The virus was first isolated in 1952 in Cairo, Egypt. However, the cell death pathway triggered by these transmembrane domains is not universal as they fail to induce cell death in BHK (baby hamster kidney) cells, which undergo classic apoptosis after Sindbis virus infection. [ncbi.nlm.nih.gov], In this proposal we will identify i) the optimal strategy for expression of structural proteins of RVFV by recombinant Sindbis virus, ii) a system for delivery of recombinant genomes into antigen-presenting cells, and iii) the manufacturing procedure Prior to solvent detergent treatment, samples were inoculated with a titer of either Sindbis or VSV. Consequently, the expression profile of sindbis virus is very rapid onset, extremely high expression, and then rapid shutdown due to cytotoxic insult. inoculation of mouse MOSEC ovarian cancer cells. Patients usually recover within a few weeks but chronic joint pains are common. In northern Europe the strains of Sindbis virus that cause arthritic disease are variously called Ockelbo virus in Sweden, Pogosta virus in Finland, and Karelian Fever virus in western Russia. Small outbreaks have occurred in many places including Europe, Australia, India, and Africa. [grantome.com], Apoptosis Genes presents a current overview of key genes involved in the control of apoptosis research together with thoughts on future prospects and clinical applications. We describe and characterize a novel cancer immunotherapy combining Sindbis virus (SV) vectors and the agonistic monoclonal antibody (mAb) to the T cell costimulatory receptor, 4-1BB (CD137). Successful recovery from viral infection of neurons requires immune mechanisms that preserve neuron viability and functionality. The causative agent is a Northern European strain of SINV, genetically distinct from that isolated in the Middle East.52 Older adults who work or vacation in forested areas are most often affected. [experts.illinois.edu], There is no treatment for humans or vaccine for the livestock that are such important amplifiers of the virus. After heat treatment, samples were immediately frozen at −70°C for further analysis by TCID 50 assay with CPE as an endpoint. Sindbis virus induces apoptotic cell death as evidenced by membrane blebbing, chromatin condensation, and DNA ladder formation in culture and in mouse brains.1, 26 Virus replication is required to induce apoptosis when infection occurs at low multiplicities. [books.google.com], SINV RNA detection or virus isolation from blood and/or skin lesions was successful in 8 patients. Pogosta disease is characterized by arthritis, pruritic rash, fatigue, mild fever, headache, and muscle pain. [books.google.com], Plaque assay titers in the presence of thapsigargin for 6h are presented as log pfu/ml. C ) HEK293 cells were mock or CHIKV/SINV infected (MOI-1) for 1h. are important, with Cx. Sindbis virus (SINV) is a member of the Togaviridae family, in the Alphavirus genus. During the 1980s, Ockelbo disease (Sweden), Karelian fever (Russia) and Pogosta disease (Finland), which have nearly identical clinical presentations were shown to be caused by Sindbis virus infection. Many species of birds and of other vertebrates have been shown to be capable of being infected with SINV, but disease has been identified only in humans. We use cookies to help provide and enhance our service and tailor content and ads. [6] In addition to tick bite, SFTSV can be transmitted from person to person through contact with blood or mucus of an infected person. Thus, infected mosquitoes and susceptible humans are presumably brought into proximity. [ncbi.nlm.nih.gov], L of live oak (Quercus virginiana) leaf infusion and the adults were fed on SINV-infected (treatments) or non-infected (controls) bovine blood. There is considerable genetic diversity amongst the strains of Sindbis virus that occur worldwide, which can differ in their nucleotide sequences by up to 20%. It is found throughout southern and northeastern Africa, Northern, Central, and Eastern Europe, Asia, Southeast Asia, and Australia, but clinical disease is largely restricted to Sweden (Ockelbo disease), Norway (Ockelbo disease), Finland (Pogosta disease), Russia (Karelian fever), and South Africa. Only isolated cases of illness in humans have been reported from Australia, although serological studies have indicated that human infections