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96-499: HVJ may refer to: Hemagglutinating virus of Japan , or Sendai virus HVJ Associates , American engineering firm HVJ Gas Pipeline , in India Vatican Radio , which used the callsign HVJ Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title HVJ . If an internal link led you here, you may wish to change

192-419: A model pathogen . The virus is infectious for many cancer cell lines (see below), and has oncolytic properties demonstrated in animal models and in naturally-occurring cancers in animals. SeV's ability to fuse eukaryotic cells and to form syncytium was used to produce hybridoma cells capable of manufacturing monoclonal antibodies in large quantities. Recent applications of SeV-based vectors include

288-411: A pattern recognition receptor NLRC5 , which is a cytosolic protein expressed mainly in hematopoietic cells . This production activates the cryopyrin (NALP3) inflammasome . Using human monocytic cell line -1 (THP-1) it has been shown that SeV can activate signal transduction by mitochondrial antiviral-signaling protein signaling (MAVS) , which is a mitochondria-associated adaptor molecule that

384-599: A phase II clinical trial . In Japan intranasal Sendai virus-based SARS-CoV-2 vaccine was created and tested in a mouse model. SeV replication occurs exclusively in the cytoplasm of the host cell. The virus is using its own RNA polymerase. One replication cycle takes approximately 12–15 hours with one cell yielding thousands of virions. The virus is responsible for a highly transmissible respiratory tract infection in mice, hamsters, guinea pigs, rats, and occasionally marmosets, with infection passing through both air and direct contact routes. Natural infection occurs by way of

480-586: A host organism. HMPV was responsible for 12% of cases of acute respiratory tract illness in otherwise-healthy children in a US outpatient clinic and 15% and 8% of cases (respectively) of community-acquired pneumonia requiring hospitalization in children under and over the age of 5 in the United States. The virus is distributed worldwide and, in temperate regions, has a seasonal distribution generally following that of RSV and influenza virus during late winter and spring. Serologic studies have shown that by

576-487: A modified protease cleavage site in the F-protein. The modification allowed the recombinant virus to specifically infect cancer cells that expressed the corresponding proteases. Another approach of making Sendai virus non-pathogenic included the short-term treatment of the virions with ultraviolet light . Such treatment causes a loss of the virus replication ability. However, even this replication-deficient virus can induce

672-504: A pathogen infection. In response to SeV infection, the production of hBD-1 mRNA and protein increases 2 hours after exposure to the virus in purified plasmacytoid dendritic cells or in PBMC. After viral infection in rodents, type I IFNs promote SeV clearance and speed up the migration and maturation of dendritic cells. However, soon after viral infection, animals efficiently generate cytotoxic T cells independently of type I IFN signaling and clear

768-537: A potential of becoming a safe and effective therapeutic agent against a wide range of human cancers. High genomic stability of SeV is a very desirable trait for oncolytic viruses. SeV is not likely to evolve into a pathogenic strain or into a virus with decreased oncolytic potential. The cytoplasmic replication of the virus results in a lack of host genome integration and recombination, which makes SeV safer and more attractive candidate for broadly used therapeutic oncolysis compared to some DNA viruses or retroviruses. One of

864-519: A successful human pathogen, does not express V proteins, only C proteins. So, all needed functions provided by V in SeV can be provided by C in HPIV1. Thus, C and V have these "overlapping functions" because of the multi-faceted nature of host defense that can be countered at so many places, and exactly how well and where will in part explain host restriction. The C-protein also appears to be responsible for limiting

960-455: Is an enveloped , 150-200 nm–diameter, negative sense, single-stranded RNA virus of the family Paramyxoviridae . It typically infects rodents and it is not pathogenic for humans or domestic animals. Sendai virus (SeV) is a member of the genus Respirovirus . The virus was isolated in the city of Sendai in Japan in the early 1950s. Since then, it has been actively used in research as

1056-434: Is dominant over the others and none of them are known to cause varying levels of severity. hMPV is most likely spread from infected individuals to others through 1. secretions from coughing and sneezing, 2. close personal contact (ex. touching, shaking hands, etc), and 3. touching objects with viruses on them then touching your mouth, nose, or eyes. Development of a reliable antiviral therapy treatment or vaccine to prevent

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1152-810: Is highly expressed on the outer membranes of brain metastases cells that originate from an extremely broad range of cancer, while GD1a, GT1b and GQ1b can be detected in human gliosarcomas. However, their quantity is not exceeding the quantity in normal frontal cerebral cortex. The asialoglycoprotein receptors that bind Sendai virus. and serve as SeV cell entry receptors are highly expressed in liver cancers . (sLeX/CD15s) (CD65s) Cellular expression of glycoproteins can be evaluated by various molecular biology methods, which include RNA and protein measurements. However, cellular expression of gangliosides , which are sialic acid-containing glycosphingolipids , cannot be evaluated by these methods. Instead, it can be measured using anti-glycan antibodies, and despite

