Alphavirus Infections: Virus diseases caused by members of the ALPHAVIRUS genus of the family TOGAVIRIDAE.Alphavirus: A genus of TOGAVIRIDAE, also known as Group A arboviruses, serologically related to each other but not to other Togaviridae. The viruses are transmitted by mosquitoes. The type species is the SINDBIS VIRUS.Sindbis Virus: The type species of ALPHAVIRUS normally transmitted to birds by CULEX mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. Serotypes (differing by less than 17% in nucleotide sequence) include Babanki, Kyzylagach, and Ockelbo viruses.Encephalitis Virus, Venezuelan Equine: A species of ALPHAVIRUS that is the etiologic agent of encephalomyelitis in humans and equines. It is seen most commonly in parts of Central and South America.Semliki forest virus: A species of ALPHAVIRUS isolated in central, eastern, and southern Africa.Chikungunya virus: A species of ALPHAVIRUS causing an acute dengue-like fever.Ross River virus: A species of ALPHAVIRUS associated with epidemic EXANTHEMA and polyarthritis in Australia.Encephalitis Virus, Western Equine: A species of ALPHAVIRUS that is the etiologic agent of encephalomyelitis in humans and equines in the United States, southern Canada, and parts of South America.Swallows: The family Hirundinidae, comprised of small BIRDS that hunt flying INSECTS while in sustained flight.Replicon: Any DNA sequence capable of independent replication or a molecule that possesses a REPLICATION ORIGIN and which is therefore potentially capable of being replicated in a suitable cell. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Cimicidae: A family of wingless, blood-sucking insects of the suborder HETEROPTERA, including the bedbugs and related forms. Cimex (BEDBUGS), Heamatosiphon, and Oeciacus are medically important genera. (From Dorland, 28th ed)Encephalitis Virus, Eastern Equine: A species of ALPHAVIRUS causing encephalomyelitis in Equidae and humans. The virus ranges along the Atlantic seaboard of the United States and Canada and as far south as the Caribbean, Mexico, and parts of Central and South America. Infections in horses show a mortality of up to 90 percent and in humans as high as 80 percent in epidemics.Culicidae: A family of the order DIPTERA that comprises the mosquitoes. The larval stages are aquatic, and the adults can be recognized by the characteristic WINGS, ANIMAL venation, the scales along the wing veins, and the long proboscis. Many species are of particular medical importance.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Aedes: A genus of mosquitoes (CULICIDAE) frequently found in tropical and subtropical regions. YELLOW FEVER and DENGUE are two of the diseases that can be transmitted by species of this genus.Encephalomyelitis, Venezuelan Equine: A form of arboviral encephalitis endemic to Central America and the northern latitudes of South America. The causative organism (ENCEPHALITIS VIRUS, VENEZUELAN EQUINE) is transmitted to humans and horses via the bite of several mosquito species. Human viral infection may be asymptomatic or remain restricted to a mild influenza-like illness. Encephalitis, usually not severe, occurs in a small percentage of cases and may rarely feature SEIZURES and COMA. (From Joynt, Clinical Neurology, 1996, Ch26, pp9-10)Arboviruses: Arthropod-borne viruses. A non-taxonomic designation for viruses that can replicate in both vertebrate hosts and arthropod vectors. Included are some members of the following families: ARENAVIRIDAE; BUNYAVIRIDAE; REOVIRIDAE; TOGAVIRIDAE; and FLAVIVIRIDAE. (From Dictionary of Microbiology and Molecular Biology, 2nd ed)Togaviridae Infections: Virus diseases caused by the TOGAVIRIDAE.Salmo salar: A commercially important species of SALMON in the family SALMONIDAE, order SALMONIFORMES, which occurs in the North Atlantic.Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of TOGAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; BUNYAVIRIDAE INFECTIONS; PICORNAVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RETROVIRIDAE INFECTIONS; and ARENAVIRIDAE INFECTIONS.Startle Reaction: A complex involuntary response to an unexpected strong stimulus usually auditory in nature.Sensory Gating: The ability of the BRAIN to suppress neuronal responses to external sensory inputs, such as auditory and visual stimuli. Sensory filtering (or gating) allows humans to block out irrelevant, meaningless, or redundant stimuli.Bordetella Infections: Infections with bacteria of the genus BORDETELLA.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Epitopes: Sites on an antigen that interact with specific antibodies.Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.Mosquito Control: The reduction or regulation of the population of mosquitoes through chemical, biological, or other means.Insect Vectors: Insects that transmit infective organisms from one host to another or from an inanimate reservoir to an animate host.Culex: A genus of mosquitoes (CULICIDAE) commonly found in tropical regions. Species of this genus are vectors for ST. LOUIS ENCEPHALITIS as well as many other diseases of man and domestic and wild animals.Dictionaries, MedicalDictionaries as Topic: Lists of words, usually in alphabetical order, giving information about form, pronunciation, etymology, grammar, and meaning.Flavivirus: A genus of FLAVIVIRIDAE containing several subgroups and many species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is YELLOW FEVER VIRUS.Flavivirus Infections: Infections with viruses of the genus FLAVIVIRUS, family FLAVIVIRIDAE.Laboratories: Facilities equipped to carry out investigative procedures.Clinical Laboratory Techniques: Techniques used to carry out clinical investigative procedures in the diagnosis and therapy of disease.Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Viral Envelope Proteins: Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.Morpholinos: Synthetic analogs of NUCLEIC ACIDS composed of morpholine ring derivatives (MORPHOLINES) linked by phosphorodimidates. One standard DNA nucleic acid base (ADENINE; GUANINE; CYTOSINE; OR THYMINE) is bound to each morpholine ring.Containment of Biohazards: Provision of physical and biological barriers to the dissemination of potentially hazardous biologically active agents (bacteria, viruses, recombinant DNA, etc.). Physical containment involves the use of special equipment, facilities, and procedures to prevent the escape of the agent. Biological containment includes use of immune personnel and the selection of agents and hosts that will minimize the risk should the agent escape the containment facility.MorpholinesCommunicable DiseasesCape Verde: The republic consists of islands that are located in the mid-Atlantic Ocean about 300 miles off the west coast of Africa. The archipelago includes 10 islands and 5 islets, divided into the windward (Barlavento) and leeward (Sotavento) groups. The capital is Praia.Anomura: An infraorder of CRUSTACEA, in the order DECAPODA comprising the hermit crabs and characterized by a small fifth pair of legs.Senegal: A republic in western Africa, southwest of MAURITANIA and east of MALI. Its capital is Dakar.Africa, Western: The geographical area of Africa comprising BENIN; BURKINA FASO; COTE D'IVOIRE; GAMBIA; GHANA; GUINEA; GUINEA-BISSAU; LIBERIA; MALI; MAURITANIA; NIGER; NIGERIA; SENEGAL; SIERRA LEONE; and TOGO.Atlantic Islands: Widely scattered islands in the Atlantic Ocean as far north as the AZORES and as far south as the South Sandwich Islands, with the greatest concentration found in the CARIBBEAN REGION. They include Annobon Island, Ascension, Canary Islands, Falkland Islands, Fernando Po (also called Isla de Bioko and Bioko), Gough Island, Madeira, Sao Tome and Principe, Saint Helena, and Tristan da Cunha.Newcastle disease virus: The most well known avian paramyxovirus in the genus AVULAVIRUS and the cause of a highly infectious pneumoencephalitis in fowl. It is also reported to cause CONJUNCTIVITIS in humans. Transmission is by droplet inhalation or ingestion of contaminated water or food.Newcastle Disease: An acute febrile, contagious, viral disease of birds caused by an AVULAVIRUS called NEWCASTLE DISEASE VIRUS. It is characterized by respiratory and nervous symptoms in fowl and is transmissible to man causing a severe, but transient conjunctivitis.Cell-Free System: A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)DNA Replication: The process by which a DNA molecule is duplicated.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Biotinylation: Incorporation of biotinyl groups into molecules.Biotin: A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.

