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Sample records for sabin live poliovirus

  1. The Sabin live poliovirus vaccination trials in the USSR, 1959.

    PubMed Central

    Horstmann, D. M.

    1991-01-01

    Widespread use of the Sabin live attenuated poliovirus vaccine has had tremendous impact on the disease worldwide, virtually eliminating it from a number of countries, including the United States. Early proof of its safety and effectiveness was presented in 1959 by Russian investigators, who had staged massive trials in the USSR, involving millions of children. Their positive results were at first viewed in the United States and elsewhere with some skepticism, but the World Health Organization favored proceeding with large-scale trials, and responded to the claims made by Russian scientists by sending a representative to the USSR to review in detail the design and execution of the vaccine programs and the reliability of their results. The report that followed was a positive endorsement of the findings and contributed to the acceptance of the Sabin vaccine in the United States, where it has been the polio vaccine of choice since the mid-1960s. PMID:1814062

  2. Sabin Vaccine Reversion in the Field: a Comprehensive Analysis of Sabin-Like Poliovirus Isolates in Nigeria

    PubMed Central

    Chang, Stewart; Iber, Jane; Zhao, Kun; Adeniji, Johnson A.; Bukbuk, David; Baba, Marycelin; Behrend, Matthew; Burns, Cara C.; Oberste, M. Steven

    2015-01-01

    ABSTRACT To assess the dynamics of genetic reversion of live poliovirus vaccine in humans, we studied molecular evolution in Sabin-like poliovirus isolates from Nigerian acute flaccid paralysis cases obtained from routine surveillance. We employed a novel modeling approach to infer substitution and recombination rates from whole-genome sequences and information about poliovirus infection dynamics and the individual vaccination history. We confirmed observations from a recent vaccine trial that VP1 substitution rates are increased for Sabin-like isolates relative to the rate for the wild type due to increased nonsynonymous substitution rates. We also inferred substitution rates for attenuating nucleotides and confirmed that reversion can occur in days to weeks after vaccination. We combine our observations for Sabin-like virus evolution with the molecular clock for VP1 of circulating wild-type strains to infer that the mean time from the initiating vaccine dose to the earliest detection of circulating vaccine-derived poliovirus (cVDPV) is 300 days for Sabin-like virus type 1, 210 days for Sabin-like virus type 2, and 390 days for Sabin-like virus type 3. Phylogenetic relationships indicated transient local transmission of Sabin-like virus type 3 and, possibly, Sabin-like virus type 1 during periods of low wild polio incidence. Comparison of Sabin-like virus recombinants with known Nigerian vaccine-derived poliovirus recombinants shows that while recombination with non-Sabin enteroviruses is associated with cVDPV, the recombination rates are similar for Sabin isolate-Sabin isolate and Sabin isolate–non-Sabin enterovirus recombination after accounting for the time from dosing to the time of detection. Our study provides a comprehensive picture of the evolutionary dynamics of the oral polio vaccine in the field. IMPORTANCE The global polio eradication effort has completed its 26th year. Despite success in eliminating wild poliovirus from most of the world, polio

  3. Development and introduction of inactivated poliovirus vaccines derived from Sabin strains in Japan.

    PubMed

    Shimizu, Hiroyuki

    2016-04-01

    During the endgame of global polio eradication, the universal introduction of inactivated poliovirus vaccines is urgently required to reduce the risk of vaccine-associated paralytic poliomyelitis and polio outbreaks due to wild and vaccine-derived polioviruses. In particular, the development of inactivated poliovirus vaccines (IPVs) derived from the attenuated Sabin strains is considered to be a highly favorable option for the production of novel IPV that reduce the risk of facility-acquired transmission of poliovirus to the communities. In Japan, Sabin-derived IPVs (sIPVs) have been developed and introduced for routine immunization in November 2012. They are the first licensed sIPVs in the world. Consequently, trivalent oral poliovirus vaccine was used for polio control in Japan for more than half a century but has now been removed from the list of vaccines licensed for routine immunization. This paper reviews the development, introduction, characterization, and global status of IPV derived from attenuated Sabin strains. PMID:25448090

  4. Hematopoietic Cancer Cell Lines Can Support Replication of Sabin Poliovirus Type 1

    PubMed Central

    van Eikenhorst, Gerco; de Gruijl, Tanja D.; van der Pol, Leo A.; Bakker, Wilfried A. M.