1248-467: Is involved in chemotaxis , induction of apoptosis, regulation of cell growth and mediation of angiostatic effects. Human mast cell infection with SeV induces expression of interferon-stimulated genes MxA and IFIT3 in addition to activation of expression of type 1 IFN , MDA-5 , RIG-1 and TLR-3 . Sendai virus can induce the production of many cytokines that enhance cellular immune responses . Some evidence that demonstrates that SeV activates

1344-409: Is nearly as common and as severe as influenza in older adults. HMPV is associated with more severe disease in people with asthma and adults with chronic obstructive pulmonary disease ( COPD ). Numerous outbreaks of HMPV have been reported in long-term care facilities for children and adults, causing fatalities. The genomic organisation of HMPV is similar to RSV ; however, HMPV lacks

1440-418: Is one of SeV cell entry receptors, on the outer cell membrane, correlates with invasion potential of malignant cells, tumor recurrence, and overall patient survival for an extremely wide range of cancers. Therefore, SeV virus preferentially can enter such cells. Metastatic cancer cells frequently express a high density of glycoproteins or glycolipids - molecules that are rich in sialic acid . Expression of

1536-592: Is recognized that Sendai virus disease causing infection is host restrictive for rodents and the virus does not cause disease in humans or domestic animals, which are natural hosts for their own parainfluenza viruses. After experimental SeV infection the virus can replicate and shed from the upper and lower respiratory tract of African green monkeys and chimpanzees, but it is not causing any disease. Sendai virus has been used and demonstrated high safety profile in clinical trials involving both adults and children to immunize against human parainfluenza virus type 1, since

1632-478: Is required for optimal NALP3 - inflammasome activity. Through MAVS signaling SeV stimulates the oligomerization of NALP3 and triggers NALP3-dependent activation of caspase-1 that, in turn, stimulates caspase 1-dependent production of interleukine -1 beta (IL-1β) . SeV is a very effective stimulant of expression of human beta-defensin-1 (hBD-1) . This protein is a member of the beta-defensin family of proteins that bridges innate and adaptive immune responses to

1728-467: Is restricted to conventional dendritic cells (DCs]) subsets, such as CD4 and double negative (dnDC). The UV-inactivated SeV (and likely the alive virus as well) can stimulate dendritic cells to secrete chemokines and cytokines such as interleukin-6 , interferon-beta , chemokine (C-C motif) ligand 5 , and chemokine (C-X-C motif) ligand 10 . These molecules activate both CD8 T cells as well as natural killer cells . UV-inactivated SeV triggers

1824-535: Is still a relatively new virus and has not yet been researched very heavily, hMPV and its replication cycle still have a lot of mystery surrounding them. However, researchers have been able to elucidate some principal steps of hMPV's replication cycle, basing their approach and experimentation on the current knowledge we have of the viral life cycles and reproductive measures of the rest of the Paramyxoviridae family. With that being said, it has been determined that

1920-419: Is still listed as a virus that can cause disease in pigs. Similar information is provided by Encyclopædia Britannica . In reality, the multiple isolates of paramyxoviruses in pigs, using modern nucleic acid sequencing methods, have never been identified as SeV. All viruses in the family Paramyxoviridae are antigenically stable; therefore the family representatives that are close relatives and belong to

2016-551: Is that hMPV's fusion events occur at acidic pH levels while other viruses’ fusion events occur at neutral pH levels; however, more research needs to be conducted in this area to get a better understanding of what is different about the hMPV fusion mechanism and why. Although its specific function is uncertain, it is important to note the presence of the SH glycoprotein which seemingly does not have any effects on replication kinetics, cytopathic effects, or plaque formation of hMPV. After fusion,

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2112-422: Is yet known, but ribavirin has shown effectiveness in an animal model. American pharmaceutical corporation Moderna has conducted a clinical trial for a candidate modRNA vaccine against metapneumovirus. As of October 2019, the vaccine candidate has passed through phase I , with reports that the vaccine is well-tolerated at all dose levels at two months, and provokes an immune response which boosts

2208-612: The cytoplasm without DNA intermediates or a nuclear phase and it does not cause any disease in humans or domestic animals. Sendai virus is used as a backbone for vaccine development against Mycobacterium tuberculosis that causes tuberculosis , against HIV-1 that causes AIDS and against other viruses, including those that cause severe respiratory infections in children. The latter include Human Respiratory Syncytial Virus (HRSV) , Human Metapneumovirus (HMPV) and Human Parainfluenza Viruses (HPIV) . The vaccine studies against M. tuberculosis, HMPV , HPIV1 and, HPIV2 are in

2304-422: The 1950s-1960s. Recently published study also showed this wide spread detection. The study that was published in 2011 demonstrated that SeV neutralizing antibodies (which were formed due to human parainfluenza virus type 1 past infection) can be detected in 92.5% of human subjects worldwide with a median EC 50 titer of 60.6 and values ranging from 5.9 to 11,324. Low anti-SeV antibodies background does not block