Mayaro virus disease: an emerging mosquito-borne zoonosis in tropical South America. (1/604)

This report describes the clinical, laboratory, and epidemiological findings on 27 cases of Mayaro virus (MV) disease, an emerging mosquito-borne viral illness that is endemic in rural areas of tropical South America. MV disease is a nonfatal, dengue-like illness characterized by fever, chills, headache, eye pain, generalized myalgia, arthralgia, diarrhea, vomiting, and rash of 3-5 days' duration. Severe joint pain is a prominent feature of this illness; the arthralgia sometimes persists for months and can be quite incapacitating. Cases of two visitors from the United States, who developed MV disease during visits to eastern Peru, are reported. MV disease and dengue are difficult to differentiate clinically.  (+info)

Vectors of Chikungunya virus in Senegal: current data and transmission cycles. (2/604)

Chikungunya fever is a viral disease transmitted to human beings by Aedes genus mosquitoes. From 1972 to 1986 in Kedougou, Senegal, 178 Chikungunya virus strains were isolated from gallery forest mosquitoes, with most of them isolated from Ae. furcifer-taylori (129 strains), Ae. luteocephalus (27 strains), and Ae. dalzieli (12 strains). The characteristics of the sylvatic transmission cycle are a circulation periodicity with silent intervals that last approximately three years. Few epidemics of this disease have been reported in Senegal. The most recent one occurred in 1996 in Kaffrine where two Chikungunya virus strains were isolated from Ae. aegypti. The retrospective analysis of viral isolates from mosquitoes, wild vertebrates, and humans allowed to us to characterize Chikungunya virus transmission cycles in Senegal and to compare them with those of yellow fever virus.  (+info)

