The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Vincent R Racaniello - One of the best experts on this subject based on the ideXlab platform.
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mda 5 is cleaved in Poliovirus infected cells
Journal of Virology, 2007Co-Authors: Paola M Barral, Juliet Morrison, Jennifer Drahos, Pankaj Gupta, Devanand Sarkar, Paul B Fisher, Vincent R RacanielloAbstract:Infections with RNA viruses are sensed by the innate immune system through membrane-bound Toll-like receptors or the cytoplasmic RNA helicases RIG-I and MDA-5. It is believed that MDA-5 is crucial for sensing infections by picornaviruses, but there have been no studies on the role of this protein during infection with Poliovirus, the prototypic picornavirus. Beginning at 4 h postinfection, MDA-5 protein is degraded in Poliovirus-infected cells. Levels of MDA-5 declined beginning at 6 h after infection with rhinovirus type 1a or encephalomyocarditis virus, but the protein was stable in cells infected with rhinovirus type 16 or echovirus type 1. Cleavage of MDA-5 is not carried out by either Poliovirus proteinase 2A pro or 3C pro . Instead, degradation of MDA-5 in Poliovirus-infected cells occurs in a proteasome- and caspase-dependent manner. Degradation of MDA-5 during Poliovirus infection correlates with cleavage of poly(ADP) ribose polymerase (PARP), a hallmark of apoptosis. Induction of apoptosis by puromycin leads to cleavage of both PARP and MDA-5. The MDA-5 cleavage product observed in cells treated with puromycin is ∼90 kDa, similar in size to the putative cleavage product observed in Poliovirus-infected cells. Poliovirus-induced cleavage of MDA-5 may be a mechanism to antagonize production of type I interferon in response to viral infection.
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One Hundred Years of Poliovirus Pathogenesis
Virology, 2006Co-Authors: Vincent R RacanielloAbstract:Poliovirus was first isolated nearly 100 years ago in a landmark experiment that established the viral etiology of poliomyelitis. This discovery stimulated investigation of the pathogenesis of poliomyelitis in many laboratories. Nearly 50 years later, when two effective Poliovirus vaccines were developed, the impetus to study Poliovirus pathogenesis waned. The identification of the cell receptor for Poliovirus, CD155, and its use in the development of transgenic mice susceptible to Poliovirus revived interest in understanding how the virus causes disease. Experiments in CD155 transgenic mice have provided new information on the initial sites of virus replication in the host, how the virus spreads to the central nervous system through the blood and by axonal transport, the determinants of viral tropism, and the basis for the attenuation phenotype of the Sabin vaccine strains. Despite these advances, our understanding of Poliovirus pathogenesis is still incomplete. The dilemma is not how to answer the remaining questions, but whether there will be sufficient time to do so before global eradication of poliomyelitis leads to cessation of research on the disease.
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Differences in the UV-Crosslinking Patterns of the Poliovirus 5′-Untranslated Region with Cell Proteins from Poliovirus-Susceptible and -Resistant Tissues
Virology, 1997Co-Authors: Ana Lorena Gutiérrez-escolano, Vincent R Racaniello, Fernando Medina, Rosa M. Del AngelAbstract:Abstract The restricted tissue tropism observed in Poliovirus infection is not governed solely by the expression of the Poliovirus receptor (PVR) gene, but might be controlled at stages beyond virus entry, such as translation, replication, or assembly. Translation of Poliovirus RNA by a cap-independent mechanism requires interactions of the 5′-untranslated region (5′UTR) with cell proteins. To determine whether the patterns of these interacting proteins differ in HeLa cells and permissive and nonpermissive tissues, UV-crosslinking assays using the Poliovirus 5′UTR and tissue extracts from PVR transgenic mice were performed. The results indicate a correlation between the presence of a 97-kDa UV-crosslinked protein and permissivity to Poliovirus infection. Acquired Poliovirus susceptibility in in vitro -cultured kidney cells also correlates with the presence of a 97-kDa crosslinked band. The interaction of the 97-kDa protein from HeLa cells and mouse brain with the Poliovirus 5′UTR is stable and specific. Whether the 97-kDa protein plays a role in Poliovirus translation and tissue susceptibility remains to be determined.
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CD44 is not required for Poliovirus replication.