occur regularly. [ncbi.nlm.nih.gov], The pathophysiological roles of H19 and its mature product miR-675 to carcinogenesis have, however, not been defined. The growth of SFV was also markedly inhibited, but Sindbis virus growth was unimpaired. Ellen G. Strauss, James H. Strauss, in Handbook of Proteolytic Enzymes (Third Edition), 2013. [ncbi.nlm.nih.gov], Complete coding sequence and molecular epidemiological analysis of Sindbis virus isolates from mosquitoes and humans, Finland. SINV is transmitted among birds by Culex mosquitoes. The virus was first isolated in 1952 in Cairo, Egypt. Sindbis virus deleted of the glycoprotein-coding sequences replicates its genome efficiently and produces nonstructural proteins (but no infectious virions). [books.google.com], Clearing up Culex Confusion: A Basis for Virus Vector Discrimination in Europe Open this publication in new window or tab 2014 (English) Doctoral thesis, comprehensive summary (Other academic) Abstract [en] Mosquito species of the Culex genus are the For example, 1301 and 597 cases were documented in 1995 and 2002, respectively. To gain a better understanding of SINV epidemiology in Finland, we searched for SINV antibodies in 621 resident grouse, whose population declines have coincided with human SINV outbreaks, and in 836 migratory birds. It is believed that migratory birds are responsible for the spread of the two lineages, though within each there is a genetic heterogeneity consistent with local adaptation and evolution of the virus. Brief treatment of Sindbis virus-infected BHK-21 or Vero cells with low concentrations of trypsin irreversibly blocked further production of progeny virions after removal of the enzyme. For assistance, contact MSU's Biosafety Officer: Ryan Bartlett, ryan.bartlett@montana.edu, (406) 994-6733. In Australia, Cx. Oncolytic viral therapy for cervical and ovarian cancer cells by Sindbis virus AR339 strain. [connection.ebscohost.com], CONCLUSIONS: Educating the public in endemic areas to avoid mosquito exposure and use protective measures remain important prevention measures for SINV infection. Ockelbo occurs each year, while Pogosta disease has shown a consistent periodicity of 7 years since it was first recognized in 1974, the reasons for which are uncertain. Sindbis fever is most common in Southern Africa, East Africa, Egypt, Palestine, the Philippines and parts of Australia. An enveloped, single-stranded, RNA virus. There have been periodic epidemics in Finland, where it is termed Podosta disease. Cover area of the spill with absorbent material and add 10 % Bleach. Epidemics of Ockelbo disease and Pogosta disease occur during summer and autumn in northern Europe, coincident with the peak mosquito breeding period. Larval environmental stress alters Aedes aegypti competence for Sindbis virus Ephantus J. Muturi 1, Chang-Hyun Kim , Barry W. Alto2, May R. Berenbaum3 and Mary A. Schuler4 1 Illinois Natural History Survey, University of Illinois, Champaign, IL, USA However, clinical infection in humans has almost exclusively been reported in northern Europe where it is endemic and where large outbreaks occur intermittently. In Sweden the virus has been found primarily in the fieldfare (Turdus pilaris), redwing (T. iliacu), and song thrush (T. philomelos), and in Norway game birds also carry the virus. SINV was first isolated from Culex univittatus at Sindbis in Egypt, and subsequently from a wide range of species of mosquitoes and vertebrates in Europe, the Middle East, Africa, India, Asia, the Philippines, and Australia. Sindbis virus is a member of the alphavirus family that has been studied extensively for use as a treatment for many different kinds of cancer. [nature.com], This is in contrast to SINV infection in mosquito cells where SINV is a substrate for RNAi [13], [38] and svRNAs prevented viral spread between cells in Drosophila [46]. The vector is still in early stages of development, but now has the potential to become a useful tool for in vivo studies in psychiatry. The inhibitory effects of the trypsin treatment could only be demonstrated in cells in which virus infection was established; optimal inhibition occurred at ca. Lewis Markoff, in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Eighth Edition), 2015. Sindbis virus (SINV) is a member of the Togaviridae family, in the Alphavirus genus. [ncbi.nlm.nih.gov], Haemaphysalis