Geographic distribution and evolution of Sindbis virus in Australia. (3/604)

The molecular epidemiology and evolution of Sindbis (SIN) virus in Australia was examined. Several SIN virus strains isolated from other countries were also included in the analysis. Two regions of the virus genome were sequenced including a 418 bp region of the E2 gene and a 484 bp region containing part of the junction region and the 5' end of the C gene. Analysis of the nucleotide and deduced amino acid sequence data from 40 SIN virus isolates clearly separated the Paleoarctic/Ethiopian and Oriental/Australian genetic types of SIN virus. Examination of the Australian strains showed a temporal rather than geographic relationship. This is consistent with the virus having migratory birds as the major vertebrate host, as it allows for movement of virus over vast areas of the continent over a relatively short period of time. The results suggest that the virus is being periodically redistributed over the continent from an enzootic focus of evolving SIN virus. However, SIN virus strains isolated from mosquitoes collected in the south-west of Australia appear to represent a new SIN virus lineage, which is distinct from the Paleoarctic/Ethiopian and Oriental/Australian lineages. Given the widespread geographic dispersal of the Paleoarctic/Ethiopian and Oriental/Australian lineages, it is surprising that the South-west genetic type is so restricted in its area of circulation. Nucleotide sequence data from the C gene of the prototype strain of the alphavirus Whataroa were also determined. This virus was found to be genetically distinct from the SIN virus isolates included in the present study; however, it is clearly SIN-like and appears to have evolved from a SIN-like ancestral virus.  (+info)

Salmon pancreas disease virus, an alphavirus infecting farmed Atlantic salmon, Salmo salar L. (4/604)

A 5.2-kb region at the 3' terminus of the salmon pancreas disease virus (SPDV) RNA genome has been cloned and sequenced. The nucleotide and predicted amino acid sequences show that SPDV shares considerable organizational and sequence identity to members of the genus alphavirus within the family Togaviridae. The SPDV structural proteins encoded by the 5.2-kb region contain a number of unique features when compared to other sequenced alphaviruses. Based on cleavage site homologies, the predicted sizes of the SPDV envelope glycoproteins E2 (438 aa) and E1 (461 aa) are larger than those of other alphaviruses, while the predicted size of the alphavirus 6K protein is 3.2 K (32 aa) in SPDV. The E2 and E1 proteins each carry one putative N-linked glycosylation site, with the site in E1 being found at a unique position. From amino acid sequence comparisons of the SPDV structural region with sequenced alphaviruses overall homology is uniform, ranging from 32 to 33%. While nucleotide sequence analysis of the 26S RNA junction region shows that SPDV is similar to other alphaviruses, analysis of the 3'-nontranslated region reveals that SPDV shows divergence in this region.  (+info)

Virus infection induces neuronal apoptosis: A comparison with trophic factor withdrawal. (5/604)

Multicellular organisms can employ a number of defences to combat viral replication, the most dramatic being implementation of a cell autonomous apoptotic process. The overall cost to the viability of an organism of losing infected cells by apoptosis may be small if the dying cells can be substituted. In contrast, suicide of irreplaceable cells such as highly specialised neurons may have a more dramatic, even fatal consequence. Previous in vitro approaches to understanding whether neurotropic viruses cause neurons to apoptose have utilised transformed cell lines. These are not in the appropriate state of differentiation to provide an accurate indication of events in vivo. We have chosen to characterise the ability of a model CNS disease-causing virus, Semliki Forest virus (SFV), to infect and trigger apoptosis in primary cultures of nerve growth factor (NGF)-dependent sensory neurons. These cells are known to die when deprived of NGF and constitute a useful indicator of apoptosis. We observe that infection causes cell death which bears the morphological hallmarks of apoptosis, this occurs even in the present of survival promoting NGF and is concomitant with new virus production. Using the TUNEL (transferase dUTP nick end labelling) technique we show that SFV-induced apoptosis involves DNA fragmentation and requires caspase (CED-3/ICE cysteine protease) activation, as does apoptosis induced by NGF-deprivation. Extensive areas of apoptosis, as defined using a combination of ultrastructural analysis and TUNEL occur in infected neonatal mouse brains. The novel evidence that infection of primary neurons with SFV induces apoptosis with activation of one or more caspases defines a system for the further anlaysis of apoptosis regulation in physiologically relevant neurons.  (+info)

Recombinant Semliki Forest virus and Sindbis virus efficiently infect neurons in hippocampal slice cultures. (6/604)