Journal of virology, 1997Co-Authors: Michael J. Bouchard, Vincent R RacanielloAbstract:The identification of a monoclonal antibody, AF3, which recognizes a single isoform of the cell surface protein CD44 and preferentially blocks binding of serotype 2 Poliovirus to HeLa cells, suggested that CD44 might be an accessory molecule to Pvr, the cell receptor for Poliovirus, and that it could play a role in the function of the Poliovirus receptor site. We show here that only AF3 blocks binding of serotype 2 Poliovirus to HeLa cells and, in contrast to a previously published report, that the anti-CD44 monoclonal antibodies A3D8 and IM7 are unable to block binding of Poliovirus. To determine whether CD44 is involved in Poliovirus infection, we analyzed the replication of all three serotypes of Poliovirus in human neuroblastoma cells which lack or express CD44 and in mouse neuroblastoma cells which lack Pgp-1, the mouse homolog of human CD44, and which express Pvr. All three Poliovirus serotypes replicate with normal kinetics and to normal levels in the absence or presence of CD44 or in the absence of Pgp-1. Furthermore, the binding affinity constants of all three Poliovirus serotypes for Pvr are unaffected by the presence or absence of CD44 in the human neuroblastoma cell line. We conclude that CD44 and Pgp-1 are not required for Poliovirus replication and are unlikely to be involved in Poliovirus pathogenesis.
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Expression of the Poliovirus Receptor in Intestinal Epithelial Cells Is Not Sufficient To Permit Poliovirus Replication in the Mouse Gut
Journal of virology, 1997Co-Authors: Suhua Zhang, Vincent R RacanielloAbstract:Although the initial site of Poliovirus replication in humans is the intestine, previously isolated transgenic mice which carry the human Poliovirus receptor (PVR) gene (TgPVR mice), which develop poliomyelitis after intracerebral inoculation, are not susceptible to infection by the oral route. The low levels of PVR expressed in the TgPVR mouse intestine might explain the absence of Poliovirus replication at that site. To ascertain whether PVR is the sole determinant of Poliovirus susceptibility of the mouse intestine, we have generated transgenic mice by using the promoter for rat intestine fatty acid binding protein to direct PVR expression in mouse gut. Pvr was detected by immunohistochemistry in the enterocytes and M cells of transgenic mouse (TgFABP-PVR) small intestine. Upon oral inoculation with Poliovirus, no increase in virus titer was detected in the feces of TgFABP-PVR mice, and no virus replication was observed in the small intestine, although Poliovirus replicated in the brain after intracerebral inoculation. The failure of Poliovirus to replicate in the TgFABP-PVR mouse small intestine was not due to lack of virus binding sites, because Poliovirus could attach to fragments of small intestine from these mice. These results indicate that the inability of Poliovirus to replicate in the mouse alimentary tract is not solely due to the absence of virus receptor, and other factors are involved in determining the ability of Poliovirus to replicate in the mouse gut.
Hiromichi Yonekawa - One of the best experts on this subject based on the ideXlab platform.
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the alpha beta interferon response controls tissue tropism and pathogenicity of Poliovirus
Journal of Virology, 2005Co-Authors: Miki Idahosonuma, Tomoki Yoshikawa, Mitsutoshi Yoneyama, Choji Taya, Takuya Iwasaki, Yuko Sato, Tetsutaro Sata, Noriyo Nagata, Takashi Fujita, Hiromichi YonekawaAbstract:Poliovirus selectively replicates in neurons in the spinal cord and brainstem, although Poliovirus receptor (PVR) expression is observed in both the target and nontarget tissues in humans and transgenic mice expressing human PVR (PVR-transgenic mice). We assessed the role of alpha/beta interferon (IFN) in determining tissue tropism by comparing the pathogenesis of the virulent Mahoney strain in PVR-transgenic mice and PVR-transgenic mice deficient in the alpha/beta IFN receptor gene (PVR-transgenic/Ifnar knockout mice). PVR-transgenic/Ifnar knockout mice showed increased susceptibility to Poliovirus. After intravenous inoculation, severe lesions positive for the Poliovirus antigen were detected in the liver, spleen, and pancreas in addition to the central nervous system. These results suggest that the alpha/beta IFN system plays an important role in determining tissue tropism by protecting nontarget tissues that are potentially susceptible to infection. We subsequently examined the expression of IFN and IFN-stimulated genes (ISGs) in the PVR-transgenic mice. In the nontarget tissues, ISGs were expressed even in the noninfected state, and the expression level increased soon after Poliovirus infection. On the contrary, in the target tissues, ISG expression was low in the noninfected state and sufficient response after Poliovirus infection was not observed. The results suggest that the unequal IFN response is one of the important determinants for the differential susceptibility of tissues to Poliovirus. We consider that Poliovirus replication was observed in the nontarget tissues of PVR-transgenic/Ifnar knockout mice because the IFN response was null in all tissues.
