to complicated disease and pathogenesis of severe infections are discussed. Using immunohistochemistry, immunofluorescence, flow cytometry, and ELISA techniques, we studied the cellular targets of dengue virusinfection, at both the
Mary Marovich; Geraldine Grouard-Vogel; Mark Louder; Michael Eller; Wellington Sun; Shuenn-Ju Wu; Ravithat Putvatana; Gerald Murphy; Boonrat Tassaneetrithep; Timothy Burgess; Deborah Birx; Curtis Hayes; Sarah Schlesinger-Frankel; John Mascola; M. Marovitch
A high prevalence and diversity of avian influenza (AI) viruses were detected in a population of wild mallards sampled during summer 2011 in California, providing an opportunity to compare results obtained before and after virus culture. We tested cloacal swab samples prior to culture by matrix real-time PCR, and by amplifying and sequencing a 640bp portion of the hemagglutinin (HA) gene. Each sample was also inoculated into embryonated chicken eggs, and full genome sequences were determined for cultured viruses. While low matrix Ct values were a good predictor of virus isolation from eggs, samples with high or undetectable Ct values also yielded isolates. Furthermore, a single passage in eggs altered the occurrence and detection of viral strains, and mixed infections (different HA subtypes) were detected less frequently after culture. There is no gold standard or perfect reference comparison for surveillance of unknown viruses, and true negatives are difficult to distinguish from false negatives. This study showed that sequencing samples prior to culture increases the detection of mixed infections and enhances the identification of viral strains and sequences that may have changed or even disappeared during culture.
Lindsay, LeAnn L.; Kelly, Terra R.; Plancarte, Magdalena; Schobel, Seth; Lin, Xudong; Dugan, Vivien G.; Wentworth, David E.; Boyce, Walter M.
Reference is made to results reported in literature as well as to some of the author's own findings for a summary account of specific immune responses to influenza virusinfections. Some introductory comments on the correlations that exist between morphology and function of structural components of the influenza virus as well as on the pathogenesis and its relevance to the immunological responses are followed by a description of the humoral immune response. An assured correlation has been found to exist between the titres of hemagglutination-inhibiting antibodies with responses specific of subtypes and of strains for the protection against homologous influenza virusinfection in terms of prevention of outbreak or mitigation of the pathological course. Anti-neuraminidase antibodies have influence upon virus expansion in the organism and in the given population as well as upon the severity of the disease. Particular importance has been attributed to the secretory immunoglobulins. Used in conjunction with interferone, they obviously had an infection-preventing function, wheras the primary role of serum anibodies was a reduction of severity. The studies into cell-mediated immune responses were much less intensive than those conducted into antibody formation. Cell-mediated immune response is thought to emanate from induction of hemagglutinin and is directed against the latter. Sufficient results have not become available as yet on the importance of cellular immune response to protection. PMID:81042
Infections with bovine virus diarrhoea virus (BVDV) are widespread throughout the world. Although the prevalence of infection varies among surveys, the infection tends to be endemic in many populations, reaching a maximum level of 12% of the cattle being persistently infected (PI) and 6085% of the cattle being antibody positive. Persistently infected cattle are the main source for transmission of
During an epidemic of respiratory syncytial (R.S.) virus in Newcastle upon Tyne 13 children developed R.S. virusinfections while in hospital with other conditions. R.S. virusinfection was also noted in four members of the staff. In two of the hospital wards outbreaks developed. All children infected with R.S. virus developed symptoms. The symptoms varied with age; two children aged
R. K. Ditchburn; Joyce McQuillin; P. S. Gardner; S. D. M. Court
Howard, C. J., Clarke, M. C. and Brownlie, J., 1989. Protection against respiratory infection with bovine virus diarrhoea virus by passively acquired antibody. Vet. Microbiol., 19: 195-203. Susceptibility to infection with bovine virus diarrhoea virus (BVDV) was compared for calves with varying amounts of specific antibody in their sera passively acquired from the ingestion of colostrum. Challenge consisted of intranasal
Inasmuch as orf, milker's nodules and bovine papular stomatitis pox are clinically identical in man and are induced by currently indistinguishable parapox viruses, we propose a new generic term 'farmyard pox' for these diseases. This affords the clinician a diagnosis based on a common set of clinical and electron microscopic findings rather than one based on an uncertain or even misleading history. A case in point is reported in which the history failed to reveal a specific animal source of the virus, but electron microscopy confirmed the presence of parapox infection. PMID:6305384
Some studies have suggested that hepatitis E virus is more frequent in human immunodeficiency virus (HIV) patients and can progress to chronic infection. We aimed to determine the prevalence of hepatitis E virus antibodies and RNA in a series of 100 HIV-infected patients in Tehran, Iran, with comparison to 52 healthy HIV, hepatitis B and C-negative blood donors as controls. HIV-infected patients were also tested for hepatitis E virus-RNA. Among the HIV-infected patients, 10% had antibodies to hepatitis E virus - a finding not significantly different from the uninfected controls (11.5%). No HIV-infected patients had hepatitis E virus IgM antibodies nor did any have detectable hepatitis E virus-RNA. We found no associations between anti-hepatitis E virus IgG-seropositivity and age, sex, route of HIV acquisition, aminotransferases levels, CD4, antiretroviral therapy, hepatitis B virus and hepatitis C virus co-infection. Hepatitis E virus is relatively prevalent in our HIV-infected patients, although without evidence of chronic infection and no more common than among HIV-negative controls or the general population. For the present, we do not recommend routine screening for hepatitis E virusinfection in HIV-infected patients in our moderately endemic region. PMID:23970597
Simian immunodeficiency virus (SIV) SIVsmm naturally infects sooty mangabeys (SMs) and is the source virus of pathogenic infections with human immunodeficiency virus type 2 (HIV-2) and SIVmac of humans and macaques, respectively. In previous studies we characterized SIVsmm diversity in naturally SIV-infected SMs and identified nine different phylogenetic subtypes whose genetic distances are similar to those reported for the different
Cristian Apetrei; Rajeev Gautam; Beth Sumpter; Anders C. Carter; Thaidra Gaufin; Silvija I. Staprans; J. Else; M. Barnes; R. Cao; S. Garg; J. M. Milush; D. L. Sodora; I. Pandrea; G. Silvestri
Superinfection exclusion is the ability of an established virusinfection to interfere with infection by a second virus. In this study, we found that Huh-7.5 cells acutely infected with hepatitis C virus (HCV) genotype 2a (chimeric strain J6\\/JFH) and cells harboring HCV genotype 1a, 1b, or 2a full-length or subgenomic replicons were resistant to infection with cell culture-produced HCV (HCVcc).
Donna M. Tscherne; Matthew J. Evans; Thomas von Hahn; Christopher T. Jones; Zania Stamataki; Jane A. McKeating; Brett D. Lindenbach; Charles M. Rice
We performed a retrospective review of 9 patients who underwent intracavity drainage under local anesthesia for emphysematous bulla and infected bulla between 1996 and 2010. Three patients with giant emphysematous bulla were treated intracavity drainage. Pneumothorax occurred and was treated by chest tube in all cases. Radiographic and symptomatic improvement occurred in all patients. After that, bullectomy was performed safely in 2 patients and intrabullar suction with fibrin glue was performed in 1. There were 6 cases with infected bulla that was not improved by the administration of antibiotics. After intracavity drainage, control of infection was achieved, and all but 1 patient were discharged without drain and complications. Intracavity drainage under local anesthesia is a safe and effective treatment for giant emphysematous bulla and infected bulla. PMID:21491728
Following the boom in respiratory virology in the 1960s, species of rhinoviruses, coronaviruses, enteroviruses, adenoviruses, parainfluenza viruses and respiratory syncytial virus were added to influenza and measles viruses as causes of respiratory tract infection. In restricted patient groups, such as the immunocompromised, members of the family of herpesviruses including herpes simplex, cytomegalovirus, varicella-zoster virus, Epstein-Barr virus and human herpes virus
A recent outbreak of West Nile virus has allowed for observations as to the clinical course of this emerging pathogen during pregnancy. We present three cases of West Nile virusinfection during pregnancy. Case 1 presented at term with focal subjective weakness and fever. With supportive care, her symptoms were resolved within 7 days, and she subsequently delivered an unaffected term infant. Case 2 presented in the first trimester with fever and headache. Her symptoms were resolved in 8 days with supportive care. Case 3 was diagnosed during the first trimester during workup of nonspecific respiratory symptoms, with resolution of all symptoms in 24 days. Obstetricians need to be aware of the varied clinical presentation of West Nile virus during pregnancy.
Stewart, Robert D.; Bryant, Stefanie N.; Sheffield, Jeanne S.
SUMMARY Bean leaves that had been doubly infected systemically with the legume strain of tobacco mosaic virus (CP-TMV) and bean golden mosaic virus (BGMV) were studied ultrastructurally. Virus particles and the cytopathological changes associated with each virus in single infections occurred within the same cell when plants were doubly infected, indicating that individual systemically infected host cells can multiply viruses
A rapid, in-process assessment of virus replication is disired to quickly investigate the effects of process parameters on virusinfection, and to monitor consistency of process in routine manufacturing of viral vaccines. Live virus potency assays are generally based on plaque formation, cytopathic effect, or antigen production (TCID50) and can take days to weeks to complete. Interestingly, when infected with
Rahul Singhvi; Julia F. Markusen; Bonnie Ky; Brian J. Horvath; John G. Aunins
Epstein-Barr virus (EBV), an ubiquitous human B lymphotropic virus, is the cause of infectious mononucleosis. Moreover, EBV infection can be followed by lymphoproliferative diseases in patients with inherited and acquired immunodeficiencies. Primary EBV infection may be a threat to all children after marrow or organ transplantation or those receiving chronic immunosuppressive treatment for various other reasons. The virus has been
Respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract infection in young children, with significant numbers of premature infants and those with other risk factors requiring hospitalization in Canada each year. Palivizumab, an RSV-specific monoclonal antibody, can reduce the hospitalization rate and severity of illness for a small group of high-risk or premature infants during their first RSV season. The present statement reviews the published literature and provides recommendations regarding its use in premature and other at-risk infants, for Canadian physicians.
When amoebae are simultaneously infected with Acanthamoeba polyphaga Mimivirus (APM) and the strictly intracellular BABL1 bacterium, the latter is always lost after serial subculturing. We showed that the virophage Sputnik 1, by reducing APM fitness, preserved BABL1 growth in acute and chronic models. This capability of a virophage to modulate the virulence of mimiviruses highlights the competition that occurs between them during natural host infection. PMID:23388714
Slimani, Meriem; Pagnier, Isabelle; Raoult, Didier; La Scola, Bernard
Systemic virusinfection of plants involves; intracellular<\\/span>replication, cell-to-cell movement within the inoculated leaf, and subsequently, long-distance spread to other plant parts via the vasculature (vascular movement).<\\/span>Cell-to-cell movement occurs through the plasmodesma (PD), which are regulated channels in the cell wall connecting adjacent cells. These PD are modified by plant viral movement proteins (MPs) to allow passage of a
Treatment of patients with chronic hepatitis B virus (HBV) infection who have advanced disease or comorbidities can be challenging, and recommendations may differ from standard guidelines. Among the special populations that merit specific consideration are patients with compensated or decompensated cirrhosis, organ transplantation, acute hepatitis B, pregnancy, coinfection with hepatitis C and/or D virus, chronic renal failure, and children. Major advances have been made in management of many of these special populations because of recent increasing availability of oral nucleosides, which are generally well tolerated and highly effective despite presence of other morbidities or viral infections. Also important have been changes in the management of hepatitis B during the peri-liver transplantation period that allows for prevention of reinfection in the majority of cases. However, much remains to be done to determine which patients should be treated and which should be monitored on no specific therapy. Outcomes of chronic HBV infection in persons with coinfection and in children have varied from different areas of the world, but it is not clear whether these differences are due to host and racial differences or to viral genotypic differences. Further studies are particularly needed in assessing the safety and efficacy of therapy in pregnant women, in children, and in patients with hepatitis D and C virus coinfection. PMID:19399810
Summary: West Nile Virus was introduced into the Western Hemisphere during the late summer of 1999 and has been causing significant and sometimes severe human diseases since that time. This article briefly touches upon the biology of the virus and provides a comprehensive review regarding recent discoveries about virus transmission, virus acquisition, and human infection and disease.
Colpitts, Tonya M.; Conway, Michael J.; Montgomery, Ruth R.
African horsesickness (AHS) is a devastating disease of horses. The disease is caused by the double-stranded RNA-containing African horsesickness virus (AHSV). Using electron cryomicroscopy and three-dimensional image reconstruction, we determined the architecture of an AHSV serotype 4 (AHSV-4) reference strain. The structure revealed triple-layered AHS virions enclosing the segmented genome and transcriptase complex. The innermost protein layer contains 120 copies of VP3, with the viral polymerase, capping enzyme, and helicase attached to the inner surface of the VP3 layer on the 5-fold axis, surrounded by double-stranded RNA. VP7 trimers form a second, T=13 layer on top of VP3. Comparative analyses of the structures of bluetongue virus and AHSV-4 confirmed that VP5 trimers form globular domains and VP2 trimers form triskelions, on the virion surface. We also identified an AHSV-7 strain with a truncated VP2 protein (AHSV-7 tVP2) which outgrows AHSV-4 in culture. Comparison of AHSV-7 tVP2 to bluetongue virus and AHSV-4 allowed mapping of two domains in AHSV-4 VP2, and one in bluetongue virus VP2, that are important in infection. We also revealed a protein plugging the 5-fold vertices in AHSV-4. These results shed light on virus-host interactions in an economically important orbivirus to help the informed design of new vaccines.
Manole, Violeta; Laurinmaki, Pasi; Van Wyngaardt, Wouter; Potgieter, Christiaan A.; Wright, Isabella M.; Venter, Gert J.; van Dijk, Alberdina A.; Sewell, B. Trevor
Herpes simplex virus (HSV) type 1\\/2 and Epstein-Barr virus (EBV) belong to the human herpes viruses and are among the most ubiquitous viruses in the adult population. In spite of the fact that a large proportion of women at childbearing age are seropositive to these viruses, especially to HSV, primary or secondary infections with these viruses may occur during pregnancy.Genital
The following state-of-the-art seminar was delivered as part of the Aspen Lung Conference on Pulmonary Hypertension and Vascular Diseases held in Aspen, Colorado in June 2012. This paper will summarize the lecture and present results from a nonhuman primate model of infection with Simian (Human) Immunodeficiency Virus - nef chimeric virions as well as the idea that polymorphisms in the HIV-1 nef gene may be driving the immune response that results in exuberant inflammation and aberrant endothelial cell (EC) function. We will present data gathered from primary HIV nef isolates where we tested the biological consequences of these polymorphisms and how their presence in human populations may predict patients at risk for developing this disease. In this article, we also discuss how a dysregulated immune system, in conjunction with a viral infection, could contribute to pulmonary arterial hypertension (PAH). Both autoimmune diseases and some viruses are associated with defects in the immune system, primarily in the function of regulatory T cells. These T-cell defects may be a common pathway in the formation of plexiform lesions. Regardless of the route by which viruses may lead to PAH, it is important to recognize their role in this rare disease.
We have studied the action of ascorbate (vitamin C) on human immunodeficiency virus type 1 (HIV-1), the etiological agent clinically associated with AIDS. We report the suppression of virus production and cell fusion in HIV-infected T-lymphocytic cell lines grown in the presence of nontoxic concentrations of ascorbate. In chronically infected cells expressing HIV at peak levels, ascorbate reduced the levels of extracellular reverse transcriptase (RT) activity (by greater than 99%) and of p24 antigen (by 90%) in the culture supernatant. Under similar conditions, no detectable inhibitory effects on cell viability, host metabolic activity, and protein synthesis were observed. In freshly infected CD4+ cells, ascorbate inhibited the formation of giant-cell syncytia (by approximately 93%). Exposure of cell-free virus to ascorbate at 37 degrees C for 1 day had no effect on its RT activity or syncytium-forming ability. Prolonged exposure of virus (37 degrees C for 4 days) in the presence of ascorbate (100-150 micrograms/ml) resulted in the drop by a factor of 3-14 in RT activity as compared to a reduction by a factor of 25-172 in extracellular RT released from chronically infected cells. These results indicate that ascorbate mediates an anti-HIV effect by diminishing viral protein production in infected cells and RT stability in extracellular virions. Images
Viruses are obligate intracellular parasites, relying to a major extent on the host cell for replication. An active replication of the viral genome results in a lytic infection characterized by the release of new progeny virus particles, often upon the lysis of the host cell. Another mode of virusinfection is the latent phase, where the virus is quiescent (a state in which the virus is not replicating). A combination of these stages, where virus replication involves stages of both silent and productive infection without rapidly killing or even producing excessive damage to the host cells, falls under the umbrella of a persistent infection. Reactivation is the process by which a latent virus switches to a lytic phase of replication. Reactivation may be provoked by a combination of external and/or internal cellular stimuli. Understanding this mechanism is essential in developing future therapeutic agents against viral infection and subsequent disease. This article examines the published literature and current knowledge regarding the viral and cellular proteins that may play a role in viral reactivation. The focus of the article is on those viruses known to cause latent infections, which include herpes simplex virus, varicella zoster virus, EpsteinBarr virus, human cytomegalovirus, human herpesvirus 6, human herpesvirus 7, Kaposis sarcoma-associated herpesvirus, JC virus, BK virus, parvovirus and adenovirus.
Traylen, Christopher M; Patel, Hersh R; Fondaw, Wylder; Mahatme, Sheran; Williams, John F; Walker, Lia R; Dyson, Ossie F; Arce, Sergio; Akula, Shaw M
Seroepidemiologic and virologic studies since 1889 suggested that human influenza pandemics were caused by H1, H2, and H3 subtypes of influenza A viruses. If not for the 1997 avian A/H5N1 outbreak in Hong Kong of China, subtype H2 is the likely candidate for the next pandemic. However, unlike previous poultry outbreaks of highly pathogenic avian influenza due to H5 that were controlled by depopulation with or without vaccination, the presently circulating A/H5N1 genotype Z virus has since been spreading from Southern China to other parts of the world. Migratory birds and, less likely, bird trafficking are believed to be globalizing the avian influenza A/H5N1 epidemic in poultry. More than 200 human cases of avian influenza virusinfection due to A/H5, A/H7, and A/H9 subtypes mainly as a result of poultry-to-human transmission have been reported with a > 50% case fatality rate for A/H5N1 infections. A mutant or reassortant virus capable of efficient human-to-human transmission could trigger another influenza pandemic. The recent isolation of this virus in extrapulmonary sites of human diseases suggests that the high fatality of this infection may be more than just the result of a cytokine storm triggered by the pulmonary disease. The emergence of resistance to adamantanes (amantadine and rimantadine) and recently oseltamivir while H5N1 vaccines are still at the developmental stage of phase I clinical trial are causes for grave concern. Moreover, the to-be pandemic strain may have little cross immunogenicity to the presently tested vaccine strain. The relative importance and usefulness of airborne, droplet, or contact precautions in infection control are still uncertain. Laboratory-acquired avian influenza H7N7 has been reported, and the laboratory strains of human influenza H2N2 could also be the cause of another pandemic. The control of this impending disaster requires more research in addition to national and international preparedness at various levels. The epidemiology, virology, clinical features, laboratory diagnosis, management, and hospital infection control measures are reviewed from a clinical perspective. PMID:16424427
Abstract Influenza infection is a respiratory disease of viral origin that can cause major epidemics in man. The influenza virusinfects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembl...
The problem of human immunodeficiency virus (HIV) infection and that of the acquired immunodeficiency syndrome (AIDS) are becoming increasingly important in clinical transplantation. The epidemiologic characteristics of this infection are important factors in determining the impact of this infection on transplant patients: in particular, the presence of a transmissible virus in the blood, tissues, and body fluids of even asymptomatic
Diatoms are a major phytoplankton group that play important roles in maintaining oxygen levels in the atmosphere and sustaining the primary nutritional production of the aquatic environment. Among diatoms, the genus Chaetoceros is one of the most abundant and widespread. Temperature, climate, salinity, nutrients, and predators were regarded as important factors controlling the abundance and population dynamics of diatoms. Here we show that a viral infection can occur in the genus Chaetoceros and should therefore be considered as a potential mortality source. Chaetoceros salsugineum nuclear inclusion virus (CsNIV) is a 38-nm icosahedral virus that replicates within the nucleus of C. salsugineum. The latent period was estimated to be between 12 and 24 h, with a burst size of 325 infectious units per host cell. CsNIV has a genome structure unlike that of other viruses that have been described. It consists of a single molecule of covalently closed circular single-stranded DNA (ssDNA; 6,005 nucleotides), as well as a segment of linear ssDNA (997 nucleotides). The linear segment is complementary to a portion of the closed circle creating a partially double-stranded genome. Sequence analysis reveals a low but significant similarity to the replicase of circoviruses that have a covalently closed circular ssDNA genome. This new host-virus system will be useful for investigating the ecological relationships between bloom-forming diatoms and other viruses in the marine system. Our study supports the view that, given the diversity and abundance of plankton, the ocean is a treasury of undiscovered viruses.
Long-term antigen expression is believed to play an important role in modulation of T-cell responses to chronic virusinfections. However, recent studies suggest that immune responses may occur late after appar- ently acute infections. We have now analyzed the CD8 T-cell response to vesicular stomatitis virus (VSV), which is thought to cause to an infection characterized by rapid virus clearance
Damian L. Turner; Linda S. Cauley; Kamal M. Khanna; Leo Lefrancois
Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV). DENV belongs to the family Flaviviridae, genus Flavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease) in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFN? and TNF? cytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virusinfection, to test antiviral drugs, as well as to evaluate candidate vaccines. PMID:22666132
Gonçalves, Denise; de Queiroz Prado, Rafael; Almeida Xavier, Eric; Cristina de Oliveira, Natália; da Matta Guedes, Paulo Marcos; da Silva, João Santana; Moraes Figueiredo, Luiz Tadeu; Aquino, Victor Hugo
Our molecular understanding of cancer biology has made substantial progress during the last two decades. During recent years it became evident that inflammation is a major driving force in tumor development since chronic virusinfection and carcinogenesis are closely correlated. These insights refined our view on the decisive role of persistent virusinfection and chronic inflammation in tumor onset, growth, and metastatic progression. Explanations have been delivered how tumor cells interact and correspond with neighbouring epithelia and infiltrating immune cells for shaping the so-called 'tumor-microenvironment' and establishing tumor-specific tolerance. This extended view on malignant diseases should now allow for rational design of interventions targeting inflammation and underlying pathways for prevention and therapy of inflammation-associated cancer. This chapter outlines the role of virus-mediated inflammations in tumorigenesis thereby shedding light on the mechanisms of cancer-related inflammation and on characteristic features of the tumor-microenvironment, which has been recently identified to play a key role in maintenance and progression of tumors. Finally, the chapter discusses latest aspects in prevention of inflammation-related cancer and provides a short outlook on the future prospects of cancer immunotherapy. PMID:24008292
Cattle are the natural hosts of bovine viral diarrhea virus (BVDV), which causes mucosal disease, respiratory and gastrointestinal tract infections, and reproductive problems in cattle. However, BVDV can also infect goats, sheep, deer, and pigs. The prevalence of BVDV infection in pig herds has substantially increased in the last several years, causing increased economic losses to the global pig breeding industry. This article is a summary of BVDV infections in pigs, including a historical overview, clinical signs, pathology, source of infection, genetic characteristics, impacts of porcine BVDV infection for diagnosis of classical swine fever virus (CSFV), differentiation of infection with CSFV and BVDV, and future prospects of porcine BVDV infection. PMID:23587625
The flavonoids, quercetin and vitexin were proved to reduce lesion number in the local hosts Datura stramonium and Chenopodium amaranticolor infected with Tobacco mosaic virus (TMV). Both flavonoids also reduced the virus concentration in systemically infected tobacco plants. This effect was restricted to an early stage of infection and correlated with an induced synthesis of salicylic acid (SA) and kaempferol suggesting their possible defensive role in the infected plant tissue. Since the tested flavonoids did not bind to the virus particles, their antiphytoviral activity was probably not based on a direct virus inactivation. PMID:18564899
Background The discovery of giantviruses with genome and physical size comparable to cellular organisms, remnants of protein translation machinery and virus-specific parasites (virophages) have raised intriguing questions about their origin. Evidence advocates for their inclusion into global phylogenomic studies and their consideration as a distinct and ancient form of life. Results Here we reconstruct phylogenies describing the evolution of proteomes and protein domain structures of cellular organisms and double-stranded DNA viruses with medium-to-very-large proteomes (giantviruses). Trees of proteomes define viruses as a fourth supergroup along with superkingdoms Archaea, Bacteria, and Eukarya. Trees of domains indicate they have evolved via massive and primordial reductive evolutionary processes. The distribution of domain structures suggests giantviruses harbor a significant number of protein domains including those with no cellular representation. The genomic and structural diversity embedded in the viral proteomes is comparable to the cellular proteomes of organisms with parasitic lifestyles. Since viral domains are widespread among cellular species, we propose that viruses mediate gene transfer between cells and crucially enhance biodiversity. Conclusions Results call for a change in the way viruses are perceived. They likely represent a distinct form of life that either predated or coexisted with the last universal common ancestor (LUCA) and constitute a very crucial part of our planets biosphere.
Acquired immunodeficiency syndrome is associated with considerable morbidity in infants and children. It is caused by human immunodeficiency virus (HIV) which can be transmitted vertically from mother to infant early in pregnancy. Transmission might also occur via breast milk. Although the exact transmission rate of HIV from mother to infant is not known, HIV can become a major threat to child survival. This threat is already present in Africa where high seroprevalences have been reported among infants and young children. Transmission via blood products is decreasing due to reliable methods of screening donors for HIV antibody. Where these tests are not available, parenteral transmission will increase the incidence of HIV infection. The clinical picture of HIV infection in children presents with failure to thrive, pulmonary interstitial pneumonitis, hepatosplenomegaly and recurrent bacterial infections. These are common manifestations of diseases prevalent in children in Africa where malnutrition and recurrent parasitic infections already cause immunosuppression. Recognition of the syndrome is therefore difficult. There is no available cure for HIV infection. Supportive treatment and relief of pain and suffering are the only means of management at present. Prevention of spread of the illness to infants and young children is therefore of paramount importance. PMID:2456715
Abstract Respiratory syncitial virus (RSV) is the most common cause of lower respiratory tract infections (LRTI) in children worldwide and it is associated with significant childhood morbidity. Acute infection may result in respiratory failure with varying degrees of severity, and increasing evidence supports a role of RSV infection as a key determinant for the development of subsequent chronic respiratory disease. Independent predictors of RSV severity include; prematurity, congenital heart disease, cystic fibrosis, immune defects and neuromuscular disorders. Passive immunization with palivizumab has proven to be safe and effective for preventing RSV hospitalization in infants at higher risk of acquiring severe RSV infection, but its expense and cumbersome monthly intravenous delivery schedule make it inaccessible to many. Furthermore, implementing prophylaxis in 32- to 35-week-gestational age infants and the mode of its administration still represent areas of uncertainty. In this review, we describe several aspects of RSV infection and analyze recent advances in the assessment of cost-effective palivizumab prophylaxis. PMID:24059554
Del Vecchio, Antonio; Ferrara, Teresa; Maglione, Marco; Capasso, Letizia; Raimondi, Francesco
The development of animal models of dengue virus (DENV) infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs) can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the 'vascular-leak' syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines. PMID:22355452
The use of polyacrylamide jells has facilitated the investigation of virus-specific proteins both in the form of virions and in cells infected by the virus. This method has made possible the separation of virus-specific proteins of the polio-virus and the...
Although respiratory syncytial virus (RSV) was discovered > 40 years ago, treatment remains largely supportive. There are no safe and effective vaccines or specific treatments other than prophylaxis with passive antibody therapy (palivizumab). However, there are good reasons to think that the scene may soon change. As the pace of development of anti-viral drugs accelerates and optimism over vaccines increases, novel therapies are set to make a major impact in the management of this very common infection. The use and effect of such interventions are not easy to anticipate, but could ultimately include the interruption of RSV's transmission resulting in profound changes to the impact of RSV on human health.