Gene transfer into nervous tissue is a powerful tool for the analysis of gene function. By using a rat hippocampal slice culture preparation, we show here that Semliki Forest virus (SFV) and Sindbis virus (SIN) vectors are useful for the effective infection of neurons. The stratum pyramidale and/or the granular cell layer were injected with recombinant virus encoding beta-galactosidase (LacZ) or green fluorescent protein (GFP). By using low concentrations of injected SFV-LacZ or SIN-LacZ, we detected LacZ staining of pyramidal cells, interneurons, and granule cells. About 60% of the infected cells showed clear neuronal morphology; thus, relatively few glial cells expressed the transgene. Expression of GFP from SFV and SIN vectors gave similar results, with an even higher percentage (>90%) of the GFP-positive cells identified as neurons. Infected pyramidal cells were readily recognized in living slices, displaying GFP fluorescence in dendrites of up to fourth order and in dendritic spines. They appeared morphologically normal and viable at 1-5 days postinfection. We conclude that both SFV and SIN vectors efficiently transfer genes into neurons in hippocampal slice cultures. In combination with the GFP reporter, SFV and SIN vectors will allow the physiological examination of identified neurons that have been modified by overexpression or suppression of a specific gene product.  (+info)

Enzyme distributions in subcellular fractions of BHK cells infected with Semliki forest virus: evidence for a major fraction of sphingomyelin synthase in the trans-golgi network. (7/604)

BHK cells either untreated or infected with Semliki Forest virus have been fractionated on sucrose density gradients. Virus infection caused an increase in density of a membrane fraction enriched in sphingomyelin (SM), cholesterol, SM synthase and sialyltransferase activity. This increase in density was related to incorporation of viral proteins into this fraction, which is likely to contain trans-Golgi network (TGN) membranes. In contrast, glucosylceramide synthase and galactosyltransferase activities (markers for cis/medial and trans-Golgi respectively) underwent no density shift and alkaline phosphodiesterase, a plasma membrane marker, was only slightly density-shifted in infected cells. When cells were incubated with NBD-ceramide to enable them to synthesise NBD-SM and then washed with albumin to remove surface label, fluorescence in untreated cells was concentrated in a single juxtanuclear spot but in infected cells this region of bright fluorescence was larger and extended around the nucleus. After fractionation of these cells, NBD-SM (but only a small proportion of the NBD-ceramide) was found to be shifted into the higher density fraction in infected cells. This work provides further evidence that SM synthase is not mainly localised in the early Golgi cisternae as previously thought, but is associated more with a cholesterol-rich compartment which could be the TGN.  (+info)

Human MxA protein protects mice lacking a functional alpha/beta interferon system against La crosse virus and other lethal viral infections. (8/604)

The human MxA protein is part of the antiviral state induced by alpha/beta interferon (IFN-alpha/beta). MxA inhibits the multiplication of several RNA viruses in cell culture. However, its antiviral potential in vivo has not yet been fully explored. We have generated MxA-transgenic mice that lack a functional IFN system by crossing MxA-transgenic mice constitutively expressing MxA with genetically targeted (knockout) mice lacking the beta subunit of the IFN-alpha/beta receptor (IFNAR-1(-/-) mice). These mice are an ideal animal model to investigate the unique antiviral activity of human MxA in vivo, because they are unable to express other IFN-induced proteins. Here, we show that MxA confers resistance to Thogoto virus, La Crosse virus, and Semliki Forest virus. No Thogoto virus progeny was detectable in MxA-transgenic mice, indicating an efficient block of virus replication at the primary site of infection. In the case of La Crosse virus, MxA restricted invasion of the central nervous system. In contrast, Semliki Forest virus multiplication in the brain was detectable in both MxA-expressing and nonexpressing IFNAR-1(-/-) mice. However, viral titers were clearly reduced in MxA-transgenic mice. Our results demonstrate that MxA does not need the help of other IFN-induced proteins for activity but is a powerful antiviral agent on its own. Moreover, the results suggest that MxA may protect humans from potential fatal infections by La Crosse virus and other viral pathogens.  (+info)