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The Alpha/Beta Interferon Response Controls Tissue Tropism and Pathogenicity of Poliovirus
Journal of virology, 2005Co-Authors: Miki Ida-hosonuma, Tomoki Yoshikawa, Mitsutoshi Yoneyama, Choji Taya, Takuya Iwasaki, Yuko Sato, Tetsutaro Sata, Noriyo Nagata, Takashi Fujita, Hiromichi YonekawaAbstract:Poliovirus selectively replicates in neurons in the spinal cord and brainstem, although Poliovirus receptor (PVR) expression is observed in both the target and nontarget tissues in humans and transgenic mice expressing human PVR (PVR-transgenic mice). We assessed the role of alpha/beta interferon (IFN) in determining tissue tropism by comparing the pathogenesis of the virulent Mahoney strain in PVR-transgenic mice and PVR-transgenic mice deficient in the alpha/beta IFN receptor gene (PVR-transgenic/Ifnar knockout mice). PVR-transgenic/Ifnar knockout mice showed increased susceptibility to Poliovirus. After intravenous inoculation, severe lesions positive for the Poliovirus antigen were detected in the liver, spleen, and pancreas in addition to the central nervous system. These results suggest that the alpha/beta IFN system plays an important role in determining tissue tropism by protecting nontarget tissues that are potentially susceptible to infection. We subsequently examined the expression of IFN and IFN-stimulated genes (ISGs) in the PVR-transgenic mice. In the nontarget tissues, ISGs were expressed even in the noninfected state, and the expression level increased soon after Poliovirus infection. On the contrary, in the target tissues, ISG expression was low in the noninfected state and sufficient response after Poliovirus infection was not observed. The results suggest that the unequal IFN response is one of the important determinants for the differential susceptibility of tissues to Poliovirus. We consider that Poliovirus replication was observed in the nontarget tissues of PVR-transgenic/Ifnar knockout mice because the IFN response was null in all tissues.
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Comparison of neuropathogenicity of Poliovirus in two transgenic mouse strains expressing human Poliovirus receptor with different distribution patterns.
Journal of General Virology, 2002Co-Authors: Miki Ida-hosonuma, Hiromichi Yonekawa, Choji Taya, Takuya Iwasaki, Yuko Sato, Noriyo Nagata, Satoshi KoikeAbstract:In order to determine the influence of Poliovirus receptor (PVR) expression on Poliovirus cell tropism and neuropathogenesis, two transgenic (tg) mouse models were produced in which PVR was expressed under the transcriptional control of the human PVR gene promoter (hg–PVR mice) and the CAG promoter (CAG–PVR mice). Then the pathogenicity of Poliovirus after intracerebral inoculation of the type 1 Mahoney strain was compared. These showed completely different clinical and pathological changes. In the former, the expression of PVR in neurons in the central nervous system (CNS) confered susceptibility to Poliovirus, and a paralytic disease that resembled the human poliomyelitis occurred. In the latter, PVR expression was detected in glial and ependymal cells in addition to the neurons. Paralysis of the limbs and death were rarely observed and mice survived without showing substantial clinical abnormality. Histopathological examination revealed that glial and ependymal cells also became susceptible to Poliovirus infection. Poliovirus antigens were mainly detected in ependymal and glial cells and hippocampal neurons near the lateral ventricles in the brain, but were not frequently detected in neurons in the brainstem unlike in the hg–PVR mice. The levels of viral antigens and virus recovered from the CNS of CAG–PVR mice began to decrease as early as 2 days after inoculation, which suggested induction of a fast immune response. These results suggest that the neuropathogenicity of Poliovirus changes markedly depending on the specific expression of the PVR molecule in the CNS.