A filamentous virus and a spherical virus were detected from partial purification with natural-infected Araceae plants. The filamentous virus was confirmed as dasheen mosaic virus (DsMV) by RNA spot hybridization (RSH) and sequence determination, while the spherical virus was identified as a new strain of cucumber mosaic virus (CMV) by enzyme-linked immunosorbent assay and sequence determination of the 3' end genes of RNA3. CMV was firstly confirmed as one of the principal virusesinfecting the Araceae plants under natural condition. According to the sequence similarity of coat protein, Araceae-infecting CMV was then decided belonging to CMV subgroup I, but independent from other isolates in this subgroup. By dot-RNA hybridization to DsMV and CMV probes with total RNA extracted from leaf tissue, field samples collected from some parts of southern China were detected for their natural infection. The infection ratio of field samples infected by DsMV and CMV were 73.3% and 46.7% for samples collected from Hainan Province, 100% and 38.5% for those from Hunan Province, 93.0% and 38.5% for that from Zhejiang Province, and 100% and no infection for samples from Shanghai, respectively. The infection of viruses on Araceae plants was obviously affected by such ecological factors as geological distribution, climate and host species. The occurrence of CMV was greatly influenced by the above factors, but DsMV always existed as the most commonly distributed virus. PMID:15334946
The conversion of simian virus 40 (SV40) component II deoxyribonucleic acid to component I has been used to assay polynucleotide ligase in extracts of tissue culture cells. All cell types examined, including chicken, hamster, mouse, monkey, and human cells, contained adenosine triphosphate-dependent ligase. After infection of mouse embryo, monkey kidney, and HeLa cells with polyoma virus, SV40, and vaccinia virus, respectively, the enzyme activity increased, but its cofactor requirement was unchanged. In vaccinia virus-infected cells, the increased activity was localized in the cytoplasm. Ligase induction occurred in the presence of cytosine arabinoside but was prevented by puromycin. Rifampicin blocked the production of infectious vaccinia particles but had little effect on the induction of ligase.
A fatal Encephalomyocarditis virus (EMCV) infection epidemic involving fifteen primates occurred between October 2006 and February 2007 at the Natura Viva Zoo. This large open-field zoo park located near Lake Garda in Northern Italy hosts one thousand animals belonging to one hundred and fifty different species, including various lemur species. This lemur collection is the most relevant and rich in Italy. A second outbreak between September and November 2008 involved three lemurs. In all cases, the clinical signs were sudden deaths generally without any evident symptoms or only with mild unspecific clinical signs. Gross pathologic changes were characterized by myocarditis (diffuse or focal pallor of the myocardium), pulmonary congestion, emphysema, oedema and thoracic fluid. The EMCV was isolated and recognized as the causative agent of both outbreaks. The first outbreak in particular was associated with a rodent plague, confirming that rats are an important risk factor for the occurrence of the EMCV infection.
A proteome-wide mapping of interactions between hepatitis C virus (HCV) and human proteins was performed to provide a comprehensive view of the cellular infection. A total of 314 proteinprotein interactions between HCV and human proteins was identified by yeast two-hybrid and 170 by literature mining. Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. A global analysis on the basis of functional annotation highlighted the enrichment of cellular pathways targeted by HCV. A network of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGF? pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was identified as a new function affected by HCV, mainly by NS3 and NS5A proteins.
de Chassey, B; Navratil, V; Tafforeau, L; Hiet, M S; Aublin-Gex, A; Agaugue, S; Meiffren, G; Pradezynski, F; Faria, B F; Chantier, T; Le Breton, M; Pellet, J; Davoust, N; Mangeot, P E; Chaboud, A; Penin, F; Jacob, Y; Vidalain, P O; Vidal, M; Andre, P; Rabourdin-Combe, C; Lotteau, V
SUMMARY Adult rats were infected with bovine leukaemia virus (BLV). Inoculated rats persistently produced antibodies directed against viral structural proteins. No major pathogenesis in infected rats was found during 2 years of observation. It was possible to recover the virus from rat spleen several months after infection. A cell line, R(BLV), was established from rat spleen; this contained integrated BLV
VERONIKA ALTANEROVA; DANIEL PORTETELLE; RICHARD KETTMANN; CESTMIR ALTANER
The purpose of this review is to provide an overview of the effects of adenovirus and influenza virusinfections on obesity in various experimental models. We reviewed studies that were conducted within the past 10years and were related to virusinfection and obesity prevalence. Here, we discuss a different causal relationship between adenovirus and influenza infections with obesity. Adenovirus infection can cause obesity, whereas obesity can be a risk factor for increasing influenza virusinfection and increases the risk of morbidity and mortality. The prevalence of obesity due to adenovirus infections may be due to an increase in glucose uptake and reduction in lipolysis caused by an increase in corticosterone secretion. Adenovirus infections may lead to increases in appetite by decreasing norepinephrine and leptin levels and also cause immune dysfunction. The relationship between obesity and influenza virusinfection could be summarized by the following features: decreases in memory T-cell functionality and interferon (IFN)-?, IFN-?, and IFN-? mRNA expression, increases in viral titer and infiltration, and impaired dendritic cell function in obese individuals. Moreover, leptin resistance may play an important role in increasing influenza virusinfections in obese individuals. In conclusion, prevention of adenovirus infections could be a good approach for reducing obesity prevalence, and prevention of obesity could reduce influenza virusinfections from the point of view of viral infections and obesity. PMID:24007799
Hur, Sun Jin; Kim, Doo Hwan; Chun, Se Chul; Lee, Si Kyung
With the increased survival of human immunodeficiency virus (HIV)-infected individuals resulting from therapy, disorders in\\u000a other target organs of the virus, such as the brain, are becoming more prevalent. Here the author reviews his laboratorys\\u000a work on the simian immunodeficiency virus (SIV)\\/nonhuman model of acquired immunodeficiency syndrome (AIDS), which has revealed\\u000a unique characteristics of both the virus that infects the
Herpes simplex virus (HSV) is a significant human pathogen causing mucocutaneous lesions primarily in the oral or genital mucosa. Although acyclovir (ACV) and related nucleoside analogs provide successful treatment, HSV remains highly prevalent worldwide and is a major cofactor for the spread of human immunodeficiency virus. Encephalitis, meningitis, and blinding keratitis are among the most severe diseases caused by HSV. ACV resistance poses an important problem for immunocompromised patients and highlights the need for new safe and effective agents; therefore, the development of novel strategies to eradicate HSV is a global public health priority. Despite the continued global epidemic of HSV and extensive research, there have been few major breakthroughs in the treatment or prevention of the virus since the introduction of ACV in the 1980s. A therapeutic strategy at the moment not fully addressed is the use of small peptide molecules. These can be either modeled on viral proteins or derived from antimicrobial peptides. Any peptide that interrupts protein-protein or viral protein-host cell membrane interactions is potentially a novel antiviral drug and may be a useful tool for elucidating the mechanisms of viral entry. This review summarizes current knowledge and strategies in the development of synthetic and natural peptides to inhibit HSV infectivity. PMID:23389903
We report the case of a two year old boy who developed a large tumour on his face. The lesion resembled a pyogenic granuloma clinically and histologically. Viral studies indicated a parapox infection and a bovine source was supported on epidemiological grounds. The lesion was removed by shave excision and the area healed without significant scarring. PMID:2562071
Rogers, M; Bale, P; De Silva, L M; Glasson, M J; Collins, E
Hepatitis C virus (HCV) chronic infection is recognized as the major cause of mixed cryoglobulinemia (MC). Its persistence represents a continuous stimulus for host immune system with production of circulating immune complexes (ICs), one-third of them with cryoprecipitate property. Several factors contribute to the biological activities of ICs, many of which are not completely known. Among them, complement factors play a crucial role in the cold-insoluble ICs-mediated vasculitis, involving primarily small blood vessels in different tissues including skin, kidney, peripheral, and central nervous system. Liver represents the major target of HCV infection with inflammatory infiltrates, resembling secondary lymphoid follicles. Cytokine like CXCL13 contribute to B-cell homing in intraportal lymphoid aggregates, in which B-cell clonal selection may arise. B-cell clonal expansion starts as an antigen-driven event and expands towards indolent and malignant B-cell proliferation. Occurrence of intrahepatic B-cell clonalities correlates with extrahepatic clinical manifestations of HCV infection. In this context, cryoglobulinemic patients should be considered a peculiar HCV-infected population that needs a clinical multidisciplinary approach and more articulated therapeutic measures.
Background Chikungunya (CHIK) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle. Methodology/Principal Findings Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells), and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virusinfection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection. Conclusions/Significance This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans.
Orf is a disease of sheep and goats which is caused by a parapox virus. It can be transmitted to humans, and is considered an occupational hazard by those handling sheep. In this paper we present the first report of both cell-mediated and humoral immune responses to naturally acquired orf virusinfection in humans. Lymphoproliferative responses of peripheral blood mononuclear cells of patients to an orf virus antigen were vigorous soon after infection, but rapidly declined. Orf virus antibody levels, detected by ELISA, were shown to rise during infection. Western blot analysis confirmed this, and demonstrated that the antibody produced in response to the infection was directed against the 40-kDa viral surface tubule protein. Where direct comparisons were possible, the immune response of humans to orf virusinfection was similar to that previously reported for sheep. Evidence was obtained suggesting that prior exposure to vaccinia virus (smallpox vaccination) provided no protection from subsequent orf virusinfection. In addition, orf virusinfection did not enhance immune responses to vaccinia virus antigens. PMID:8186108
Cholesterol is known to play an important role in stabilizing particular cellular membrane structures, so-called lipid or membrane rafts. For several viruses, a dependence on cholesterol for virus entry and\\/or morphogenesis has been shown. Using flow cytometry and fluorescence microscopy, we demonstrate that infection of cells by canine distemper virus (CDV) was not impaired after cellular cholesterol had been depleted
Heidi Imhoff; Veronika von Messling; Georg Herrler; Ludwig Haas
A successful outcome for the host of virusinfection of the central nervous system (CNS) requires the elimination of the virus without damage to essential non-renewable cells, such as neurons. As a result, inflammatory responses must be tightly controlled, and many unique mechanisms seem to contribute to this control. In addition to being important causes of human disease, RNA viruses
Background It is known that insects and crustaceans can carry simultaneous, active infections of two or more viruses without showing signs of disease, but it was not clear whether co-infectingviruses occupied the same cells or different cells in common target tissues. Our previous work showed that successive challenge of mosquito cell cultures followed by serial, split-passage resulted in stabilized cultures with 100% of the cells co-infected with Dengue virus (DEN) and an insect parvovirus (densovirus) (DNV). By addition of Japanese encephalitis virus (JE), we tested our hypothesis that stable, persistent, triple-virus co-infections could be obtained by the same process. Results Using immunocytochemistry by confocal microscopy, we found that JE super-challenge of cells dually infected with DEN and DNV resulted in stable cultures without signs of cytopathology, and with 99% of the cells producing antigens of the 3 viruses. Location of antigens for all 3 viruses in the triple co-infections was dominant in the cell nuclei. Except for DNV, this differed from the distribution in cells persistently infected with the individual viruses or co-infected with DNV and DEN. The dependence of viral antigen distribution on single infection or co-infection status suggested that host cells underwent an adaptive process to accommodate 2 or more viruses. Conclusions Individual mosquito cells can accommodate at least 3 viruses simultaneously in an adaptive manner. The phenomenon provides an opportunity for genetic exchange between diverse viruses and it may have important medical and veterinary implications for arboviruses.
Animal infectivity models have been important in the demonstration of enhanced susceptibility to viral and bacterial infection as a result of low?level toxicant exposure. This study demonstrated an enhanced and prolonged viral infection using an influenza virusinfectivity model in the rat following exposure to the toxicant gas phosgene. Fischer?344 rats exposed to either air or a sublethal concentration of
The invention is concerned with methods of inhibiting the infectivity of Human Immunodeficiency Virus-1 (HIV-1) in infected human cells. The invention is further concerned with methods of inhibiting the infectivity of HIV-1 in the cells of an infected pat...
Many mint clones at the USDA-ARS National Clonal Germplasm Repository at Corvallis, Oregon have exhibited symptoms similar to those associated with virusinfection. For example, Mentha x gentiles L. 'Variegata' (NCGR MEN-454) has shown dramatic vein-banding symptoms. Virus purification from infected...
We investigated whether the administration of melatonin (MLT) reduces the death rate and evolution of the disease in mice infected with Venezuelan equine encephalomyelitis (VEE) virus. Our results show that MLT protects mice infected with the virus. The mortality rate was reduced from 100% to 16% merely by increasing the dose from 0 to 1000 wg\\/MLT per kg body weight
E. Bonilla; N. Valero-Fuenmayor; H. Pons; L. Chacín-Bonilla
The polymerase chain reaction (PCR) was shown to be a sensitive and useful method for detection of infection by members of the group of avian reticuloendotheliosis virus (REV). Genomic DNA extracted from chick embryo fibroblasts (CEFs), blood and tumours of chickens experimentally infected with the spleen necrosis virus (SNV) strain of REV was used as the target for chain elongation.
BACKGROUND: Viruses are obligate intracellular parasites that rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virusinfection and\\/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. RESULTS: Candidate genes required for lytic reovirus infection were identified by tagged
Edward L Organ; Jinsong Sheng; H Earl Ruley; Donald H Rubin
Pertussis (whooping cough) is frequently complicated by concomitant infections with respiratory viruses. Here we report the effect of Bordetella pertussis infection on subsequent influenza virus (PR8) infection in mouse models and the role of pertussis toxin (PT) in this effect. BALB\\/c mice infected with a wild-type strain of B. pertussis (WT) and subsequently (up to 14 days later) infected with
Victor I. Ayala; John R. Teijaro; Donna L. Farber; Susan G. Dorsey; Nicholas H. Carbonetti; Eliane Namie Miyaji
We used flow cytometry to examine the process of cell death in the bloom-forming alga Heterosigma akashiwo during infection by a double-stranded DNA virus (OIs1) and a single-stranded RNA virus (H. akashiwo RNA virus [HaRNAV]). These viruses were isolated from the same geographic area and infect the same strain of H. akashiwo. By use of the live/dead stains fluorescein diacetate and SYTOX green as indicators of cellular physiology, cells infected with OIs1 showed signs of infection earlier than HaRNAV-infected cultures (6 to 17 h versus 23 to 29 h). Intracellular esterase activity was lost prior to increased membrane permeability during infection with OIs1, while the opposite was seen with HaRNAV-infected cultures. In addition, OIs1-infected cells accumulated in the cultures while HaRNAV-infected cells rapidly disintegrated. Progeny OIs1 viruses consisted of large and small morphotypes with estimated latent periods of 11 and 17 h, respectively, and about 1,100 and 16,000 viruses produced per cell, respectively. In contrast, HaRNAV produced about 21,000 viruses per cell and had a latent period of 29 h. This study reveals that the characteristics of viral infection in algae are virus dependent and therefore are variable among virusesinfecting the same species. This is an important consideration for ecosystem modeling exercises; calculations based on in situ measurements of algal physiology must be sensitive to the diverse responses of algae to viral infection. PMID:17041155
Lawrence, Janice E; Brussaard, Corina P D; Suttle, Curtis A
In the present study, we established an animal model for dengue virusinfection using severe combined immunodeficient mice transplanted with a human hepatocarcinoma cell line (HepG2). At 78 weeks after transplantation, the HepG2-grafted mice were infected intraperitoneally with dengue virus type 2 (DEN-2). A higher titer of the virus was detected in the liver and serum but not in the
Hendra virus (HeV) and Nipah virus (NiV) are emerging zoonotic viruses that cause severe and often lethal respiratory illness and encephalitis in humans. Henipaviruses can infect a wide range of species and human-to-human transmission has been observed for NiV. While the exact route of transmission in humans is not known, experimental infection in different animal species suggests that infection can be efficiently initiated after respiratory challenge. The limited data on histopathological changes in fatal human cases of HeV and NiV suggest that endothelial cells are an important target during the terminal stage of infection; however, it is unknown where these viruses initially establish infection and how the virus disseminates from the respiratory tract to the central nervous system and other organs. Here we review the current concepts in henipavirus pathogenesis in humans. PMID:23592639
Escaffre, Olivier; Borisevich, Viktoriya; Rockx, Barry
Infection with hepatitis C virus (HCV) is characterized by inflammatory liver damage and a long viral persistence associated with an increased risk of developing hepatocellular carcinoma. Both in liver damage and in oncogenesis a disturbance of apoptosis has been implicated, although the underlying mechanisms in these apparently opposite processes are incompletely understood. HCV-triggered liver injury is mediated mainly by host immune mechanisms and eventually by direct cytopathic effects of HCV. Recent data shows that caspase activation, either triggered by death ligands, other cytokines, granzyme B or HCV proteins, is considerably upregulated in HCV-infected liver. Interestingly, caspase activation appears to correlate closely with the inflammatory response. Data about the role of single HCV proteins, either in cultured cells or transgenic animals models, however, are contradictory, as both pro- and anti-apoptotic effects have been observed. Nevertheless, apoptosis induction upon HCV infection may critically contribute to liver damage, while inhibition of apoptosis may result in HCV persistence and development of hepatocellular carcinoma. PMID:12655346
Respiratory syncytial virus (RSV) is now recognized as a significant problem in certain adult populations. These include the elderly, persons with cardiopulmonary diseases, and immunocompromised hosts. Epidemiological evidence indicates that the impact of RSV in older adults may be similar to that of nonpandemic influenza. In addition, RSV has been found to cause 2 to 5% of adult community-acquired pneumonias. Attack rates in nursing homes are approximately 5 to 10% per year, with significant rates of pneumonia (10 to 20%) and death (2 to 5%). Clinical features may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing, and low-grade fever. Bone marrow transplant patients prior to marrow engraftment are at highest risk for pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably due to low viral titers in nasal secretions, but early bronchoscopy is valuable in immunosuppressed patients. Treatment of RSV in the elderly is largely supportive, whereas early therapy with ribavirin and intravenous gamma globulin is associated with improved survival in immunocompromised persons. An effective RSV vaccine has not yet been developed, and thus prevention of RSV infection is limited to standard infection control practices such as hand washing and the use of gowns and gloves.
IN both experimentally infected animals1,2 and in asymptomatic human subjects3,4 herpes simplex virus (HSV) can establish a latent infection in the sensory ganglia of the nervous system. It is probably the periodic reactivation of virus within these ganglia that gives rise to recurrent herpetic eruptions on epithelial surfaces innervated by the infected ganglia. The ganglia of the peripheral autonomic nervous
Richard W. Price; Barrett J. Katz; Abner Louis Notkins
BACKGROUND: Nipah virus (NiV), a recently discovered zoonotic virusinfects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches. RESULTS: Method for separation of the NiV-infected
Li-Yen Chang; AR Mohd Ali; Sharifah Syed Hassan; Sazaly AbuBakar
Autophagy is a constitutive, catabolic process leading to the lysosomal degradation of cytosolic proteins and organelles. However, it is also induced under stress conditions, remodeling the eukaryotic cell by regulating energy, protein, and lipid homeostasis. It is likely that the autophagosomal/lysosomal pathway evolved primordially to recycle cell components, but further functionally developed as to become part of the immune system to defend against invading pathogens. Likewise, pathogenic, foreign agents developed strategies to fight back and even to employ the autophagy machinery to their own benefit. Hence, the regulation of autophagy has many implications on human health and disease. This review summarizes the molecular dynamics of autophagosome formation, maturation, and target selection. Membrane dynamics, as well as proteinprotein and proteinmembrane interactions are particularly addressed. In addition, it recapitulates current knowledge of the influences of influenza virusinfection on the process.
Tuberculosis is the most common opportunistic infection in human immunodeficiency virus (HIV) infected persons. HIV-infected\\u000a patients have a high incidence of tuberculous meningitis as well. The exact incidence and prevalence of tuberculous meningitis\\u000a in HIV-infected patients are not known. HIV infection does not significantly alter the clinical manifestations, laboratory,\\u000a radiographic findings, or the response to therapy. Still, some differences have
Summary Attenuated, gene-deletion mutants of pseudorabies virus (PRV) were tested for their ability to establish a reactivatable latent infection in pigs. The viruses (designated A, B, and C) were from each of three vaccines commercially available in the United States. Viruses A and C were similar in that they had genetically engineered gene deletions for thymidine kinase (TK) and glycoprotein
Subgroup J avian leukosis viruses (ALVs), which are a recombinant virus between exogenous and endogenous ALVs, can spread by either vertical or horizontal transmission. Exogenous and endogenous ALVs, can be detected in feather pulp. In this study, virus titers in feather pulp of chickens infected w...
It has been recognized that other than habitat loss, degradation and fragmentation, the infection of the roundworm Baylisascaris schroederi (B. schroederi) is one of the major causes of death in wild giant pandas. However, the prevalence and intensity of the parasite infection has been inconsistently reported through a method that uses sedimentation-floatation followed by a microscope examination. This method fails
Nipah virus (NiV), a member of the Paramyxoviridae family, causes a zoonotic infection in which the reservoir, the fruit bat, may pass the infection to pigs and eventually to humans. In humans, the infection leads to encephalitis with >40 to 70% mortality. We have previously shown that polyclonal antibody directed to either one of two glycoproteins, G (attachment protein) or
V. Guillaume; H. Contamin; P. Loth; I. Grosjean; M. C. Georges Courbot; V. Deubel; R. Buckland; T. F. Wild
Human endothelial cells or human foreskin fibroblasts infected with herpes simplex viruses (HSVs) potently inhibit the lytic activity of natural killer cells and interleukin 2-activated killer cells. The inhibition occurs after as little as 8 hr of viral infection and requires contact between effector cells and HSV-infected targets. Inhibition evidently stems from direct blockade of killer cell function because killer
Dennis L. Confer; Gregory M. Vercellotti; Dusan Kotasek; Jesse L. Goodman; Augusto Ochoa; Harry S. Jacob
Primary genital herpes simplex virus (HSV) infection is com- monly associated with systemic symptoms. A systematic eval- uation of HSV viremia during primary genital infection has not been performed previously. Plasma samples from adults with a first clinical episode of genital HSV infection were as- sayed for HSV DNA by polymerase chain reaction. One hun- dredsixty-fouradultshadconfirmedprimarygenitalHSVin- fection. Of these, 40
Christine Johnston; Amalia Magaret; Stacy Selke; Michael Remington; Lawrence Corey; Anna Wald
Background: Patients infected with human immuno- deficiency virus (HIV) are at an increased risk for pre- mature coronary artery disease. However, the clinical out- come of HIV-infected patients who have had an acute myocardial infarction (AMI) is unknown. Methods: We studied 24 consecutive HIV-infected patients admitted because of AMI. During the hospital phase, the patients were examined for recurrent ische-
James O. Hill; Daniel Bessesen; Philip A. Masters; Thomas A. O'Bryan; John Zurlo; Debra Q. Miller; Nirmal Joshi; James D. Lewis; Kimmie Ng; Kenneth E. Hung; Warren B. Bilker; Jesse A. Berlin; Colleen Brensinger; Anil K. Rustgi; Shannon M. Bates; John Lister-James; Jim A. Julian; Raymond Taillefer; Brian R. Moyer; Jeffrey S. Ginsberg; Shlomo Matetzky; Michelle Domingo; Saibal Kar; Marko Noc; Prediman K. Shah; Sanjay Kaul; Eric Daar; Bojan Cercek
Vaccinia virus (VACV) was used as a surrogate of Variola virus (genus Orthopoxvirus), the causative agent of smallpox, to study orthopoxvirus infection via the respiratory airway. Lung surfactant, a physiological barrier to infection encountered by the virus, is predominantly composed of phospholipids whose role during orthopoxvirus infection has not been investigated. An attenuated Lister strain, derived from the traditional smallpox vaccine and the Western Reserve (WR) strain, lethal for mice infected by the respiratory route, were examined for their ability to bind various surfactant phospholipids. Dipalmitoyl phosphatidylglycerol (DPPG) was found to interact with both VACV strains. DPPG incorporated in small unilamellar vesicle (SUV-DPPG) inhibited VACV cell infection, unlike other phospholipids tested. Both pre-incubation of virus with SUV-DPPG and pretreatment of the cell with SUV-DPPG inhibited cell infection. This specific DPPG effect was shown to be concentration and time dependent and to prevent the first step of the viral cycle, i.e. virus cell attachment. Cryo-electron microscopy highlighted the interaction between the virus and SUV-DPPG. In the presence of the phospholipid, virus particles displayed a hedgehog-like appearance due to the attachment of lipid vesicles. Mice infected intranasally with VACV-WR pre-incubated with SUV-DPPG survived a lethal infection. These data suggest that DPPG in lung surfactant could reduce the amount of orthopoxvirus particles able to infect pneumocytes at the beginning of a respiratory poxvirus infection. The knowledge acquired during this study of virus-DPPG interactions may be used to develop novel chemotherapeutic strategies for smallpox. PMID:21095206
Light scattering patterns have been calculated for a simple optical model constructed for single smooth and nonsmooth lymphocytes of healthy and infected individuals. It has been shown that the smooth and nonsmooth cells can be resolved using the intensities of the sideward and backward scattered light. We have found by calculations and validated by the flow-cytometer experiments that intensity distributions for the cells of lymphocyte populations can be used as a preliminary signatures of some virusinfections. Potential biomedical applications of the findings for label-free flowcytometry detecting of individuals infected with viruses of hepatitises B or C and some others viruses are presented.
Ruban, Gennady I.; Berdnik, Vladimir V.; Marinitch, Dmitry V.; Goncharova, Natalia V.; Loiko, Valery A.
Experiments were conducted to examine the aerosol stability and respiratory infectivity of Japanese B encephalitis virus. At 75 degrees F (about 24 degrees C), survival of the virus as aerosol was inversely related to relative humidity. After correction for physical decay, the mean virus half-lives of the virus were 28, 38, and 62 min at relative humiditis of 80, 55, and 30%, respectively. Virus recoveries as aerosol at 4 min aftr dissemination generally exceeded the theoretical limit of 100%, based on the amount disseminated, to suggest that the process of dissemination operated to deagglomerate or release bound virus from the tissue cells in suspension. Swiss-ICR mice and golden Syrian hamsters were highly susceptible to lethal infections after respiratory challenge. Hartley strain guinea pigs and Fisher-Dunning rats, although infected, based on seroconversion observations, survived the infections. Deaths occurred in squirrel monkeys only after exposure to a high aerosol dose of virus (10(6.0) plaque-forming units). Studies of the virus concentration dynamics and histopathological findings in mouse tissues after aerosol challenge supported a hypothesis for direct transport of virus across the foramina of the cribriform plate to the tissues of the central nervous system to produce primary encephalitis.
|A study involving 1,235 residents of Sonoma Developmental Center found 3 residents had hepatitis C virusinfections, and 633 had past or current hepatitis B virusinfections. The prevalence of hepatitis B virusinfection rose rapidly with longer residence in institutions. Hepatitis A virusinfection had occurred in 494 residents. (Contains
Visceral leishmaniasis (VL) caused by Leishmania infantum is a common disease in human immunodefi- ciency virus (HIV)-infected people in the Mediterranean basin. However, most such cases are asymptomatic, and little information about the prevalence of these infections in HIV-infected individuals is available. The aim of this study was to assess the prevalence of subclinical infection and the relationship between several
Angela Camacho; Cristina Riera; Francisco Morillas-Marquez; Salvador Vergara; Juan Macõ ´ as; Juan A. Pineda
The apparent worldwide resurgence of invasive Streptococcus pyogenes infection in the last two decades remains unexplained. At present, animal models in which toxic shock-like syndrome or necrotizing fasciitis is induced after S. pyogenes infection are not well developed. We demonstrate here that infection with a nonlethal dose of influenza A virus 2 days before intranasal infection with a nonlethal dose
Several Burkitt's lymphoma and lymphobiastoid cell lines with Epstein-Barr virus derived from different origins have been investigated cytogenetically. Giant group A marker chromosome was detected only in three lymphobiastoid cell lines from nasopharyngea...
Despite significant research since it was discovered more than 50 years ago, respiratory syncytial virus (RSV) continues to be the leading agent causing infant hospitalization and respiratory distress worldwide. Although RSV normally does not cause mortality, this virus is recognized as a major public health and economic burden around the globe. RSV can modulate host immunity leading to an inflammatory response that produces lung damage and virus dissemination in the host airways. Remarkably, infection with the virus elicits poor immunity that in most cases fails to protect against subsequent exposures. Here, we review advances made on the understanding of the lifecycle of the virus, some of the molecular mechanisms it has evolved to cause pathology and ineffective immunity during infection. Hopefully, ongoing research will contribute to developing new drugs and candidate vaccines that will decrease the health burden caused by this virus. PMID:23157678
González, P A; Carreño, L J; Bueno, S M; Riedel, C A; Kalergis, A M
A number of sulfhydryl (-SH) compounds and the nonsulfur analogs of some of these compounds were tested for their effect on the infectivity of partially purified eastern equine encephalitis virus during storage at 4 C. Thiourea the ost effective stabilize...
The generalized viral disease caused by a herpes virus in owl monkeys (Aotus trivirgatus) is an acute fulminating disease that has been 100% fatal. The incubation period for all experimentally inoculated owl monkeys except the intracerebrally infected ani...
The acquired immune deficiency syndrome (AIDS) is the clinically apparent preterminal stage of the prolonged infection with the human immunodeficiency virus (HIV), most often manifested as Pneumocystis carinii pneumonia, Kaposi's sarcoma, or other opportu...
Efforts to stimulate lymphocytes from measles seropositive and two patients with subacute sclerosing panencephalitis (SSPE) with either commercially available measles virus or virus isolated from a known case of SSPE failed to show any significant data using a microculture assay. Similar results were obtained using lymphocytes from two patients with active cytomegalovirus (CMV) infections and CMV seropositive individuals using CMV suspensions. On the other hand, lymphocytes from the patients with subacute sclerosing panencephalitis exhibited in vitro blastogenesis in culture with SSPE virus-infected HeLa cells. Similarly, lymphocytes from the CMV-infected patients demonstrated blastogenesis when cocultivated with CMV-infected WI-38 cells. This affords a new method for determining the cell-mediated immune capacity of patients with "slow" virus diseases.