  • View DIVA Project profile » By using my experience in network visualization and analysis, I collaborate with researchers at the Institute for Human Infections and Immunity and the Galveston National Laboratory to analyze complex data related to infectious diseases, in addition to developing new methods that accelerate the translation of discoveries into effective treatments. (
  • Humoral immunity is important for protection against viral infection and neutralization of extracellular virus, but clearance of virus from infected tissues is thought to be mediated solely by cellular immunity. (
  • In addition to her original findings about Beclin-1's importance in tumor suppression and innate immunity against viral infections, Beth and her lab described many other contexts in which autophagy supports tissue function and homeostasis. (
  • Humoral immunity is an essential component of the immune response to WNV and other flaviviruses because neutralizing antibodies limit dissemination of infection. (
  • Chikungunya virus infection is believed to confer lifelong immunity. (
  • However, studies of some of these pathogens have provided evidence that antibodies can provide immunity if present during the initiation of infection. (
  • Here, we examined immunity against infection by Ehrlichia chaffeensis , an obligate intracellular bacterium that causes human monocytic ehrlichiosis. (
  • Although cellular immunity is required for complete bacterial clearance, the data show that antibodies can play a significant role in the elimination of this obligate intracellular bacterium during active infection and thus challenge the paradigm that humoral responses are unimportant for immunity to such organisms. (
  • Indeed, it has often been difficult to demonstrate a significant role for humoral immunity during intracellular bacterial infection, although exceptions exist ( 12 , 28 ). (
  • To further address the role of cellular and humoral immunity during intracellular bacterial infection, we have examined the immunological basis of resistance and susceptibility to infection by Ehrlichia chaffeensis , an obligate intracellular bacterium that infects cells of the monocyte/macrophage lineage. (
  • Members of the Institute for Human Infections & Immunity are University of Texas Medical Branch faculty actively engaged in the study of infectious diseases and immunity. (
  • However, in a SCID mouse model of persistent alphavirus encephalomyelitis, adoptive transfer of hyperimmune serum resulted in clearance of infectious virus and viral RNA from the nervous system, whereas adoptive transfer of sensitized T lymphocytes had no effect on viral replication. (
  • Thus, the balance between type I IFN induction and the ability of the virus to develop further rounds of infection is determined in the first few hours of virus replication, when only low numbers of cells and infectious virus are involved. (
  • One of the critical characteristics of alphaviruses is their efficient replication in vivo and in many commonly used cell lines of vertebrate origin ( 37 ). (
  • The replication cycle of alphavirus takes place in the cytoplasm of the host cells. (
  • The alphavirus genome resembles eukaryotic mRNA, which possesses a 5′ cap and 3′ poly (A) tail and codes for early non-structural and late structural phases during replication. (
  • Viruses are parasites of host cell metabolism and alphaviruses have been shown to increase glycolytic flux during infection to aid viral replication. (
  • The efficacy of Imatinib treatment at inhibiting alphavirus replication was confirmed at different times post infection (6, 12, 18, and 24 hours post infection), different levels of infection (multiplicities of infection= 0.1, 1, and 10), and within different cell lines (BHK, Huh7 and HEK). (
  • Further analysis in mouse or other animal models is needed to confirm the utility of Imatinib as a therapeutic option for treating alphavirus infection, but the data are promising and shows a significant reduction in viral replication and may represent a novel treatment option for alphavirus infections. (
  • Vector particle seed stocks could be amplified after low multiplicity of infection of PCLs, again without generating replication-competent virus, suggesting utility for production of large-scale vector preparations. (
  • Alphaviruses are attractive candidates for such applications because of their high levels of replication and gene expression, their ability to infect a variety of diverse cell types, and the ability to manipulate cDNA clones from which infectious viral RNA may be transcribed (for review, see refs. (
  • A structural and functional perspective of alphavirus replication and assembly. (
  • 2016. Atlantic salmon (Salmo salar L.) post-smolts challenged two or nine weeks after seawater-transfer show differences in their susceptibility to salmonid alphavirus subtype 3 (SAV3). (
  • Old and New World alphaviruses cluster in separate phylogenetic groups ( 6 ), but limited information is available about pathogenesis and host range of alphaviruses from Africa and pathogenesis in animals. (
  • The purpose of our study was to investigate the host range and association of alphaviruses from Africa with neurologic disease and death, as well as to increase knowledge on pathogenesis and the zoonotic potential of these 2 viruses. (
  • Rennos Fragkoudis is a virologist whose main research interest is the pathogenesis of arthropod-borne viruses (arboviruses) and in particular of alphaviruses and bunyaviruses. (
  • One of the most advanced and mature research programs at the Vaccine and Gene Therapy Institute is the AIDS pathogenesis and vaccine program to focus on the development of novel immunotherapeutic approaches that provide for viral control (and perhaps even virus elimination) and/or immune restoration, in untreated infections or full normalization of immune function with optimally suppressive anti-retroviral therapy. (
  • Understanding the pathogenesis of infection is required to develop and assess medical countermeasures. (