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Transgenic mice susceptible to Poliovirus
Proceedings of the National Academy of Sciences of the United States of America, 1991Co-Authors: Satoshi Koike, Hiromichi Yonekawa, Choji Taya, I Ise, Takeshi Kurata, Shinobu Abe, Akio NomotoAbstract:Abstract Poliovirus-sensitive transgenic mice were produced by introducing the human gene encoding cellular receptors for Poliovirus into the mouse genome. Expression of the receptor mRNAs in tissues of the transgenic mice was analyzed by using RNA blot hybridization and the polymerase chain reaction. The human gene is expressed in many tissues of the transgenic mice just as in tissues of humans. The transgenic mice are susceptible to all three Poliovirus serotypes, and the mice inoculated with Poliovirus show clinical symptoms similar to those observed in humans and monkeys. Rabbit antiPoliovirus serum detects the antigens mainly in motor neurons in the anterior horn of the spinal cord and in nerve cells in the medulla oblongata and pons of the paralyzed transgenic mice. Therefore, cell types sensitive to Poliovirus in the central nervous system of the transgenic mice appear to be identical to those of humans and monkeys. Furthermore, many more doses of oral Poliovirus vaccine strains than of the virulent strains are required to cause paralysis in the transgenic mice. This may reflect the observation that the virulent strain multiplies more efficiently in the central nervous system than the attenuated strain. Thus, the transgenic mice may become an excellent new animal model to study molecular mechanisms of pathogenesis of Poliovirus and to assess oral Poliovirus vaccines.
R W Sutter - One of the best experts on this subject based on the ideXlab platform.
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type 2 Poliovirus detection after global withdrawal of trivalent oral vaccine
The New England Journal of Medicine, 2018Co-Authors: Isobel M Blake, R W Sutter, Margarita Ponssalort, Natalie A Molodecky, Ousmane M Diop, Paul Chenoweth, Ananda S Bandyopadhyay, Michel Zaffran, Nicholas C. GrasslyAbstract:Abstract Background Mass campaigns with oral Poliovirus vaccine (OPV) have brought the world close to the eradication of wild Poliovirus. However, to complete eradication, OPV must itself be withdrawn to prevent outbreaks of vaccine-derived Poliovirus (VDPV). Synchronized global withdrawal of OPV began with serotype 2 OPV (OPV2) in April 2016, which presented the first test of the feasibility of eradicating all Polioviruses. Methods We analyzed global surveillance data on the detection of serotype 2 Sabin vaccine (Sabin-2) Poliovirus and serotype 2 vaccine–derived Poliovirus (VDPV2, defined as vaccine strains that are at least 0.6% divergent from Sabin-2 Poliovirus in the viral protein 1 genomic region) in stool samples from 495,035 children with acute flaccid paralysis in 118 countries and in 8528 sewage samples from four countries at high risk for transmission; the samples were collected from January 1, 2013, through July 11, 2018. We used Bayesian spatiotemporal smoothing and logistic regression to ide...
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seroprevalence of anti polio antibodies in children from polio high risk area of afghanistan a cross sectional survey 2017
Vaccine, 2018Co-Authors: Imtiaz Hussain, Ondrej Mach, William C. Weldon, Nasir A Hamid, Zaid Bhatti, Deborah Moore, Steven M Oberste, Shahid Khan, Hasan Khan, R W SutterAbstract:Abstract Background Afghanistan is one of the remaining wild-Poliovirus (WPV) endemic countries. We conducted a seroprevalence survey of anti-Poliovirus antibodies in Kandahar Province. Methods Children in two age groups (6–11 months and 36–48 months) visiting Mirwais hospital in Kandahar for minor ailments unrelated to polio were enrolled. After obtaining informed consent, we collected venous blood and conducted neutralization assay to detect Poliovirus neutralizing antibodies. Results A total of 420 children were enrolled and 409/420 (97%) were analysed. Seroprevalence to Poliovirus type 1 (PV1) was 97% and 100% in the younger and older age groups respectively; it was 71% and 91% for PV2; 93% and 98% for PV3. Age group (RR = 3.6, CI 95% = 2.2–5.6) and place of residence outside of Kandahar city (RR = 1.8, CI 95% = 1.2–2.6) were found to be significant risk factors for seronegativity. Conclusions The polio eradication program in Kandahar achieved high serological protection, especially against PV1 and PV3. Lower PV2 seroprevalence in the younger age group is a result of a withdrawal of live type 2 vaccine in 2016 and is expected. Ability to reach all children with Poliovirus vaccines is a pre-requisite for achieving Poliovirus eradication.
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Decay of Sabin inactivated Poliovirus vaccine (IPV)-boosted Poliovirus antibodies.