    2015-01-01

    Viral vaccines can be produced in adherent or in suspension cells. The objective of this work was to screen human suspension cell lines for the capacity to support viral replication. As the first step, it was investigated whether poliovirus can replicate in such cell lines. Sabin poliovirus type 1 was serially passaged on five human cell lines, HL60, K562, KG1, THP-1, and U937. Sabin type 1 was capable of efficiently replicating in three cell lines (K562, KG1, and U937), yielding high viral titers after replication. Expression of CD155, the poliovirus receptor, did not explain susceptibility to replication, since all cell lines expressed CD155. Furthermore, we showed that passaged virus replicated more efficiently than parental virus in KG1 cells, yielding higher virus titers in the supernatant early after infection. Infection of cell lines at an MOI of 0.01 resulted in high viral titers in the supernatant at day 4. Infection of K562 with passaged Sabin type 1 in a bioreactor system yielded high viral titers in the supernatant. Altogether, these data suggest that K562, KG1, and U937 cell lines are useful for propagation of poliovirus. PMID:25815312

  5. Innovative IPV from attenuated Sabin poliovirus or newly designed alternative seed strains.

    PubMed

    Hamidi, Ahd; Bakker, Wilfried A M

    2012-11-01

    This article gives an overview of the patent literature related to innovative inactivated polio vaccine (i-IPV) based on using Sabin poliovirus strains and newly developed alternative recombinant poliovirus strains. This innovative approach for IPV manufacturing is considered to attribute to the requirement for affordable IPV in the post-polio-eradication era, which is on the horizon. Although IPV is a well-established vaccine, the number of patent applications in this field was seen to have significantly increased in the past decade. Currently, regular IPV appears to be too expensive for universal use. Future affordability may be achieved by using alternative cell lines, alternative virus seed strains, improved and optimized processes, dose sparing, or the use of adjuvants. A relatively short-term option to achieve cost-price reduction is to work on regular IPV, using wild-type poliovirus strains, or on Sabin-IPV, based on using attenuated poliovirus strains. This price reduction can be achieved by introducing efficiency in processing. There are also multiple opportunities to work on dose sparing, for example, by using adjuvants or fractional doses. Renewed interest in this field was clearly reflected in the number and diversity of patent applications. In a later stage, several innovative approaches may become even more attractive, for example the use of recombinant virus strains or even a totally synthetic vaccine. Currently, such work is mainly carried out by research institutes and universities and therefore clinical data are not available. PMID:24236927

  6. Stool screening of Syrian refugees and asylum seekers in Germany, 2013/2014: Identification of Sabin like polioviruses.

    PubMed

    Böttcher, Sindy; Neubauer, Katrin; Baillot, Armin; Rieder, Gabriele; Adam, Maja; Diedrich, Sabine

    2015-10-01

    Germany is a partner of the Global Polio Eradication Initiative. Assurance of polio free status is based on enterovirus surveillance, which focuses on patients with signs of acute flaccid paralysis or aseptic meningitis/encephalitis, representing the key symptoms of poliovirus infection. In response to the wild poliovirus outbreak in Syria 2013 and high number of refugees coming from Syria to Germany, stool samples from 629 Syrian refugees/asylum seekers aged <3 years were screened for wild poliovirus between November 2013 and April 2014. Ninety-three samples (14.8%) were positive in an enterovirus specific PCR. Of these, 12 contained Sabin-like polioviruses. The remaining 81 samples were characterized as non-polio enteroviruses representing several members of groups A-C as well as rhinovirus. Wild-type poliovirus was not detected via stool screening involving molecular and virological methods, indicating a very low risk for the importation by Syrian refugees and asylum seekers at that time. PMID:26321005