Thurman, G. B.; Ahmed, A.; Strong, D. M.; Knudsen, R. C.; Grace, W. R.; Sell, K. W.
The development of antiviral drugs for Ebola and Marburg viruses has been slow. To date, beyond supportive care, no effective treatments, prophylactic measures, therapies or vaccines are approved to treat or prevent filovirus infections. In this review, w...
B. E. Julia G. W. Thomas M. R. Vanessa O. G. Gene W. Victoria
Infection with human immunodeficiency virus type 2 (HIV-2) occurs mainly in West Africa, but an increasing number of cases have been recognized in Europe, India, and the United States. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we present information on recent clinical advances in our understanding of HIV-2 infection and highlight remaining diagnostic and therapeutic challenges.
Sialic acid is known to be an essential part of influenza virus receptors, but the specific identity of the receptor molecules\\u000a on target cells is still not defined. In particular, the relative roles played by cellular sialylglycoproteins and gangliosides\\u000a in virus entry into target cells remain unclear. To test whether gangliosides are essential for virusinfection, we used the\\u000a GM-95
Mikhail Matrosovich; Takashi Suzuki; Yoshio Hirabayashi; Wolfgang Garten; Robert G. Webster; Hans-Dieter Klenk
A total of 12 horses of different breeds and ages were infected with West Nile virus (WNV) via the bites of infected Aedes albopictus mosquitoes. Half the horses were infected with a viral isolate from the brain of a horse (BC787), and half were infected with an isolate from crow brain (NY99-6625); both were NY99 iso- lates. Postinfection, uninfected female
Michel L. Bunning; Richard A. Bowen; C. Bruce Cropp; Kevin G. Sullivan; Brent S. Davis; Nicholas Komar; Marvin S. Godsey; Dale Baker; Danielle L. Hettler; Derek A. Holmes; Brad J. Biggerstaff; Carl J. Mitchell
A human isolate of Nipah virus from an outbreak of febrile encephalitis in Malaysia that coincided with a field outbreak of disease in pigs was used to infect eight 6-week-old pigs orally or subcutaneously and two cats oronasally. In pigs, the virus induced a respiratory and neurological syndrome consistent with that observed in the Malaysian pigs. Not all the pigs
D. J. Middleton; H. A. Westbury; C. J. Morrissy; B. M. van der Heide; G. M. Russell; M. A. Braun; A. D. Hyatt
BACKGROUND: Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the
Juana M Sánchez-Puig; Laura Sánchez; Garbiñe Roy; Rafael Blasco
|Discusses how the infection of the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus, as well as neuropsychiatric abnormalities in the brain. (TW)|
Influenza virus RNA-dependent RNA polymerase is composed of three viral proteins, PB1, PB2, and PA. The host protein Ebp1 (ErbB3-binding protein1) interacts with PB1, and inhibits both in vitro RNA synthesis and virus replication. On Western blotting, the induction of Ebp1 was observed after influenza virusinfection. To understand the induction of Ebp1 by influenza virusinfection, we introduced a series of deletions within the 981-nucleotide long sequence located upstream of the Ebp1 gene (-664 to +317 nt from the transcription initiation site) and ligated them to the GFP gene. GFP expression assays indicated that the 981-nt upstream region was required for expression of GFP in not all cells but some cells. Microscopic analysis of the transformants showed that GFP expression was up-regulated by the influenza virusinfection. Furthermore, quantitative real-time PCR indicated that influenza virusinfection induced Ebp1 mRNA expression. Our data showed that (i) the newly synthesized vRNP of influenza virus induces Ebp1 expression; (ii) the Ebp1 promoter localizes between -664 nt and the initiation site of the Ebp1 gene, +317-nt long sequence in the noncoding region is required for regulation of Ebp1 gene expression; and (iii) Ebp1 expression level is correlated with virus protein expression level. PMID:21794029
Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes
Rebecca S. Rudicell; James Holland Jones; Emily E. Wroblewski; Gerald H. Learn; Yingying Li; Joel D. Robertson; Elizabeth Greengrass; Falk Grossmann; Shadrack Kamenya; Lilian Pintea; Deus C. Mjungu; Elizabeth V. Lonsdorf; Anna Mosser; Clarence Lehman; D. Anthony Collins; Brandon F. Keele; Jane Goodall; Beatrice H. Hahn; Anne E. Pusey; Michael L. Wilson
The prevalence of West Nile virus (WNV) infections and associated morbidity has accelerated in recent years. Of particular concern is the recent demonstration that this virus can be transmitted by blood products and can cause severe illness and mortality in transfusion recipients. We have evaluated methylene blue (MB)+light as a safe and cost-effective means to inactivate WNV in vitro. This
To determine the proportion of acute undifferentiated fevers without neurologic deficits related to infec- tion with Japanese encephalitis (JE) virus, flavivirus serology (dengue and JE) was performed in a cohort of 156 adults presenting to a hospital in Chiangrai, Thailand. Recent flavivirus infection was diagnosed for any individual with an IgM result > 40 units. A ratio of dengue virus
To determine whether guinea pigs are infected with influenza virus in nature, we conducted a serologic study in domestic guinea pigs in Ecuador. Detection of antibodies against influenza A and B raises the question about the role of guinea pigs in the ecology and epidemiology of influenza virus in the region.
Leyva-Grado, Victor H.; Mubareka, Samira; Krammer, Florian; Cardenas, Washington B.
In contrast to the situation concerning bacterial and, to a lesser extent, animal RNA viruses, little is known about the biochemical processes occurring in plant cells due to plant RNA virusinfection. Such processes are difficult to study using intact plants or leaves. Great effort has therefore been spent in developing in vitro cultures of plant protoplasts, but the use
Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that causes neurobehavioral disorders in a wide variety of warm-blooded animals. Recent evidence has revealed that BDV uses a unique strategy in its transcription and replication and directly affects cellular functions of infected central nervous systems. BDV research will provide new insights not only into the biology of neurotropic RNA
We previously identified a novel insect picorna-like virus, termed Kakugo virus (KV), from the brains of aggressive worker honeybees that had counterattacked a giant hornet. To survey the prevalence of KV in worker populations engaged in various labors, we quantified KV genomic RNA. KV was detected specifically from aggressive workers in some colonies, while it was also detected from other worker populations in other colonies where the amount of KV detected in the workers was relatively high, suggesting that KV can infect various worker populations in the honeybee colonies. To investigate whether the KV strains detected were identical, phylogenetic analysis was performed. There was less than a 2% difference in the RNA-dependent RNA polymerase (RdRp) sequences between KV strains from aggressive workers and those from other worker populations, suggesting that all of the viruses detected were virtually the same KV. We also found that some of the KV-infected colonies were parasitized by Varroa mites, and the sequences of the KV strains detected from the mites were the same as those detected from the workers of the same colonies, suggesting that the mites mediate KV prevalence in the honeybee colonies. KV strains had approximately 6% and 15% sequence differences in the RdRp region from deformed wing virus and Varroa destructor virus 1, respectively, suggesting that KV represents a viral strain closely related to, but distinct from, these two viruses.
Hepatitis C virusinfection among kidney transplant recipients. The extent of hepatitis C virus (HCV) infection among kidney recipients was investigated in 67 patients by testing for anti-HCV paired serum samples, collected at time of transplantation and during follow-up (average 32 ± 20 months). Prevalence of anti-HCV at transplant time was 48%, and was related to the time on dialysis
Esther Ponz; Joseph M Campistol; Miguel Bruguera; Joseph M Barrera; Cristina Gil; Joao B Pinto; Jordi Andreu
West Nile virus is a mosquito-borne flavivirus causing to humans a variety of symptoms, from asymptomatic or mild infection, to severe, and often fatal, infection of the central nervous system. The present review aims to describe the main clinical characteristics of the disease, to provide the recent epidemiological data, including those from the recent outbreaks in Greece, and to discuss the environmental factors which might play a role in the virus emergence and its wider dispersal. PMID:23562617
Using literature data, daily infection risks of chickens and humans with\\u000aH5N1 avian influenza virus (AIV) by drinking water consumption were\\u000aestimated for the Netherlands. A highly infectious virus and less than 4\\u000alog10 drinking water treatment (reasonably inefficient) may lead to a\\u000ahigh infection risk (more than 1%) of poultry farms with more than 10 000\\u000achickens. Well treated
It has been confirmed that respiratory virusinfections can induce abberant cytokine production in the host. These cytokines may be associated with both elimination of the virus and complications in the host, such as virus-induced asthma. Representative host defense mechanisms against pathogens, including bacteria and viruses, are mediated by the innate immune system. Cells of the innate immune system express essential molecules, namely pattern recognition receptors (PRRs), such as Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, and retinoic acid-inducible gene-I-like receptors. These PRRs can recognize components of pathogens such as bacterial lipopolysaccharide, viral antigens, and their genomes (DNA and RNA). Furthermore, PRRs activate various signaling pathways resulting in cytokine production against pathogen infection. However, the exact mechanisms remain unknown. In this review, we mainly focus on the representative mechanisms of cytokine production through PRRs and signaling pathways due to virusinfections, including respiratory virusinfections. In addition, we describe the relationships between respiratory infections and virus-induced asthma.
The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virusinfections. PMID:21987744
An inhalation exposure system was characterized to deliver aerosolized monkeypox virus (MPXV), and a non-human primate (NHP) inhalation monkeypox model was developed in cynomolgus macaques. A head-only aerosol exposure system was characterized, and two sampling methods were evaluated: liquid impingement via an impinger and impaction via a gelatin filter. The aerosol concentrations obtained with the gelatin filter and impinger were virtually identical, indicating that either method is acceptable for sampling aerosols containing MPXV. The mass median aerodynamic diameter (MMAD) for individual aerosol tests in the aerosol system characterization and the NHP study ranged from 1.08 to 1.15 ?m, indicating that the aerosol particles were of a sufficient size to reach the alveoli. Six cynomolgus macaques (four male and two female) were used on study. The animals were aerosol exposed with MPXV and received doses between 2.51 × 10(4) to 9.28 × 10(5) plaque forming units (PFUs) inhaled. Four of the six animals died or were euthanized due to their moribund conditions. Both animals that received the lowest exposure doses survived to the end of the observation period. The inhalation LD(50) was determined to be approximately 7.8 × 10(4) pfu inhaled. These data demonstrate that an inhalation MPXV infection model has been developed in the cynomolgus macaque with disease course and lethal dose similar to previously published data. PMID:23061051
Barnewall, Roy E; Fisher, David A; Robertson, Ashley B; Vales, Pauline A; Knostman, Katherine A; Bigger, John E
The virological and cellular consequences of persistent hepatitis C virus (HCV) infection have been elusive due to the absence of the requisite experimental systems. Here, we report the establishment and the charac- teristics of persistent in vitro infection of human hepatoma-derived cells by a recently described HCV genotype 2a infectious molecular clone. Persistent in vitro infection was characterized by the
Jin Zhong; Pablo Gastaminza; Josan Chung; Zania Stamataki; Masanori Isogawa; Guofeng Cheng; Jane A. McKeating; Francis V. Chisari
Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with a global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FIV can cause an acquired immunodeficiency syndrome that increases the risk of developing opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia) and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less important as a deadly infectious agent as in the last 20 years prevalence has been decreasing in most countries. PMID:21807418
Several factors, such as age and nutritional status, can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virusinfections in rodent models. Influenza virus primarily infects and replicates in respiratory epithelial cells, which are also a major targets for inhaled DE. Using in vitro models of human respiratory epithelial cells, we determined the effects of an aqueous-trapped solution of DE (DE(as)) on influenza infections. Differentiated human nasal and bronchial epithelial cells, as well as A549 cells, were exposed to DE(as) and infected with influenza A/Bangkok/1/79. DE(as) enhanced the susceptibility to influenza virusinfection in all cell models and increased the number of influenza-infected cells within 24 h post-infection. This was not caused by suppressing antiviral mediator production, since interferon (IFN) beta levels, IFN-dependent signaling, and IFN-stimulated gene expression were also enhanced by exposure to DE(as). Many of the adverse effects induced by DE exposure are mediated by oxidative stress. Exposure to DE(as) used in these studies generated oxidative stress in respiratory epithelial cells, and addition of the antioxidant glutathione-ethylester (GSH-ET) reversed the effects of DE(as) on influenza infections. Furthermore, DE(as) increased influenza virus attachment to respiratory epithelial cells within 2 h post-infection. Taken together, the results presented here suggest that in human respiratory epithelial cells oxidative stress generated by DE(as) increases the susceptibility to influenza infection and that exposure to DE(as) increases the ability of the virus to attach to and enter respiratory epithelial cells. PMID:15772371
Jaspers, Ilona; Ciencewicki, Jonathan M; Zhang, Wenli; Brighton, Luisa E; Carson, Johnny L; Beck, Melinda A; Madden, Michael C
In 1999, an outbreak of human West Nile encephalitis occurred in New York City. During the outbreak, 62 cases of human West Nile virus (WNV) infection were diagnosed, with 7 deaths. This was the first time that human WNV infections were detected in the Western Hemisphere. By 2002, the total number of human cases of WNV that year alone reached
Investigations conducted in immunocompetent patients and blood donors have shown infections with the previously discovered blood-borne hepatitis G virus (HGV) to be fl'equent, mostly asymptomatic and transmissible by transfusions it, 2]. Yet the clinical impact of HGV infection is still unclear, particularly as far as members of high risk groups are concerned, such as intravenous drug users (!VDU), patients on
Y. Poovorawan; A. Theamboonlers; A. Surastian; P. Seksarn
In the summer of 1996, we screened 18,931 calves in 128 beef herds located in five US states for persistent bovine viral diarrhea virus (BVDV) infection. Of these, 76 herds were randomly selected from the client database of collaborating veterinary practices, and 52 herds were suspected by the collaborating veterinarians to have BVDV infection based on history or clinical signs.
T. E Wittum; D. M Grotelueschen; K. V Brock; W. G Kvasnicka; J. G Floyd; C. L Kelling; K. G Odde
Background: The relative contributions to risk of hepatitis C virus (HCV) infection resulting from unsafe sexual behaviours and exposures to blood (e.g., tattooing, body piercing and injection drug use) among youths at risk are not well known. We interviewed street youths about risk factors for HCV infection and docu- mented their HCV antibody status. Methods: From December 1995 to September
Respiratory syncytial virus, one of the most common causes of respiratory infections in immunocompetent individuals, is frequently spread to recipients of HSCT by family members, other patients, and health care workers. In immunosuppressed individuals, progression from upper respiratory tract disease to pneumonia is common, and usually fatal if left untreated. We performed a retrospective analysis of RSV infections in recipients
TN Small; A Casson; SF Malak; F Boulad; TE Kiehn; J Stiles; HM Ushay; KA Sepkowitz
Dapsone, administered at various doses and schedules, has been proven to be a safe and effective alternative to trimethoprim-sulfamethoxazole for prevention of Pneumocystis carinii pneumonia (PCP) in adults with human immunodeficiency virus (HIV) infection. Dapsone is also recommended by the Centers for Disease Control for PCP prophylaxis in HIV-infected children. However, the suggested dosage regimen is based upon clinical experience
GIORGIO GATTI; ANNA LOY; ROSETTA CASAZZA; FRANCA MILETICH; MARIO CRUCIANI
epatitis C (HCV) infection occurs in as many as 33% of the patients with human im- munodeficiency virus (HIV) infection. In view of their improved survival, liver disease will become more clinically significant in patients coinfected with HIV\\/HCV. Several studies in patients with hemophilia have shown that coinfected patients develop ear- lier and more severe liver disease, including hepatocellular carcinoma.
During 2010, an outbreak of West Nile virusinfection occurred in Greece. A total of 197 patients with neuroinvasive disease were reported, of whom 33 (17%) died. Advanced age and a history of heart disease were independently associated with death, emphasizing the need for prevention of this infection in persons with these risk factors.
Summary Focal meningoencephalitis is commonly caused by Herpes simplex virusinfection, which typically affects temporal or frontal lobes, and carries a mortality rate of 70% if untreated. On rare occasions, however, the infection is restricted to the brain stem. Polymerase chain reaction analysis of cerebrospinal fluid is the gold standard for the diagnosis of herpes simplex encephalitis. A 46-year-old male
Matjaz Jereb; Mitja Lainscak; Jozica Marin; Mara Popovic
OBJECTIVE: To study thyroid function in children infected with human immunodeficiency virus (HIV) and determine whether there are correlates of thyroid dysfunction with disease progression. STUDY DESIGN: Total and free thyroxine, triiodothyronine, reverse triiodothyronine, thyrotropin, and thyroxine binding globulin (TBG) were measured in 167 children with HIV infection (age, 1 to 19 years; mean, 9.15 years). SETTING: Pediatric Branch, National
Steven Hirschfeld; Louisa Laue; Gordon B. Cutler; Philip A. Pizzo
Foamy virus (FV) vectors have been demonstrated to transduce human hematopoietic stem cells with a high frequency. We have developed FV vectors that can block HIV infection with the intention of developing a therapeutic vector. Additional features of FV vectors that support their use in clinical gene therapy include: a) no evidence of disease from the prototypic FV in infected
Jason Taylor; Ingrid Bahner; Lucia Vojtech; Erik Olson; James Allen; Dorothee von Laer; Donald B. Kohn; David W. Russell; Robert E. Richard
Viral fusion proteins mediate cell entry by undergoing a series of conformational changes that result in virion-target cell membrane fusion. Class I viral fusion proteins, such as those encoded by influenza virus and human immunodeficiency virus (HIV), contain two prominent alpha helices. Peptides that mimic portions of these alpha helices inhibit structural rearrangements of the fusion proteins and prevent viral
Yancey M Hrobowski; Robert F Garry; Scott F Michael
Swine Influenza virus (SIV) infection and associated complications are a leading cause of morbidity and mortality. It is appreciated that SIV is often complicated by secondary bacterial infection. Tracheal epithelial cells (TEC) and pulmonary cells respond to infection with proinflammatory cytokin...
Hepatitis C virus (HCV) infection typically leads to antibody response within weeks after primary infection. Here, we describe the case of a child infected with HCV by mother-to-child transmission who remained persistently seronegative despite the presence of high levels of circulating HCV RNA.
Larouche, Ariane; Gaetan, Genevieve; El-Bilali, Nabil; Quesnel-Vallieres, Mathieu; Martin, Steven R.; Alvarez, Fernando; Shoukry, Naglaa H.
Background A 57 year old Italian female with a 3 year history of constituitional symptoms with non-HIV Kaposi sarcoma was referred to the immunology clinic. She was previously diagnosed with chronic human herpes virus 8 (HHV8) infection with positive HHV8 polymerase chain reaction in serum. Objective Is valganciclovir effective in treating chronic human herpes virus 8 infection without Multicentric Castleman's Disease (MCD)? Results She was started on valganciclovir, resulting in remission of her symptoms, improvement in inflammatory markers and clearing of detectable HHV8 viraemia Conclusion Valganciclovir is effective in treating symptomatic HHV8 infections without MCD.
Graves' disease (GD) is generally presented by thyrotoxicosis with hyperthyroidism, and it is an organ-specific autoimmune disease induced by thyroid-stimulating hormone receptor autoantibodies. However, among diverse etiologies, viral infections have been suggested to trigger or to be involved in the pathogenesis of GD. Hantaan virusinfection causing hemorrhagic fever with renal syndrome (HFRS) is common in South Korea and its pathogenesis is suggested to be an immunologic mechanism. We have experienced a patient who was diagnosed as HFRS with thyrotoxicosis. So we herein report the case as GD combined with the hantaan virusinfection.
Jin, Heung Yong; Kang, Seon Mee; Kim, So Young; Park, Ji Hyun; Baek, Hong Sun
In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4+ cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans.
Gomes, Juliana Assis Silva; de Araujo, Fernanda Fortes; Trindade, Giliane de Souza; Quinan, Barbara Resende; Drumond, Betania Paiva; Ferreira, Jaqueline Maria Siqueira; Mota, Bruno Eduardo Fernandes; Nogueira, Mauricio Lacerda; Kroon, Erna Geessien; Abrahao, Jonatas Santos; Correa-Oliveira, Rodrigo; da Fonseca, Flavio Guimaraes
The most common neuromuscular manifestation of West Nile virus (WNV) infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis) to four limbs (quadriparesis), with or without brainstem involvement and respiratory failure. This syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. Although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsible for neuromuscular signs, inflammation also may involve skeletal or cardiac muscle (myositis, myocarditis), motor axons (polyradiculitis), and peripheral nerves [GuillainBarré syndrome (GBS), brachial plexopathy]. In addition, involvement of spinal sympathetic neurons and ganglia provides an explanation for autonomic instability seen in some patients. Many patients also experience prolonged subjective generalized weakness and disabling fatigue. Despite recent evidence that WNV may persist long-term in the central nervous system or periphery in animals, the evidence in humans is controversial. WNV persistence would be of great concern in immunosuppressed patients or in those with prolonged or recurrent symptoms. Support for the contention that WNV can lead to autoimmune disease arises from reports of patients presenting with various neuromuscular diseases that presumably involve autoimmune mechanisms (GBS, other demyelinating neuropathies, myasthenia gravis, brachial plexopathies, stiff-person syndrome, and delayed or recurrent symptoms). Although there is no specific treatment or vaccine currently approved in humans, and the standard remains supportive care, drugs that can alter the cascade of immunobiochemical events leading to neuronal death may be potentially useful (high-dose corticosteroids, interferon preparations, and intravenous immune globulin containing WNV-specific antibodies). Human experience with these agents seems promising based on anecdotal reports.
The most common neuromuscular manifestation of West Nile virus (WNV) infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis) to four limbs (quadriparesis), with or without brainstem involvement and respiratory failure. This syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. Although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsible for neuromuscular signs, inflammation also may involve skeletal or cardiac muscle (myositis, myocarditis), motor axons (polyradiculitis), and peripheral nerves [Guillain-Barré syndrome (GBS), brachial plexopathy]. In addition, involvement of spinal sympathetic neurons and ganglia provides an explanation for autonomic instability seen in some patients. Many patients also experience prolonged subjective generalized weakness and disabling fatigue. Despite recent evidence that WNV may persist long-term in the central nervous system or periphery in animals, the evidence in humans is controversial. WNV persistence would be of great concern in immunosuppressed patients or in those with prolonged or recurrent symptoms. Support for the contention that WNV can lead to autoimmune disease arises from reports of patients presenting with various neuromuscular diseases that presumably involve autoimmune mechanisms (GBS, other demyelinating neuropathies, myasthenia gravis, brachial plexopathies, stiff-person syndrome, and delayed or recurrent symptoms). Although there is no specific treatment or vaccine currently approved in humans, and the standard remains supportive care, drugs that can alter the cascade of immunobiochemical events leading to neuronal death may be potentially useful (high-dose corticosteroids, interferon preparations, and intravenous immune globulin containing WNV-specific antibodies). Human experience with these agents seems promising based on anecdotal reports. PMID:22461779
It has been recognized that other than habitat loss, degradation and fragmentation, the infection of the roundworm Baylisascaris schroederi (B. schroederi) is one of the major causes of death in wild giant pandas. However, the prevalence and intensity of the parasite infection has been inconsistently reported through a method that uses sedimentation-floatation followed by a microscope examination. This method fails to accurately determine infection because there are many bamboo residues and/or few B. schroederi eggs in the examined fecal samples. In the present study, we adopted a method that uses PCR and capillary electrophoresis combined with a single-strand conformation polymorphism analysis (PCR/CE-SSCP) to detect B. schroederi infection in wild giant pandas at a nature reserve, and compared it to the traditional microscope approach. The PCR specifically amplified a single band of 279-bp from both fecal samples and positive controls, which was confirmed by sequence analysis to correspond to the mitochondrial COII gene of B. schroederi. Moreover, it was demonstrated that the amount of genomic DNA was linearly correlated with the peak area of the CE-SSCP analysis. Thus, our adopted method can reliably detect the infectious prevalence and intensity of B. schroederi in wild giant pandas. The prevalence of B. schroederi was found to be 54% in the 91 fecal samples examined, and 48% in the fecal samples of 31 identified individual giant pandas. Infectious intensities of the 91 fecal samples were detected to range from 2.8 to 959.2 units/gram, and from 4.8 to 959.2 units/gram in the fecal samples of the 31 identified giant pandas. For comparison, by using the traditional microscope method, the prevalence of B. schroederi was found to be only 33% in the 91 fecal samples, 32% in the fecal samples of the 31 identified giant pandas, and no reliable infectious intensity was observed. PMID:22911871
It has been recognized that other than habitat loss, degradation and fragmentation, the infection of the roundworm Baylisascaris schroederi (B. schroederi) is one of the major causes of death in wild giant pandas. However, the prevalence and intensity of the parasite infection has been inconsistently reported through a method that uses sedimentation-floatation followed by a microscope examination. This method fails to accurately determine infection because there are many bamboo residues and/or few B. schroederi eggs in the examined fecal samples. In the present study, we adopted a method that uses PCR and capillary electrophoresis combined with a single-strand conformation polymorphism analysis (PCR/CE-SSCP) to detect B. schroederi infection in wild giant pandas at a nature reserve, and compared it to the traditional microscope approach. The PCR specifically amplified a single band of 279-bp from both fecal samples and positive controls, which was confirmed by sequence analysis to correspond to the mitochondrial COII gene of B. schroederi. Moreover, it was demonstrated that the amount of genomic DNA was linearly correlated with the peak area of the CE-SSCP analysis. Thus, our adopted method can reliably detect the infectious prevalence and intensity of B. schroederi in wild giant pandas. The prevalence of B. schroederi was found to be 54% in the 91 fecal samples examined, and 48% in the fecal samples of 31 identified individual giant pandas. Infectious intensities of the 91 fecal samples were detected to range from 2.8 to 959.2 units/gram, and from 4.8 to 959.2 units/gram in the fecal samples of the 31 identified giant pandas. For comparison, by using the traditional microscope method, the prevalence of B. schroederi was found to be only 33% in the 91 fecal samples, 32% in the fecal samples of the 31 identified giant pandas, and no reliable infectious intensity was observed.
Treatment for human immunodeficiency virus (HIV) infection has enabled more children and youths to attend school and participate in school activities. Children and youths with HIV infection should receive the same education as those with other chronic illnesses. They may require special services, including home instruction, to provide continuity of education. Confidentiality about HIV infection status should be maintained with parental consent required for disclosure. Youths also should assent or consent as is appropriate for disclosure of their diagnosis. PMID:10835083
[3H]Uridine-labeled Rauscher leukemia virus was used to infect mouse embryo fibroblasts. After the infected cells were separated into nuclear and cytoplasmic fractions nucleic acid was extracted by sodium dodecyl sulfate-phenol-chloroform treatment and analyzed by Cs2SO4 and sucrose density gradient centrifugation. Between 45 and 70 min after infection a transient and synchronized shift of the acid-insoluble radioactive peak toward the RNA-DNA
Epstein-Barr virus infectious mononucleosis can cause transient immune deficiency which may predispose to reactivation of latent herpes simplex virus (HSV) infection in the immunocompetent host. We report the case of a 15-year-old male who presented with severe odynophagia and herpes labialis during the course of Epstein-Barr virus infectious mononucleosis that had been diagnosed ten days before. Esophagoscopy revealed extensive ulcerations
M. Tzouvala; A. Gaglia; N. Papantoniou; K. Triantafyllou; G. Karamanolis
LCM virus antigen was visualized in infected tissue cultures and mouse tissues by the direct immunofluorescent procedure. In all instances, antigen was localized to the cytoplasm. In intracerebrally infected mice, antigen was almost completely restricted to meninges, choroid plexus, and ependyma; at no time were neurons involved. Mice infected by intraperitoneal inoculation of a viscerotropic strain demonstrated antigen chiefly in liver parenchyma, splenic reticulum, bronchi, and alveolar cells. Congenitally infected mice showed antigen in almost all cell types observed, but generally in only a minority of cells; infection was often focal in distribution. Liver, kidney, pregnant uterus, and trophoblast were most extensively involved. No antigen was observable in ova of a pregnant mouse.