Trials in vaccinology, 2015Co-Authors: Sonia Resik, Hiromasa Okayasu, Alina Tejeda, Magile Fonseca, Carolyn Sein, Lai Heng Hung, Yenisleidys Martinez, Manuel Quintana Díaz, R W SutterAbstract:We conducted a follow-on study to a phase I randomized, controlled trial conducted in Cuba, 2012, to assess the persistence of Poliovirus antibodies at 21-22 months following booster dose of Sabin-IPV compared to Salk-IPV in adults who had received multiple doses of oral Poliovirus vaccine (OPV) during childhood. In 2012, 60 healthy adult males aged 19-23 were randomized to receive one booster dose, of either Sabin-inactivated Poliovirus vaccine (Sabin-IPV), adjuvanted Sabin-IPV (aSabin-IPV), or conventional Salk-IPV. In the original study, blood was collected at days 0 (before) and 28 (after vaccination), respectively. In this study, an additional blood sample was collected 21-22 months after vaccination, and tested for neutralizing antibodies to Sabin Poliovirus types 1, 2 and 3. We collected sera from 59/60 (98.3%) subjects; 59/59 (100%) remained seropositive to all Poliovirus types, 21-22 months after vaccination. The decay curves were very similar among the study groups. Between day 28 and 21-22 months, there was a reduction of ⩾87.4% in median antibody levels for all Poliovirus types in all study groups, with no significant differences between the study groups. The decay of Poliovirus antibodies over a 21-22-month period was similar regardless of the type of booster vaccine used, suggesting the scientific data of Salk IPV long-term persistence and decay may be broadly applicable to Sabin IPV.
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review and assessment of Poliovirus immunity and transmission synthesis of knowledge gaps and identification of research needs
Risk Analysis, 2013Co-Authors: Radboud Duintjer J Tebbens, Tapani Hovi, R W Sutter, M A Pallansch, Konstantin Chumakov, Neal A Halsey, Philip D Minor, John F Modlin, Peter A Patriarca, Peter F WrightAbstract:With the intensifying global efforts to eradicate wild Polioviruses, policymakers face complex decisions related to achieving eradication and managing posteradication risks. These decisions and the expanding use of inactivated Poliovirus vaccine (IPV) trigger renewed interest in Poliovirus immunity, particularly the role of mucosal immunity in the transmission of Polioviruses. Sustained high population immunity to Poliovirus transmission represents a key prerequisite to eradication, but Poliovirus immunity and transmission remain poorly understood despite decades of studies. In April 2010, the U.S. Centers for Disease Control and Prevention convened an international group of experts on Poliovirus immunology and virology to review the literature relevant for modeling Poliovirus transmission, develop a consensus about related uncertainties, and identify research needs. This article synthesizes the quantitative assessments and research needs identified during the process. Limitations in the evidence from oral Poliovirus vaccine (OPV) challenge studies and other relevant data led to differences in expert assessments, indicating the need for additional data, particularly in several priority areas for research: (1) the ability of IPV-induced immunity to prevent or reduce excretion and affect transmission, (2) the impact of waning immunity on the probability and extent of Poliovirus excretion, (3) the relationship between the concentration of Poliovirus excreted and infectiousness to others in different settings, and (4) the relative role of fecal-oral versus oropharyngeal transmission. This assessment of current knowledge supports the immediate conduct of additional studies to address the gaps.
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Expert review on Poliovirus immunity and transmission.
Risk analysis : an official publication of the Society for Risk Analysis, 2012Co-Authors: Radboud J. Duintjer Tebbens, Tapani Hovi, R W Sutter, M A Pallansch, Konstantin Chumakov, Neal A Halsey, Philip D Minor, John F Modlin, Peter A Patriarca, Peter F WrightAbstract:Successfully managing risks to achieve wild Polioviruses (WPVs) eradication and address the complexities of oral Poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of Poliovirus immunity and transmission. With increased shifting from OPV to inactivated Poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to Poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of Poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to Poliovirus transmission, the relationship between the concentration of Poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data.
Casey D Morrow - One of the best experts on this subject based on the ideXlab platform.