  7. Sporadic Isolation of Sabin-Like Polioviruses and High-Level Detection of Non-Polio Enteroviruses during Sewage Surveillance in Seven Italian Cities, after Several Years of Inactivated Poliovirus Vaccination

    PubMed Central

    Battistone, A.; Buttinelli, G.; Fiore, S.; Amato, C.; Bonomo, P.; Patti, A. M.; Vulcano, A.; Barbi, M.; Binda, S.; Pellegrinelli, L.; Tanzi, M. L.; Affanni, P.; Castiglia, P.; Germinario, C.; Mercurio, P.; Cicala, A.; Triassi, M.; Pennino, F.

    2014-01-01

    Sewage surveillance in seven Italian cities between 2005 and 2008, after the introduction of inactivated poliovirus vaccination (IPV) in 2002, showed rare polioviruses, none that were wild-type or circulating vaccine-derived poliovirus (cVDPV), and many other enteroviruses among 1,392 samples analyzed. Two of five polioviruses (PV) detected were Sabin-like PV2 and three PV3, based on enzyme-linked immunosorbent assay (ELISA) and PCR results. Neurovirulence-related mutations were found in the 5′ noncoding region (5′NCR) of all strains and, for a PV2, also in VP1 region 143 (Ile > Thr). Intertypic recombination in the 3D region was detected in a second PV2 (Sabin 2/Sabin 1) and a PV3 (Sabin 3/Sabin 2). The low mutation rate in VP1 for all PVs suggests limited interhuman virus passages, consistent with efficient polio immunization in Italy. Nonetheless, these findings highlight the risk of wild or Sabin poliovirus reintroduction from abroad. Non-polio enteroviruses (NPEVs) were detected, 448 of which were coxsackievirus B (CVB) and 294 of which were echoviruses (Echo). Fifty-six NPEVs failing serological typing were characterized by sequencing the VP1 region (nucleotides [nt] 2628 to 2976). A total of 448 CVB and 294 Echo strains were identified; among those strains, CVB2, CVB5, and Echo 11 predominated. Environmental CVB5 and CVB2 strains from this study showed high sequence identity with GenBank global strains. The high similarity between environmental NPEVs and clinical strains from the same areas of Italy and the same periods indicates that environmental strains reflect the viruses circulating in the population and highlights the potential risk of inefficient wastewater treatments. This study confirmed that sewage surveillance can be more sensitive than acute flaccid paralysis (AFP) surveillance in monitoring silent poliovirus circulation in the population as well as the suitability of molecular approaches to enterovirus typing. PMID:24814793

  8. Sporadic isolation of sabin-like polioviruses and high-level detection of non-polio enteroviruses during sewage surveillance in seven Italian cities, after several years of inactivated poliovirus vaccination.

    PubMed

    Battistone, A; Buttinelli, G; Fiore, S; Amato, C; Bonomo, P; Patti, A M; Vulcano, A; Barbi, M; Binda, S; Pellegrinelli, L; Tanzi, M L; Affanni, P; Castiglia, P; Germinario, C; Mercurio, P; Cicala, A; Triassi, M; Pennino, F; Fiore, L