Worldwide, there are thousands of new cases of human immunodeficiency virus-1 (HIV-1) infection per day. The effectiveness of current combination antiretroviral therapy (ART) is relative; to prioritize finding vaccines and/or cure-oriented initiatives should be reinforced because there is little room, if any, for procrastination. Basic and clinical findings on HIV-1 reservoirs suggest that disruption of virus latency is feasible. Because the goal is curing HIV-1 infection, we should be aware that the challenge is to eradicate the viruses of every single infected cell and consequently acting upon virus latency is necessary but not sufficient. The large majority of the virus reservoir, CD4(+) T lymphocytes, is readily accessible but other minor reservoirs, where ART does not diffuse, require innovative strategies. The situation closely resembles that currently faced in the treatment of cancer. Exploiting the fact that histone deacetylase inhibitors, mainly vorinostat, may disrupt the latency of HIV-1, we propose to supplement this effect with a programmed interference in the metabolic stress of infected cells. Metformin and chloroquine are cheap and accessible modulators of pro-survival mechanisms to which viruses are constantly confronted to generate alternative energy sources and maximize virus production. Metformin restrains the use of the usurped cellular biosynthetic machinery by viral genes and chloroquine contributes to death of infected cells. We suggest that the combination of vorinostat, chloroquine and metformin should be combined with ART to pursue viral eradication in infected cells. PMID:23639282
Alonso-Villaverde, Carlos; Menéndez, Javier A; Joven, Jorge
SUMMARY Evidence is presented that defective interfering (DI) Semliki Forest virus (SFV) can modulate the systemic infection in mice initiated by intraperitoneal inoculation of l0 LDso SFV. Either the mean time of death was delayed or mice failed completely to develop any sign of disease. This prophylactic activity of DI virus was not due to the stimulation of an adaptive
A protocol is described to measure the protection of the bovine fetus against an experimental bovine virus diarrhea virus (BVDV) infection after vaccination.Two inactivated experimental vaccines were applied twice with a 3 week interval. A mixture of three different Dutch field strains was used as challenge on mainly the 82nd day of gestation to vaccinated and unvaccinated control animals. The
G. M. Zimmer; G. H. Wentink; C. Bruschke; F. J. Westenbrink; J. Brinkhof; I. de Goey
The threat of smallpox release and use as a bioweapon has encouraged the search for new vaccines and antiviral drugs, as well as development of new small-animal models in which their efficacy can be determined. Here, we reinvestigate a rabbit model in which the intradermal infection of rabbits with very low doses of either rabbitpox virus (RPV) or vaccinia virus
Human immunodeficiency virus (HIV) infection lead to a prolonged struggle between a rapidly evolving viral population and\\u000a a potent immune response. In the vast majority of infected individuals, the virus wins this struggle. In my laboratory, we\\u000a focus on understanding both the viral and immune factors that contribute to this outcome. The results of our studies and those\\u000a of many
Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes severe diseases in animals and humans. Endothelial cell (EC) infection is an established hallmark of NiV infection in vivo. Despite systemic virus spread via the vascular system, EC in brain and lung are preferentially infected whereas EC in other organs are less affected. As in vivo, we found differences in the infection of EC in cell culture. Only brain-derived primary or immortalized EC were found to be permissive to NiV infection. Using a replication-independent fusion assay, we could show that the lack of infection in non-brain EC was due to a lack of receptor expression. The NiV entry receptors ephrinB2 (EB2) or ephrinB3 were only expressed in brain endothelia. The finding that EB2 expression in previously non-permissive aortic EC rendered the cells permissive to infection then demonstrated that EB2 is not only necessary but also sufficient to allow the establishment of a productive NiV infection. This strongly suggests that limitations in receptor expression restrict virus entry in certain EC subsets in vivo, and are thus responsible for the differences in EC tropism observed in human and animal NiV infections.
Erbar, Stephanie; Diederich, Sandra; Maisner, Andrea
Epizootic subtype IAB and IC Venezuelan equine encephalitis viruses (VEEV) readily infect the epizootic mosquito vector Aedes taeniorhynchus. The inability of enzootic subtype IE viruses to infect this mosquito species provides a model system for the identification of natural viral determinants of vector infectivity. To map mosquito infection determinants, reciprocal chimeric viruses generated from epizootic subtype IAB and enzootic IE
We screened 1,200 living heart, lung, liver, and kidney transplant recipients for hepatitis E virusinfection by reverse transcription PCR. In 12 (1%) patients, hepatitis E virusinfection was identified; in 11 patients, chronic infection developed. This immunocompromised population is at risk for hepatitis E virusinfection.
Pas, Suzan D.; de Man, Rob A.; Mulders, Claudia; Balk, Aggie H.M.M.; van Hal, Peter T.W.; Weimar, Willem; Koopmans, Marion P.G.; Osterhaus, Albert D.M.E.
Sindbis virus, which belongs to the family Togaviridae genus Alphavirus infects a variety of vertebrate and invertebrate cells. The initial steps of Sindbis virusinfection involve attachment, penetration and uncoating. Two different pathways of infection have been proposed for Alphaviruses. One proposed mechanism involves receptor mediated virion endocytosis followed by membrane fusion triggered by endosome acidification. This virus-host membrane fusion model, well established by influenza virus, has been applied to other unrelated membrane-containing viruses including Alphaviruses. The other mechanism proposes direct penetration of the cell plasma membrane by the virus glycoproteins in the absence of membrane fusion. This alternate model is supported by both ultrastructural [Paredes, A.M., Ferreira, D., Horton, M., Saad, A., Tsuruta, H., Johnston, R., Klimstra, W., Ryman, K., Hernandez, R., Chiu, W., Brown, D.T., 2004. Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion. Virology 324(2), 373-386] and biochemical [Koschinski, A., Wengler, G., Wengler, G., and Repp, H., 2005. Rare earth ions block the ion pores generated by the class II fusion proteins of alphaviruses and allow analysis of the biological functions of these pores. J. Gen. Virol. 86(Pt. 12), 3311-3320] studies. We have examined the ability of Sindbis virus to infect Baby Hamster Kidney (BHK) cells at temperatures which block endocytosis. We have found that under these conditions Sindbis virusinfects cells in a temperature- and time-dependent fashion.
Wang Gongbo [Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695 (United States); Hernandez, Raquel [Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695 (United States); Weninger, Keith [Department of Physics, North Carolina State University, Raleigh, NC 27695 (United States); Brown, Dennis T. [Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695 (United States)]. E-mail: firstname.lastname@example.org
Domestic cats serve as the reservoir hosts of Bartonella henselae and may develop mild clinical symptoms or none after experimental infection. In humans, B. henselae infection can result in self-limiting cat scratch disease. However, immunocompromised patients may suffer from more-severe courses of infection or may even develop the potentially lethal disease bacillary angiomatosis. It was reasoned that cats with immunocompromising viral infections may react similarly to B. henselae infection. The aim of our study was to investigate the influence of the most important viruses known to cause immunosuppression in catsFeline leukemia virus (FeLV), Feline immunodeficiency virus (FIV), and Feline panleukopenia virus (FPV)on natural B. henselae infection in cats. Accordingly, 142 cats from animal shelters were necropsied and tested for B. henselae and concurrent infections with FeLV, FIV, or FPV by PCR and immunohistochemistry. A significant association was found between B. henselae and FeLV infections (P = 0.00028), but not between B. henselae and FIV (P = 1.0) or FPV (P = 0.756) infection, age (P = 0.392), or gender (P = 0.126). The results suggest that susceptibility to B. henselae infection is higher in cats with concurrent FeLV infections, regardless of whether the infection is latent or progressive. Histopathology and immunohistochemistry for B. henselae failed to identify lesions that could be attributed specifically to B. henselae infection. We conclude that the course of natural B. henselae infection in cats does not seem to be influenced by immunosuppressive viral infections in general but that latent FeLV infection may predispose cats to B. henselae infection or persistence.
Buchmann, Alexandra U.; Kershaw, Olivia; Kempf, Volkhard A. J.; Gruber, Achim D.
Domestic cats serve as the reservoir hosts of Bartonella henselae and may develop mild clinical symptoms or none after experimental infection. In humans, B. henselae infection can result in self-limiting cat scratch disease. However, immunocompromised patients may suffer from more-severe courses of infection or may even develop the potentially lethal disease bacillary angiomatosis. It was reasoned that cats with immunocompromising viral infections may react similarly to B. henselae infection. The aim of our study was to investigate the influence of the most important viruses known to cause immunosuppression in cats-Feline leukemia virus (FeLV), Feline immunodeficiency virus (FIV), and Feline panleukopenia virus (FPV)-on natural B. henselae infection in cats. Accordingly, 142 cats from animal shelters were necropsied and tested for B. henselae and concurrent infections with FeLV, FIV, or FPV by PCR and immunohistochemistry. A significant association was found between B. henselae and FeLV infections (P = 0.00028), but not between B. henselae and FIV (P = 1.0) or FPV (P = 0.756) infection, age (P = 0.392), or gender (P = 0.126). The results suggest that susceptibility to B. henselae infection is higher in cats with concurrent FeLV infections, regardless of whether the infection is latent or progressive. Histopathology and immunohistochemistry for B. henselae failed to identify lesions that could be attributed specifically to B. henselae infection. We conclude that the course of natural B. henselae infection in cats does not seem to be influenced by immunosuppressive viral infections in general but that latent FeLV infection may predispose cats to B. henselae infection or persistence. PMID:20610682
Buchmann, Alexandra U; Kershaw, Olivia; Kempf, Volkhard A J; Gruber, Achim D
The mechanism by which the hepatitis C virus (HCV) causes chronic, progressive liver damage is unknown. Factors other than the virus itself have been implicated. The role of liver steatosis has been recently studied. Hepatic steatosis is a common histological finding occurring in more 50% of patients with chronic hepatitis C. Both host and viral factors have been demonstrated to
Background From 2001-2003 monodon slow growth syndrome (MSGS) caused severe economic losses for Thai shrimp farmers who cultivated the native, giant tiger shrimp, and this led them to adopt exotic stocks of the domesticated whiteleg shrimp as the species of cultivation choice, despite the higher value of giant tiger shrimp. In 2008, newly discovered Laem-Singh virus (LSNV) was proposed as a necessary but insufficient cause of MSGS, and this stimulated the search for the additional component cause(s) of MSGS in the hope that discovery would lead to preventative measures that could revive cultivation of the higher value native shrimp species. Results Using a universal shotgun cloning protocol, a novel RNA, integrase-containing element (ICE) was found in giant tiger shrimp from MSGS ponds (GenBank accession number FJ498866). In situ hybridization probes and RT-PCR tests revealed that ICE and Laem-Singh virus (LSNV) occurred together in lymphoid organs (LO) of shrimp from MSGS ponds but not in shrimp from normal ponds. Tissue homogenates of shrimp from MSGS ponds yielded a fraction that gave positive RT-PCR reactions for both ICE and LSNV and showed viral-like particles by transmission electron microscopy (TEM). Bioassays of this fraction with juvenile giant tiger shrimp resulted in retarded growth with gross signs of MSGS, and in situ hybridization assays revealed ICE and LSNV together in LO, eyes and gills. Viral-like particles similar to those seen in tissue extracts from natural infections were also seen by TEM. Conclusions ICE and LSNV were found together only in shrimp from MSGS ponds and only in shrimp showing gross signs of MSGS after injection with a preparation containing ICE and LSNV. ICE was never found in the absence of LSNV although LSNV was sometimes found in normal shrimp in the absence of ICE. The results suggest that ICE and LSNV may act together as component causes of MSGS, but this cannot be proven conclusively without single and combined bioassays using purified preparations of both ICE and LSNV. Despite this ambiguity, it is recommended in the interim that ICE be added to the agents such as LSNV already listed for exclusion from domesticated stocks of the black tiger shrimp.
To determine if a specific pathogenic threshold of plasma viral RNA could be defined irrespective of virus strain, RNA levels in the plasma of more than 50 infected rhesus macaques (Macaca mulatta) were measured. Animals were inoculated intravenously with either simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) strains of known pathogenic potential (SIV8980, SIVsmm-3, SIVmac32H\\/J5, SIVmac32H\\/1XC, reverse transcriptase-SHIV,
PETER TEN HAAFT; BABS VERSTREPEN; KLAUS UBERLA; BRIGITTE ROSENWIRTH; JONATHAN HEENEY
To determine the proportion of acute undifferentiated fevers without neurologic deficits related to infection with Japanese encephalitis (JE) virus, flavivirus serology (dengue and JE) was performed in a cohort of 156 adults presenting to a hospital in Chiangrai, Thailand. Recent flavivirus infection was diagnosed for any individual with an IgM result > 40 units. A ratio of dengue virus IgM to JE virus IgM < 0.91 defined a JE virusinfection. Diagnostic criteria for Japanese encephalitis were met in 22 individuals (14%), and were unequivocal in 8 patients. The admission findings in these eight subjects were similar to those described for other flavivirus infections. Thrombocytopenia was the most striking laboratory abnormality (median platelet count = 119,000/mm3, range = 44,000-236,000/mm3). Headache (75%), nausea (50%), myalgia (38%), rash (38%), and diarrhea (25%) were the most frequently encountered signs and symptoms. Infection with Japanese encephalitis virus is an underappreciated cause of acute undifferentiated fever in Asia. PMID:12887030
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share a common route of transmission so that about one third of HIV infected individuals show HCV co-infection. Highly active antiretroviral therapy has offered a longer and better life to infected patients. While has removed AIDS-related diseases from the list of most common causes of death their place has been taken by complications of HCV infection, such as cirrhosis, end stage liver disease and hepatocellular carcinoma (HCC). HIV/HCV co-infection requires complex management, especially when HCC is present. Co-infected patients with HCC undergo the same therapeutic protocol as their mono-infected counterparts, but special issues such as interaction between regimens, withdrawal of therapy and choice of immunosuppressive agents, demand a careful approach by specialists. All these issues are analyzed in this minireview. PMID:23805356
Simian immunodeficiency virus (SIV) SIVsmm naturally infects sooty mangabeys (SMs) and is the source virus of pathogenic infections with human immunodeficiency virus type 2 (HIV-2) and SIVmac of humans and macaques, respectively. In previous studies we characterized SIVsmm diversity in naturally SIV-infected SMs and identified nine different phylogenetic subtypes whose genetic distances are similar to those reported for the different HIV-1 group M subtypes. Here we report that, within the colony of SMs housed at the Yerkes National Primate Research Center, at least four SIVsmm subtypes cocirculate, with the vast majority of animals infected with SIVsmm subtype 1, 2, or 3, resulting in the emergence of occasional recombinant forms. While SIVsmm-infected SMs show a typically nonpathogenic course of infection, we have observed that different SIVsmm subtypes are in fact associated with specific immunologic features. Notably, while subtypes 1, 2, and 3 are associated with a very benign course of infection and preservation of normal CD4+ T-cell counts, three out of four SMs infected with subtype 5 show a significant depletion of CD4+ T cells. The fact that virus replication in SMs infected with subtype 5 is similar to that in SMs infected with other SIVsmm subtypes suggests that the subtype 5-associated CD4+ T-cell depletion is unlikely to simply reflect higher levels of virus-mediated direct killing of CD4+ T-cells. Taken together, this systematic analysis of the subtype-specific features of SIVsmm infection in natural SM hosts identifies subtype-specific differences in the pathogenicity of SIVsmm infection.
A yearling quarter horse, which was raised in southern California, received routine vaccinations for prevention of infection by Eastern equine encephalomyelitis virus (EEEV). One week later, severe neurologic signs developed, and the horse was humanely destroyed because vaccine-related encephalomyelitis was suspected. A final diagnosis of EEEV infection was established on the basis of acute onset of the neurologic signs, histopathologic and serologic testing, and isolation and molecular characterization of EEEV from brain tissue. The vaccine was extensively tested for viral inactivation. Nucleotide sequences from the vaccine and the virus isolated in the affected horse were also compared. In California, arboviral encephalomyelitides are rarely reported, and EEEV infection has not previously been documented. This report describes the occurrence of EEEV infection in the horse and the investigation to determine the source of infection, which was not definitively identified.
Kinde, Hailu; Jay, Michele T.; Kramer, Laura D.; Green, Emily-Gene N.; Chiles, Robert E.; Ostlund, Eileen; Husted, Stan; Smith, Jonathan; Parker, Michael D.
Chicken anaemia virus (CAV) is a small virus of a unique type with a particle diameter of 23 to 25 nm and a genome consisting of a circular single?stranded (minus?strand) DNA. This DNA multiplies in infected cells via a circular double?stranded replicative intermediate, which was recently cloned. DNA analysis of CAV strains isolated in different continents revealed only minor differences
Summary. Young adult and weanling pigs were challenged with the New York 99 strain of West Nile virus through the bite of infected mosquitoes. Each of six adult pigs seroconverted, but virus was isolated from serum of only one pig following challenge. Three of five weanling pigs developed viremia, with peak titers of 101.9 and 103.1?PFU\\/mL. Clinical signs attributable to
M. L. Teehee; M. L. Bunning; S. Stevens; R. A. Bowen
The first human virus in the genus Cardiovirus was described in 2007 and named Saffold virus (SAFV). Cardioviruses can cause severe infections of the myocardium and central nervous system in animals, but SAFV has not yet been convincingly associated with disease in humans. To study a possible association between SAFV and infections in the human central nervous system, we designed a real-time PCR for SAFV and tested cerebrospinal fluid (CSF) samples from children <4 years of age. SAFV was detected in 2 children: in the CSF and a fecal sample from 1 child with monosymptomatic ataxia caused by cerebellitis; and in the CSF, blood, and myocardium of another child who died suddenly with no history of illness. Virus from each child was sequenced and shown to be SAFV type 2. These findings demonstrate that SAFV can cause serious invasive infection in children. PMID:22261113
Nielsen, Alex Christian Yde; Böttiger, Blenda; Banner, Jytte; Hoffmann, Thomas; Nielsen, Lars Peter
Recent RNA interference (RNAi) studies have identified many host proteins that modulate virusinfection, but small interfering RNA off-target effects and the use of transformed cell lines limit their conclusiveness. As murine embryonic stem (mES) cells can be genetically modified and resources exist where many and eventually all known mouse genes are insertionally inactivated, it was reasoned that mES cells would provide a useful alternative to RNAi screens. Beyond allowing investigation of hostpathogen interactions in vitro, mES cells have the potential to differentiate into other primary cell types, as well as being used to generate knockout mice for in vivo studies. However, mES cells are poorly characterized for virusinfection. To investigate whether ES cells can be used to explore hostvirus interactions, this study characterized the responses of mES cells following infection by herpes simplex virus type 1 (HSV-1) and influenza A virus. HSV-1 replicated lytically in mES cells, although mES cells were less permissive than most other cell types tested. Influenza virus was able to enter mES cells and express some viral proteins, but the replication cycle was incomplete and no infectious virus was produced. Knockdown of the host protein AHCYL1 in mES cells reduced HSV-1 replication, showing the potential for using mES cells to study hostvirus interactions. Transcriptional profiling, however, indicated the lack of an efficient innate immune response in these cells. mES cells may thus be useful to identify host proteins that play a role in virus replication, but they are not suitable to determine factors that are involved in innate host defence.
Rice-infectingviruses have caused serious damage to rice production in Asian, American, and African countries, where about 30 rice viruses and diseases have been reported. To control these diseases, developing accurate, quick methods to detect and diagnose the viruses in the host plants and any insect vectors of the viruses is very important. Based on an antigenantibody reaction, serological methods such as latex agglutination reaction and enzyme-linked immunosorbent assay have advanced to detect viral particles or major proteins derived from viruses. They aid in forecasting disease and surveying disease spread and are widely used for virus detection at plant protection stations and research laboratories. From the early 2000s, based on sequence information for the target virus, several other methods such as reverse transcription-polymerase chain reaction (RT-PCR) and reverse transcription-loop-mediated isothermal amplification have been developed that are sensitive, rapid, and able to differentiate closely related viruses. Recent techniques such as real-time RT-PCR can be used to quantify the pathogen in target samples and monitor population dynamics of a virus, and metagenomic analyses using next-generation sequencing and microarrays show potential for use in the diagnosis of rice diseases.
Marburg and Ebola viruses can cause large hemorrhagic fever (HF) outbreaks with high case fatality (8090%) in human and great apes. Identification of the natural reservoir of these viruses is one of the most important topics in this field and a fundamental key to understanding their natural history. Despite the discovery of this virus family almost 40 years ago, the search for the natural reservoir of these lethal pathogens remains an enigma despite numerous ecological studies. Here, we report the discovery of Marburg virus in a common species of fruit bat (Rousettus aegyptiacus) in Gabon as shown by finding virus-specific RNA and IgG antibody in individual bats. These Marburg virus positive bats represent the first naturally infected non-primate animals identified. Furthermore, this is the first report of Marburg virus being present in this area of Africa, thus extending the known range of the virus. These data imply that more areas are at risk for MHF outbreaks than previously realized and correspond well with a recently published report in which three species of fruit bats were demonstrated to be likely reservoirs for Ebola virus.
Towner, Jonathan S.; Pourrut, Xavier; Albarino, Cesar G.; Nkogue, Chimene Nze; Bird, Brian H.; Grard, Gilda; Ksiazek, Thomas G.; Gonzalez, Jean-Paul; Nichol, Stuart T.; Leroy, Eric M.
Allergic processes play a very significant role in the clinical picture of many viral diseases. The macromolecular formations, which appear in the developing processes of the virus and the destruction of the organism's cells, form special antigenic substa...
Neutral protease activity of allantoic fluid from embryonated chicken eggs was quantified during the course of influenza virusinfection. Antigenic subtypes of influenza A viruses selected for study were H1N1 strains PR/8/34, Brazil/8/78, FM/1/47, the H3N2 strain Bangkok/1/80 and the H5N9 Turkey/ /Ontario/66 as well as the Sendai strain of parainfluenza type 1 virus. Three different types of profiles of allantoic fluid proteases could be readily distinguished after infection of eggs with various virus strains. In all profiles, periodic peaks of protease activity always preceded the partial shut down of protamine cleaving proteases which paralleled the production of near maximum titers of infectious virus. To determine the mechanism involved in this reduction of proteolytic activity, infectious allantoic fluids were analysed for the presence of protease inhibitors. Acid heat treated 48 hour virus-infected allantoic fluids of different influenza strains could inhibit the activities of subtilisin and allantoic fluid proteolytic enzymes. PMID:2873727
C3H mice chronically infected with LCM virus were found to be lethally affected by small doses of immunosuppression which caused bone marrow aplasia but had no effect on the amount of virus carried by the mouse. Humoral immune response of SWR/J mice to acute LCM infection was found to be totally suppressed by repeated single doses of 300 R/wk with no alteration in the level of virus carried by the mouse. In contrast, the established anti-LCM humoral immune response encountered in mice chronically infected with LCM virus was not suppressed by the same irradiation procedure. Over half of the chronic LCM carrier SWR/J mice treated with cyclophosphamide for 6 mo had total anti-LCM humoral immunosuppression, but showed no change in the level of virus carried. The glomerulonephritis which occurs in chronic LCM carrier mice was prevented by cyclophosphamide treatment in 90% of the mice. The humoral immune response which occurs in chronic LCM carrier mice appears to play no role in controlling the amount of virus carried by the mouse. Suppression of the LCM immune response by cyclophosphamide does prevent the development of glomerulonephritis in these mice.
This study describes the prevalence and association of Torque teno virus (TTV) infection with blood-transmitted viral hepatitis including hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in patients with chronic renal failure (CRF) on maintenance hemodialysis (HD). TTV infection was diagnosed by detection of TTV-DNA in serum, using the polymerase chain reaction (PCR) technique. TTV-DNA was estimated in a total number of one hundred patients with CRF and in 100 voluntary blood donors as controls. The markers of HBV and HCV were also tested in sera samples of these patients. TTV-DNA was detected in 39 of 100 patients (39%) with CRF and in 27 of 100 (27%) healthy controls. The analysis of the results demonstrated HBsAg, IgM anti-HBc, anti-HCV, and HCV core antigen in 5.0, 3.0, 6.0, and 4.0% of patients, respectively. This study could not show any association of TTV with HBV and HCV infections for the transmission pattern or any impact on severity of diseases caused by these viruses in CRF patients. TTV also could not show any association with demographic characteristics of patients, duration of dialysis, number of blood transfusions and renal/liver function of the patients. As such, this study concludes that TTV appears as a benign pathogen, showing no sign of renal/liver damage or any change in the severity of diseases caused by blood-borne hepatitis viruses. PMID:19777363
Irshad, Mohammad; Mandal, Kishore; Singh, Shiwani; Agarwal, S K
Since the discovery of hepatitis C virus (HCV) by molecular cloning almost a quarter of a century ago, unprecedented at the time because the virus had never been grown in cell culture or detected serologically, there have been impressive strides in many facets of our understanding of the natural history of the disease, the viral life cycle, the pathogenesis, and antiviral therapy. It is apparent that the virus has developed multiple strategies to evade immune surveillance and eradication. This Review covers what we currently understand of the temporal and spatial immunological changes within the human innate and adaptive host immune responses that ultimately determine the outcomes of HCV infection. PMID:24084744
African swine fever virus (ASFV) is an arbovirus which is vectored by soft ticks of the Ornithodoros spp. and in the sylvatic cycle infects wart hogs and bush pigs. ASFV infection of domestic swine causes a high mortality disease. On the other hand, ASFV infection of the tick can result in a high-titered and persistent infection depending upon the ASFV isolate and the tick combination. Recently, morphological, classical virology (titration) and recombinant ASFV have been used to study the cellular, molecular and genetic interactions that occur between ASFV and its host tick. PMID:23085123
Extremophilic archaea, both hyperthermophiles and halophiles, dominate in habitats where rather harsh conditions are encountered. Like all other organisms, archaeal cells are susceptible to viral infections, and to date, about 100 archaeal viruses have been described. Among them, there are extraordinary virion morphologies as well as the common head-tailed viruses. Although approximately half of the isolated archaeal viruses belong to the latter group, no three-dimensional virion structures of these head-tailed viruses are available. Thus, rigorous comparisons with bacteriophages are not yet warranted. In the present study, we determined the genome sequences of two of such viruses of halophiles and solved their capsid structures by cryo-electron microscopy and three-dimensional image reconstruction. We show that these viruses are inactivated, yet remain intact, at low salinity and that their infectivity is regained when high salinity is restored. This enabled us to determine their three-dimensional capsid structures at low salinity to a ?10-Å resolution. The genetic and structural data showed that both viruses belong to the same T-number class, but one of them has enlarged its capsid to accommodate a larger genome than typically associated with a T=7 capsid by inserting an additional protein into the capsid lattice. PMID:23283946
Pietilä, Maija K; Laurinmäki, Pasi; Russell, Daniel A; Ko, Ching-Chung; Jacobs-Sera, Deborah; Butcher, Sarah J; Bamford, Dennis H; Hendrix, Roger W
Extremophilic archaea, both hyperthermophiles and halophiles, dominate in habitats where rather harsh conditions are encountered. Like all other organisms, archaeal cells are susceptible to viral infections, and to date, about 100 archaeal viruses have been described. Among them, there are extraordinary virion morphologies as well as the common head-tailed viruses. Although approximately half of the isolated archaeal viruses belong to the latter group, no three-dimensional virion structures of these head-tailed viruses are available. Thus, rigorous comparisons with bacteriophages are not yet warranted. In the present study, we determined the genome sequences of two of such viruses of halophiles and solved their capsid structures by cryo-electron microscopy and three-dimensional image reconstruction. We show that these viruses are inactivated, yet remain intact, at low salinity and that their infectivity is regained when high salinity is restored. This enabled us to determine their three-dimensional capsid structures at low salinity to a ?10-Å resolution. The genetic and structural data showed that both viruses belong to the same T-number class, but one of them has enlarged its capsid to accommodate a larger genome than typically associated with a T=7 capsid by inserting an additional protein into the capsid lattice.
Pietila, Maija K.; Laurinmaki, Pasi; Russell, Daniel A.; Ko, Ching-Chung; Jacobs-Sera, Deborah; Butcher, Sarah J.
The histopathology of Machupo virusinfection in intracerebrally inoculated suckling hamsters was studied and compared to the histopathology of a virus isolated from a case of hemorrhagic fever from Cochabamba, Bolivia. Both virus isolates were pathogenic...