  • Upon low-dose infection of wild-type C57B/6 mice, asymptomatic and symptomatic groups were established and compared to mock-infected mice to measure general health and baseline neurological function, including the acoustic startle response and prepulse inhibition paradigm. (
  • This virus-specific inhibition of the antiviral and innate responses makes an additional contribution to rapid spread of alphavirus infections. (
  • One of the most efficient means of interference with the innate immune response utilized by alphaviruses is inhibition of cellular transcription. (
  • For the New World alphaviruses, the capsid protein has been found to be a key player in transcription inhibition ( 2 , 15 , 17 ). (
  • In cells permissive to viral infection, this leads to robust transcription inhibition within 4 to 6 h postinfection and, thus, prevents activation of antiviral genes. (
  • Alphavirus Infection: Host Cell Shut-Off and Inhibition of Antiviral Responses. (
  • Here, using mouse models of alphavirus-induced musculoskeletal disease, we demonstrate that NLRP3 inhibition in vivo can reduce inflammatory pathology and that further development of therapeutic solutions targeting inflammasome function could help treat arboviral diseases. (
  • Johnson, K. E., Chikoti, L. & Chandran, B. Herpes simplex virus 1 infection induces activation and subsequent inhibition of the IFI16 and NLRP3 inflammasomes. (
  • Lupfer C, Stein DA, Mourich DV, Tepper SE, Iversen PL, Pastey M. Inhibition of influenza A H3N8 virus infections in mice by morpholino oligomers. (
  • Inhibition of Respiratory Syncytial Virus Infections With Morpholino Oligomers in Cell Cultures and in Mice. (
  • There are very limited vaccines and treatment options available to those infected with alphaviruses, resulting in significant human and animal morbidity and mortality each year. (
  • Arthropod-borne alphaviruses are distributed worldwide and cause considerable human morbidity and mortality. (
  • Studies in two Canadian psychiatric hospitals observed that 32 patients had antibodies against WEEV or a related encephalitic virus ( Fulton and Burton, 1953 ), leading the authors to suggest that viral infection may have contributed to the patients neurological disease. (
  • Treatment of alphavirus-infected primary cultured rat neurons with these monoclonal antibodies to E2 resulted in decreased viral protein synthesis, followed by gradual termination of mature infectious virion production. (
  • We screened a panel of mouse and human monoclonal antibodies (MAbs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. (
  • The beauty of alphaviruses is that they are naturally attracted to dendritic cells, cells that stimulate the production of large numbers of T cells and antibodies," says Morse. (
  • Thesis: "Detection of antibodies against alphaviruses in sera of human and animal origin using recombinant antigens and virus-specific monoclonal antibodies. (
  • The importance of antibodies in the protection against WNV infection has been highlighted by recent studies in antibody-deficient mice ( 11 ). (
  • Transfer of immune serum or antibodies obtained from immunocompetent C57BL/6 mice to C57BL/6 scid mice provided significant although transient protection from infection. (
  • The failure in many studies to observe a role for antibodies has led to general acceptance of the tenet that antibodies play little or no role in host defense during intracellular bacterial infection, although antibodies are well known to exert neutralizing effects during virus infections. (
  • Incorporation of alphavirus replicons into plasmid DNA vectors to direct the amplification of RNA expressing the gene of interest has been an exciting approach toward improving DNA vaccination ( 8 ). (
  • Vectors encoding the alphavirus-derived RNA replicase have been shown to be immunogenic in murine models at doses up to 1,000-fold lower than those used for conventional plasmid vectors ( 11 , 16 ) and are effective when used as vaccines against cancer ( 7 , 12 , 15 , 16 ) or viral infections ( 3 , 5 , 11 , 14 ). (
  • Thus, alphavirus plasmid replicons may offer both quantitative and qualitative advantages compared with conventional plasmid vectors. (
  • Alphavirus vectors are being developed for possible human vaccine and gene therapy applications. (
  • The general strategy for construction of alphavirus-based expression vectors has been to substitute the viral structural protein genes with a heterologous gene, maintaining transcriptional control via the highly active subgenomic RNA promoter ( 1 , 2 , 4 ). (
  • As such, these vector replicons are suicide vectors, incapable of packaging progeny vector particles and causing productive infection. (
  • These issues have begun to be addressed through the conversion of alphavirus vectors into functional plasmid DNA formats that directly transcribe RNA vector replicons in vivo ( 8 - 13 ) and the development of split structural protein gene packaging systems ( 2 , 7 , 14 ). (
  • The invention discloses a single dose administration of two types of recombinant viral vectors: one expressing interferon and another expressing the structural proteins of alphaviruses or a single dose administration of the recombinant viral vector co-expressing both interferon and the structural proteins of alphaviruses. (
  • During 2010-2018, a total of 608 clinical samples from wildlife and nonequine domestic animals that had febrile, neurologic signs or unexplained deaths were tested for alphaviruses. (
  • A TaqMan-based quantitative PCR was used to assess SAV load in the heart, a main target organ of the virus, and also liver, which does not normally display any pathological changes during clinical infections, but exhibited severe degenerative lesions in the present study. (
  • This study describes the clinical and pathological findings of mice infected with WEEV by the aerosol route, and use as a model for WEEV infection in humans. (