    2014-08-01

    Sewage surveillance in seven Italian cities between 2005 and 2008, after the introduction of inactivated poliovirus vaccination (IPV) in 2002, showed rare polioviruses, none that were wild-type or circulating vaccine-derived poliovirus (cVDPV), and many other enteroviruses among 1,392 samples analyzed. Two of five polioviruses (PV) detected were Sabin-like PV2 and three PV3, based on enzyme-linked immunosorbent assay (ELISA) and PCR results. Neurovirulence-related mutations were found in the 5'noncoding region (5'NCR) of all strains and, for a PV2, also in VP1 region 143 (Ile>Thr). Intertypic recombination in the 3D region was detected in a second PV2 (Sabin 2/Sabin 1) and a PV3 (Sabin 3/Sabin 2). The low mutation rate in VP1 for all PVs suggests limited interhuman virus passages, consistent with efficient polio immunization in Italy. Nonetheless, these findings highlight the risk of wild or Sabin poliovirus reintroduction from abroad. Non-polio enteroviruses (NPEVs) were detected, 448 of which were coxsackievirus B (CVB) and 294 of which were echoviruses (Echo). Fifty-six NPEVs failing serological typing were characterized by sequencing the VP1 region (nucleotides [nt] 2628 to 2976). A total of 448 CVB and 294 Echo strains were identified; among those strains, CVB2, CVB5, and Echo 11 predominated. Environmental CVB5 and CVB2 strains from this study showed high sequence identity with GenBank global strains. The high similarity between environmental NPEVs and clinical strains from the same areas of Italy and the same periods indicates that environmental strains reflect the viruses circulating in the population and highlights the potential risk of inefficient wastewater treatments. This study confirmed that sewage surveillance can be more sensitive than acute flaccid paralysis (AFP) surveillance in monitoring silent poliovirus circulation in the population as well as the suitability of molecular approaches to enterovirus typing. PMID:24814793

  9. Comparative in vivo efficiencies of hand-washing agents against hepatitis A virus (HM-175) and poliovirus type 1 (Sabin).

    PubMed Central

    Mbithi, J N; Springthorpe, V S; Sattar, S A

    1993-01-01

    The abilities of 10 hygienic hand-washing agents and tap water (containing approximately 0.5 ppm of free chlorine) to eliminate strain HM-175 of hepatitis A virus (HAV) and poliovirus (PV) type 1 (Sabin) were compared by using finger pad and whole-hand protocols with three adult volunteers. A mixture of the two viruses was prepared in a 10% suspension of feces, and 10 microliters of the mixture was placed on each finger pad. The inoculum was allowed to dry for 20 min, and the contaminated area was exposed to a hand-washing agent for 10 s, rinsed in tap water, and dried with a paper towel. In the whole-hand protocol, the hands were contaminated with 0.5 ml of the virus mixture, exposed for 10 s to a hand-washing agent, washed, and dried as described above. Tryptose phosphate broth was used to elute any virus remaining on the finger pads or hands. One part of the eluate was assayed directly for PV with FRhK-4 cells, while the other part was first treated with a PV-neutralizing serum and then assayed for HAV with the same cell line. The results are reported as mean percentages of reduction in PFU compared with the amount of infectious virus detectable after initial drying.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8250567

  10. Modeling population immunity to support efforts to end the transmission of live polioviruses.

    PubMed

    Thompson, Kimberly M; Pallansch, Mark A; Tebbens, Radboud J Duintjer; Wassilak, Steve G; Cochi, Stephen L

    2013-04-01

    Eradication of wild poliovirus (WPV) types 1 and 3, prevention and cessation of circulating vaccine-derived polioviruses, and achievement and maintenance of a world free of paralytic polio cases requires active risk management by focusing on population immunity and coordinated cessation of oral poliovirus vaccine (OPV). We suggest the need for a complementary and different conceptual approach to achieve eradication compared to the current case-based approach using surveillance for acute flaccid paralysis (AFP) to identify symptomatic poliovirus infections. Specifically, we describe a modeling approach to characterize overall population immunity to poliovirus transmission. The approach deals with the realities that exposure to live polioviruses (e.g., WPV, OPV) and/or vaccination with inactivated poliovirus vaccine provides protection from paralytic polio (i.e., disease), but does not eliminate the potential for reinfection or asymptomatic participation in poliovirus transmission, which may increase with time because of waning immunity. The AFP surveillance system provides evidence of symptomatic poliovirus infections detected, which indicate immunity gaps after outbreaks occur, and this system represents an appropriate focus for controlling disease outbreaks. We describe a conceptual dynamic model to characterize population immunity to poliovirus transmission that helps identify risks created by immunity gaps before outbreaks occur, which provides an opportunity for national and global policymakers to manage the risk of poliovirus and prevent outbreaks before they occur. We suggest that dynamically modeling risk represents an essential tool as the number of cases approaches zero. PMID:22985171