J. L. Stookey R. O. Spertzel R. W. Kuehne T. G. Terrell
It is thought that interference during human immunodeficiency virus type 1 (HIV-1) infection is established by downmodulation of the principal virus receptor, CD4. Here we present evidence to the contrary. At various times after primary infection, we superinfected T cells in vitro by exposure to a genetically distinct viral clone or to a virus carrying the chloramphenicol acetyltransferase gene. Replication
DAVID J. VOLSKY; MALGORZATA SIMM; MUHAMMAD SHAHABUDDIN; GONGRONG LI; WEI CHAO; ANDMARY JANE POTASH
The long-term persistence of Modoc virus (MODV) infection was investigated in a hamster model. Golden hamsters (Mesocricetus auratus) were infected by subcutaneous inoculation with MODV, in which fatal encephalitis developed in 12.5% (2 of 16). Surviving hamsters shed infectious MODV in their urine during the first five months after infection, and infectious MODV was recovered by co-cultivation of kidney tissue up to eight months after infection. There were no histopathologic changes observed in the kidneys despite detection of viral antigen for 250 days after infection. Mild inflammation and neuronal degeneration in the central nervous system were the primary lesions observed during early infection. These findings confirm previous reports of persistent flavivirus infection in animals and suggest a mechanism for the maintenance of MODV in nature. PMID:23358636
Adams, A Paige; Travassos da Rosa, Amelia P A; Nunes, Marcio R; Xiao, Shu-Yuan; Tesh, Robert B
Although neurological manifestations associated with dengue infections have been reported in endemic countries, the viral or host characteristics determining the infection or alteration of nervous function have not been described. In order to investigate neurobiological conditions related to central nervous system dengue virus (DENV) infection, we established a mouse model of neuroinfection. A DENV-4 isolate was first adapted to neuroblastoma cells, later inoculated in suckling mice brain, and finally, this D4MB-6 viral variant was inoculated intraperitoneally in Balb/c mice at different postnatal days (pnd). Virus-induced fatal encephalitis in 2 and 7 pnd mice but infected at 14 and 21 pnd mice survived. The younger mice presented encephalitis at the sixth day postinfection with limb paralysis and postural instability concomitant with efficient viral replication in brain. In this mice model, we found activated microglial cells positive to viral antigen. Neurons, oligodendrocytes, and endothelial cells were also infected by the D4MB-6 virus in neonatal mice, which showed generalized and local plasma leakage with blood-brain barrier (BBB) severe damage. These results suggest that there was a viral fitness change which led to neuroinfection only in immune or neurological immature mice. Infection of neurons, endothelial, and microglial cells may be related to detrimental function or architecture found in susceptible mice. This experimental neuroinfection model could help to have a better understanding of neurological manifestations occurring during severe cases of dengue infection. PMID:22825914
Velandia-Romero, Myriam Lucia; Acosta-Losada, Orlando; Castellanos, Jaime E
Background Tahyna virus (TAHV) is a human pathogen of the California encephalitis virus (CEV) serogroup (Bunyaviridae) endemic to Europe, Asia, and Africa. TAHV maintains an enzootic life cycle with several species of mosquito vectors and hares, rabbits, hedgehogs, and rodents serving as small mammal amplifying hosts. Human TAHV infection occurs in summer and early fall with symptoms of fever, headache, malaise, conjunctivitis, pharyngitis, and nausea. TAHV disease can progress to CNS involvement, although unlike related La Crosse virus (LACV), fatalities have not been reported. Human infections are frequent with neutralizing antibodies present in 60-80% of the elderly population in endemic areas. Results In order to determine the genomic sequence of wild-type TAHV, we chose three TAHV isolates collected over a 26-year period from mosquitoes. Here we present the first complete sequence of the TAHV S, M, and L segments. The three TAHV isolates maintained a highly conserved genome with both nucleotide and amino acid sequence identity greater than 99%. In order to determine the extent of genetic relatedness to other members of the CEV serogroup, we compared protein sequences of TAHV with LACV, Snowshoe Hare virus (SSHV), Jamestown Canyon virus (JCV), and Inkoo virus (INKV). By amino acid comparison, TAHV was most similar to SSHV followed by LACV, JCV, and INKV. The sequence of the GN protein is most conserved followed by L, N, GC, NSS, and NSM. In a weanling Swiss Webster mouse model, all three TAHV isolates were uniformly neurovirulent, but only one virus was neuroinvasive. In rhesus monkeys, the virus was highly immunogenic even in the absence of viremia. Cross neutralization studies utilizing monkey immune serum demonstrated that TAHV is antigenically distinct from North American viruses LACV and JCV. Conclusions Here we report the first complete sequence of TAHV and present genetic analysis of new-world viruses, LACV, SSHV, and JCV with old-world viruses, TAHV and INKV. Using immune serum generated in monkeys against TAHV, LACV, and JCV, we have demonstrated cross-neutralization within the CEV serogroup. Such cross reactivity may complicate virus identification, especially following JCV infection which elicited antibodies that cross neutralized both LACV and TAHV. These data also suggest that a single vaccine could generate a cross-neutralizing antibody response which may provide protection against CEV serogroup viruses from a wide geographic range.
Transovarial transmission of California encephalitis (CE) virus was shown to occur in Aedes melanimon collected in the Sacramento amd San Joaquin Valleys and experimentally infected with virus in the laboratory. When parental females were infected with CE...
Quantitation of the hepatitis C virus (HCV) provides a powerful epidemiologic and therapeutic method for the evaluation of infected patients. In this study semiquantitative reverse transcriptase polymerase chain reaction (PCR) is compared with a new branched DNA signal amplification methodology. Samples from HCV-infected patients as well as from human immunodeficiency virus-infected patients were evaluated. Reverse transcriptase PCR correlated well with the branched DNA assay (r = 0.7036, P < 0.05). HCV RNA was found to occur at significantly higher titers (P < 0.05) in patients coinfected with the human immunodeficiency virus compared with titers in those infected with HCV alone. Immune status as defined by the CD4+ count was not associated with the observed difference in viral titer. PMID:8253965
Sherman, K E; O'Brien, J; Gutierrez, A G; Harrison, S; Urdea, M; Neuwald, P; Wilber, J
Influenza viruses are important human pathogens, associated throughout history with worldwide outbreaks and pandemics. The antiviral effects of interferon (IFN)-?s/? against influenza virusinfections are well recognized, yet the mechanisms whereby IFNs exert their immunomodulatory effects on an anti-influenza response remain ill-defined. Here, we describe the effects of IFN-? treatment on the immune response during a respiratory influenza (A/WSN/33) A virusinfection of mice. A single dose of IFN-? (1×10(5)U) enhanced DC migration into the draining lymph node (DLN) on day 3 post-intranasal infection, and subsequently inhibited the migration from the lungs into the DLN of a newly identified late activator antigen-presenting cell population associated with type 2 immunity, LAPC. IFN-? treatment polarized the immune response towards a type 1 immune response, eliciting enhanced T(H)1 effector and cytolytic T cell responses, but diminished T(H)2 effector T cell responses in both the DLN and lung tissues of influenza virus-infected mice. Associated with the polarization towards a type 1 immune response, IFN-? treatment of mice resulted in accelerated viral clearance and diminished pulmonary eosinophilia in infected lung tissues. PMID:20659503
Apoptosis is one of several mechanisms by which human immunodeficiency virus type 1 (HIV-1) exerts its cytopathic effects. CD4+ Jurkat T-cell lines overexpressing the adenovirus E1B 19K protein, a potent inhibitor of apoptosis, were used to examine the consequences of inhibition of apoptosis during acute and chronic HIV-1 infections. E1B 19K protein expression inhibited HIV-induced apoptosis, enhanced virus production, and established high levels of persistent viral infection. One E1B 19K-expressing line appeared to undergo HIV-induced death via a nonapoptotic mechanism, illustrating that HIV infection results in lymphocyte depletion through multiple pathways. Increased virus production associated with sustained cell viability suggests that therapeutic approaches involving inhibition of HIV-induced programmed cell death may be problematic.
Background Although a marked proportion of thalassemic patients acquire Torque teno virus (TTV) through blood transfusion, its clinical importance is unclear. This study was designed to investigate the clinical importance of TTV infection in thalassemic patients with and without hepatitis C virus (HCV) co-infection in Iran. Methods In this case-control study, 107 thalassemic patients on chronic transfusion and 107 healthy individuals were selected. According to HCV and TTV infection status (detected by semi-nested PCR), patients were categorized into 4 groups: TTV and HCV negative, TTV positive, HCV positive, and TTV and HCV positive. Blood ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in these 4 groups were assessed. Results Approximately half of the thalassemic patients (50.5%) and 27.1% of controls had TTV infection. Thalassemic patients had a greater chance of TTV infection compared to the control group with a sex-adjusted OR of 4.13 (95% CI=2.28-8.13). The increased levels of ALT, AST, and ferritin in the TTV and HCV-infected group were not significantly different from those in the TTV and HCV negative group. Co-infection with TTV and HCV did not significantly increase ALT, AST, and ferritin levels compared to infection with TTV alone. Conclusion Although common in thalassemic patients, TTV infection appears to have a negligible role in increasing the severity of liver disease, even when co-infection with HCV occurs.
Vaccination against virusinfections has proven to be an effective strategy in the improvement of human health. In this study, we evaluated two plasmid DNA vaccines expressing the glycoprotein (G) gene of the challenge virus standard (CVS) rabies virus for their ability to elicit neutralizing antibody and protect BALB\\/cByJ mice against lethal rabies virus challenge. A single inoculation of 10
Objective: Herpes simplex virus 1 (HSV1) is a widespread virus that primarily causes orofacial infection. Methods: We present a case of HSV1 infection on a free radial forearm flap used to reconstruct a palate defect. Initially, the free flap appeared healthy; however, after 48 hours the free flap appeared in distress, with dark red colour and fast capillary refill. Venous congestion was suspected, and the patient underwent a second operation where no vascular compromise was found. Vesicles were noted on the free flap; swabs revealed HSV1 infection. Results: Complete recovery of the free flap was achieved with acyclovir. Discussion: To the best of our knowledge, this is the first report of HSV1 infection on a free flap that was found to be responsible for the free flap appearing distressed.
To determine whether bonnet monkeys are susceptible to infection and disease due to respiratory syncytial virus (RSV), 4 juvenile bonnet monkeys (Macaca radiata) were inoculated with RSV intratracheally and sacrificed at 3, 5, 7 and 9 days post infection. RSV was cultured from pre-autopsy broncheoalveolar lavage fluid from all 4 animals with a peak titre of virus on day 9. Serum RSV neutralizing antibody was present by day 7. Animals developed tachypnoea and chest retractions by 5th day post infection and 2 animals had lobular pneumonia on chest radiography. The pathological changes were of a bronchovascular inflammation, interstitial pneumonia and alveolitis, akin to that seen in humans. These findings show that bonnet monkeys can be infected with RSV, and can develop immune response and clinical and pathological changes similar to those seen in human infants with RSV disease. Thus intractracheal RSV inoculation of juvenile bonnet monkeys appears to be a good model to study pathogenesis of RSV disease. PMID:9838875
Babu, P G; Selvan, A; Christuraj, S; David, J; John, T J; Simoes, E A
Detection of West Nile virus (WNV) RNA in urine has been anecdotally described and proposed for the diagnosis of WNV infection. This study reports the routine use of real-time reverse-transcription polymerase chain reaction for the detection of WNV RNA in urine to support diagnosis of WNV infection during the large outbreak that occurred in northeastern Italy in 2012. Fourteen of 32 patients (43.8%) with symptomatic WNV infection, defined as neuroinvasive disease and fever, had detectable WNV RNA in urine at the time of diagnosis, at a higher rate and load and for a longer time than detection of WNV RNA in blood. Detection of WNV RNA in urine was less frequent (2 of 14 patients [14.2%]) in blood donors in whom WNV infection was identified by WNV nucleic acid amplification testing. Infectious virus was isolated from the urine of a patient with neuroinvasive disease and a high WNV RNA load in urine. PMID:23821721
The mechanisms underlying the development of disease during arenavirus infection are poorly understood. However, common to all hemorrhagic fever diseases is the involvement of macrophages as primary target cells, suggesting that the immune response in these cells may be of paramount importance during infection. Thus, in order to identify features of the immune response that contribute to arenavirus pathogenesis, we have examined the growth kinetics and cytokine profiles of two closely related New World arenaviruses, the apathogenic Tacaribe virus (TCRV) and the hemorrhagic fever-causing Junin virus (JUNV), in primary human monocytes and macrophages. Both viruses grew robustly in VeroE6 cells; however, TCRV titres were decreased by approximately 10 fold compared to JUNV in both monocytes and macrophages. Infection of both monocytes and macrophages with TCRV also resulted in the release of high levels of IL-6, IL-10 and TNF-?, while levels of IFN-?, IFN-? and IL-12 were not affected. However, we could show that the presence of these cytokines had no direct effect on growth of either TCRV of JUNV in macrophages. Further analysis also showed that while the production of IL-6 and IL-10 are dependent on viral replication, production of TNF-? also occurs after exposure to UV-inactivated TCRV particles and is thus independent of productive virusinfection. Surprisingly, JUNV infection did not have an effect on any of the cytokines examined indicating that, in contrast to other viral hemorrhagic fever viruses, macrophage-derived cytokine production is unlikely to play an active role in contributing to the cytokine dysregulation observed in JUNV infected patients. Rather, these results suggest that an early, controlled immune response by infected macrophages may be critical for the successful control of infection of apathogenic viruses and prevention of subsequent disease, including systemic cytokine dysregulation.
BACKGROUND: In cell culture-based influenza vaccine production the monitoring of virus titres and cell physiology during infection is of great importance for process characterisation and optimisation. While conventional virus quantification methods give only virus titres in the culture broth, data obtained by fluorescence labelling of intracellular virus proteins provide additional information on infection dynamics. Flow cytometry represents a valuable tool
Lipid biosynthesis was measured in cultured chicken embryo cells after infection with fowlpox virus. Between 24 and 72 h postinfection, fowlpox virus-infected cells incorporated less [14C]acetate and 3H2O into fatty acids and sterols than did mock-infected cells, demonstrating a virus-dependent inhibition of general lipid metabolism. Two specific effects of fowlpox virusinfection were an accumulation of C-4 alkylated sterol intermediates and inhibition of monounsaturated fatty acid biosynthesis.
Background From 2001-2003 monodon slow growth syndrome (MSGS) caused severe economic losses for Thai shrimp farmers who cultivated the\\u000a native, giant tiger shrimp, and this led them to adopt exotic stocks of the domesticated whiteleg shrimp as the species of\\u000a cultivation choice, despite the higher value of giant tiger shrimp. In 2008, newly discovered Laem-Singh virus (LSNV) was\\u000a proposed as a
Infection with respiratory syncytial virus (RSV) is known to be associated with central nervous system symptoms such as convulsions.\\u000a We investigated cytokines, nitrogen oxide (NO)\\u000a x\\u000a , and the viral genome in cerebrospinal fluid (CSF) obtained from children with RSV infection-related convulsions or central\\u000a nervous symptoms and compared the data with type of encephalopathy. Of nine patients enrolled (six boys
Viral-induced apoptosis might be mediated by oxidative stress. It has already been described that cell death in vesicular stomatitis virus (VSV)-infected cells occurs by apoptosis. In this study, oxidative stress parameters present in VSV-infected Vero cells were analyzed. Lipid peroxides (LP) were evaluated in cellular extracts and expressed as thiobarbituric acid-reactive substances. LP levels exhibited a rise at different times
Diego A. Riva; María C. Ríos de Molina; Iara Rocchetta; Elizabeth Gerhardt; Félix C. Coulombié; Susana E. Mersich
Respiratory syncytial virus (RSV) infection, which primarily manifests as bronchiolitis or pneumonia, is the leading cause\\u000a of lower respiratory tract infection in infants and young children. It is associated with more than 100,000 pediatric hospitalizations\\u000a each year in the United States. Infants who were premature; have chronic lung disease, congenital heart disease, or immunodeficiency\\u000a disorders; or have underlying metabolic or
Infection by influenza virus leads to respiratory failure characterized by acute lung injury associated with alveolar edema,\\u000a necrotizing bronchiolitis, and excessive bleeding. Severe reactions to infection that lead to hospitalizations and\\/or death\\u000a are frequently attributed to an exuberant host response, with excessive inflammation and damage to the epithelial cells that\\u000a mediate respiratory gas exchange. The respiratory mucosa serves as a
Catherine J. Sanders; Peter C. Doherty; Paul G. Thomas
Increasing evidences have shown that pathogens might promote atherosclerosis and trigger acute myocardial infarction (AMI).\\u000a But the conclusions from various studies on the correlation between previous influenza virus (IV) infection and AMI were inconsistent.\\u000a We conducted a case-control study to assess the association of previous IV infection and AMI. Questionnaire survey was conducted\\u000a to collect information about demographic characteristics and
Pediatric human immunodeficiency virus (HIV) infection is now the seventh leading cause of death in U.S. chldren 1 to 14 years of age and the leading cause of death in children 2 to 5 years of age in many U.S. cities. The key to enhancing the quality and duration of life in HIV-infected children is to recognize and diagnose HIV
Arlene M. Butz; Mary Joyner; Donna Greenberg Friedman; Nancy Hutton
The family Poxviridae consists of large double-stranded DNA containing viruses that replicate exclusively in the cytoplasm of infected cells. Members of the orthopox genus include variola, the causative agent of human small pox, monkeypox, and vaccinia (VAC), the prototypic member of the virus family. Within the relatively large (approximately 200 kb) vaccinia genome, three classes of genes are encoded: early, intermediate, and late. While all three classes are transcribed by virally-encoded RNA polymerases, each class serves a different function in the life cycle of the virus. Poxviruses utilize multiple strategies for modulation of the host cellular environment during infection. In order to understand regulation of both host and virus gene expression, we have utilized genome-wide approaches to analyze transcript abundance from both virus and host cells. Here, we demonstrate time course infections of HeLa cells with Vaccinia virus and sampling RNA at several time points post-infection. Both host and viral total RNA is isolated and amplified for hybridization to microarrays for analysis of gene expression. PMID:19365326
The family Poxviridae consists of large double-stranded DNA containing viruses that replicate exclusively in the cytoplasm of infected cells. Members of the orthopox genus include variola, the causative agent of human small pox, monkeypox, and vaccinia (VAC), the prototypic member of the virus family. Within the relatively large (approximately 200 kb) vaccinia genome, three classes of genes are encoded: early, intermediate, and late. While all three classes are transcribed by virally-encoded RNA polymerases, each class serves a different function in the life cycle of the virus. Poxviruses utilize multiple strategies for modulation of the host cellular environment during infection. In order to understand regulation of both host and virus gene expression, we have utilized genome-wide approaches to analyze transcript abundance from both virus and host cells. Here, we demonstrate time course infections of HeLa cells with Vaccinia virus and sampling RNA at several time points post-infection. Both host and viral total RNA is isolated and amplified for hybridization to microarrays for analysis of gene expression. PMID:19488021
The family Poxviridae consists of large double-stranded DNA containing viruses that replicate exclusively in the cytoplasm of infected cells. Members of the orthopox genus include variola, the causative agent of human small pox, monkeypox, and vaccinia (VAC), the prototypic member of the virus family. Within the relatively large (approximately 200 kb) vaccinia genome, three classes of genes are encoded: early, intermediate, and late. While all three classes are transcribed by virally-encoded RNA polymerases, each class serves a different function in the life cycle of the virus. Poxviruses utilize multiple strategies for modulation of the host cellular environment during infection. In order to understand regulation of both host and virus gene expression, we have utilized genome-wide approaches to analyze transcript abundance from both virus and host cells. Here, we demonstrate time course infections of HeLa cells with Vaccinia virus and sampling RNA at several time points post-infection. Both host and viral total RNA is isolated and amplified for hybridization to microarrays for analysis of gene expression. PMID:19363464
Poxviruses produce complement regulatory proteins to subvert the host's immune response. Similar to the human pathogen variola virus, ectromelia virus has a limited host range and provides a mouse model where the virus and the host's immune response have coevolved. We previously demonstrated that multiple components (C3, C4, and factor B) of the classical and alternative pathways are required to survive ectromelia virusinfection. Complement's role in the innate and adaptive immune responses likely drove the evolution of a virus-encoded virulence factor that regulates complement activation. In this study, we characterized the ectromelia virus inhibitor of complement enzymes (EMICE). Recombinant EMICE regulated complement activation on the surface of CHO cells, and it protected complement-sensitive intracellular mature virions (IMV) from neutralization in vitro. It accomplished this by serving as a cofactor for the inactivation of C3b and C4b and by dissociating the catalytic domain of the classical pathway C3 convertase. Infected murine cells initiated synthesis of EMICE within 4 to 6 h postinoculation. The levels were sufficient in the supernatant to protect the IMV, upon release, from complement-mediated neutralization. EMICE on the surface of infected murine cells also reduced complement activation by the alternative pathway. In contrast, classical pathway activation by high-titer antibody overwhelmed EMICE's regulatory capacity. These results suggest that EMICE's role is early during infection when it counteracts the innate immune response. In summary, ectromelia virus produced EMICE within a few hours of an infection, and EMICE in turn decreased complement activation on IMV and infected cells.
Moulton, Elizabeth A.; Bertram, Paula; Chen, Nanhai; Buller, R. Mark L.; Atkinson, John P.
Renal complications of influenza A virusinfections are uncommon but can contribute to a deterioration in the patient's condition, which include acute kidney injury (AKI) in critically ill patients, rhabdomyolysis, hemolytic uremic syndrome (HUS), acute glomerulonephritis (AGN), disseminated intravascular coagulation (DIC), Goodpasture's syndrome, and acute tubulointerstitial nephritis (TIN). The clinical characteristics of AKI in critically ill patients with pandemic influenza A(H1N1) 2009 virus (A(H1N1)pdm09) infection are similar to uninfected patients. Underlying conditions associated with AKI include older age, diabetes mellitus, obesity, pregnancy, history of asthma, and chronic kidney disease. Histologic examination of the kidneys from patients with A(H1N1)pdm09 infection who died include acute tubular necrosis (ATN), myoglobin pigment, and DIC. A(H1N1)pdm09 is present in the kidneys of some patients. The clinical characteristics of patients with rhabdomyolysis associated with influenza A include younger age and the frequent occurrence of muscle symptoms. AKI occurs in approximately one third of patients with rhabdomyolysis due to influenza A. HUS is associated with A(H1N1)pdm09 as follows: Streptococcus pneumoniae-associated HUS following A(H1N1)pdm09 infection, HUS triggered by A(H1N1)pdm09 in patients with genetic complement dysregulation, and HUS associated with A(H1N1)pdm09 without known underlying disorder. AGN, Goodpasture's syndrome, and acute TIN are extremely rare complications of influenza A virusinfection. Although the pathogenesis underlying renal injuries due to influenza A virus has not been delineated, some hypotheses have been advanced, including ATN due to renal hypoperfusion or rhabdomyolysis, glomerular microthrombosis due to DIC, direct viral injury to the kidney, and an altered immune system with systemic mononuclear cell activation following influenza A virusinfections. PMID:23064728
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The interplay between the virus and host innate and adaptive immune responses determines the outcome of infection. There is increasing evidence that host neutralizing responses play a relevant role in the resulting pathogenesis. Furthermore, viral evasion from host neutralizing antibodies has been revealed to be an important contributor in leading both to viral persistence in acute liver graft infection following liver transplantation, and to chronic viral infection. The development of novel model systems to study HCV entry and neutralization has allowed a detailed understanding of the molecular mechanisms of virus-host interactions during antibody-mediated neutralization. The understanding of these mechanisms will ultimately contribute to the development of novel antiviral preventive strategies for liver graft infection and an urgently needed vaccine. This review summarizes recent concepts of the role of neutralizing antibodies in viral clearance and protection, and highlights consequences of viral escape from neutralizing antibodies in the pathogenesis of HCV infection.
Fafi-Kremer, Samira; Fauvelle, Catherine; Felmlee, Daniel J.; Zeisel, Mirjam B.; Lepiller, Quentin; Fofana, Isabel; Heydmann, Laura; Stoll-Keller, Francoise; Baumert, Thomas F.
Herpes simplex viruses type 1 (buccal) and type 2 (genital) present a serious threat to neonates. Infection may occur in utero, by transplacental or ascending infection, by exposure to genital lesions during delivery, or postnatally from relatives or attendants. Antiviral drugs, vidarabine and acyclovir are of equal efficacy and toxicity when used in infants with herpes simplex infections. Transplacental infection during early pregnancy is a very rare cause of congenital abnormality but there have been no recommendations for intervention. Most neonatal infections are acquired from the mother during delivery. Antepartum screening for virus excretion is of no value in predicting exposure at delivery and should not be performed. Caesarean section should be reserved for women who have active lesions at delivery. Even if active lesions are present, in women with a history of recurrent herpes, the risks to the infant are low. Prophylactic acyclovir during pregnancy cannot be recommended until evidence of safety and efficacy has been obtained from controlled trials. Staff should be alert to the dangers of postnatal infection and measures should be taken to exclude, or reduce virus excretion from, staff members or visitors who have orolabial or cutaneous herpes lesions. PMID:1803497
Bovine vaccinia virus outbreaks have been occurring in different regions of Brazil. We report here the time course of natural human infection by vaccinia virus and describe important clinical and epidemiological aspects of this zoonotic infection. The diagnosis of vaccinia virusinfection was based on clinical, serological, and molecular procedures.
de Souza Trindade, Giliane; Drumond, Betania Paiva; Guedes, Maria Isabel Maldonado Coelho; Leite, Juliana Almeida; Mota, Bruno Eduardo Fernandes; Campos, Marco Antonio; da Fonseca, Flavio Guimaraes; Nogueira, Mauricio Lacerda; Lobato, Zelia Ines Portela; Bonjardim, Claudio Antonio; Ferreira, Paulo Cesar Peregrino; Kroon, Erna Geessien
Handling of Vaccinia virus represents a risk for laboratory-acquired infections, especially in individuals without completed vaccination. We report the case of a Vaccinia infection in a previously vaccinated researcher working with various genetically modified strains. We could confirm the infection by electron microscopy, positive cell culture, virus-specific PCR, sequence analysis, and viral neutralization test. The isolated virus carried a functionally
Martin Mempel; Gisela Isa; Norbert Klugbauer; Hermann Meyer; Gregor Wildi; Johannes Ring; Franz Hofmann; Heidelore Hofmann
Hepatitis C virusinfection is now recognized as a common and serious complication of injection drug use and will be encountered frequently in methadone maintenance patients. Approximately 1.8% of the United States population, or 3.9 million persons, are infected with hepatitis C virus. A majority of acute hepatitis C virusinfections are associated with injection drug use, and 64 -
Hospital acquired infections with respiratory syncytial virus are a major problem. The virus is spread predominantly by infected nasal secretions and we investigated whether we could reduce its incidence by cohorting babies on each ward into designated areas and encouraging staff and parents to wash their hands. We examined the incidence of hospital acquired infection due to respiratory syncytial virus
D Isaacs; H Dickson; C OCallaghan; R Sheaves; A Winter; E R Moxon
Here, we report that specific manipulations of the cellular response to virusinfection can cause prevention of apoptosis and consequent establishment of persistent infection. Infection of several human cell lines with Sendai virus (SeV) or human parainfluenza virus 3, two prototypic paramyxoviruses, caused slow apoptosis, which was markedly accelerated upon blocking the action of phosphatidylinositol 3-kinases (PI3 kinases) in the
Kristi Peters; Saurabh Chattopadhyay; Ganes C. Sen
The heterogeneity of HIV and the different human leukocyte antigen (HLA) backgrounds of infected individuals have posed challenges to understanding the pathogenesis of HIV infection. But continuing advances in our knowledge of the role of immune responses in controlling HIV viremia should help to define goals for immune-based therapies and vaccine strategies against AIDS.
After the acute infection period, birds persistently infected with West Nile virus (family Flaviviridae, genus Flavivirus, WNV) occasionally shed virus into the bloodstream, but these virions normally are inactivated by neutralizing antibody. The current work tested the hypothesis that these host neutralizing antibodies protect mosquito vectors from WNV infection and reevaluated the minimum WNV infectious dose necessary to infect Culex tarsalis Coquillett. To determine whether host antibodies protect mosquitoes from infection, Cx. tarsalis and Culex stigmatosoma Dyar were fed bloodmeals containing avian blood, WNV, and sera with or without WNV-specific neutralizing antibodies. When viral particles were completely bound by antibody, mosquitoes were protected from infection; however, when incompletely bound, WNV titers as low as 10(2.3) plaque-forming units (pfu)/ml resulted in 5% infection. These data indicated that avian antibodies were protective to mosquito vectors and were not dissociated during digestion. Because recrudescent viremias may not attain the same magnitude as initial acute viremias, Cx. tarsalis vector competence was reevaluated focusing on the fate of low-titered bloodmeals. Females were evaluated for vector competence after ingesting bloodmeals containing 10(2.2), 10(3.4), 10(4.5), 10(5.5), or 10(6.5) WNV pfu/ml. Infection increased with bloodmeal titer, with 1% of the mosquitoes ingesting 10(3.4) pfu/ml and 45% of the mosquitoes ingesting 10(6.5) pfu/ml developing disseminated infections. The incomplete neutralization of recrudescent virus may be sufficient to infect a low proportion of competent blood-feeding Culex mosquitoes and perhaps allow persistently infected birds to provide a mechanism for arbovirus overwintering. PMID:22897050
Wheeler, Sarah S; Vineyard, Meighan P; Barker, Christopher M; Reisen, William K
Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 102 PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 104 PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics.
Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 10(2) PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 10(4) PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics. PMID:23345518
The host response to viruses includes multiple cell types that have regulatory function. Most information focuses on CD4(+) regulatory T cells that express the transcription factor Foxp3(+) (Tregs), which are the topic of this review. We explain how viruses through specific and non-specific means can trigger the response of thymus-derived natural Tregs as well as induce Tregs. The latter derive under appropriate stimulation conditions either from uncommitted precursors or from differentiated cells that convert to become Tregs. We describe instances where Tregs appear to limit the efficacy of antiviral protective immunity and other, perhaps more common, immune-mediated inflammatory conditions, where the Tregs function to limit the extent of tissue damage that occurs during a virusinfection. We discuss the controversial roles that Tregs may play in the pathogenesis of human immunodeficiency and hepatitis C virusinfections. The issue of plasticity is discussed, as this may result in Tregs losing their protective function when present in inflammatory environments. Finally, we mention approaches used to manipulate Treg numbers and function and assess their current value and likely future success to manage the outcome of virusinfection, especially those that are responsible for chronic tissue damage. PMID:23947355
Veiga-Parga, Tamara; Sehrawat, Sharvan; Rouse, Barry T
Venezuelan equine encephalitis virus (VEEV) may cause encephalitis in humans, for which no FDA-approved antiviral treatment is available. Carbocyclic cytosine (carbodine) has broad-spectrum activity but toxicity has limited its utility. It was anticipated that one of the enantiomers of carbodine would show enhanced activity and reduced toxicity. The activity of the D-(-) enantiomer of carbodine [(-)-carbodine] was evaluated by infectious cell culture assay and was found to have a 50% effective concentration (EC50) of 0.2 ?g/ml against the TC-83 vaccine strain of VEEV in Vero cells, while the L-(+) enantiomer had no activity. Virus titer inhibition correlated with intracellular cytidine triphosphate reduction after treatment with (-)-carbodine, as determined by HPLC analysis. Pre-treatment with 200 mg/kg/d resulted in significant improvement in survival, virus load in the brain, weight change, and mean day to death in a mouse model of TC-83 VEEV disease. A single dose of (-)-Carbodine resulted in a slight extension of mean time to death in mice infected with wild-type VEEV. Post-virus exposure treatment with (-)-carbodine was effective in significantly improving disease parameters in mice infected with TC-83 VEEV when treatment was initiated as late as 4 days post-virus installation (dpi). It is remarkable that (-)-carbodine is effective when initiated after the establishment of brain infection.
Bowen, Richard A.; Rao, Jagadeeshwar R.; Day, Craig; Shafer, Kristiina; Smee, Donald F.; Morrey, John D.; Chu, Chung K.
Background Viruses are obligate intracellular parasites that rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virusinfection and/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. Results Candidate genes required for lytic reovirus infection were identified by tagged sequence mutagenesis, a process that permits rapid identification of genes disrupted by gene entrapment. One hundred fifty-one reovirus resistant clones were selected from cell libraries containing 2 × 105 independently disrupted genes, of which 111 contained mutations in previously characterized genes and functionally anonymous transcription units. Collectively, the genes associated with reovirus resistance differed from genes targeted by random gene entrapment in that known mutational hot spots were under represented, and a number of mutations appeared to cluster around specific cellular processes, including: IGF-II expression/signalling, vesicular transport/cytoskeletal trafficking and apoptosis. Notably, several of the genes have been directly implicated in the replication of reovirus and other viruses at different steps in the viral lifecycle. Conclusions Tagged sequence mutagenesis provides a rapid, genome-wide strategy to identify candidate cellular genes required for virusinfection. The candidate genes provide a starting point for mechanistic studies of cellular processes that participate in the virus lifecycle and may provide targets for novel anti-viral therapies.
Organ, Edward L; Sheng, Jinsong; Ruley, H Earl; Rubin, Donald H
Nearly one fourth of individuals with human immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a significant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV mono-infection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to anti-HCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in co-infected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection (33% vs 72%, P = 0.07). A better understanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome and survival.
Depletion in the number of lymphocytes and viral persistence are thought to be the most important outcomes of classical swine fever virus (CSFV) infection. To define the change in peripheral blood mononuclear cells (PBMC) and virus replication in leukocytes after CSFV infection, 8-week old pigs were infected with the LPC vaccine strain or virulent CSFV (HCV-YL strain). Changes in the
Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis. PMID:22393386
Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.
To detect orthopoxvirus in the Brazilian Amazon, we conducted a serosurvey of 344 wild animals. Neutralizing antibodies against orthopoxvirus were detected by plaque-reduction neutralizing tests in 84 serum samples. Amplicons from 6 monkey samples were sequenced. These amplicons identified vaccinia virus genetically similar to strains from bovine vaccinia outbreaks in Brazil. PMID:20507750
Abrahão, Jônatas S; Silva-Fernandes, André T; Lima, Larissa S; Campos, Rafael K; Guedes, Maria I M C; Cota, Marcela M G; Assis, Felipe L; Borges, Iara A; Souza-Júnior, Milton F; Lobato, Zélia I P; Bonjardim, Cláudio A; Ferreira, Paulo C P; Trindade, Giliane S; Kroon, Erna G
This book contains over 50 papers. Some of the titles are: Structure and Replication of the Genome of Hepatitis Delta Virus; Clinical Significance of HDV RNA in HDV Disease; HBV DNA in Delta Chronic Carriers; Prevalance of HBV-DNA Among Anti-Hd Positive Patients; and Characterization of LKM/sub 1/ and LKM/sub 2/ Antigens.
Pichinde Virus (PIC) is the animal model for human Lassa Fever. The pathogenic mechanisms were examined by comparing a virulent guinea pig (GP) adapted PIC strain, adPIC and the GP avirulent prototype PIC strain PIC3739. adPIC replicated to higher titers ...
Sexual contact is thought to be an inefficient mode of hepatitis C virus (HCV) transmission. However, reports of sexually\\u000a transmitted HCV infection among HIV-infected men who have sex with men (MSM) began to appear in 2004. The patients were of\\u000a early middle age with well-controlled HIV infection, participated in unprotected receptive sex, and frequently used noninjection\\u000a recreational drugs. Molecular studies
The ability of rinderpest virus (RPV) to replicate in vitro in adherent peripheral blood monocytes and monocyte- derived macrophages under non-stimulation conditions was investigated. When flow cytometry analysis on bovine peripheral blood mononuclear cells (PBMC) was performed, monocytic cells were seen to be targets for infection by the cell culture-attenuated RBOK vaccine strain of RPV. Viral glycoprotein (H) and nucleoprotein
Julia E. Rey Nores; John Anderson; Robin N. Butcher; Genevieve Libeau; Kenneth C. McCullough
The absence of urban yellow fever virus (YFV) in Bolivian cities has been attributed to the lack of competent urban mosquito vectors. Experiments with Aedes aegypti from Santa Cruz, Bolivia, demonstrated infection (100%), dissemination (20%), and transmission of a Bolivian YFV strain (CENETROP-322).
Mutebi, John-Paul; Gianella, Alberto; Travassos da Rosa, Amelia; Tesh, Robert B.; Barrett, Alan D. T.
Since the advent of highly active antiretroviral therapy (HAART), the resultant decline in mortality rate associated with human immunodeficiency virus (HIV) infection (1) has allowed patients and clinicians to consider other important health issues beyond short-term survival. Included among these issues is the maintenance of normal gonadal function, as well as ethical and practical considerations for those in- dividuals who
Our investigation was conducted in order to verify a recent severe epidemic at several swine farms in northern China that indicated a newly emerging disease. Evidence confirmed that the epidemic was caused by a virulent Pseudorabies virusinfection in swine herds.
The Hsp70 chaperone plays a central role in multiple processes within cells, including protein translation, folding, intracellular trafficking, and degradation. This protein is implicated in the replication of numerous viruses. We have shown that rabies virusinfection induced the cellular expression of Hsp70, which accumulated in Negri body-like structures, where viral transcription and replication take place. In addition, Hsp70 is present in both nucleocapsids purified from infected cells and in purified virions. Hsp70 has been shown to interact with the nucleoprotein N. The downregulation of Hsp70, using specific chaperone inhibitors, such as quercetin or RNA interference, resulted in a significant decrease of the amount of viral mRNAs, viral proteins, and virus particles. These results indicate that Hsp70 has a proviral function during rabies virusinfection and suggest that Hsp70 is involved in at least one stage(s) of the viral life cycle, such as viral transcription, translation, and/or production. The mechanism by which Hsp70 controls viral infection will be discussed.
West Nile virus (WNV) is a mosquito-borne member of the Flaviviridae family (genus Flavivirus) transmitted among bird populations by mosquitoes and incidentally infecting mammals. First recognized in the United States in 1999, WNV has spread across the United States in subsequent years. Numerous cas...
West Nile virus (WNV) is a member of the Flaviviridae family (genus Flavivirus), transmitted among bird populations by mosquitoes and incidentally infects mammals. First recognized in the United States in the New York City area in 1999, WNV has subsequently spread across the United States. Numerous ...
BACKGROUND: Since its first occurrence in the New York City area during 1999, West Nile virus (WNV) has spread rapidly across North America and has become a major public health concern in North America. By 2002, WNV was reported in 40 states and the District of Columbia with 4,156 human and 14,539 equine cases of infection. Mississippi had the highest
Guiming Wang; Richard B Minnis; Jerrold L Belant; Charles L Wax
To date there have been only five reported cases of females with genital ulceration associated with primary Epstein-Barr virusinfection. We describe two further patients and review the clinical features of all seven cases, noting the typical features, particularly purple ulcer margins and systemic symptoms, which should alert the physician to consider this diagnosis. PMID:9924475
To date there have been only five reported cases of females with genital ulceration associated with primary Epstein-Barr virusinfection. We describe two further patients and review the clinical features of all seven cases, noting the typical features, particularly purple ulcer margins and systemic symptoms, which should alert the physician to consider this diagnosis. ???
Taylor, S.; Drake, S. M.; Dedicoat, M.; Wood, M. J.
Occult hepatitis B virus (HBV) infection (OBI) is defined as the presence of HBV DNA in the liver (with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative. Until recently, the clinical effect of OBI was unclear on the progression of liver disease; on the development of hepatocellular carcinoma; and on the risk for reactivation or transmission of HBV infection. Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease, but its role in the progression to cirrhosis remains unclear. Although OBI has been well documented in human immunodeficiency virus (HIV)-positive patients, especially among those coinfected with hepatitis C virus, further studies are needed to determine its current clinical impact in HIV setting.
Romero, Miriam; Madejon, Antonio; Fernandez-Rodriguez, Conrado; Garcia-Samaniego, Javier
Bats (Chiroptera) host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat) or Yangochiroptera (genera Carollia and Tadarida) for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV), a porcine coronavirus, or to infection mediated by the Spike (S) protein of SARS-coronavirus (SARS-CoV) incorporated into pseudotypes based on vesicular stomatitis virus (VSV). The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3) were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus) and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed. PMID:24023659
GB virus B (GBV-B) is a hepatotropic virus that is closely related to hepatitis C virus (HCV). GBV-B causes acute hepatitis in infected marmosets and tamarins and is therefore a useful small-animal model for the study of HCV. We investigated virus-specific T-cell responses in marmosets infected with GBV-B. Gamma interferon (IFN-) enzyme-linked immunospot (ELISPOT) assay responses in the peripheral blood
David J. Woollard; Gholamreza Haqshenas; Xuebin Dong; Bridget F. Pratt; Stephen J. Kent; Eric J. Gowans
Modified vaccinia virus Ankara (MVA) has been used as an experimental vaccine vector against respiratory infections. We have tested the safety and immunogenicity of a recombinant virus expressing the hemagglutinin of measles virus (MVA-MV-H) using the mouse model of measles virus induced encephalitis and the cotton rat model for respiratory infection. MVA-MV-H proved to induce a TH1 response, neutralizing antibodies
Gerald Weidinger; Marion Ohlmann; Bernd Schlereth; Gerd Sutter; Stefan Niewiesk
The hepatitis C virus (HCV) is a global health issue with no vaccine available and limited clinical treatment options. Like other obligate parasites, HCV requires host cellular components of an infected individual to propagate. These host-virus interactions during HCV infection are complex and dynamic and involve the hijacking of host cell environments, enzymes and pathways. Understanding this unique molecular biosystem has the potential to yield new and exciting strategies for therapeutic intervention. Advances in genomics and proteomics have opened up new possibilities for the rapid measurement of global changes at the transcriptional and translational levels during infection. However, these techniques only yield snapshots of host-virus interactions during HCV infection. Other new methods that involve the imaging of biomolecular interactions during HCV infection are required to identify key interactions that may be transient and dynamic. Herein we highlight systems biology based strategies that have helped to identify key host-virus interactions during HCV replication and infection. Novel biophysical tools are also highlighted for identification and visualization of activities and interactions between HCV and its host hepatocyte. As some of these methods mature, we expect them to pave the way forward for further exploration of this complex biosystem and elucidation of mechanisms for HCV pathogenesis and carcinogenesis. PMID:20549003
Pezacki, John Paul; Singaravelu, Ragunath; Lyn, Rodney K
Plasma zinc and copper concentrations, erythrocyte zinc concentration, copper-zinc superoxide dismutase activity and urinary zinc concentrations were determined for control subjects and individuals with AIDS, ARC, or asymptomatic HIV infection. Significant differences among the population groups were not noted for the above parameters with the exception of plasma copper which was higher in the AIDS group than in other patient groups. These results do not support the idea that zinc deficiency is a common contributory factor of HIV infectivity or clinical expression, nor that HIV infection induces a zinc deficiency.
Walter, R.M. Jr.; Oster, M.H.; Lee, T.J.; Flynn, N.; Keen, C.L. (Univ. of California, Davis (USA))
Characterization of virus-specific immune responses to human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) is important to understanding the early virus-host interactions that may determine the course of virusinfection and disease. Using a comprehensive panel of serological assays, we have previously demonstrated a complex and lengthy maturation of virus-specific antibody responses elicited by attenuated strains of
KELLY STEFANO COLE; MICHAEL MURPHEY-CORB; OPENDRA NARAYAN; SANJAY V. JOAG; GEORGE M. SHAW; RONALD C. MONTELARO; Marion Merrell Dow
Influenza viruses continue to cause yearly epidemics and occasional pandemics in humans. In recent years, the threat of a possible influenza pandemic arising from the avian influenza A(H5N1) virus has prompted the development of comprehensive pandemic preparedness programs in many countries. The recent emergence of the pandemic influenza A(H1N1) 2009 virus from the Americas in early 2009, although surprising in its geographic and zoonotic origins, has tested these preparedness programs and revealed areas in which further work is necessary. Nevertheless, the plethora of epidemiologic, diagnostic, mathematical and phylogenetic modeling, and investigative methodologies developed since the severe acute respiratory syndrome outbreak of 2003 and the subsequent sporadic human cases of avian influenza have been applied effectively and rapidly to the emergence of this novel pandemic virus. This article summarizes some of the findings from such investigations, including recommendations for the management of patients infected with this newly emerged pathogen. PMID:20674794
Tang, Julian W; Shetty, Nandini; Lam, Tommy T Y; Hon, K L Ellis
AIMS--To assess the association between active hepatitis C virus (HCV) infection and liver damage in randomly selected patients with antibodies to the virus. METHODS--Thirty three consecutive subjects with serologically confirmed positivity for antibodies to HCV were studied for the presence of liver and circulating viral sequences by using the reverse transcription polymerase chain reaction (RT-PCR) and specific primers for the
E Petrelli; A Manzin; S Paolucci; A Cioppi; M Brugia; P Muretto; M Clementi
An earlier finding that lymphocytes from African patients with the acquired immune deficiency syndrome (AIDS) react with rabbit antiserum to purified antigens of bovine leukemia virus (BLV) prompted a study of the possible cross-reactions between a BLV-infected ovine cell line and human lymphocytes inoculated with a strain of lymphadenopathy syndrome-associated virus (LAV). A solid-phase radioimmunoassay was used to detect antigenic
L. Thiry; S. Sprecher-Goldberger; P. Jacquemin; J. Cogniaux; A. Burny; C. Bruck; D. Portetelle; S. Cran; N. Clumeck
Common intestinal infections caused by human enteroviruses (HEVs) are considered major environmental factors predisposing to type 1 diabetes (T1D). In spite of the active research of the field, the HEV-induced pathogenetic processes are poorly understood. Recently, after the first documented report on HEV infections in the pancreatic islets of deceased T1D patients, several groups became interested in the issue and studied valuable human material, the autopsy pancreases of diabetic and/or autoantibody-positive patients for HEV infections. In this review, the data on HEV infections in human pancreatic islets are discussed with special reference to the methods used. Likewise, mechanisms that could increase viral access to the pancreas are reviewed and discussed. PMID:20680525
Although Singapore is in an endemic region for hepatitis B infection, the hepatitis B carriage rate of 5-6% is relatively low. The highest positivity rates for hepatitis B surface antigen (HBsAg) are found in the paediatric age group, with another peak in 40-49 year olds. Studies suggest that, although perinatal transmission is an important route of infection, most children acquire
Sera were collected from 6 large farrow-to-finish swine herds infected with pseudorabies virus (PRV) in Illinois. All herds were participating in the Large Herd Cleanup Study, a USDA-initiated project to evaluate the feasibility of eradicating pseudorabies from large farms (greater than 400 sows) by use of a combination of vaccination and management changes. Herd size ranged between 425 and 1,500 breeding females. Between April and July 1990, sera for measurement of PRV antibodies were obtained from 113 to 156 sows and 112 to 162 finishing pigs (body weight greater than 70 kg)/herd. Duplicate sera from 30 sows and 30 market-weight pigs/herd were obtained for measurement of serum antibodies to the following associated organisms: swine influenza virus, transmissible gastroenteritis virus, encephalomyocarditis virus, Actinobacillus pleuropneumoniae, Eperythrozoon suis, and 6 serovars of Leptospira interrogans. Prevalence of PRV antibodies attributable to field virusinfection ranged between 53.8 and 100% for sows and between 0.7 and 97.3% for finishing pigs, as determined by the appropriate differential test for the vaccine being used on each farm. In only 1 herd, PRV seroprevalence was increased with higher sow parity. For associated infections, the risk of seropositivity attributable to PRV was not significant (for most infections) on all farms and varied among farms. Thus, pseudorabies did not appear, in general, to increase susceptibility to infection with other disease agents. PMID:1651912
Hall, W F; Weigel, R M; Siegel, A M; Wiemers, J F; Lehman, J R; Taft, A C; Annelli, J F
Secalonic acid D (SAD), a hepatotoxic, teratogenic, and slightly mutagenic metabolite of Penicillium oxalicum has been identified as a natural contaminant of grain dust. Secalonic acid D was administered intraperitoneally to male ICR mice that were exposed to influenza virus aerosols 5 days earlier. The mortality rate was significantly higher (p less than 0.001) in mice subjected to both influenza and SAD than those subjected to influenza alone. Virus titers in lung tissue samples at selected time intervals appeared similar for both influenza and influenza-SAD treated groups of mice for 9 days after exposure to the virus. After 9 days, influenza-SAD treated mice appeared to have higher virus titers. No difference in the pathological progression of pneumonia was discernible between these two groups of mice. The influenza-SAD group, in addition to pneumonia, exhibited severe hepatic necrosis characteristic of SAD administration. Mice infected with influenza virus followed by administration of SAD responded with significantly lower (p less than 0.05) antibody titers to influenza virus than mice exposed to influenza virus alone. Images FIGURE 2.
Fleischhacker, D S; Akers, T G; Katz, S P; Palmgren, M S
In an experiment with infectious bovine rhinotracheitis (IBR) virus in two bulls, observed over a period of 122 weeks, the pattern of virus release was studied. Recurrent, unprovoked release of virus was demonstrated after one year in a nasal washing from one of the bulls and in preputial washings of both on 13 and 4 occasions, respectively, and finally in weeks 113 and 110, although clinical disease was not observed. During periods of recurrent virus release, concentrations of virus in the prepuce were generally much lower than during the period of primary infection; usually, however, they were not of negligible titer. The frequency of such periods and the virus titers observed strongly suggest that an IBR antibody carrier should always be considered as a potential source of infection to other animals. When virus was demonstrated in semen an almost equal amount was found in the preputial washing (50 ml). In week 120, virus replication in the respiratory tract and prepuce was induced in both bulls by prednisolone injections. It is concluded that antibody carriers will rarely attain a state of absolute immunity.
Hepatitis D virus (HDV) is a subviral satellite with hepatitis B virus (HBV) as its natural helper virus. After entry into hepatocytes, it utilizes host cellular enzymes to replicate by a double-rolling-circle mechanism. HDV is most often transmitted by contact with contaminated blood and body fluid, similar to HBV infection. Approximately 5% of the global HBV carriers are coinfected with HDV, leading to a total of 10-15 million HDV carriers worldwide. HDV infection can occur concurrently with HBV infection (coinfection) or in a patient with established HBV infection (superinfection). The pathogenesis of HDV remains controversial. A decline in the prevalence of both acute and chronic hepatitis D (CHD) has been observed worldwide. At present, therapy for chronic HDV infection is by the use of interferon-alpha. Compared to chronic hepatitis B or C, CHD treatment requires a higher dosage and a longer duration of treatment, and post-treatment relapses are common. In order to prevent the progression of CHD and its related morbidity and mortality, more effective treatments are needed. PMID:17098688
There is uncertainty regarding the pathogenic nature of cytomegalovirus in cutaneous lesions co-infected with herpes simplex virus. It is widely believed that herpes simplex virus is the main pathogenic factor in such lesions and that cytomegalovirus plays little if any role. There are, however, isolated case reports that describe cytomegalovirus as an important driving pathogen in such lesions. The authors present two human immunodeficiency virus patients who have cytomegalovirus and herpes simplex virus co-infected perigenital ulcers, one of whom improved on valacyclovir, while the other, who was already on valacyclovir for chronic herpes simplex virus suppression, showed no improvement with a single dose of cidofovir. He only showed rapid improvement when treated with valganciclovir. The latter patient underscores the viewpoint that at least in some cases, cytomegalovirus may be an important driving force behind the formation of such lesions. The authors therefore recommend that clinicians be aware of the possible pathogenic role of cytomegalovirus in these ulcers, and, in nonhealing ulcers, use anti-cytomegalovirus agents to prevent the onset of systemic disease. These results warrant further study of the pathogenesis of cytomegalovirus in co-infected herpes simplex virus ulcers.
Seroepidemiologic and virologic studies since 1889 suggested that human influenza pandemics were caused by H1, H2, and H3 subtypes of influenza A viruses. If not for the 1997 avian A\\/H5N1 outbreak in Hong Kong of China, subtype H2 is the likely candidate for the next pandemic. However, unlike previous poultry outbreaks of highly pathogenic avian influenza due to H5 that
The human immunodeficiency virus (HIV) epidemic is clearly one of the most serious health-care crises in the professional lives of contemporary physicians. It cannot be regarded as a curiosity to be dealt with by inner-city infectious-disease experts, but rather must be considered a problem for all health-care providers and a problem in which the obstetrician-gynecologist has a special role to play.
Background Parainfluenza virus (PIV) infections are an important cause of morbidity in children with upper or lower respiratory tract infection (URTI and LRTI respectively). However, the epidemiology of PIV infections in children with cancer has not been well studied. Methods This retrospective study sought to determine the epidemiology of PIV infections and risk factors for progression to a LRTI in 1,381 children diagnosed with leukemia or lymphoma, between 2000 and 2009. Results PIV infections were diagnosed in 83 (10%) of 820 children tested for respiratory infections. PIV-3 accounted for 49 (61%) of the PIV infections. Of the 83 infections, 75 (90%) were community-acquired. Children less than 2 years of age were more likely to have PIV infection (p=0.002, odds ratio 2.69; 95% CI 1.54.8). PIV infections were more common in children with acute lymphoblastic leukemia as compared with other malignancies (p<0.0001, odds ratio 4.13; 95% CI 2.377.21). The majority of patients, 66 (80%) had URTI. Children with LRTI had a median age of 27 months as compared with 56 months for children with URTI (p=0.005). Fever with severe neutropenia was more common in patients with LRTI than with URTI (p=0.02). LRTI was significantly associated with ANC<500 cells/µL (p=0.002) and ALC<100 cells/µL (p=0.008) at onset of PIV infection. There was no mortality attributed to PIV infections, although 3 children required mechanical ventilation for respiratory failure due to PIV infection. Conclusions PIV was the second most common respiratory viral infection in this population after influenza (A and B). Young children were more likely to have PIV infection and LRTI. Severe neutropenia and lymphopenia was associated with LRTI.
Srinivasan, Ashok; Wang, Chong; Yang, Jie; Inaba, Hiroto; Shenep, Jerry L.; Leung, Wing H.; Hayden, Randall T.
West Nile virus (WNV) is a small, enveloped, spherical virus that belongs to the family Flaviviridae, genus Flavivirus, Japanese encephalitis serocomplex. Natural reservoirs of WNV are birds, and the main vectors are mosquitoes of the genus Culex. There are seven genetic lineages of WNV. Lineages 1 and 2 are the most widely distributed (Africa, North and South America, Europe, Asia and Australia). About 80% of infections are asymptomatic. In 20% of patients nonspecific febrile disease occurs (West Nile fever). Less than 1% of infected persons will develop neuroinvasive WNV disease (meningitis, encephalitis, and poliomyelitis). In Croatia, antibodies to WNV were demonstrated in humans,bears and horses. In August-September 2012 clinical cases of human WNV neuroinvasive disease and asymptomatic acute infection in horses were reported for the first time in three eastern Croatian counties. The diagnosis was confirmed by serologic tests (enzyme immunoassay, IgG avidity, plaque-reduction neutralization test). PMID:23898697
Ubiquitous viruses have frequently been proposed as a cause or trigger of chronic immune-mediated diseases. Infections are reported to be temporally associated with clinical exacerbations in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We examined immunological parameters of herpesvirus infections in untreated patients with CIDP compared to demographically matched controls. Patients with CIDP were uniformly seropositive for EBV-specific IgG and the disease was associated with a moderately enhanced IgG reactivity to EBV-encoded antigens expressed during both B cell transformation and productive viral replication. Moreover, cellular EBV copy numbers were 3-fold increased in patients with CIDP. In contrast, humoral immune responses to other herpesviruses (HCMV, HSV) as well as virus-specific IgM responses were unchanged in CIDP. These data indicate that host-pathogen interactions during chronic EBV infection are dysregulated in treatment-naïve patients with CIDP. PMID:19939466
Lünemann, J D; Tackenberg, B; Stein, A; Wandinger, K P; Oertel, W H; Wagner, H J; Münz, C; Meisel, H; Sommer, N; Zipp, F
To evaluate the prevalence of hepatitis C virusinfection in our hemodialysis population, we carried out a survey of 273 adult hemodialysis patients in three hemodialysis units in Jordan using a second generation rapid enzyme immunoassay. Sixty seven patients were seropositive with a prevalence of 24.5%. All patients were transfusion dependent except two. More than 85% of the patients have been on hemodialysis for more than two years. Co-infection with hepatitis B virus was observed in six patients. Abnormal liver functions were seen in five patients, but liver biopsies were not done. The prevalence of hepatitis C antibody in healthy blood donors in Jordan is 1.7%. We conclude that HCV infection prevalence in hemodialysis patients in Jordan is 24.5%, a percentage similar to what has been reported around the world and in the neighboring countries. PMID:18583853
FeLV infection is still considered to account for most disease-related deaths in pet cats. Different treatment attempts with various drugs were performed in the past but none resulted in healing or complete virus elimination. Therefore, it caused a sensation when Horber and Mayr [Horber, D., Mayr, B., 1991. Prax. 19, 311-314; Horber, D., Schnabl, W., Mayr, B., 1992. Tierarztl. Umschau 47, 556-560; Mayr, B., Horber, D., 1992. Kleintierprax. 37, 515-518] published that they were able to cure 80 to 100% FeLV-infected cats from viremia by using an immunomodulating compound. Articles in cat breeder and cat owner journals appeared assuming that obviously there is a rescue for FeLV-infected cats suffering from this deadly infection. The immunomodulator [Buttner, M., 1993. Comp. Immun. Microbiol. Infect. Dis. 18, 1-10] used in those studies was the so-called 'paramunity inducer' PIND-ORF (Baypamun, Bayer, Leverkusen, Germany) consisting of inactivated parapox ovis virus. Since that time, Baypamun is the most commonly used drug for treatment of FeLV infection in Germany and other European countries. Four placebo-controlled double-blind trials were performed to determine the therapeutic efficacy of Baypamun and other compounds in naturally FeLV-infected cats under controlled conditions. PMID:10515279
Utilization of quantum dots (QDs) for single virus tracking has attracted growing interest. Through modification of viral surface proteins, viruses can be labeled with various functionalized QDs and used for tracking the routes of viral infections. However, incorporation of QDs on the viral surface may affect the efficiency of viral entry and alter virus-cell interactions. Here, we describe that QDs can be encapsulated into the capsid of vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentivirus (PTLV) in living cells without modification of the viral surface. QDs conjugated with modified genomic RNAs (gRNAs), which contain a packaging signal (Psi) sequence for viral genome encapsulation, can be packaged into virions together with the gRNAs. QD-containing PTLV demonstrated similar entry efficiency as the wild-type PTLV. After infection, QD signals entered the Rab5+ endosome and then moved to the microtubule organizing center of the infected cells in a microtubule-dependent manner. Findings in this study are consistent with previously reported infection routes of VSV and VSV-G pseudotyped lentivirus, indicating that our established QD packaging approach can be used for enveloped virus labeling and tracking. PMID:23560365
To define the role of sexual transmission in the spread of hepatitis C virus (HCV) infection, a seroprevalence study of antibodies against HCV was performed in populations at high risk for sexually transmitted diseases. Subjects included 310 female prostitutes, 88 clients of prostitutes, 168 homosexual men and 147 stable heterosexual partners of index cases reactive for anti-HCV (98 of whom
E. Lissen; H. J. Alter; M. A. Abad; Y. Torres; M. Pérez-Romero; M. Leal; J. A. Pineda; R. Torronteras; A. Sánchez-Quijano
Epstein-Barr virus infectious mononucleosis can cause transient immune deficiency which may predispose to reactivation of latent herpes simplex virus (HSV) infection in the immunocompetent host. We report the case of a 15-year-old male who presented with severe odynophagia and herpes labialis during the course of Epstein-Barr virus infectious mononucleosis that had been diagnosed ten days before. Esophagoscopy revealed extensive ulcerations with distinct borders and whitish exudates at the mid and distal esophagus. Polymerase chain reaction detected HSV-1 DNA in the biopsy specimens. The patient was treated with intravenous acyclovir. The symptoms resolved rapidly within 3 days, in accordance with improved endoscopic findings.