  • Alphaviruses have been used before in designing treatments for infectious diseases, but we believe this is the first time one has been used in patients with cancer," said Michael Morse, MD , associate professor of medicine at Duke and the lead author of the study appearing online in the Journal of Clinical Investigation . (
  • Whether infection occurs in fish, reptiles, or amphibians, clinical disease is typically acute and can affect a high proportion of the population. (
  • The viraemic phase of alphaviruses is 2-8 days, so the success of RT-PCR to detect the virus depends on early presentation and the clinical suspicion of a possible alphavirus infection. (
  • Pre-clinical experiments conducted by researchers at Griffith University's Institute for Glycomics on the Gold Coast have demonstrated world-first results showing that the historic drug, pentosan polysulfate sodium (PPS), can successfully treat both the acute and chronic disease manifestations symptoms of alphavirus infections in the animal model. (
  • It is important to rule out dengue virus infection because proper clinical management of dengue can improve outcome. (
  • In 2006, a Chikungunya outbreak occurred in La Réunion Island, during which we constituted a prospective cohort of viremic patients (n = 180) and defined the clinical and biological features of acute infection. (
  • Suhrbier, A. & La Linn, M. Clinical and pathologic aspects of arthritis due to Ross River virus and other alphaviruses. (
  • 2 provide structural insights into the regulation of the membrane-fusion proteins of enveloped alphaviruses during the viruses' entry into and exit from the host cell. (
  • 2. A method for the post-exposure protection of a susceptible animal from alphavirus infection comprising inoculating said animal with a vaccine comprising a recombinant viral vector containing a DNA sequence capable of producing the viral proteins of alphaviruses that stimulate an immune response in said animal in an amount effective for conferring a protective response in the animal. (
  • 6. A method for the prevention of a susceptible animal from alphavirus infection comprising inoculating said animal with a vaccine comprising a recombinant viral vector containing a DNA sequence capable of producing the viral proteins of alphaviruses that stimulate an immune response in said animal in an amount effective for conferring a protective response in the animal before said animal is exposed to said alphaviruses. (
  • Effector proteins that are secreted during infection to manipulate the host and to promote disease are a key element in fungal virulence. (
  • In all these strategies, proteins secreted by the pathogen during infection and acting on host proteins and cellular processes play a key role [ 1 - 3 ]. (
  • In fungal pathogens, the main class of effectors are small secreted proteins of less than 200 amino acids expressed specifically during infection and often rich in cysteins [ 4 - 6 ]. (
  • A major obstacle an arbovirus has to overcome during its infection cycle inside the mosquito is the midgut escape barrier, representing the exit mechanism arboviruses utilize when disseminating from the midgut. (
  • Laboratory diagnosis has been directed toward infection with this flavivirus, which could prevent the identification of other important arboviruses eventually circulating in the population, including those never before reported in Brazil. (
  • Chikungunya virus was responsible for millions of human infections in new territories, and although the case-fatality rate was low, outbreaks resulted in major illness and long-term sequelae in affected persons ( 4 , 5 ). (
  • Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, raising concerns that they might cause human epidemics and pandemics. (
  • Our results suggest that B domain antigenic determinants could be targeted for vaccine or antibody therapeutic development against multiple alphaviruses of global concern. (
  • Knowing more about how often people are exposed to CMV in the community will help us prepare for future vaccine studies in which CMV is used as part of a vaccine to prevent infections such as HIV and tuberculosis. (
  • Mixed models comparing influence of infection on antibody concentration revealed no effect of prenatal infection status for most vaccine outcomes. (
  • The results suggest that the treatment of maternal infections in pregnancy may be able to moderate the previously observed effect of antenatal maternal infections on infant vaccine responses. (
  • This book addresses various aspects of such emergences, such as pathogenetic mechanisms of viruses, diagnosis of viral infections, viral host-management strategies, viral genetics, vaccine development and application. (
  • There is no vaccine or drug to prevent the parasitic infection, which is transmitted through sandfly bites. (
  • View Sealy Center for Molecular Medicine profile » Dr. Bao's research focuses on host-virus interaction, particularly in the infection of RSF and hMPV, with the goal of generating suitable vaccine candidates to prevent paramyxovirus infection. (
  • Little is known of the host factors that influence susceptibility and resistance to HME, although some studies have suggested that humoral immune responses might play an important role during infections by related ehrlichiae ( 18 , 33 ). (
  • Susceptibility of salmonid alphavirus to a range of chemical disinfectants. (
  • During the 3 years following acute infection, 60% of patients had experienced symptoms of arthralgia, with most reporting episodic relapse and recovery periods. (
  • Large outbreaks of infection have been recorded in humans in South Africa since 1974 ( 8 ). (
  • There are thirty alphaviruses able to infect various vertebrates such as humans, rodents, fish, birds, and larger mammals such as horses as well as invertebrates. (
  • In humans, the elderly and immunocompromised are at greatest risk for disseminated West Nile virus (WNV) infection, yet the immunologic basis for this remains unclear. (
  • Persons with chronic health conditions, a weakened immune system, infants, and older persons are at risk of developing complications with this infection. (