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Immunization of mice with Poliovirus replicons expressing the C-fragment of tetanus toxin protects against lethal challenge with tetanus toxin
Vaccine, 1997Co-Authors: Donna C. Porter, Zina Moldoveanu, Sylvia A. Mcpherson, Jun Wang, Casey D MorrowAbstract:Abstract In this study, we describe the construction of Poliovirus genomes or “replicons” which contain the C fragment gene of tetanus toxin substituted for the Poliovirus P1 capsid. Upon transfection of replicon RNA into cells, we immunoprecipitated a protein corresponding to the C-fragment of tetanus toxin using tetanus-specific antibodies. Using a recombinant vaccinia virus expressing Poliovirus P1 capsid protein (VV-P1) to provide P1 protein, the replicon RNA was encapsidated; stocks of the replicons were generated by passage with VV-P1. The immunogenicity of the replicons was determined by immunization of transgenic mice which are susceptible to Poliovirus. A serum antibody response to Poliovirus and tetanus toxoid was detected in all of the immunized mice. Protection against a lethal dose of tetanus toxin generally correlated with the levels of serum anti-tetanus antibodies. To address whether pre-existing antibodies to Poliovirus limit the effectiveness of the replicon as a vaccine vector, mice were first immunized with the inactivated Poliovirus vaccine followed by immunization with the replicons expressing C-fragment protein. Anti-tetanus antibodies were detected in these mice after a single administration of the replicon; these antibodies conferred protection upon challenge with tetanus toxin. These results demonstrate the potential use of Poliovirus replicons encoding foreign proteins to induce a protective antibody response, even in the presence of pre-existing antibodies to Poliovirus.
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Methods for the Use of Poliovirus Vectors for Gene Delivery
Methods in molecular medicine, 1997Co-Authors: Casey D Morrow, David C. Ansardi, Donna C. PorterAbstract:Poliovirus is a member of the Picornaviridae family of viruses. Characteristic of all members of this family, the Poliovirus genome consrsis of approx 7500 bp of RNA of the plus sense polarity (1,2). Poliovirus is undoubtedly one of the most thoroughly characterized animal viruses. The three-dimensional structure of the entire virion is known (3), an infectious cDNA clone of the Poliovirus genome has been generated (4,5), the entire nucleic acid sequence of Poliovirus has been determined (1), and the cellular receptor that pohovirus uses to enter cells has been cloned and sequenced (6). The availability of a transgenic mouse expressing the Poliovirus receptor has facilitated further description of the pathogenesis of Poliovirus (7,8).
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Characterization of Poliovirus Replicons Encoding Carcinoembryonic Antigen
Cancer research, 1994Co-Authors: David C. Ansardi, Zina Moldoveanu, Donna C. Porter, Sylvia A. Mcpherson, Donald E. Walker, Robert M. Conry, Albert F. Lobuglio, Casey D MorrowAbstract:Abstract Recombinant vaccines hold great promise for the prevention and therapy of infectious diseases and cancer. We have explored the use of Poliovirus as a recombinant vector to deliver genes into cells for the purpose of vaccination. For our studies, we have chosen to express the gene-encoding carcinoembryonic antigen (CEA) using a novel Poliovirus vector. We have constructed a recombinant CEA-Poliovirus replicon in which the CEA gene was substituted for the Poliovirus capsid gene. Following in vitro transcription, the RNA was transfected into cells to demonstrate CEA expression. We found that a genome in which the region encoding the signal sequence of the CEA protein (amino acids 1–34) was removed was replication competent (i.e., referred to as a replicon). We encapsidated the CEA-Poliovirus replicon by transfecting this RNA into cells previously infected with a recombinant vaccinia virus (VV-P1) which expresses the Poliovirus capsid protein (P1). Serial passage in the presence of VV-P1 resulted in the generation of stocks of these encapsidated replicons. Infection of cells with the encapsidated replicon containing the CEA-Poliovirus genome resulted in expression of the CEA protein. To test immunogenicity, mice susceptible to Poliovirus were given three doses of the encapsidated replicons via the i.m. route. By the third administration, a CEA-specific antibody response was detected. Potential future use of the Poliovirus replicon system as both a parenteral and oral vaccine vector is discussed.
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Complementation of a Poliovirus defective genome by a recombinant vaccinia virus which provides Poliovirus P1 capsid precursor in trans.