2400-539: The C proteins (see the section "genome structure" below). C proteins of SeV are able to suppress apoptosis. The antiapoptotic activity of the C proteins supports SeV infection in the host cells. The virus prevents the stimulation of type 1 IFN production and subsequent cell apoptosis in response to virus infection by inhibiting the activation of IRF-3 . Two virus proteins: C and V are mainly involved in this process. SeV can attenuate cell defense mechanisms and allow itself to escape from host innate immunity by inhibiting

2496-458: The ELISA for its high sensitivity (unlike the hemagglutination assay) and its fairly early detection (unlike the immunofluorescence assay). In a natural setting, the respiratory infection of Sendai virus in mice is acute. From the extrapolation of the infection of laboratory mice, the presence of the virus may first be detected in the lungs 48 to 72 hours following exposure. As the virus replicates in

2592-591: The F-coding gene of SeV to tumor cells in model animals trigger the production of RANTES (CCL5) in tumor-infiltrated T-lymphocytes . SeV induces the production of B cell-activating factor by monocytes and by some other cells. Heat-inactivated SeV virus induces the production of IL-10 and IL-6 cytokines by dendritic cells (DC) . Most likely, F protein is responsible for this induction because reconstituted liposomes containing F protein can stimulate IL-6 production by DC . The production of IL-6 in response to SeV infection

2688-439: The G protein is not required for rest of the replication cycle. Next in the cycle is the fusion of the viral and host membranes which is likely mediated by the F protein. Though the fusion mechanism is very similar to that of other Paramyxoviridae family members and involves conformational changes of the F protein, the mechanism for hMPV does not depend on the G protein for fusion like its family members, showing consistency with

2784-459: The IFN response pathway. HeLa cells can be infected with SeV; however, incubation of these cells with IFN-beta causes inhibition of SeV replication. Multiple interferon stimulated genes (ISG) were identified as being required for this inhibition including IRF-9 , TRIM69 , NPIP , TDRD7 , PNPT1 and so on. One of this genes TDRD7 was investigated in more detail. The functional TDRD7 protein inhibits

2880-926: The Sendai virus can cause rodent disease, which is a problem for research strategies. Two approaches have been used to overcome this problem and make Sendai virus non-pathogenic for mice and rats. One of these approaches included the creation of a set of genetically modified attenuated viral strains. Representatives of this set were tested on model animals carrying a wide range of transplantable human tumors. It has been shown that they can cause suppression or even eradication of fibrosarcoma , neuroblastoma , hepatocellular carcinoma , melanoma , squamous cell and prostate carcinomas. SeV construct suppresses micrometastasis of head and neck squamous cell carcinoma in an orthotopic nude mouse model. Complete eradication of established gliosarcomas in immunocompetent rats has also been observed. SeV constructs have also been created with

2976-545: The Vim2 antigen, which is another SeV cell entry receptor, is very important for the extravascular infiltration process of acute myeloid leukemia cells. GD1a, ganglioside also serves as SeV receptor and is found in large quantities on the surfaces of breast cancer stem cells . High cell surface expression of another SeV receptor - ganglioside sialosylparagloboside /SPG/ NeuAcα2-3PG. characterizes lymphoid leukemia cells . Among other receptors represented by gangliosides GT1b

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3072-453: The ability of SeV-base vaccine to promote antigen-specific T cell immunity. In 1952, Kuroya and his colleagues attempted to identify an infectious agent in human tissue samples at Tohoku University Hospital, Sendai, Japan. The samples were taken from the lung of a newborn child that was affected by fatal pneumonia. The primary isolate from the samples was passaged in mice and subsequently in embryonated eggs. The isolated infectious agent

3168-538: The ability of SeV-base vaccine to promote antigen-specific T cell immunity. Sendai virus administration to non-natural hosts results in shedding virions in the airways. Thus, 10 hours later after intranasal SeV administration, infectious virions carrying foreign trans genes can be detected in sheep's’ lungs. Moreover, SeV replicates to detectable levels in the upper and lower respiratory tract of African green monkeys and chimpanzees . SeV can overcome antiviral mechanisms in some of its natural hosts (some rodents), but

3264-451: The ability to replicate and to grow to high titers in human monocyte-derived DCs. On the other hand, pDCs do not produce a significant number of SeV virions after infection. When SeV is inactivated UV irradiation, it triggers lower levels of IFN-α production in pDCs compared to the levels induced by live virus. Additionally, SeV has been shown to induce the production of IFN type III (IFN-lambda) by human plasmacytoid dendritic cells . In

3360-571: The action of viral fusion proteins on the surface, effectively spreading the virus's genome. The rest of the replication cycle following RNA and viral protein synthesis are unclear and require further research. HMPV infects airway epithelial cells in the nose and lung. HMPV is thought to attach to the target cell via the glycoprotein (G) protein interactions with heparan sulfate and other glycosaminoglycans. The HMPV fusion (F) protein encodes an RGD (Arg-Gly-Asp) motif that engages RGD-binding integrins as cellular receptors, then mediates fusion of