Tzouvala, M.; Gaglia, A.; Papantoniou, N.; Triantafyllou, K.; Karamanolis, G.
The effect of immunization with inactivated herpes virus vaccines, including a vaccine free of all nucleic acid, was investigated in a mouse model system. Protection against oral lesions induced by herpes simplex virus type 1 was demonstrated by several criteria: (i) reduction in the incidence and severity of primary oral lesions; (ii) decrease in acute and latent infection of the regional sensory ganglia; and (iii) protection from viral encephalitis and death. The immune response of mice to the vaccine and to subsequent virus challenge was measured by following serum-neutralizing antibody titers.
Valproic acid (VPA) is a short-chain fatty acid commonly used for treatment of neurological disorders. As VPA can interfere with cellular lipid metabolism, its effect on the infection of cultured cells by viruses of seven viral families relevant to human and animal health, including eight enveloped and four nonenveloped viruses, was analyzed. VPA drastically inhibited multiplication of all the enveloped viruses tested, including the zoonotic lymphocytic choriomeningitis virus and West Nile virus (WNV), while it did not affect infection by the nonenveloped viruses assayed. VPA reduced vesicular stomatitis virusinfection yield without causing a major blockage of either viral RNA or protein synthesis. In contrast, VPA drastically abolished WNV RNA and protein synthesis, indicating that this drug can interfere the viral cycle at different steps of enveloped virusinfection. Thus, VPA can contribute to an understanding of the crucial steps of viral maturation and to the development of future strategies against infections associated with enveloped viruses.
Vazquez-Calvo, Angela; Saiz, Juan-Carlos; Sobrino, Francisco; Martin-Acebes, Miguel A.
There are several similarities between the small, circular, single-stranded-DNA genomes of circoviruses that infect vertebrates and the nanoviruses that infect plants. We analyzed circovirus and nanovirus replication initiator protein (Rep) sequences and confirmed that an N-terminal region in circovirus Reps is similar to an equivalent region in nanovirus Reps. However, we found that the remaining C-terminal region is related to an RNA-binding protein (protein 2C), encoded by picorna-like viruses, and we concluded that the sequence encoding this region of Rep was acquired from one of these single-stranded RNA viruses, probably a calicivirus, by recombination. This is clear evidence that a DNA virus has incorporated a gene from an RNA virus, and the fact that none of these viruses code for a reverse transcriptase suggests that another agent with this capacity was involved. Circoviruses were thought to be a sister-group of nanoviruses, but our phylogenetic analyses, which take account of the recombination, indicate that circoviruses evolved from a nanovirus. A nanovirus DNA was transferred from a plant to a vertebrate. This transferred DNA included the viral origin of replication; the sequence conservation clearly indicates that it maintained the ability to replicate. In view of these properties, we conclude that the transferred DNA was a kind of virus and the transfer was a host-switch. We speculate that this host-switch occurred when a vertebrate was exposed to sap from an infected plant. All characterized caliciviruses infect vertebrates, suggesting that the host-switch happened first and that the recombination took place in a vertebrate.
In healthy individuals, influenza virus (IAV) infection generally remains localized to the epithelial cells of the respiratory tract. Previously, IAV-specific effector CD8 T cells found systemically during the course of IAV infection were thought to have been primed in lung-draining lymph nodes with subsequent migration to other tissues. However, little is known about whether other lymphoid sites participate in the generation of virus-specific CD8 T cells during localized IAV infection. Here, we present evidence of early CD8 T cell priming in the spleen following respiratory IAV infection independent of lung-draining lymph node priming of T cells. Although we found early indications of CD8 T cell activation in the lymph nodes draining the respiratory tract, we also saw evidence of virus-specific CD8 T cell activation in the spleen. Furthermore, CD8 T cells primed in the spleen differentiated into memory cells of equivalent longevity and with similar recall capacity as CD8 T cells primed in the draining lymph nodes. These data showed that the spleen contributes to the virus-specific effector and memory CD8 T cell populations that are generated in response to respiratory infection. PMID:23388712
Turner, Damian L; Bickham, Kara L; Farber, Donna L; Lefrançois, Leo
In healthy individuals, influenza virus (IAV) infection generally remains localized to the epithelial cells of the respiratory tract. Previously, IAV-specific effector CD8 T cells found systemically during the course of IAV infection were thought to have been primed in lung-draining lymph nodes with subsequent migration to other tissues. However, little is known about whether other lymphoid sites participate in the generation of virus-specific CD8 T cells during localized IAV infection. Here, we present evidence of early CD8 T cell priming in the spleen following respiratory IAV infection independent of lung-draining lymph node priming of T cells. Although we found early indications of CD8 T cell activation in the lymph nodes draining the respiratory tract, we also saw evidence of virus-specific CD8 T cell activation in the spleen. Furthermore, CD8 T cells primed in the spleen differentiated into memory cells of equivalent longevity and with similar recall capacity as CD8 T cells primed in the draining lymph nodes. These data showed that the spleen contributes to the virus-specific effector and memory CD8 T cell populations that are generated in response to respiratory infection.
Turner, Damian L.; Bickham, Kara L.; Farber, Donna L.
Objective: Our purpose was to ascertain the prevalence, incidence, and predictors of gynecologic disorders among women infected with human immunodeficiency virus. Study Design: We serially assessed 292 women infected with human immunodeficiency virus and 681 uninfected women. Outcomes were incidence and prevalence of sexually transmitted diseases, viral shedding, findings of Papanicolaou smears, fungal infections, and menstrual disorders. Results: Women infected
Howard L. Minkoff; Debra Eisenberger-Matityahu; Joseph Feldman; Robert Burk; Lorraine Clarke
Mild encephalopathy with reversible splenial lesions has mainly been associated with influenza A and B virusinfection. Patients present with neurologic symptoms 1 to 3 days after a prodromal illness and recover completely within a few days. Magnetic resonance imaging typically shows reversible lesions with reduced diffusion in the corpus callosum, predominantly in the splenium. We report on a 5-year old Caucasian boy who was referred with recurrent seizures and decreased level of consciousness after a 2-day prodromal fever and cough. Magnetic resonance imaging showed cytotoxic edema of the entire corpus callosum and the adjacent periventricular white matter with diffusion restriction and faint T(2)-hyperintensity. Parainfluenza virus type 1-3 infection was documented by direct immunofluorescence in the initial nasopharyngeal swab, but polymerase chain reaction for parainfluenza virus type 1-4 in the cerebrospinal fluid remained negative. This is-to our knowledge-the first description of mild encephalopathy with reversible splenial lesions in association with parainfluenza virusinfection. The pathogenesis of mild encephalopathy with reversible splenial lesions, however, still remains unclear, and further studies investigating detailed mechanisms that lead to the typical brain lesions are warranted. PMID:23419480
SUMMARY Splenic leukocytes derived from N- and P-line chickens exposed to turkey herpesvirus (HVT-4), and from UCD-003 chickens exposed to the non-oncogenic SB-1 clone of Marek's disease virus were fractionated into subpopulations at various days post-exposure. The level of infection in these fractions was determined by enumeration of plaque-forming units after co-cultivation of leukocytes with virus-permissive chicken embryo fibroblasts. At
Context Since the introduction of highly active anti-retroviral regimen for human immunodeficiency virus-1 infection, a significant increase in the incidence of hepatocellular carcinoma has been reported in patients already chronically infected with hepatitis B virus and then given this form of regimen for their retroviral infection. Evidence Acquisition This phenomenon was initially attributed to the far more prolonged survival of those patients who received this new regimen, which provided sufficient time, allowing hepatitis B virus-induced hepatocellular carcinoma to develop. Results The current belief is that the increased incidence of hepatocellular carcinoma is because of co-infection with the two viruses, one known to be hepatocarcinogenic and the other suspected to increase the carcinogenic potential of the other. Because both hepatitis B virus and human immunodeficiency virus -1 are endemic in the Black population of sub-Saharan Africa and are transmitted in similar ways, as many as 20% of this population are co-infected with the two viruses. In this way, the already high risk of Black African patients developing hepatitis B virus-induced hepatocellular carcinoma is further increased. Conclusions The pathogenetic mechanism or mechanisms involved in the carcinogenic interaction between the hepatitis B virus and the human immunodeficiency virus-1 in sub-Saharan Black Africans and other populations co-infected with these viruses have yet to be determined.
To demonstrate that pandemic (H1N1) 2009 virus may cause respiratory disease in cats, we intratracheally infected cats. Diffuse alveolar damage developed. Seroconversion of sentinel cats indicated cat-to-cat virus transmission. Unlike in cats infected with highly pathogenic avian influenza virus (H5N1), extrarespiratory lesions did not develop in cats infected with pandemic (H1N1) 2009 virus.
van den Brand, Judith M.A.; Stittelaar, Koert J.; van Amerongen, Geert; van de Bildt, Marco W.G.; Leijten, Lonneke M.E.; Kuiken, Thijs
Mice were infected with lymphocytic choriomeningitis virus (LCMV) to determine if changes in CD1d expression occurred during an acute virusinfection. It is interesting that a de- crease in CD1d expression on splenic dendritic cells (DC) and macrophages (M) was observed for at least 3 months post-LCMV infection, and vac- cinia virus and vesicular stomatitis virus induced similar changes in
Yinling Lin; Tonya J. Roberts; Philip M. Spence; Randy R. Brutkiewicz
Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae and cause severe hemorrhagic fever in humans and nonhuman primates. Despite the discovery of EBOV (Reston virus) in nonhuman primates and domestic pigs in the Philippines and the serological evidence for its infection of humans and fruit bats, information on the reservoirs and potential amplifying hosts for filoviruses in Asia is lacking. In this study, serum samples collected from 353 healthy Bornean orangutans (Pongo pygmaeus) in Kalimantan Island, Indonesia, during the period from December 2005 to December 2006 were screened for filovirus-specific IgG antibodies using a highly sensitive enzyme-linked immunosorbent assay (ELISA) with recombinant viral surface glycoprotein (GP) antigens derived from multiple species of filoviruses (5 EBOV and 1 MARV species). Here we show that 18.4% (65/353) and 1.7% (6/353) of the samples were seropositive for EBOV and MARV, respectively, with little cross-reactivity among EBOV and MARV antigens. In these positive samples, IgG antibodies to viral internal proteins were also detected by immunoblotting. Interestingly, while the specificity for Reston virus, which has been recognized as an Asian filovirus, was the highest in only 1.4% (5/353) of the serum samples, the majority of EBOV-positive sera showed specificity to Zaire, Sudan, Cote dIvoire, or Bundibugyo viruses, all of which have been found so far only in Africa. These results suggest the existence of multiple species of filoviruses or unknown filovirus-related viruses in Indonesia, some of which are serologically similar to African EBOVs, and transmission of the viruses from yet unidentified reservoir hosts into the orangutan populations. Our findings point to the need for risk assessment and continued surveillance of filovirus infection of human and nonhuman primates, as well as wild and domestic animals, in Asia.
Nidom, Reviany V.; Alamudi, Mohamad Y.; Daulay, Syafril; Dharmayanti, Indi N. L. P.; Dachlan, Yoes P.; Amin, Mohamad; Igarashi, Manabu; Miyamoto, Hiroko; Yoshida, Reiko; Takada, Ayato
This note serves as a warning that a recently mutated virus, deviatoric stressitis, has infected many in the Earth science community. The good news is that this virus, nicknamed deveitis (dee vee' i-tis), is not lethal and its victims can hope for a complete recovery. The bad news is that deveitis has spread like wildfire and leads to great confusion about Earth stress in papers, abstracts, and discussions by any of its victims.Deveitis is easy to recognize. The most common symptom is the use of the term, deviatoric stress, in papers, abstracts, and discussions.
Direct inoculation of a cloned bovine leukemia virus (BLV) provirus into sheep has allowed study of the viral infectivity of genetic mutants in vivo. Three BLV variants cloned from BLV-induced tumors and 12 in vitro-modified proviruses were isolated and analyzed for viral expression in cell culture. The proviruses were then inoculated into sheep in order to assess viral infectivity in vivo. Of three variants cloned from BLV-induced tumors (344, 395, and 1345), one (344) was found infectious in vivo. This particular provirus was used to engineer 12 BLV mutants. A hybrid between the 5' region of the complete but noninfectious provirus 395 and the 3' end of mutant 344 was infectious in vivo, suggesting that the tax/rex sequences were altered in virus 395. As expected, several regions of the BLV genome appeared to be essential for viral infection: the protease, pol, and env genes. Even discrete modifications in the fusion peptide located at the NH2 end of the transmembrane gp30 glycoprotein destroyed the infectious potential. In contrast, mutations and deletions in the X3 region present between the env gene and the 3' tax/rex region did not interfere with viral infection in vivo. This region of unknown function could thus be used to introduce foreign sequences. A BLV recombinant carrying a ribozyme directed against the tax/rex sequences was still infectious in vivo. Cotransfection of two noninfectious mutants carrying deletions led to infection in two of four independent injections, the infectious virus being then a recombinant between the two deletants. The experimental approach described here should help to gain insight into essential mechanisms such as in vivo viral replication, cooperation between deletants for viral infectivity, and viral superinfections. The gene products in the X3 and X4 region which are dispensable for in vivo infection could be involved in leukemogenesis, and thus proviruses deleted in these sequences could constitute the basis for a live attenuated vaccine. PMID:8389918
Cross-protection between Junin virus and five other Tacaribe complex viruses and the serological response of guinea pigs inoculated with Tacaribe virus are reported here. Previous infection with Tamiami or Pichinde viruses significantly delayed guinea pig deaths. A 58% survival rate was found among animals immunized with three doses of Amapari virus, while guinea pigs inoculated with one dose of Machupo or Tacaribe virus were fully protected against Junin virus. Neutralization tests performed in serum samples of guinea pigs immunized with five doses of Tacaribe virus showed that they developed monologous and heterologous neutralizing antibodies. PMID:178627
Among the different definitions of viruses, 'pirates of the cell' is one of the most picturesque, but also one of the most appropriate. Viruses have been known for a long time to utilize a variety of strategies to penetrate cells and, once inside, to take over the host nucleic acid and protein synthesis machinery to build up their own components and produce large amounts of viral progeny. As their genomes carry a minimal amount of information, encoding only a few structural and regulatory proteins, viruses are largely dependent on their hosts for survival; however, despite their apparent simplicity, viruses have evolved different replicative strategies that are regulated in a sophisticated manner. During the last years, the study of the elaborate relationship between viruses and their hosts has led to the understanding of how viral pathogens not only are able to alter the host metabolism via their signaling proteins, but are also able to hijack cellular signaling pathways and transcription factors, and control them to their own advantage. In particular, the nuclear factor-kappaB (NF-kappaB) pathway appears to be an attractive target for common human viral pathogens. This review summarizes what is known about the control of NF-kappaB by viruses, and discusses the possible outcome of NF-kappaB activation during viral infection, which may benefit either the host or the pathogen. PMID:12773372
Santoro, M Gabriella; Rossi, Antonio; Amici, Carla
A rapid immunochromatographic test was compared to the hemagglutination inhibition assay for separate determinations of dengue virus-specific immunoglobulin M (IgM) and IgG levels in paired serum specimens from 92 patients (34 with primary dengue virusinfection, 35 with secondary dengue virusinfection, and 23 without dengue virusinfection). The rapid test showed 99% sensitivity in the diagnosis of dengue virusinfection. The majority (30 of 34 [88%]) of patients with primary infection showed positive IgM but negative IgG, while 34 of 35 (97%) patients with secondary infection showed positive IgG with or without IgM. Specificity in nonflavivirus infections was 96% (1 of 23 positive). The rapid test should be a useful aid in rapid diagnosis of dengue virusinfection.
Sang, Chew Theng; Hoon, Lim Siew; Cuzzubbo, Andrea; Devine, Peter
A rapid immunochromatographic test was compared to the hemagglutination inhibition assay for separate determinations of dengue virus-specific immunoglobulin M (IgM) and IgG levels in paired serum specimens from 92 patients (34 with primary dengue virusinfection, 35 with secondary dengue virusinfection, and 23 without dengue virusinfection). The rapid test showed 99% sensitivity in the diagnosis of dengue virusinfection. The majority (30 of 34 [88%]) of patients with primary infection showed positive IgM but negative IgG, while 34 of 35 (97%) patients with secondary infection showed positive IgG with or without IgM. Specificity in nonflavivirus infections was 96% (1 of 23 positive). The rapid test should be a useful aid in rapid diagnosis of dengue virusinfection. PMID:9606000
Dual infections of pigs with porcine reproductive and respiratory syndrome virus (PRRSV) followed by a second common respiratory virus, either porcine respiratory coronavirus (PRCV) or swine influenza virus (SIV), were studied. The aim was to determine if dual infections, as compared to single virusinfections, result in enhanced clinical manifestations. It was also examined if PRRSV replication affects replication of
Kristien Van Reeth; Hans Nauwynck; Maurice Pensaert
Highly pathogenic H5N1 virus remains a potential threat to humans. Over 289 fatalities have been reported in WHO confirmed human cases since 2003, and lack of effective vaccines and early treatments contribute to increasing numbers of cases and fatalities. H5N1 encephalitis is a recognized cause of death in Vietnamese cases, and brain pathology is described in other human cases and naturally infected animals. However, neither pathogenesis of H5N1 viral infection in human brain nor post-infection effects in survivors have been fully investigated. We report the brain pathology in a ferret model for active infection and 18-day survival stages. This model closely resembles the infection pattern and progression in human cases of influenza A, and our report is the first description of brain pathology for longer term (18-day) survival in ferrets. We analyzed viral replication, type and severity of meningoencephalitis, infected cell types, and cellular responses to infection. We found viral replication to very high titers in ferret brain, closely correlating with severity of meningoencephalitis. Viral antigens were detected predominantly in neurons, correlating with inflammatory lesions, and less frequently in astrocytes and ependymal cells during active infection. Mononuclear cell infiltrates were observed in early stages predominantly in cerebral cortex, brainstem, and leptomeninges, and less commonly in cerebellum and other areas. Astrogliosis was mild at day 4 post-infection, but robust by day 18. Early and continuous treatment with an antiviral agent (peramivir) inhibited virus production to non-detectable levels, reduced severity of brain injury, and promoted higher survival rates. PMID:22176758
Highly pathogenic avian influenza H5N1 virus causes a severe, often fatal, pneumonia in humans. The tropism and pathogenesis of highly pathogenic avian influenza H5N1 virus can partly be explained by the presence of H5N1 virus receptors in the human alveoli, which are the site of inflammation during pneumonia. Although studies on the distribution of influenza virus receptors in normal respiratory tract tissues have provided significant insights into the cell tropism and pathogenesis of influenza viruses, the distribution of influenza virus receptors have not been studied during influenza virusinfection. Therefore, we studied the distribution of H5N1 virus receptors, by virus and lectin histochemistry, during highly pathogenic avian influenza H5N1 virusinfection in alveolar tissues of humans, macaques, ferrets, and cats. In all species, we observed a decrease of H5N1 virus receptors in influenza virus-infected and neighboring cells. The observed decrease of H5N1 virus receptors was associated with the presence of MxA, a known marker for interferon activity. Taken together, our data suggest that the decrease of H5N1 virus receptors might be part of a defense mechanism that limits viral replication in the lower respiratory tract. PMID:23993779
van Riel, Debby; Leijten, Lonneke M; Kochs, George; Osterhaus, Ab D M E; Kuiken, Thijs
Background Unlike most acute viral infections controlled with the appearance of virus-specific neutralizing antibodies (NAbs), primary HIV infections are not met with such potent and early antibody responses. This brings into question if or how the presence of potent antibodies can contribute to primary HIV control, but protective efficacies of antiviral antibodies in primary HIV infections have remained elusive; and, it has been speculated that even NAb induction could have only a limited suppressive effect on primary HIV replication once infection is established. Here, in an attempt to answer this question, we examined the effect of passive NAb immunization post-infection on primary viral replication in a macaque AIDS model. Methods and Findings The inoculums for passive immunization with simian immunodeficiency virus mac239 (SIVmac239)-specific neutralizing activity were prepared by purifying polyclonal immunoglobulin G from pooled plasma of six SIVmac239-infected rhesus macaques with NAb induction in the chronic phase. Passive immunization of rhesus macaques with the NAbs at day 7 after SIVmac239 challenge resulted in significant reduction of set-point plasma viral loads and preservation of central memory CD4 T lymphocyte counts, despite the limited detection period of the administered NAb responses. Peripheral lymph node dendritic cell (DC)-associated viral RNA loads showed a remarkable peak with the NAb administration, and DCs stimulated in vitro with NAb-preincubated SIV activated virus-specific CD4 T lymphocytes in an Fc-dependent manner, implying antibody-mediated virion uptake by DCs and enhanced T cell priming. Conclusions Our results present evidence indicating that potent antibody induction post-infection can result in primary immunodeficiency virus control and suggest direct and indirect contribution of its absence to initial control failure in HIV infections. Although difficulty in achieving requisite neutralizing titers for sterile HIV protection by prophylactic vaccination has been suggested, this study points out a possibility of non-sterile HIV control by prophylactic vaccine-induced, sub-sterile titers of NAbs post-infection, providing a rationale of vaccine-based NAb induction for primary HIV control.
Measles virus (MV) is hypothesized to enter the host by infecting epithelial cells of the respiratory tract, followed by viremia mediated by infected monocytes. However, neither of these cell types express signaling lymphocyte activation molecule (CD150), which has been identified as the receptor for wild-type MV. We have infected rhesus and cynomolgus macaques with a recombinant MV strain expressing enhanced green fluorescent protein (EGFP); thus bringing together the optimal animal model for measles and a virus that can be detected with unprecedented sensitivity. Blood samples and broncho-alveolar lavages were collected every 3 d, and necropsies were performed upon euthanasia 9 or 15 d after infection. EGFP production by MV-infected cells was visualized macroscopically, in both living and sacrificed animals, and microscopically by confocal microscopy and FACS analysis. At the peak of viremia, EGFP fluorescence was detected in skin, respiratory and digestive tract, but most intensely in all lymphoid tissues. B- and T-lymphocytes expressing CD150 were the major target cells for MV infection. Highest percentages (up to 30%) of infected lymphocytes were detected in lymphoid tissues, and the virus preferentially targeted cells with a memory phenotype. Unexpectedly, circulating monocytes did not sustain productive MV infection. In peripheral tissues, large numbers of MV-infected CD11c+ MHC class-II+ myeloid dendritic cells were detected in conjunction with infected T-lymphocytes, suggesting transmission of MV between these cell types. Fluorescent imaging of MV infection in non-human primates demonstrated a crucial role for lymphocytes and dendritic cells in the pathogenesis of measles and measles-associated immunosuppression.
de Swart, Rik L; Yanagi, Yusuke; van Amerongen, Geert; McQuaid, Stephen; Yuksel, Selma; Geijtenbeek, Teunis B. H; Duprex, W. Paul; Osterhaus, Albert D. M. E
Forty-three stool samples from 27 human immunodeficiency virus (HIV)-seropositive children and 38 samples from 38 HIV-negative children, collected during a 15-month period, were examined for enteric viruses. Diagnostic assays included enzyme immunoassays for rotavirus, adenovirus, and Norwalk virus; polyacryl- amide gel electrophoresis for picobirnavirus and atypical rotavirus; and PCR for astrovirus and enterovirus. Specimens from HIV-positive children were more likely
MARY B. LISTE; IVELISSE NATERA; FLOR H. PUJOL; FERDINANDO LIPRANDI; JUAN E. LUDERT
The role of sexual transmission in the diffusion of HCV infection, was studied through the seroprevalence of anti-HCV antibodies in the heterosexual habitual partners of 83 anti-HCV positive subjects. The index cases were represented by 10 dialysed subjects, 31 patients with chronic liver disease and 42 healthy carriers. Seroprevalence of anti-HCV positivity reported in partners was 8.43%, with a higher
G. Scotto; A. M. Savastano; V. Fazio; P. E. Conte; S. Ferrara; A. Mangano; G. Tantimonaco
The putative envelope glycoproteins of hepatitis C virus (HCV) likely play an important role in the initiation of viral infection. Available information suggests that the genomic regions encoding the putative envelope glycoproteins, when expressed as recombinant proteins in mammalian cells, largely accumulate in the endo- plasmic reticulum. In this study, genomic regions which include the putative ectodomain of the E1
L. MARTIN LAGGING; KEITH MEYER; RANDALL J. OWENS; RANJIT RAY
Genotype C of hepatitis B virus (HBV) has been shown to be associated with a poor clinical outcome, compared to genotype B. To explore the clinical phenotypes, with special reference to the seroconversion of hepatitis B e antigen (HBeAg) and frequency of acute exacerbation between patients infected with HBV genotypes B and C, a cohort of 272 Taiwanese patients with
West Nile virus (WNV) has caused disease in humans, equids, and birds at lower frequency in Mexico than in the United States. We hypothesized that the seemingly reduced virulence in Mexico was caused by attenuation of the Tabasco strain from southeastern Mexico, resulting in lower viremia than that caused by the Tecate strain from the more northern location of Baja California. During 20062008, we tested this hypothesis in candidate avian amplifying hosts: domestic chickens, rock pigeons, house sparrows, great-tailed grackles, and clay-colored thrushes. Only great-tailed grackles and house sparrows were competent amplifying hosts for both strains, and deaths occurred in each species. Tecate strain viremia levels were higher for thrushes. Both strains produced low-level viremia in pigeons and chickens. Our results suggest that certain avian hosts within Mexico are competent for efficient amplification of both northern and southern WNV strains and that both strains likely contribute to bird deaths.