Journal of virology, 1993Co-Authors: David C. Ansardi, Donna C. Porter, Casey D MorrowAbstract:Defective interfering (DI) RNA genomes of Poliovirus which contain in-frame deletions in the P1 capsid protein-encoding region have been described. DI genomes are capable of replication and can be encapsidated by capsid proteins provided in trans from wild-type Poliovirus. In this report, we demonstrate that a previously described Poliovirus DI genome (K. Hagino-Yamagishi and A. Nomoto, J. Virol. 63:5386-5392, 1989) can be complemented by a recombinant vaccinia virus, VVP1 (D. C. Ansardi, D. C. Porter, and C. D. Morrow, J. Virol. 65:2088-2092, 1991), which expresses the Poliovirus capsid precursor polyprotein, P1. Stocks of defective Polioviruses were generated by transfecting in vitro-transcribed defective genome RNA derived from plasmid pSM1(T7)1 into HeLa cells infected with VVP1 and were maintained by serial passage in the presence of VVP1. Encapsidation of the defective Poliovirus genome was demonstrated by characterizing Poliovirus-specific protein expression in cells infected with preparations of defective Poliovirus and by Northern (RNA) blot analysis of Poliovirus-specific RNA incorporated into defective Poliovirus particles. Cells infected with preparations of defective Poliovirus expressed Poliovirus protein 3CD but did not express capsid proteins derived from a full-length P1 precursor. Poliovirus-specific RNA encapsidated in viral particles generated in cells coinfected with VVP1 and defective Poliovirus migrated slightly faster on formaldehyde-agarose gels than wild-type Poliovirus RNA, demonstrating maintenance of the genomic deletion. By metabolic radiolabeling with [35S]methionine-cysteine, the defective Poliovirus particles were shown to contain appropriate mature-virion proteins. This is the first report of the generation of a pure population of defective Polioviruses free of contaminating wild-type Poliovirus. We demonstrate the use of this recombinant vaccinia virus-defective Poliovirus genome complementation system for studying the effects of a defined mutation in the P1 capsid precursor on virus assembly. Following removal of residual VVP1 from defective Poliovirus preparations, processing and assembly of Poliovirus capsid proteins derived from a nonmyristylated P1 precursor expressed by a recombinant vaccinia virus, VVP1 myr- (D. C. Ansardi, D. C. Porter, and C. D. Morrow, J. Virol. 66:4556-4563, 1992), in cells coinfected with defective Poliovirus were analyzed. Capsid proteins generated from nonmyristylated P1 did not assemble detectable levels of mature virions but did assemble, at low levels, into empty capsids.(ABSTRACT TRUNCATED AT 400 WORDS)
M A Pallansch - One of the best experts on this subject based on the ideXlab platform.
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Standardized Methods for Detection of Poliovirus Antibodies.
Methods in molecular biology (Clifton N.J.), 2016Co-Authors: William C. Weldon, M. Steven Oberste, M A PallanschAbstract:Testing for neutralizing antibodies against Polioviruses has been an established gold standard for assessing individual protection from disease, population immunity, vaccine efficacy studies, and other vaccine clinical trials. Detecting Poliovirus specific IgM and IgA in sera and mucosal specimens has been proposed for evaluating the status of population mucosal immunity. More recently, there has been a renewed interest in using dried blood spot cards as a medium for sample collection to enhance surveillance of Poliovirus immunity. Here, we describe the modified Poliovirus microneutralization assay, Poliovirus capture IgM and IgA ELISA assays, and dried blood spot polio serology procedures for the detection of antibodies against Poliovirus serotypes 1, 2, and 3.
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an economic analysis of Poliovirus risk management policy options for 2013 2052
BMC Infectious Diseases, 2015Co-Authors: Radboud Duintjer J Tebbens, M A Pallansch, Stephen L Cochi, Steven G F Wassilak, Kimberly M. ThompsonAbstract:The Global Polio Eradication Initiative plans for coordinated cessation of oral Poliovirus vaccine (OPV) after interrupting all wild Poliovirus (WPV) transmission, but many questions remain related to long-term Poliovirus risk management policies. We used an integrated dynamic Poliovirus transmission and stochastic risk model to simulate possible futures and estimate the health and economic outcomes of maintaining the 2013 status quo of continued OPV use in most developing countries compared with OPV cessation policies with various assumptions about global inactivated Poliovirus vaccine (IPV) adoption. Continued OPV use after global WPV eradication leads to continued high costs and/or high cases. Global OPV cessation comes with a high probability of at least one outbreak, which aggressive outbreak response can successfully control in most instances. A low but non-zero probability exists of uncontrolled outbreaks following a Poliovirus reintroduction long after OPV cessation in a population in which IPV-alone cannot prevent Poliovirus transmission. We estimate global incremental net benefits during 2013–2052 of approximately $16 billion (US$2013) for OPV cessation with at least one IPV routine immunization dose in all countries until 2024 compared to continued OPV use, although significant uncertainty remains associated with the frequency of exportations between populations and the implementation of long term risk management policies. Global OPV cessation offers the possibility of large future health and economic benefits compared to continued OPV use. Long-term Poliovirus risk management interventions matter (e.g., IPV use duration, outbreak response, containment, continued surveillance, stockpile size and contents, vaccine production site requirements, potential antiviral drugs, and potential safer vaccines) and require careful consideration. Risk management activities can help to ensure a low risk of uncontrolled outbreaks and preserve or further increase the positive net benefits of OPV cessation. Important uncertainties will require more research, including characterizing immunodeficient long-term Poliovirus excretor risks, containment risks, and the kinetics of outbreaks and response in an unprecedented world without widespread live Poliovirus exposure.