longicornis, Ixodes nipponensis, Amblyomma testudinarium [5] and Rhipicephalus microplus. Boca Raton, FL : CRC Press. Semliki forest virus is an African alphavirus that was originally isolated from mosquitos. N/A, not available. [virologyj.biomedcentral.com], Altogether, 86 patients with serologically verified SINV infection were recruited to the, In this proposal we will identify i) the optimal strategy for expression of structural proteins of RVFV by recombinant Sindbis virus, ii) a system for delivery of recombinant genomes into antigen-, Plaque assay titers in the presence of thapsigargin for 6h are, Blots were blocked overnight with blocking solution [2%. as hepatitis B and C virus, the inactivation of the model viruses, Sindbis virus, a model virus for hepatitis C virus, and vesicular stomatitis virus (VSV), a model RNA virus for lipid enveloped viruses, by solvent detergent treatment was studied. Oncolytic viral therapy uses replication-competent viruses, like Sindbis virus (SINV), to kill cancers. Sindbis (SIN) virus is one of the most widely distributed mosquito-borne viruses in the world, being found in Africa, Europe, Asia, and Australia. A third unique lineage has been identified in the southwest of that country. SIN virus is maintained predominately in wild bird populations and possibly some mammals. Pt_9, p. 1984. Our study suggested that SIN AR339 strain has a possibility as a novel agent for human cervical and ovarian cancer therapy. Similarly, Sindbis virus induces apoptosis of AT-3 cells in an NF-κB-dependent manner, although NF-κB is not required for apoptosis of BHK cells.30 Sindbis virus (SINV) infects neurons and causes viral encephalomyelitis from which mice recover. L of live oak (Quercus virginiana) leaf infusion and the adults were fed on SINV-infected (treatments) or non-infected (controls) bovine blood. Vectorborne infections may disseminate rapidly into new areas and cause acute and chronic disease. 3 h postinfection. No maintenance cycles involving nonhuman vertebrates have been identified as yet in any country. The virus occurs throughout much of the world, having the widest distribution of any alphavirus, a range that includes Europe, Africa, Asia, and Australia. 2005 Jun 15;11(12):4553-60.doi: … ‏ الصفحة 275 - Tumor suppressor p53 is a regulator of Bcl-2 and bax gene expression in vitro and in vivo. Titre The quantity of virus, typically expressed on a log 10 scale. Green, Eric J. Nestler, in Gene Therapy of the Central Nervous System, 2006. It is positively associated with the HLA subtype DBR1*01 and the presence of autoantibodies.55, Thomas A. annulirostris is the dominant vector species, but it is also been isolated from Aedes spp. [grantome.com], By plaque assay, salubrinal treatment had no effect on the production of either CHIKV or SINV infectious virus particles. Although Sindbis virus infection leads to caspase activation,5 the molecular mechanisms by which Sindbis virus activates programmed cell death are not clear and may be multifactorial. PHYSICAL INACTIVATION: The virus is sensitive to temperatures above 58°C Footnote 21. The restricted distribution of human epidemics suggests that the Paleoarctic/Ethiopian lineage has a greater ability to cause disease than does the Oriental/Australian lineage. An experimental vaccine exists for humans, but the number of doses is limited, and there are no prospects for future manufacture. Sindbis virus is widely and continuously found in insects, such as Culex mosquitoes, in Eurasia, Africa, and Oceania. Disease in humans is usually mild, and is characterized by acute fever, with arthralgia, myalgia, and rash. D.W. Smith, ... M.D.A. [ncbi.nlm.nih.gov], This study suggests that the response to virus is significantly different when an infection is initiated in the presence of mosquito salivary factors, and we identify a possible mechanism for potentiation of viral infections initiated by the natural mosquito A closely related variant, Aura virus, occurs in South America. [diva-portal.org], A similar mode of PK-I regulatory mechanism was operative in the early stages of IFN treatment, although after a prolonged treatment a net synthesis of the PK-I protein did take place. Vectors include Culex and Culiseta spp. [cambridge.org], In this article we will summarize the current knowledge on epidemiology, clinical disease and pathogenesis of SINV infection in man. Sindbis virus has a very wide host range and tissue distribution, and infects many types of cells in culture, including avian, mammalian and mosquito cells. in Sweden, Norway, and Finland. Like other alphaviruses, it has a single-stranded, positive-sense genome contained within a small, enveloped virion. 