3456-501: The age of five, virtually all children worldwide have been exposed to the virus. Despite near universal infection during early life, reinfections are common in older children and adults. Human metapneumovirus may cause mild upper respiratory tract infection (the common cold ). However, premature infants, immunocompromised persons, and older adults >65 years are at risk for severe disease and hospitalization. In some studies of hospitalizations and emergency room visits, HMPV

3552-572: The cancer cells death and stimulate anti-tumor immunity. It can trigger extensive apoptosis of human glioblastoma cells in culture, and it can efficiently suppress the growth of these cells in model animals. The ultraviolet light treated virus can also kill human prostate cancer cells in culture by triggering their apoptosis and eradicate tumors that originated from these cells in immunodeficient model animals. Moreover, it can stimulate immunomodulated tumor regression of colon and kidney cancers in immunocompetent mice. Similar regressions caused by

3648-479: The case of mouse dendritic cells, UV-inactivated SeV can induce the production of type I IFN . Similarly, some tumor cell lines also respond to UV-inactivated SeV by producing type I IFN. However, similar to human pDCs, UV-inactivated SeV elicits lower levels of IFN-α production in mouse pDCs compared to the response triggered by live virus. SeV can stimulate and/or inhibit the IFN-beta response pathway depending on

3744-563: The cell membrane and viral envelope in a pH-independent fashion, likely within endosomes . HMPV then induces the response of chemokines and cytokines such as IL-6, IFN-alpha, TNF-alpha, IL-2, and macrophage inflammatory proteins, which in turn leads to peribronchiolar and perivascular infiltration and inflammation. The identification of HMPV has predominantly relied on reverse-transcriptase polymerase chain reaction ( RT-PCR ) technology to amplify directly from RNA extracted from respiratory specimens. Alternative more cost-effective approaches to

3840-461: The cells of the surface of the airways regenerate. Focal interstitial pneumonia can developed accompanied by inflammation and lesions of various degrees on the lungs. Usually, the respiratory system shows signs of healing within 3 weeks of infection, however, residual lesions, inflammation, or permanent scarring can occur. 6–8 days after the infection initiation serum antibodies appear. They remain detectable for about 1 year. SeV induces lesions within

3936-592: The cells surface increases the vulnerability of these cells to natural killer cells . It has been shown in the Namalwa cells that SeV virus stimulates an expression of many genes involved in immune defense pathways, such as type I and type II IFN signaling, as well as cytokine signaling. Among the ten most virus-induced mRNAs are IFNα8 , IFNα13 , IFNβ , IFNλ: (L28α , IL28β , IL29 ), OASL , CXCL10 , CXCL11 and HERC5 . Using human embryonic kidney cells ( HEK 293T ) it has been shown that SeV can stimulate production of

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4032-469: The detection of HMPV by nucleic acid -based approaches have been employed and these include: Though hMPV was first discovered and identified in 2001, serological studies showed that hMPV, or a close relative of it, had already been circulating for at least 50 years. From this information, it is clear that the virus had not just “jumped” from birds, or some other animal reservoir, to humans shortly before its discovery. So far, peak infection from hMPV in

4128-437: The development of hMPV in the natural host. There are no conclusive studies to date; however, it is likely that transmission occurs by contact with contaminated secretions, via droplet, aerosol, or fomite vectors. Hospital-acquired infections with human metapneumovirus have been reported. HMPV has been shown to circulate during fall and winter months with alternating predominance of a single subtype each year. No treatment

4224-460: The first 72 hours of infection. Treatment of both strains with exogenous IFN before and during viral infection led to an increase in survival time in C57BL/6 mice, but all animals of both strains ultimately succumb to SeV caused disease. If a mouse survives a SeV infection, it develops a lifelong immunity to subsequent viral infections. There are SeV-resistant F344 rats and susceptible BN rats. In

4320-448: The first step of the hMPV replication cycle is attachment to the host cell, specifically the epithelial cells of the respiratory tract, using the G protein. This G protein contains a hydrophobic region that acts as an uncleaved signal peptide and a membrane anchor to facilitate its binding; however, because recombinant viruses that lack the G protein have still been able to replicate in vitro and in vivo , it seems that attachment via

4416-427: The genomic sequences of the virus could be identified; these techniques included the randomly primed PCR technique which obtained the limited sequence data needed to reveal a clear relationship between this new virus and the avian pneumovirus. It was this close relationship to AMPV that gave rise to this new virus being named human metapneumovirus to reflect both its identity as a metapneumovirus and its use of humans as