  • If you have had Chikungunya in the past, you are immune to subsequent infections. (
  • After a single infection it is believed most people become immune . (
  • Similarly, in animals, the maturation and integrity of the immune system correlates with resistance to WNV infection ( 6 - 8 ). (
  • The role of immune IgG in protection has been studied extensively in mouse models of flavivirus infection, including WNV. (
  • Our own studies with B cell-deficient mice demonstrated a ∼500-fold increase in viremia 4 d after infection, a time when only immune IgM was detected in the serum from wild-type mice ( 11 ). (
  • Because passive transfer of immune IgM against WNV, derived from wild-type mice 4 d after infection, prolonged survival of B cell-deficient mice and completely protected wild-type mice, natural or induced IgM could limit WNV infection by controlling viremia and/or by triggering an adaptive B or T cell response ( 23 , 24 ). (
  • However, approximately 50% of women are already immune to the virus and cannot develop the infection. (
  • Alphaviruses are usually highly lytic in vertebrate cells, but persistently infect susceptible mosquito cells with minimal cytopathology. (
  • The most important findings are as follows: (i) within the first 2 to 4 h postinfection, alphavirus-infected cells become unable to respond to IFN-β, and this occurs before the virus-induced decrease in STAT1 phosphorylation in response to IFN treatment. (
  • Within 6 h, infected cells begin virus release, and within 12 to 16 h postinfection they can produce 10 3 to 10 4 infectious virions per cell and they induce a next round of infection. (
  • A number of alphaviruses are also known to induce translational shutoff in infected vertebrate cells ( 18 , 20 , 38 ). (
  • Beth's landmark work in autophagy arose from an exploration into the mechanisms by which cells respond to viral infection, starting with her work in Marie Hardwick's lab at Johns Hopkins. (
  • We demonstrated previously that B cells and IgG contributed to the defense against disseminated WNV infection (Diamond, M.S., B. Shrestha, A. Marri, D. Mahan, and M. Engle. (
  • However, SFV infection of mosquito cells did not result in activation of any of these pathways and suppressed their subsequent activation by other stimuli. (
  • Upon infection of vertebrate cells in continuous culture, the alphavirus Semliki Forest virus (SFV) initiates apoptosis and IFN synthesis. (
  • 1991 ) Prevention of apoptosis by a baculovirus gene during infection of insect cells. (
  • In this study we determined the mechanism by which SinV represses the degradation of its transcripts during infection of human and mosquito cells. (
  • The results of this study demonstrate that the first hours postinfection play a critical role in infection spread and development of the antiviral response. (
  • There are currently no treatments for alphavirus infections, and detailed information on the structure and life cycle of these viruses is crucial for developing antiviral strategies and vaccines. (
  • Other than the antiviral activity of RNAi, relatively little is known about alphavirus interactions with insect cell defences. (
  • High-content analysis enables, for example, intracellular tracking of viral particles to profile the antiviral mechanisms of each compound and sensitive measurements of bacterial infection rates. (
  • The team has for the first time shown that the protein pentraxin 3 (PTX3) plays a crucial role in promoting alphavirus infection and disease. (
  • It is not known if sea trout will experience similar, less or worse infections and disease with neither SAV nor PRV. (
  • Understanding the differential diagnoses for ranaviral disease is important, and combining infection data with pathological and environmental information is essential to confirm that ranavirus is the etiologic disease agent. (
  • The historic drug, pentosan polysulfate sodium (PPS), has been observed to successfully treat both the acute and chronic disease manifestations symptoms of alphavirus infections in the animal model. (
  • IL-1β production through the NLRP3 inflammasome by hepatic macrophages links hepatitis C virus infection with liver inflammation and disease. (
  • 5 , 6 This review is based on a literature review and the authors' ongoing research and introduces the zoonotic infections and associated neuroimaging appearances in past outbreaks that have affected the CNS, to improve our understanding of the current pandemic and future zoonotic disease outbreaks. (
  • Diseases or pathological conditions can include, for example, neurodegenerative diseases, cancer and viral infections. (
  • Human cases of arbovirus infection and malaria are monitored using the National Notifiable Diseases Surveillance System (NNDSS). (
  • Using an unconventional approach that they designed, University of Pittsburgh drug discoverers and their collaborators at Walter Reed Army Institute of Research have identified compounds that hold promise for treating leishmaniasis, a parasitic infection that many consider one of the world's most overlooked diseases. (
  • present as a spectrum of diseases ranging from cutaneous lesions to fatal visceral infections [ 4 ], estimated to cause 20,000 to 40,000 deaths per year [ 5 ]. (
  • When evaluating extreme outcomes, one unfortunate patient was misdiagnosed and treated for schizophrenia after recovering from an undetected WEEV infection. (
  • Consistent with earlier studies, WEEV resistance appeared to be related to a dose-dependent midgut infection barrier, and a midgut escape barrier. (
  • Predicting human West Nile virus infections with mosquito surveillance data. (
  • The accumulation of knowledge in the subsequent two to three decades from studies of cancer, virus infections, and, most notably, the worm Caenorhabditis elegans finally produced unequivocal evidence of an evolutionarily conserved, genetically encoded program of self-elimination ( 19 - 23 ). (
  • How do health care professionals diagnose Chikungunya virus infections? (