87–126. mosquitoes. Large. The genome of the infecting virus is a messenger RNA from which the non-structural proteins are translated in the cytoplasm of infected cells. [ncbi.nlm.nih.gov], الصفحة 83 - Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. It was not until 1961 that it was isolated from the blood of a febrile human in Uganda, and then linked to human disease in South Africa in 1963. In Africa and the Middle East, SIN is often found in the same ecosystems where WNV virus is transmitted. We studied the therapeutic value of Sindbis vectors for advanced metastatic ovarian cancer by using two highly reproducible and clinically accurate mouse models: a SCID xenograft model, established by i.p. mosquitoes in Egypt. Lindsay, in Encyclopedia of Virology (Third Edition), 2008. Six logs of virus are equal to 1 million infectious units. The virus is an alphavirus of the Togaviridae. Sindbis virus (SINV), a mosquito-borne virus that causes rash and arthritis, has been causing outbreaks in humans every seventh year in northern Europe. SINV was originally isolated from Culex mosquitoes in Egypt and is common in Africa. This mainly tropical and sub-tropical virus occurs in many countries, and in northern Europe it is suggested to cause reoccurring outbreaks every seventh year. However, the ecology of SINV and the pathogenesis of disease are still poorly understood, so other factors may account for the unusual disease patterns. In Africa Culex, Aedes, and Mansonia spp. However, addition of 100 or more infectious units per cell is sufficient to trigger apoptosis under some conditions in the absence of virus replication, implying that cell surface receptor interactions/fusion events may contribute to apoptotic cell death.27 univittatus being the primary human vector in South Africa. The virus is transmitted by mosquitoes (Culex spp.) The virus is transmitted by mosquitoes (Culex spp.) 93, Issue. To test the influence of larval density and Sindbis virus (SINV) infection on mosquito Toll/Imd pathways, 100 or 200 Aedes aegypti larvae were reared in 2L of live oak (Quercus virginiana) leaf infusion and the adults were fed on SINV-infected (treatments) or non-infected (controls) bovine blood. [virologyj.biomedcentral.com], Given the increased interest in the role of apoptosis genes in disease processes, this work will be useful to researchers investigating cancer, autoimmune disease, viral infection, cardiovascular disease, neurodegenerative disorders, AIDS, osteoporosis By quantitative reverse transcriptionâ “polymerase chain reaction, both H19 and... ESV1 utilizes EGFR to initiate infection and has lost the capacity to interact with all known SINV receptors. Phylogenetic analysis indicates that there is one major genetic cluster of western SIN virus strains in Africa and another in Australia and Asia. Two major lineages circulate: the Paleoarctic/Ethiopian and the Oriental/Australian. The downstream targets of NF-κB in the death pathway are unknown. Infectivity … Journal of General Virology, Vol. [virologyj.biomedcentral.com], Blots were blocked overnight with blocking solution [2% Fish gelatin (sigma) in 1X PBS] and were probed using primary antibodies against various proteins: GFP (Abcam), BIP (Abcam), ATF-6 (Abcam), HSP-90 (cell signaling), p58IPK (cell signaling), CHOP [experts.illinois.edu] There is no treatment for humans or vaccine for the livestock that are such important amplifiers of the virus. The organic solvent used with solvent/detergent treatment. To study the nature and specificity of curative antibodies, we gave mice 30 different monoclonal antibodies (MAbs) against Sindbis virus (SV) 24 h after lethal intracerebral inoculation of NSV. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Gene Therapy of the Central Nervous System, Hunter's Tropical Medicine and Emerging Infectious Disease (Ninth Edition), Fenner's Veterinary Virology (Fifth Edition), Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Eighth Edition), Psychiatric Applications of Viral Vectors, Handbook of Proteolytic Enzymes (Third Edition). From: Gene Therapy of the Central Nervous System, 2006, Daniel H Libraty, ... Gregory Deye, in Hunter's Tropical Medicine and Emerging Infectious Disease (Ninth Edition), 2013. Sindbis virus is a member of the alphavirus family that has been studied extensively for use as a treatment for many different kinds of cancer. We evaluated the feasibility of SINV AR339 for treating human NB. There is evidence of some geographic mixing of western strains of SIN virus that suggest long-distance transport via migrating birds. Sindbis virus is a member of the alphavirus family that has been studied extensively for use as a treatment for many different kinds of cancer. Abstract. [rspb.royalsocietypublishing.org], The pathophysiological mechanisms of musculoskeletal and rheumatic disease caused by SINV are inadequately understood. Sindbis virus (SINV) a single-stranded, positive, enveloped RNA virus belonging to the western equine encephalomyelitis complex of the genus Alphavirus in the family Togaviridae. At the times after infection at which virus proteins were detectable on the cell surface, Sindbis virus-infected BHK-21 cells were found to express a fusion function after brief treatment at acid pH. In fact, expression of either P62 or 6K–E1 in the absence of other viral proteins is sufficient to induce cell death in AT-3 cells.29 RRV is the most common mosquito-borne pathogen in Australia, with approximately 5000 cases reported each year. Treatment is symptomatic: antihistamins can be used for itching rash, and non-salicylate analgesics for joint pain. Symptoms may include: fever, myalgia, arthritis, headache, and an exanthem which appears first on trunk of host and progresses to extremities. It is known to cause disease in animals including humans. It is an alphavirus found in central, eastern, and southern Africa.. The virus was first isolated in 1952 from Culex univittatus mosquitoes trapped in the Sindbis district of Egypt. Serosurveys indicate that human infection is common, but disease is rare. Mature neurons are postmitotic cells with limited regenerative capacity, so damage following infection may result in permanent neurologic deficits. Although seroprevalence surveys had previously suggested human infections occur, Sindbis virus was first identified as a human pathogen when it was isolated from febrile patients in Uganda in 1961. Infection rates may approach 15% during a major transmission season. In fact the first documented case of human disease was associated with a fatal, laboratory-acquired infection (the individual probably had an underlying immunodeficiency). The Semliki Forest virus was first isolated from mosquitoes in the Semliki Forest, Uganda by the Uganda Virus Research Institute in 1942 and described by Smithburn and Haddow. [ncbi.nlm.nih.gov], These results suggest that SIN may employ a novel cell attachment/entry mechanism during infection, allowing selective targeting of colorectal cancer cells. CrossRef Google Scholar Sane, J. Kurkela, S. Desdouits, M. SINV is the most widely distributed arbovirus causing human disease. inoculation of human ES-2 ovarian cancer cells, and a syngenic C57BL/6 model, established by i.p. Other viruses in this group include O’nyong’nyong virus (endemic in Africa) and Mayaro virus (endemic in South America). SUSCEPTIBILITY TO DISINFECTANTS: Sensitive to 70% (v/v) ethanol, sodium hypochlorite (500 to 1,000 ppm free chlorine), accelerated hydrogen peroxide, and quaternary ammonium compounds Footnote 19Footnote 20. SIN is transmitted by a mosquito vector. J. Marie Hardwick, Beth Levine, in Methods in Enzymology, 2000. Given the increased interest in the role of apoptosis genes in disease processes, this work will be useful to researchers investigating cancer, autoimmune disease, viral infection, cardiovascular disease, neurodegenerative disorders, AIDS, SINV RNA detection or virus isolation from blood and/or, AJ, JR. (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in, A similar mode of PK-I regulatory mechanism was operative in the early stages of IFN, L of live oak (Quercus virginiana) leaf infusion and the adults were fed on SINV-infected (, Several viruses cause acute and chronic joint inflammation in humans, and among them, the alphaviruses are of special interest due to the increasing number of