4512-405: The genus Respirovirus may explain why SeV antibodies were found in sick pigs, and why it was thought that SeV was the etiological causative agent of pigs disease. Human parainfluenza virus type 1, also shares common antigenic determinants with SeV and triggers the generation of cross-reactive neutralizing antibodies . This fact can explain wide spread detection of SeV antibodies in humans in

4608-414: The great advantages of the Sendai virus as a potential oncolytic agent is its safety. Even though the virus is widespread in rodent colonies and has been used in laboratory research for decades, it has never been observed that it can cause human disease. Moreover, Sendai virus has been used in clinical trials involving both adults and children to immunize against human parainfluenza virus type 1, since

4704-424: The hMPV F gene allows for neutralizing antibodies against both parainfluenza and hMPV. However promising these results and trials may seem, it is important to note that these experiments have limitations including their small-population animal models. Overall, while vaccines and antiviral therapy treatments are in the works, the biggest difficulty that researchers face at the moment is the limited data available about

4800-438: The host airways the virus titer reaches a peak after 5–6 days post infection initiation that decreases to undetectable levels by day 14. The virus promotes a descending respiratory infection, which begins in the nasal passages, passes through the trachea into the lungs and causes necrosis of the respiratory epithelium. The necrosis is mild in the first few days of infection, but later became severe by peaking around day 5. By day 9,

4896-404: The interferon response pathway in addition to inhibiting the interferon production. The table below demonstrates the inhibition mechanism. Anti-IFN activity of C protein is shared across the family Paramyxoviridae , and therefore appears to play an important role in paramyxovirus immune evasion. Human Parainfluenza Virus type 1 (HPIV1), which is a close relative of SeV and is (in contrast to SeV)

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4992-562: The large collection of such antibodies in a community resource database, they are not always available for each ganglioside. Therefore, indirect measurement of ganglioside expression by quantifying the levels of fucosyltransferases and glycosyltransferases that complete glycan synthesis is an alternative. There is evidence that expression of these enzymes and the production of gangliosides strongly correlate. At least four representatives of fucosyltransferases and several glycosyltransferases including sialyltransferases are responsible for

5088-538: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=HVJ&oldid=1062319600 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Hemagglutinating virus of Japan Murine respirovirus , formerly Sendai virus (SeV) and previously also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ),

5184-684: The medical records of the patients that experiences long-term remission are presented in the patent. Intratumoral injection of UV irradiated and inactivated SeV resulted in an antitumor effect in a few melanoma patients with stage IIIC or IV progressive disease with skin or lymph metastasis. Complete or partial responses were observed in approximately half of injected and noninjected target lesions. Sendai virus can infect and kill variable cancer cells (see section Sensitive cell lines and virus strains ). However, some malignant cells are resistant to SeV infection. There are multiple explanations for such resistance. Not all cancer cells have cell entry receptors for

5280-468: The non-breeding adults isolated for two months. The virus is a powerful immunomodulator . SeV can act in both directions: it can activate or suppress the immune response depending on the type of cell, host and time period after infection initiation. The virus can suppress the IFN production and response pathways as well as inflammation pathway. Sendai virus P gene encodes a nested set of proteins (C', C, Y1 and Y2), which are named to collectively as

5376-459: The non-structural genes , NS1 and NS2, and the HMPV antisense RNA genome contains eight open reading frames in slightly different gene order than RSV (viz. 3’-N-P-M-F-M2-SH-G-L-5’). HMPV is genetically similar to the avian metapneumoviruses A, B and in particular type C. Phylogenetic analysis of HMPV has demonstrated the existence of two main genetic lineages termed subtype A and B containing within them

5472-462: The northern hemisphere is in late winter and early spring, but it can be found globally across all continents and its distribution is very complex and dynamic. Researchers have found that hMPV is mostly localized and can differ significantly from community to community, allowing for the possibility of the strain in one location one year to be most similar to the strain in a different location the next year. This phenomenon has actually been recorded with

5568-526: The peak of RSV, which is around 2–3 months. The clinical features and severity of HMPV are similar to those of RSV. HMPV is also an important cause of disease in older adults. Human metapneumovirus was first discovered in 2001 in the Netherlands by Bernadette G. van den Hoogen and her colleagues. hMPV was first detected in the respiratory secretions of 28 young children in the Netherlands and had initially stood out from other common respiratory viruses because

5664-408: The pre-clinical stage, against HRSV a phase I clinical trail has been completed. The phase I clinical studies of SeV-based vaccination were also completed for HPIV1. They were done in adults and in 3- to 6-year-old children. As a result of vaccination against HPIV1 a significant boost in virus-specific neutralizing antibodies was observed. A SeV-based vaccine development against HIV-1 has reached

5760-448: The previously mentioned idea that the G protein is not necessary for subsequent steps of the hMPV replication cycle. Moreover, the fusion function of the F protein has been proven by its ability to bind to host cells via integrin αvβ1 using an Arginine-Glycine-Aspartate (RGD) motif , which is speculated to be the trigger for membrane fusion events. One main difference between hMPV and other Paramyxoviridae viruses’ fusion mechanisms though