Guerrero-Sanchez, Sergio; Cuevas-Romero, Sandra; Nemeth, Nicole M.; Trujillo-Olivera, Maria Teresa Jesus; Worwa, Gabriella; Dupuis, Alan; Brault, Aaron C.; Kramer, Laura D.; Komar, Nicholas
West Nile virus (WNV) has caused disease in humans, equids, and birds at lower frequency in Mexico than in the United States. We hypothesized that the seemingly reduced virulence in Mexico was caused by attenuation of the Tabasco strain from southeastern Mexico, resulting in lower viremia than that caused by the Tecate strain from the more northern location of Baja California. During 2006-2008, we tested this hypothesis in candidate avian amplifying hosts: domestic chickens, rock pigeons, house sparrows, great-tailed grackles, and clay-colored thrushes. Only great-tailed grackles and house sparrows were competent amplifying hosts for both strains, and deaths occurred in each species. Tecate strain viremia levels were higher for thrushes. Both strains produced low-level viremia in pigeons and chickens. Our results suggest that certain avian hosts within Mexico are competent for efficient amplification of both northern and southern WNV strains and that both strains likely contribute to bird deaths. PMID:22172633
Guerrero-Sánchez, Sergio; Cuevas-Romero, Sandra; Nemeth, Nicole M; Trujillo-Olivera, María Teresa Jesús; Worwa, Gabriella; Dupuis, Alan; Brault, Aaron C; Kramer, Laura D; Komar, Nicholas; Estrada-Franco, José Guillermo
Telaprevir is a recently approved direct-acting antiviral against hepatitis C virus (HCV) that works through inhibition of the NS3/4A serine protease inhibitor. Phase 2b and 3 studies have shown marked increase in sustained virologic response rates in both treatment-naïve and treatment-experienced patients with HCV genotype 1 treated with a telaprevir-containing regimen compared with pegylated interferon (Peg-IFN) and ribavirin alone. The most commonly observed side effects of telaprevir therapy are anemia to a greater degree than that observed with Peg-IFN/ribavirin alone; eczematous rash, which can be severe in a minority of patients; and anorectal discomfort. PMID:23177282
Primate lentiviruses use chemokine coreceptors in addition to the CD4 receptor to initiate virusinfection. Simian immunodeficiency virus (SIV) productively infects human cells expressing CD4 and the human allele ofthechemokinecoreceptorCCR-5asefficientlyasitinfectsmacaquecellsexpressinghumanCD4,suggesting thatSIVcanfunctionwitheitherasimianorahumancoreceptorinconjunctionwithhumanCD4.Inthesame macaque cells expressing human CD4, the replication of human immunodeficiency virus type 1 (HIV-1) is blocked at several stages of infection; some isolates are restricted prior to reverse transcription,
BRYCE CHACKERIAN; E. MICHELLE LONG; PAUL A. LUCIW; ANDJULIE OVERBAUGH
Infection of cat embryo cells by a centrifugally induced aggregate of murine sarcoma virus and feline leukemia virus gave rise to a defective, focus-forming virus which propagated in cat cells, but not in mouse cells. This virus, apparently enveloped with a feline leukemia virus coat, was later subjected to aggregation with murine leukemia virus, whereupon it regained the capacity for growth in mouse cells. PMID:5793978
Viruses causing hemorrhagic fevers in man belong to the following virus groups: togavirus (Chikungunya), flavivirus (dengue, yellow fever, Kyasanur Forest disease, Omsk hemorrhagic fever), arenavirus (Argentinian hemorrhagic fever, Bolivian hemorrhagic fever, Lassa fever), filovirus (Ebola, Marburg), phlebovirus (Rift Valley fever), nairovirus (Crimian-Congo hemorrhagic fever) and hantavirus (hemorrhagic fever with renal syndrome, nephropathic epidemia). Hemorrhagic fever virusinfections can be approached by different therapeutic strategies: (i) vaccination; (ii) administration of high-titered antibodies; and (iii) treatment with antiviral drugs. Depending on the molecular target of their interaction, antiviral agents could be classified as follows: IMP dehydrogenase inhibitors (i.e., ribavirin and its derivatives); OMP decarboxylase inhibitors (i.e., pyrazofurin); CTP synthetase inhibitors (i.e., cyclopentylcytosine and cyclopentenylcytosine); SAH hydrolase inhibitors (i.e., neplanocin A); polyanionic substances (i.e., sulfated polymers); interferon and immunomodulators. PMID:8250543
Approximately 60% of hepatitis A virusinfections in Germany occur in persons without a travel history to disease-endemic areas and for whom sources of infection are unknown. Recommendation of pretravel vaccination fails to prevent the remaining imported infections. Using enhanced surveillance in 2007-2008, we analyzed epidemiologic patterns of hepatitis A in Germany and appropriateness and adequacy of current immunization recommendations. Young patients with a migration background who had visited friends and family in their ancestral countries accounted for most imported cases. Phylogenetic analysis showed high diversity of sequence data and clustering of strains with similar regions of origin or patient migration backgrounds. Virologic findings are compatible with those of low-incidence countries, where virtually all infections are directly or indirectly imported from other regions. Germans with a migration background are seen as a special risk group so far insufficiently reached by pretravel vaccination advice. PMID:19891863
Histoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum. In immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. Clinical manifestations appear in patients with a CD4(+) lymphocyte count of less than 150 cells/?L. Coccidioidomycosis is a systemic mycosis caused by Coccidioides immitis and Coccidioides posadasii. It can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous system, the bones, and the skin. Cryptococcosis is caused by Cryptococcus neoformans (var. neoformans and var. grubii) and Cryptococcus gattii, which are members of the Cryptococcus species complex and have 5 serotypes: A, B, C, D, and AD. It is a common opportunistic infection in patients with human immunodeficiency virus (HIV)/AIDS, even those receiving antiretroviral therapy. Histopathologic examination and culture of samples from any suspicious lesions are essential for the correct diagnosis of systemic fungal infections in patients with HIV/AIDS. PMID:23107866
Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children. The pathophysiology of this infection in the respiratory system has been studied extensively, but little is known about its consequences in other systems. We studied whether RSV infects human bone marrow stromal cells (BMSCs) in vitro and in vivo, and investigated whether and how this infection affects BMSC structure and hematopoietic support function. Primary human BMSCs were infected in vitro with recombinant RSV expressing green fluorescent protein. In addition, RNA from naive BMSCs was amplified by PCR, and the products were sequenced to confirm homology with the RSV genome. The BMSC cytoskeleton was visualized by immunostaining for actin. Finally, we analyzed infected BMSCs for the expression of multiple cytokines and chemokines, evaluated their hematopoietic support capacity, and measured their chemotactic activity for both lymphoid and myeloid cells. We found that BMSCs support RSV replication in vitro with efficiency that varies among cell lines derived from different donors; furthermore, RNA sequences homologous to the RSV genome were found in naive primary human BMSCs. RSV infection disrupted cytoskeletal actin microfilaments, altered cytokine/chemokine expression patterns, decreased the ability of BMSCs to support B cell maturation, and modulated local chemotaxis. Our data indicate that RSV infects human BMSCs in vitro, and this infection has important structural and functional consequences that might affect hematopoietic and immune functions. Furthermore, we have amplified viral RNA from naive primary BMSCs, suggesting that in vivo these cells provide RSV with an extrapulmonary target.
Rezaee, Fariba; Gibson, Laura F.; Piktel, Debbie; Othumpangat, Sreekumar; Piedimonte, Giovanni
Hepatitis C virus (HCV) infection in the uterus is a significant path of vertical HCV transmission. Some studies consider vertical HCV transmission in the uterus as the result of maternal blood leakage into infant blood, whereas others theorize that HCV is transmitted by the mother to the infant through cells constituting the placenta barrier. Although trophoblasts play an important role in the placenta barrier, no definitive evidence has been presented to prove that cytotrophoblasts can be infected with HCV. The current study investigated whether or not these can be infected with HCV by conducting an experiment, in which cultured human cytotrophoblasts were infected with HCV in vitro. The results were analyzed using reverse transcription polymerase chain reaction (RT-PCR), ultrastructural characteristic changes under an electron microscope, and immunoelectron microscopy. HCV RNA in the supernatant of the cultured medium of the infected group was intermittently detected during the 16-day incubation period using RT-PCR. Under an electron microscope, the ultrastructures of infected human cytotrophoblasts were markedly different from normal cells, demonstrating lysosomal hyperplasia, rough endoplasmic reticulum, decreased lipid droplets, presence of vacuoles, and the appearance of HCV-like particles. Using immunoelectron microscopy, HCV-like particles conjoined with golden granules were also observed. Based on the data, the current study concludes that HCV infects a human cytotrophoblast cultured in vitro; moreover, its ultrastructure changes dramatically upon infection. PMID:22930506
Oropharyngeal and esophageal candidiases remain significant causes of morbidity in human immunodeficiency virus (HIV)-infected patients, despite the dramatic ability of antiretroviral therapy to reconstitute immunity. Notable advances have been achieved in understanding, at the molecular level, the relationships between the progression of HIV infection, the acquisition, maintenance, and clonality of oral candidal populations, and the emergence of antifungal resistance. However, the critical immunological defects which are responsible for the onset and maintenance of mucosal candidiasis in patients with HIV infection have not been elucidated. The devastating impact of HIV infection on mucosal Langerhans' cell and CD4+ cell populations is most probably central to the pathogenesis of mucosal candidiasis in HIV-infected patients. However, these defects may be partly compensated by preserved host defense mechanisms (calprotectin, keratinocytes, CD8+ T cells, and phagocytes) which, individually or together, may limit Candida albicans proliferation to the superficial mucosa. The availability of CD4C/HIV transgenic mice expressing HIV-1 in immune cells has provided the opportunity to devise a novel model of mucosal candidiasis that closely mimics the clinical and pathological features of candidal infection in human HIV infection. These transgenic mice allow, for the first time, a precise cause-and-effect analysis of the immunopathogenesis of mucosal candidiasis in HIV infection under controlled conditions in a small laboratory animal.
de Repentigny, Louis; Lewandowski, Daniel; Jolicoeur, Paul
Summary: Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section.
We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infec- tions in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), inter- leukin 1 (IL-1),
Natividad Benito; Asuncion Moreno; Xavier Filella; J. M. Miro; J. Gonzalez; T. Pumarola; M. E. Valls; M. Luna; F. Garcia; A. Rano; A. Torres; J. M. Gatell
Human immunodeficiency virus type 1 contains a transmembrane glycoprotein with an unusually long cytoplasmic domain. To determine the role of this domain in virus replication, a series of single nucleotide changes that result in the insertion of premature termination codons throughout the cytoplasmic domain has been constructed. These mutations delete from 6 to 192 amino acids from the carboxy terminus of gp41 and do not affect the amino acid sequence of the regulatory proteins encoded by rev and tat. The effects of these mutations on glycoprotein biosynthesis and function as well as on virusinfectivity have been examined in the context of a glycoprotein expression vector and the viral genome. All of the mutant glycoproteins were synthesized, processed, and transported to the cell surface in a manner similar to that of the wild-type glycoprotein. With the exception of mutants that remove the membrane anchor domain, all of the mutant glycoproteins retained the ability to cause fusion of CD4-bearing cells. However, deletion of more than 19 amino acids from the C terminus of gp41 blocked the ability of mutant virions to infect cells. This defect in virusinfectivity appeared to be due at least in part to a failure of the virus to efficiently incorporate the truncated glycoprotein. Similar data were obtained for mutations in two different env genes and two different target cell lines. These results indicate that the cytoplasmic domain of gp41 plays a critical role during virus assembly and entry in the life cycle of human immunodeficiency virus type 1. Images
The cellular site of herpesvirus tegument assembly has yet to be defined. We have previously used a recombinant herpes simplex virus type 1 expressing a green fluorescent protein (GFP)-tagged tegument protein, namely VP22, to show that VP22 is localized exclusively to the cytoplasm during infection. Here we have constructed a similar virus expressing another fluorescent tegument protein, YFP-VP13/14, and have visualized the intracellular localization of this second tegument protein in live infected cells. In contrast to VP22, VP13/14 is targeted predominantly to the nuclei of infected cells at both early and late times in infection. More specifically, YFP-13/14 localizes initially to the nuclear replication compartments and then progresses into intense punctate domains that appear at around 12 h postinfection. At even later times this intranuclear punctate fluorescence is gradually replaced by perinuclear micropunctate and membranous fluorescence. While the vast majority of YFP-13/14 seems to be targeted to the nucleus, a minor subpopulation also appears in a vesicular pattern in the cytoplasm that closely resembles the pattern previously observed for GFP-22. Moreover, at late times weak fluorescence appears at the cell periphery and in extracellular virus particles, confirming that YFP-13/14 is assembled into virions. This predominantly nuclear targeting of YFP-13/14 together with the cytoplasmic targeting of VP22 may imply that there are multiple sites of tegument protein incorporation along the virus maturation pathway. Thus, our YFP-13/14-expressing virus has revealed the complexity of the intracellular targeting of VP13/14 and provides a novel insight into the mechanism of tegument, and hence virus, assembly. PMID:11222680
Twenty?four laying turkey hens shown to be free of antibodies to turkey rhinotracheitis virus were inoculated intranasally with an isolate of the virus. A mild respiratory disease developed between 5 and 9 days post infection (pi). Two birds were selected at random at intervals between days 1 and 20 pi, killed and tissues examined for the presence of virus. At
R. C. Jones; R. A. Williams; C. E. Savage; G. P. Wilding
Barley tissue with an acute systemic infection of barley stripe mosaic virus contained a large amount of unencapsidated virus RNA which was stable in extracts made in ribosome isolation buffer. The virus RNA in ribosome preparations sedimented in a broad band at 80S to 100S in sucrose gradients, which is less than the virion sedimentation rate of 180S to 200S.
SUMMARY By use of monoclonal antibodies, a virus-specific cytoplasmic antigen related to phosphorylated polypeptides specific to serotype 1 of Marek's disease virus (MDV)- related viruses (MDV1) has been identified in all MD tumour cell lines examined, as well as in infected cells and in tumour lesions of chickens with MD. At least two phosphorylated polypeptides with mol. wt. 39000 (39K)
We used a molecular panel, targeting seven enteric viruses, to explore the advantage of using molecular methods to establish the etiology of enteric diseases and to evaluate the prevalence of enteric viruses in asymptomatic human immunodeficiency virus-infected patients. This approach favors rapidity and sensitivity of laboratory diagnosis of viral enteric syndromes.
Minosse, Claudia; Zaniratti, Maria S.; Calcaterra, Silvia; Carletti, Fabrizio; Muscillo, Michele; Pisciotta, Marina; Pillitteri, Letizia; Corpolongo, Angela; Lauria, Francesco Nicola; Narciso, Pasquale; Anzidei, Gianfranco; Capobianchi, Maria R.
Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2) are human neurotropic viruses that establish latent infection in dorsal root ganglia (DRG) for the entire life of the host. From the DRG they can reactivate to cause human morbidity and mortality. Although they vary, in part, in the clinical disorders they cause, and in their molecular structure, they share several features that govern the biology of their infection of the human nervous system. HSV-1 is the causative agent of encephalitis, corneal blindness, and several peripheral nervous system disorders; HSV-2 is responsible for meningoencephalitis in neonates and meningitis in adults. The biology of their ability to establish latency, maintain it for the entire life of the host, reactivate, and cause primary and recurrent disease is being studied in animal models and in humans. This review covers recent advances in understanding the biology and pathogenesis of HSV-related disease. PMID:24142852
Human immunodeficiency virus-infected hemophiliacs are at risk for bacterial and opportunitic infections with worsening immunosuppression. Thus, the risk of postoperative infection following orthopaedic surgery is of considerable concern. A survey of United States hemophilia treatment centers was conducted to determine the incidence of postoperative infection in human immunodeficiency virus-positive hemophiliacs with CD4 counts of 200 mm3 or less undergoing orthopaedic
Margaret V. Ragni; Lawrence S. Crossett; James H. Herndon
Porcine reproductive and respiratory syndrome (PRRS) virusinfection results in clinically normal, but persistently infected animals. An understanding of the carrier state is necessary for prevention, control and\\/or elimination of PRRS virus. The objective of this experiment was to estimate the proportion of PRRS virus carriers over time and determine which combination of sample and diagnostic assay could most effectively
Dennis C Horter; Roman M Pogranichniy; Chih-Cheng Chang; Richard B Evans; Kyoung-Jin Yoon; Jeffrey J Zimmerman
The mosquito Aedes taeniorhynchus is an important epidemic vector of Venezuelan equine encephalitis virus (VEEV), but detailed studies of its infection are lacking. We compared infection by an epidemic VEEV strain to that by an enzootic strain using virus titrations, immunohistochemistry, and a virus expressing the green fluorescent protein. Ae. taeniorhynchus was more susceptible to the epidemic strain, which initially
Darci R. Smith; Nicole C. Arrigo; Grace Leal; Linda E. Muehlberger; Scott C. Weaver
Differences in host response to infection with avian influenza (AI) viruses were investigated by identifying genes differentially expressed in tissues of infected ducks. Clear differences in pathogenicity were observed among ducks inoculated with five H5N1 HPAI viruses. Virus titers in tissues cor...
Infection by the parapoxvirus orf virus causes proliferative skin lesions in which extensive capillary prolif- eration and dilation are prominent histological features. This infective phenotype may be linked to a unique virus-encoded factor, a distinctive new member of the vascular endothelial growth factor (VEGF) family of molecules. We constructed a recombinant orf virus in which the VEGF-like gene was disrupted
LOREEN J. SAVORY; STEVEN A. STACKER; STEPHEN B. FLEMING; BRIAN E. NIVEN; ANDREW A. MERCER
A variety of Ross Sea summer pack ice habitats between 66 and 75°S were examined for viruses 𔒦 nm capsid diameter. Maximum abundances of these viruses likely to infect eukaryotes were 106-107 ml-1 brine in surface, interior, and bottom habitats and constituted up to 18% of the total (all sizes) viruses. There is abundant ultrastructural evidence for infection of a
This study examines the persistence and fitness of multidrug-resistant (MDR) viruses acquired during primary human immunodeficiency virusinfection (PHI). In four individuals, MDR infections persisted over the entire study period, ranging from 36 weeks to 5 years, in the absence of antiretroviral therapy. In stark contrast, identified source partners in two cases showed expected outgrowth of wild-type (WT) virus within
Bluma G. Brenner; Jean-Pierre Routy; Marco Petrella; Daniela Moisi; Maureen Oliveira; Mervi Detorio; Bonnie Spira; Vidal Essabag; Brian Conway; Richard Lalonde; Rafick-Pierre Sekaly; Mark A. Wainberg
Two patients with known human immunodeficiency virus (HIV) infections and receiving antiretroviral treatment developed neuromyelitis optica (Devic's disease). One patient tested positive for serum aquaporin-4 immunoglobulin G antibodies. Both patients were treated with high dose pulsed intravenous methylprednisolone followed by standard sessions of plasma exchange both at the onset attack and during disease relapses. For maintenance therapy, one patient received rituximab infusions and the second patient received mycophenolate mofetil orally. Despite treatment, both patients are currently wheelchair-bound due to severe paraparesis. Neuromyelitis optica can occur in the course of HIV infection and poses an ongoing therapeutic challenge. PMID:23549434
Feyissa, Anteneh M; Singh, Parbhdeep; Smith, Robert G
Hepatitis B virus (HBV) infection has been a major global cause of morbidity and mortality. The recognition of the problem led to a worldwide effort to reduce transmission of HBV through routine infant vaccination. HBV infection is the most common cause of chronic liver diseases and hepatocellular carcinoma in Korea. After hepatitis B vaccine era, seroprevalence of hepatits B surface antigen is decreasing, particularly in children. Hepatitis B vaccine is remarkably safe and shows high immunogenicity. Universal childhood immunization with three doses of hepatitis B vaccine in the first year of life is a highly effective method for prevention and control of hepatitis B.
More women than ever before are both Human Immunodeficiency Virus-infected and menopausal, because of increased survival and more frequent diagnosis in older women. Such a woman has the combined burden of her infection, its treatment, comorbid conditions, and aging. Thus she is at risk for a variety of problems such as disorders of bone mineral density and deficiencies in cognitive functioning. In addition to this, she experiences menopause in a unique fashion, with more symptoms and perhaps at an earlier age. The clinician caring for her must take a proactive approach to this multitude of factors that may affect her health and well-being.
Hepatitis C virus (HCV) is capable of disrupting different facets of lipid metabolism and lipids have been shown to play a crucial role in the viral life cycle. The aim of this study was to examine the effect HCV infection has on the hepatocyte metabolome. Huh-7.5 cells were infected using virus produced by the HCV J6/JFH1 cell culture system and cells were harvested 24, 48, and 72-hours following infection. Metabolic profiling was performed using a non-targeted multiple platform methodology combining ultrahigh performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS2) and gas chromatography/mass spectrometry (GC/MS). There was a significant increase in a number of metabolites involved in nucleotide synthesis and RNA replication during early HCV infection. NAD levels were also significantly increased along with several amino acids. A number of lipid metabolic pathways were disrupted by HCV infection, resulting in an increase in cholesterol and sphingolipid levels, altered phospholipid metabolism and a possible disruption in mitochondrial fatty acid transport. Fluctuations in 5?-methylthioadenosine levels were also noted, along with alterations in the glutathione synthesis pathway. These results highlight a number of previously unreported metabolic interactions and give a more in depth insight into the effect HCV has on host cell biochemical processes.
Roe, Barbara; Kensicki, Elizabeth; Mohney, Robert; Hall, William W.
The viral family Arenaviridae includes a number of viruses that can cause hemorrhagic fever in humans. Arenavirus infection often involves multiple organs and can lead to capillary instability, impaired hemostasis, and death. Preclinical testing for development of antiviral or therapeutics is in part hampered due to a lack of an immunologically well-defined rodent model that exhibits similar acute hemorrhagic illness or sequelae compared to the human disease. We have identified the FVB mouse strain, which succumbs to a hemorrhagic fever-like illness when infected with lymphocytic choriomeningitis virus (LCMV). FVB mice infected with LCMV demonstrate high mortality associated with thrombocytopenia, hepatocellular and splenic necrosis, and cutaneous hemorrhage. Investigation of inflammatory mediators revealed increased IFN-?, IL-6 and IL-17, along with increased chemokine production, at early times after LCMV infection, which suggests that a viral-induced host immune response is the cause of the pathology. Depletion of T cells at time of infection prevented mortality in all treated animals. Antisense-targeted reduction of IL-17 cytokine responsiveness provided significant protection from hemorrhagic pathology. F1 mice derived from FVB×C57BL/6 mating exhibit disease signs and mortality concomitant with the FVB challenged mice, extending this model to more widely available immunological tools. This report offers a novel animal model for arenavirus research and pre-clinical therapeutic testing. PMID:23300439
Schnell, Frederick J; Sundholm, Sarah; Crumley, Stacy; Iversen, Patrick L; Mourich, Dan V
Hepatitis E virus is one of the most common causes of acute hepatitis worldwide, with the majority of cases occurring in Asia. In recent years, however, an increasing number of acute and chronic hepatitis E virusinfections have been reported in industrialized countries. The importance of this infection resides in the associated morbidity and mortality. In acute cases, a high mortality rate has been reported in patients with previously undiagnosed alcoholic liver disease. Hepatitis E infection can become chronic in immunocompromised patients, such as solid organ transplant recipients, patients receiving chemotherapy, and HIV-infected patients, and lead to the development of hepatic fibrosis and cirrhosis. Hence, treatment strategies involving reductions in immunosuppressive regimens and therapy with ribavirin or peg-interferon have been evaluated. In terms of prevention, a promising new vaccine was recently licensed in China, although its efficacy is uncertain and potential adverse effects in risk groups such as chronic liver disease patients and pregnant women require investigation. In conclusion, physicians should be aware of hepatitis E as a cause of both acute and chronic hepatitis in immunocompromised patients. The best treatment option for HEV infection remains to be defined, but both ribavirin and peg-interferon may have a role in therapy for this condition. PMID:24114815
Riveiro-Barciela, Mar; Rodríguez-Frías, Francisco; Buti, María
This study is performed to gain knowledge about the quantitative distribution of bovine virus diarrhoea virus (BVDV) in tissues and white blood cells (WBC) at different intervals after acute infection. Ten specific pathogen-free calves were intranasally inoculated with 105 50% tissue culture infective dose of the non-cytopathic BVDV strain 4800. Twelve hours after inoculation tonsil biopsies were taken and WBC
Christianne J. M Bruschke; Klaas Weerdmeester; Jan T Van Oirschot; Piet A Van Rijn
Cells which are infected with measles virus have been known for some time to contain inclusion material that is distinguishable from normal cellular components by application of traditional staining methods and observation in the light microscope. The fine structure of the inclusion material contained in HeLa cells infected with Edmonston strain of measles virus has been examined in the electron microscope. Two steps have been found necessary in this study: (1) the recognition by phase-contrast microscopy of the living cell of bodies that are defined as inclusion material when the cells are classically stained; and (2) the recognition in the electron microscope of inclusion-body material that had previously been identified in the living cell. The fine structure of the nuclear and cytoplasmic inclusion material in osmium-treated cells was found to consist mainly of randomly arrayed filaments of low electron density. Dense, highly ordered arrays of filaments were found near the center of the nuclear inclusions, sometimes as a two-dimensional, nearly orthogonal arrangement. If the size of the measles virus is taken to be around 100 mµ in diameter, the strands seen in the inclusions cannot be fully formed virus.
Kallman, Frances; Adams, John M.; Williams, Robley C.; Imagawa, David T.
Marine viruses shape microbial communities with the most genetic diversity in the sea by multiple genetic exchanges and infect multiple marine organisms. Here we provide proof from experimental infection that abalone shriveling syndrome-associated virus (AbSV) can cause abalone shriveling syndrome. This malady produces histological necrosis and abnormally modified macromolecules (hemocyanin and ferritin). The AbSV genome is a 34.952-kilobase circular double-stranded DNA, containing putative genes with similarity to bacteriophages, eukaryotic viruses, bacteria and endosymbionts. Of the 28 predicted open reading frames (ORFs), eight ORF-encoded proteins have identifiable functional homologues. The 4 ORF products correspond to a predicted terminase large subunit and an endonuclease in bacteriophage, and both an integrase and an exonuclease from bacteria. The other four proteins are homologous to an endosymbiont-derived helicase, primase, single-stranded binding (SSB) protein, and thymidylate kinase, individually. Additionally, AbSV exhibits a common gene arrangement similar to the majority of bacteriophages. Unique to AbSV, the viral genome also contains genes associated with bacterial outer membrane proteins and may lack the structural protein-encoding ORFs. Genomic characterization of AbSV indicates that it may represent a transitional form of microbial evolution from viruses to bacteria. PMID:21079776
Marine viruses shape microbial communities with the most genetic diversity in the sea by multiple genetic exchanges and infect multiple marine organisms. Here we provide proof from experimental infection that abalone shriveling syndrome-associated virus (AbSV) can cause abalone shriveling syndrome. This malady produces histological necrosis and abnormally modified macromolecules (hemocyanin and ferritin). The AbSV genome is a 34.952-kilobase circular double-stranded DNA, containing putative genes with similarity to bacteriophages, eukaryotic viruses, bacteria and endosymbionts. Of the 28 predicted open reading frames (ORFs), eight ORF-encoded proteins have identifiable functional homologues. The 4 ORF products correspond to a predicted terminase large subunit and an endonuclease in bacteriophage, and both an integrase and an exonuclease from bacteria. The other four proteins are homologous to an endosymbiont-derived helicase, primase, single-stranded binding (SSB) protein, and thymidylate kinase, individually. Additionally, AbSV exhibits a common gene arrangement similar to the majority of bacteriophages. Unique to AbSV, the viral genome also contains genes associated with bacterial outer membrane proteins and may lack the structural protein-encoding ORFs. Genomic characterization of AbSV indicates that it may represent a transitional form of microbial evolution from viruses to bacteria.
Domestic dogs and cats were infected by mosquito bite and evaluated as hosts for West Nile virus (WNV). Viremia of low magnitude and short duration developed in four dogs but they did not display signs of disease. Four cats became viremic, with peak titers ranging from 103.0 to 104.0 PFU\\/mL. Three of the cats showed mild, non-neuro- logic signs of
Laura E. Austgen; Richard A. Bowen; Michel L. Bunning; Brent S. Davis; Carl J. Mitchell; Gwong-Jen J. Chang
Here, we analyze the viral divergence among hepatitis C virus (HCV) chronic cases infected with genotype 1. The intrahost viral evolution was assessed by deep sequencing using the 454 Genome Sequencer platform. The results showed a rapid nucleotide sequence divergence. This notorious short-term viral evolution is of the utmost importance for the study of HCV transmission, because direct links between related samples were virtually lost. Thus, rapid divergence of HCV significantly affects genetic relatedness studies and outbreak investigations.
Cruz-Rivera, Mayra; Carpio-Pedroza, Juan Carlos; Escobar-Gutierrez, Alejandro; Lozano, Daniela; Vergara-Castaneda, Arely; Rivera-Osorio, Pilar; Martinez-Guarneros, Armando; Chacon, Carlos A. Vazquez; Fonseca-Coronado, Salvador
In a prospective study, we analysed the anorectal lesions observed in 148 human immunodeficiency virus-infected patients and compared the data with those reported in the literature. The majority of the patients (97.3%) were homosexual or bisexual men. The mean age of the population was 34.2 years. A history of previous sexually transmitted diseases was found in 79.7% of the male
T. Puy-Montbrun; J. Denis; R. Ganansia; F. Mathoniere; N. Lemarchand; N. Arnous-Dubois
Mother-to-infant transmission of hepatitis C virus (HCV) is comparatively uncommon. The prevalence of antibody to HCV (anti-HCV) in pregnant women is 0.1% to 2.4%, although in some endemic areas it is much higher. The proportion of women with anti-HCV who have active infection with viremia is 60% to 70%. Transmission of HCV occurs only when serum HCV RNA is detectable
The objective of this article was to delineate the causes of avascular necrosis (AVN) in patients with human immunodeficiency virus (HIV). HIV-infected patients with pain in large joints were prospectively screened. Patients had radiographs and magnetic resonance imaging of their affected joints. Serum lipids, anticardiolipin antibody levels (IgG, IgM), and hemoglobin electrophoresis were performed on all patients who had radiographic
Marcia F Blacksin; Patricia C Kloser; Jocelyn Simon
Recently, attenuated Marek's disease virus (MDV) became of renewed interest as a component in bi? or polyvalent vaccines. The effect of attenuation on the pathogenesis of infection was investigated. Cloned preparations of the JM?16, BC?1A and RB?1B strains of MDV were attenuated by serial passage in chick kidney cells or chicken embryo fibroblasts. Subclones were obtained from the JM?16 strain
K. A. Schat; B. W. Calnek; J. Fabricant; D. L. Graham
BACKGROUND--A study was performed to identify the clinical, radiographic, and histopathological features of interstitial pneumonitis in patients infected with the human immunodeficiency virus. METHODS--A retrospective review was made of the case notes, chest radiographs, and histopathological results of seven HIV-1 antibody positive patients with symptomatic diffuse pulmonary disease and a pathological diagnosis of non-specific interstitial pneumonitis. RESULTS--All patients had dyspnoea,
\\u000a Primary infection with varicella-zoster virus (VZV) results in varicella which, in populations where immunization is not used,\\u000a occurs mostly in children. Varicella is a generalized rash illness with systemic features such as fever and malaise. During\\u000a varicella, VZV becomes latent in sensory ganglia of the individual, and in 70% it remains asymptomatic for their lifetime.\\u000a The remaining 30% develop reactivation