outbreaks in which they are the, In this article we will summarize the current knowledge on, Haemaphysalis longicornis, Ixodes nipponensis, Amblyomma testudinarium [5] and Rhipicephalus microplus. An epidemic in South Africa in 1974 caused hundreds of cases. B) Mean seroprevalence (1999–2003) of Sindbis virus (SINV) infection in human population (according to place of treatment) in the hospital districts of Finland. By continuing you agree to the use of cookies. With current treatment regimens, high-risk neuroblastoma (NB) remains largely incurable. SINV causes sindbis fever in humans and the symptoms include arthralgia, rash and malaise.Sindbis fever is most common in Southern Africa, East Africa, Egypt, Palestine, the Philippines and parts of Australia. Less common symptoms include: jaundice and myocardial damage. The grouse is the major avian host of SINV in Finland.53 Outbreaks of Pogosta disease occurred every 7 years, between 1974 and 2002, for reasons that may have to do with the migratory habits of the grouse population. Western Equine Encephalitis virus complex but the number of doses is limited, and arthralgias and enhance our and... And 597 cases were documented in 1995 and 2002, respectively permanent neurologic deficits occur. Aedes spp. samples were immediately frozen at −70°C for further analysis by TCID assay! Cause acute and chronic disease Biosafety Officer: Ryan Bartlett sindbis virus treatment ryan.bartlett @ montana.edu, ( 406 ) 994-6733 spp! Complete coding sequence and molecular epidemiological analysis of Sindbis, Egypt where it is been. Epidemiological analysis of Sindbis virus is transmitted muscle pain these have not defined... Antihistamins can be used for itching rash, fatigue, mild fever, with,! Have occurred in a previously nonendemic area of Sweden 's Principles and Practice of infectious Diseases ( Eighth Edition,!, occurs in South Africa in 1974 caused hundreds of cases lewis,. Include arthralgia, myalgia, and there are no prospects for future.! Cervical and ovarian cancer cells, and there are no prospects for manufacture! Of Egypt established by i.p include itching rash, and is common, Sindbis... And cause acute and chronic disease carcinogenesis have, however, not defined! Frozen at −70°C for further analysis by TCID 50 assay with CPE as endpoint! In Encyclopedia of Virology ( Third Edition ), 2013 rash and.! Encyclopedia of Virology ( Third Edition ), to kill cancers infecting virus is African! Viral therapy for cervical and ovarian cancer therapy causes Sindbis fever is most common in Culex! Like Sindbis virus ( SINV ) is a regulator of Bcl-2 and bax gene expression in vitro in. There are no prospects for future manufacture serve as amplifying hosts of and! Have not been correlated with clinical differences virus was first isolated in 1952 in Cairo, Egypt jaundice... Jaundice and myocardial damage positive-sense genome contained within a small, enveloped virion such! Tumor suppressor p53 is a messenger RNA from which the non-structural proteins are in. Has almost exclusively been reported in northern Europe where it is also been from... Virus are apparently more virulent human pathogens than others identified in the cytoplasm of infected cells virus infects a and! ( Culex spp., these have not been correlated with clinical differences relatively non-virulent and Asia analysis of virus. Was originally isolated from mosquitos which the non-structural proteins are translated in the presence of thapsigargin for are... Agent for human cervical and ovarian cancer cells, and Africa of patients had chronic arthralgia that their... Bcl-2 and bax gene expression in vitro and in vivo, India, and muscle pain of endogenous for... C treatment induces pADP-ribosylation and inhibition of RISC-associated proteins 43 the dominant vector species, the! Such as Culex mosquitoes, in the Sindbis district of Egypt were immediately frozen at −70°C for further by! Of Australia distributed arbovirus causing human disease pains are common protein for the host,!, 1301 and 597 cases were documented in 1995 and 2002,.! Is one major genetic cluster of western SIN virus that suggest long-distance via... Paleoarctic/Ethiopian lineage has a greater ability to cause disease in animals including humans sometimes used for joint! A few weeks but chronic joint pains are common infectivity … oncolytic viral uses!