5856-456: The production of NO in infected macrophages, which in turn reduces inflammation. Currently, there is no scientific data obtained using modern detection methods that would identify SeV as an infectious - disease causing agent for humans or domestic animals. Modern methods for the identification of pathogenic microorganisms have never detected SeV in pigs or other domestic animals, despite the isolation of other paramyxoviruses. Consequently, it

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5952-464: The production of an intercellular adhesion molecule -1 (ICAM-1, CD54) , which is a glycoprotein that serves as a ligand for macrophage-1 antigen (Mac-1) and lymphocyte function-associated antigen 1 ( LFA-1 ( integrin )). This induced production happens through the activation of NF-κB downstream of the mitochondrial antiviral signaling pathway and the RIG-I . The increased concentration of ICAM-1 on

6048-402: The replication of SeV and other paramyxoviruses , suppressing autophagy , which is necessary for productive infection with these viruses. SeV also triggers the expression of IFN induced Ifit2 protein that is involved in protecting mice from SeV through as yet unknown mechanism. In addition, SeV triggers the expression of the chemokine interferon-γ inducible protein 10 kDa (CXCL10) , which

6144-437: The replication-deficient Sendai virus have been observed in animals with transplanted melanoma tumors. Some cancer studies with non-rodent animals have been performed with the unmodified Sendai virus. Thus, after intratumoral injections of the virus, complete or partial remission of mast cell tumors ( mastocytomas ) was observed in dogs affected by this disease. Short-term remission after an intravenous injection of SeV

6240-470: The reprogramming of somatic cells into induced pluripotent stem cells and vaccine creation. For vaccination purpose the Sendai virus-based constructs could be delivered in a form of nasal drops, which may be beneficial in inducing a mucosal immune response . SeV has several features that are important in a vector for a successful vaccine: the virus does not integrate into the host genome , it does not undergo genetic recombination , it replicates only in

6336-451: The respiratory tract of an infected mouse, the concentration of the virus grows most quickly during the third day of infection. After that, the growth of the virus is slower but consistent. Typically, the peak concentration of the virus is on the sixth or seventh day, and rapid decline follows that by the ninth day. A fairly vigorous immune response mounted against the virus is the cause of this decline. The longest period of detected presence of

6432-423: The respiratory tract, usually associated with bacterial inflammation of the trachea and lung ( tracheitis and bronchopneumonia , respectively). However, the lesions are limited, and aren't indicative solely of SeV infection. Detection, therefore, makes use of SeV-specific antigens in several serological methods, including ELISA , immunofluorescence , and hemagglutination assays, with particular emphasis on use of

6528-500: The respiratory tract. In animal facility airborne transmission can occur over a distance of 5–6 feet as well as through air handling systems. The virus can be detected in mouse colonies worldwide, generally in suckling to young adult mice. A study in France reported antibodies to SeV in 17% of mouse colonies examined. Epizootic infections of mice are usually associated with a high mortality rate, while enzootic disease patterns suggest that

6624-440: The review. Thus, for some time, it was erroneously assumed that Sendai virus is human disease causing pathogen. The incorrect assumption that the virus was isolated from human infectious material is still reported by Encyclopædia Britannica and by ATCC in the description of the history of the viral isolate Sendai/52. It was also believed that the virus could cause disease not only in humans but also in pigs, because antibodies to

6720-428: The safety and immunogenicity of an intranasally administered replication-competent Sendai Virus–vectored HIV Type 1 gag vaccine demonstrated: induction of potent T-Cell and antibody responses in prime-boost regimens. Sendai virus also used as a backbone for vaccine against respiratory syncytial virus (RSV). For cancer studies, it is desirable that the oncolytic virus be non-pathogenic for experimental animals, but

6816-427: The same genus, most likely, share common antigenic determinants. Thus, porcine parainfluenza 1, which has high sequence homology with SeV and also belongs to the same genus Respirovirus as SeV, probably, has cross-reactive antibodies with SeV. Perhaps the porcine parainfluenza 1 was responsible for pigs disease in Japan in 1953–1956. However, the antigenic cross-reactivity among these two representatives within

6912-415: The spread of hMPV has yet to occur, but there does seem to be promising developments in that area. In some vaccine trials, researchers have observed how a live recombinant human parainfluenza virus that contains the hMPV F gene can induce hMPV-specific antibodies and can protect experimental animals from hMPV. Another similar study demonstrated how a chimeric bovine /human parainfluenza virus 3 expressing

7008-528: The subgroups A1/A2 and B1/B2 respectively. Genotyping based on sequences of the F and G genes showed that subtype B was associated with increased cough duration and increased general respiratory systems compared to HMPV-A. hMPV is estimated to have a 3–6 day incubation period and is often most active during the later winter and spring seasons in temperate climates, overlapping with the RSV and influenza seasons and possibly allowing for repeated infection. But because it