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Mechanism of Poliovirus Eradication
Molecular Biology of Picornavirus, 2014Co-Authors: Olen M. Kew, M A PallanschAbstract:Systematic international efforts to eradicate polio from the developing world began in the Americas in 1985, when the Pan American Health Organization (PAHO) declared a target date of 1990 for the eradication of polio throughout the Americas. Surveillance for wild Polioviruses has two arms: (i) acute flaccid paralysis (AFP) case investigations and (ii) virologic studies of Polioviruses obtained from clinical specimens. AFP surveillance by itself is neither highly specific nor highly sensitive for detecting individual wild Poliovirus infections. Poliovirus eradication has achieved the elimination of individual lineages (equivalent to chains of transmission), different genotypes (groups of related lineages sharing >85% nucleotide sequence identity), and probably wild Poliovirus type 2. Polio cases associated with these importations have revealed pockets of unimmunized children in the new host areas, prompting local immunization responses. However, by far the most effective response is to eliminate the source reservoirs. Various supplementary approaches are implemented to monitor ongoing laboratory performance. A serious challenge to the integrity of Poliovirus surveillance data is the occurrence of Poliovirus contamination of cultures. Recently, polio outbreaks associated with circulating vaccine-derived Poliovirus (cVDPV) have been recognized in three different parts of the world. The occurrence of iVDPVs and cVDPVs appears to be rare. Moreover, most chronic Poliovirus excretors in developed countries spontaneously stop shedding or die of complications from their immunodeficiency. As an increasing number of highly developed countries have switched to inactivated polio vaccine (IPV), the chances for the occurrence of new iVDPV infections have decreased.
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review and assessment of Poliovirus immunity and transmission synthesis of knowledge gaps and identification of research needs
Risk Analysis, 2013Co-Authors: Radboud Duintjer J Tebbens, Tapani Hovi, R W Sutter, M A Pallansch, Konstantin Chumakov, Neal A Halsey, Philip D Minor, John F Modlin, Peter A Patriarca, Peter F WrightAbstract:With the intensifying global efforts to eradicate wild Polioviruses, policymakers face complex decisions related to achieving eradication and managing posteradication risks. These decisions and the expanding use of inactivated Poliovirus vaccine (IPV) trigger renewed interest in Poliovirus immunity, particularly the role of mucosal immunity in the transmission of Polioviruses. Sustained high population immunity to Poliovirus transmission represents a key prerequisite to eradication, but Poliovirus immunity and transmission remain poorly understood despite decades of studies. In April 2010, the U.S. Centers for Disease Control and Prevention convened an international group of experts on Poliovirus immunology and virology to review the literature relevant for modeling Poliovirus transmission, develop a consensus about related uncertainties, and identify research needs. This article synthesizes the quantitative assessments and research needs identified during the process. Limitations in the evidence from oral Poliovirus vaccine (OPV) challenge studies and other relevant data led to differences in expert assessments, indicating the need for additional data, particularly in several priority areas for research: (1) the ability of IPV-induced immunity to prevent or reduce excretion and affect transmission, (2) the impact of waning immunity on the probability and extent of Poliovirus excretion, (3) the relationship between the concentration of Poliovirus excreted and infectiousness to others in different settings, and (4) the relative role of fecal-oral versus oropharyngeal transmission. This assessment of current knowledge supports the immediate conduct of additional studies to address the gaps.
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Expert review on Poliovirus immunity and transmission.
Risk analysis : an official publication of the Society for Risk Analysis, 2012Co-Authors: Radboud J. Duintjer Tebbens, Tapani Hovi, R W Sutter, M A Pallansch, Konstantin Chumakov, Neal A Halsey, Philip D Minor, John F Modlin, Peter A Patriarca, Peter F WrightAbstract:Successfully managing risks to achieve wild Polioviruses (WPVs) eradication and address the complexities of oral Poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of Poliovirus immunity and transmission. With increased shifting from OPV to inactivated Poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to Poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of Poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to Poliovirus transmission, the relationship between the concentration of Poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data.