7104-470: The synthesis of gangliosides that can serve as SeV receptors. All these proteins are often overexpressed in various tumors, and their expression levels correlate with the metastatic status of the tumor and the shorter life span of the patients. Thus, these enzymes are also potential biomarkers of SeV-oncolytic infectivity Human metapneumovirus The peak age of hospitalization for infants with HMPV occurs between 6–12 months of age, slightly older than

7200-403: The testing methods van den Hoogen et al. had tried using (immunological assays using virus-specific antibodies and PCR-based methods using virus genome-specific primers) were only able to test for known respiratory viruses and, therefore, were unable to identify the novel virus. It was not until researchers began applying molecular biology techniques that the genetic characteristics and portions of

7296-656: The transcription factor NF-κB and this activation helps in protection against SeV infection. SeV can stimulate the production of macrophage inflammatory protein-1α (MIB-1α) and –β (MIB-1β) , RANTES (CCL5) , tumor necrosis factor-alpha (TNF-alpha) , tumor necrosis factor-beta (TNF-beta) , interleukin-6 (IL-6 ) , interleukin-8 (IL-8) , interleukin-1 alpha (IL1A) , interleukin-1 beta (IL1B) , platelet-derived growth factor (PDGF-AB) and small concentrations of interleukin-2 (IL2) and GM-CSF . Sendai virus can trigger production of interleukin 12 (IL12) and interleukin 23 (IL23) in human macrophages. Even plasmids that deliver

7392-423: The treated patients, which usually disappeared within 24 hours. Occasionally, the virus administration caused inflammation of the primary tumor and metastases. Clinical outcomes were variable. A small proportion of treated patients experienced pronounced long-term remission with the disappearance of primary tumors and metastases. Sometimes the remission lasted 5–10 years or more after virotherapy. Brief descriptions of

7488-465: The two viruses share common antigenic determinants and trigger the generation of cross-reactive neutralizing antibodies . The study that was published in 2011 demonstrated that SeV neutralizing antibodies (which were formed due to human parainfluenza virus type 1 past infection) can be detected in 92.5% of human subjects worldwide with a median EC 50 titer of 60.6 and values ranging from 5.9 to 11,324. Low anti-SeV antibodies background does not block

7584-583: The two viruses share common antigenic determinants and trigger the generation of cross-reactive neutralizing antibodies .The Sendai virus administration in the form of nasal drops in doses ranging from 5 × 10 50% embryo infectious dose (EID50) to 5 × 10 EID50 induced the production of neutralizing antibodies to the human virus without any measurable side effects.The results of these trials represent additional evidence of Sendai virus safety for humans.The development of T cell-based AIDS vaccines using Sendai virus vectors reached phase II clinical trial. Evaluation of

7680-422: The type of cell and host. If SeV triggers IFN production, the produced IFN further protects cells from next rounds of SeV infection. Multiple examples of IFN-beta protecting cells from SeV are described. Pretreatment of human lung fibroblasts MRC-5 cells with IFN-beta inhibits the replication of SeV. A similar IFN-beta protection against the virus has been observed for some human malignant cells that maintain

7776-529: The vRNA and bind to each other to form the polymerase complex so that the genomic RNA can act as a matrix for viral transcription and replication in the cytoplasm. The final step in the replication process of hMPV that is relatively certain is the journeying of the envelope glycoproteins (F, G, and SH) to zones of membranous accumulation via the Golgi apparatus to be exposed at the surface of infected cells. This allows infected cells to merge with adjacent cells through

7872-499: The viral ribonucleoprotein (RNP) containing negative-sense viral RNA (vRNA) genome is released into the cytoplasm and acts as a template for mRNA and antigenomic cRNA synthesis. From here, most of our knowledge about hMPV transcription is derived from what we already know about RSV and other Paramyxoviridae viruses, including that leader and trailer sequences in the genome are partially complementary and act as promoters for transcription. We see that proteins N, P, and L dissociate from

7968-484: The virus and not all cancer cells express virus processing serine proteases. There are also other mechanisms that can make a cancer cell resistant to an oncolytic virus. For example, some cancer cells maintain interferon response system that completely or partially protects a host cells from a virus infection. Therefore, biomarkers needed to be developed to identify tumors that might succumb to SeV mediated oncolysis. SeV receptors are potential biomarkers for evaluation of

8064-639: The virus from their lungs. Moreover, even the animals that are unresponsive to type I IFN develop long-term anti-SeV immunity in a form of memory response that includes generation of CD8 T cells and neutralizing antibodies. This memory response can protect animals against further challenge with a lethal dose of virus. SeV infection causes changes in a host cell protein phosphorylation, triggering phosphorylation of at least of 1347 host proteins. Sendai virus-based anticancer therapy for model and companion animals has been reported in several scientific papers. The described studies demonstrate that Sendai virus has

8160-507: The virus genomic RNA, the replication intermediary double-stranded RNA, or the viral ribonucleoproteins, promotes IFN production and response pathways. Viral genomic and protein components can bind variable PRRs and stimulate a signaling pathway that results in the activation of the transcription factors, which relocate to nucleus and trigger type I IFNs transcription. Because of powerful interferon stimulating properties, before recombinant interferon alpha became available for medical use, SeV

8256-466: The virus in a mouse lung is fourteen days after infection. Eaton et al. advises that, when controlling an outbreak of SeV, disinfecting the laboratory environment and vaccinating the breeders, as well as eliminating infected animals and screening incoming animals, should clear the problem very quickly. Imported animals should be vaccinated with SeV and placed in quarantine, while, in the laboratory environment, breeding programs should be discontinued, and

8352-482: The virus is ineffective in overcoming these mechanisms in some other organisms that are virus resistant. Both innate and adaptive immunity promote efficient recovery from SeV infection. The main component of innate antiviral response is type I interferons (IFNs) production and most cells can produce type I IFNs , including IFN-α and -β. The recognition by cellular molecules that are called pattern recognition receptors (PRR) of triggering viral elements, such as

8448-738: The virus is latent and can be cleared over the course of a year. Sub-lethal exposure to SeV can promote long-lasting immunity to further lethal doses of SeV. The virus is immunosuppressive and may predispose to secondary bacterial infections. There are no scientific studies, which were performed using modern detection methods, which would identify SeV as an infectious and decease causative for humans or domestic animals. Inbred and outbred mouse and rat strains have very different susceptibility to Sendai virus infection. Visualization of SeV infection in live animals demonstrates this difference. The 129/J mice tested were approximately 25,000-fold more sensitive than SJL/J mice. C57BL/6 mice are highly resistant to

8544-554: The virus strains in Australia in 2001; in France in 2000 and 2002; in Canada in 1999, 2000, 2001, and 2002; in Israel in 2002; and in the Netherlands in 2001 all being very closely related based on their F gene sequences. There are at least two major genotypes of hMPV (A and B) that circulate during community outbreaks and each genotype has two of its own, but as of now, it seems that no one strain

8640-440: The virus were often found in their organisms during the swine epidemic in Japan in 1953–1956. High incidence of seropositivity to the virus was observed in pigs in 15 districts of Japan. An explanation was later found for this widespread detection of antibodies (see the section below). Yet, despite overwhelming evidence that indicate that SeV is host restrictive rodent pathogen, in some veterinary manuals. and safety leaflets, SeV

8736-435: The virus, while DBA/2J mice are sensitive. C57BL/6 mice showed slight loss of body weight after SeV administration, which returned to normal later. Only 10% mortality rate was observed in C57BL/6 mice after the administration of very high virulent dose of 1*10 TCID50. It was shown that resistance to the lethal effects of Sendai virus in mice is genetically controlled and expressed through control of viral replication within

8832-434: The vulnerability of malignant cells to the virus. They represented by glycoproteins and glycolipids (see section " SeV cell entry receptors ").The expression of some molecules that can facilitate SeV cell entry (see section “ SeV cell entry receptors ”), frequently, accelerates carcinogenesis and/or metastasis development. For example, the presence of Sialyl-Lewis antigen (cluster of differentiation 15s (CD15s)) , which

8928-642: Was described in a patient with acute leukemia treated in the Clinical Research Center of University Hospitals of Cleveland (USA) by multiple viruses in 1964. It is also reported that the Moscow strain of SeV was tested by Dr. V. Senin and his team as an anticancer agent in a few dozen patients affected by various malignancies with metastatic growth in Russia in the 1990s. The virus was injected intradermally or intratumorally and it caused fever in less than half of

9024-470: Was later called Sendai virus, which was used interchangeably with the name “Hemagglutinating Virus of Japan”. Kuroya and his colleagues were convinced that they isolated the virus, which is a new etiological agent for human respiratory infections. Later in 1954, Fukumi and his colleagues at the Japan National Institute of Health put forward an alternative explanation for the origin of the virus. It

9120-619: Was selected, among other viruses, for the industrial large-scale IFN production. A procedure involving inactivated SeV treatment of human peripheral blood leukocytes from donors’ blood was used for this production. Below is a table that listed known PRRs and interferon regulatory factors that are getting activated upon SeV infection. Among conventional DCs, only two subsets, namely CD4 and CD8α− CD4− “double negative” dendritic cells are capable of producing IFN-α and IFN-β in response to SeV infection. However, all conventional DC subsets, including CD8α can be infected with SeV. SeV has

9216-444: Was suggested that the mice used to passage the virus were infected with the mouse virus. Thus, mouse virus was later transferred to embryonated eggs, isolated and finally named the Sendai virus. This explanation of Fukumi, pointing to the mouse rather than the human origin of the virus, has been supported by numerous scientific data later. The historical aspects of the Sendai virus isolation and controversy behind it are well described in

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