  11. Pioneering figures in medicine: Albert Bruce Sabin--inventor of the oral polio vaccine.

    PubMed

    Smith, Derek R; Leggat, Peter A

    2005-01-01

    Over ten years after his death, the Sabin oral vaccine continues its profound influence on public health throughout the world. The annual incidence of polio has fallen dramatically since its introduction, with more than 300,000 lives being spared each year and an annual global saving in excess of 1 billion US dollars. In many ways, the development of an effective oral vaccine and its subsequent regulation by the World Health Organization can serve as a model for medical researchers. Our review describes the contribution of Albert Sabin as a medical researcher, and how his vaccine had a profound impact on the global reduction of polio infections. As many different factors influenced health-care last century, we describe Sabin's involvement with respect to prevailing scientific paradigms and public health issues of the time. Our paper also outlines the basic epidemiology of poliovirus and the historical development of an effective vaccine, both with and without Albert Sabin. PMID:16422178

  12. Current status of poliovirus infections.

    PubMed Central

    Melnick, J L

    1996-01-01

    Two scientists who played leading roles in the conquest of poliomyelitis died recently. In 1954, Jonas Salk provided the first licensed polio vaccine, the formalin (and heat)-inactivated virus. Albert Sabin gave us the attenuated live virus vaccine, which was licensed in 1962. This paper takes the reader through the history of the disease, including its pathogenesis, epidemiology, vaccines, and future directions. The emphasis is on vaccines, for it seems that with proper vaccination the number of new cases is falling dramatically. It is hoped that by the year 2000, we will accomplish the goal of the World Health Organization of "a world without polio." Then, because there is no animal reservoir, we can seriously discuss when and how to eliminate the need for vaccination and ultimately destroy our stocks of poliovirus. PMID:8809461

  13. Current status of poliovirus infections.

    PubMed

    Melnick, J L

    1996-07-01

    Two scientists who played leading roles in the conquest of poliomyelitis died recently. In 1954, Jonas Salk provided the first licensed polio vaccine, the formalin (and heat)-inactivated virus. Albert Sabin gave us the attenuated live virus vaccine, which was licensed in 1962. This paper takes the reader through the history of the disease, including its pathogenesis, epidemiology, vaccines, and future directions. The emphasis is on vaccines, for it seems that with proper vaccination the number of new cases is falling dramatically. It is hoped that by the year 2000, we will accomplish the goal of the World Health Organization of "a world without polio." Then, because there is no animal reservoir, we can seriously discuss when and how to eliminate the need for vaccination and ultimately destroy our stocks of poliovirus. PMID:8809461

  14. Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase

    PubMed Central

    Liu, Xinran; Musser, Derek M.; Lee, Cheri A.; Yang, Xiaorong; Arnold, Jamie J.; Cameron, Craig E.; Boehr, David D.

    2015-01-01

    The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation. PMID:26516899

  15. Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase.

    PubMed

    Liu, Xinran; Musser, Derek M; Lee, Cheri A; Yang, Xiaorong; Arnold, Jamie J; Cameron, Craig E; Boehr, David D

    2015-10-01

    The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation. PMID:26516899

  16. Multiplex PCR Method for Identifying Recombinant Vaccine-Related Polioviruses

    PubMed Central

    Kilpatrick, David R.; Ching, Karen; Iber, Jane; Campagnoli, Ray; Freeman, Christopher J.; Mishrik, Nada; Liu, Hong-Mei; Pallansch, Mark A.; Kew, Olen M.

    2004-01-01

    The recent discovery of recombinant circulating vaccine-derived poliovirus (recombinant cVDPV) has highlighted the need for enhanced global poliovirus surveillance to assure timely detection of any future cVDPV outbreaks. Six pairs of Sabin strain-specific recombinant primers were designed to permit rapid screening for VDPV recombinants by PCR. PMID:15365031

  17. Sabin-to-Mahoney Transition Model of Quasispecies Replication

    SciTech Connect

    2009-05-31

    Qspp is an agent-based stochastic simulation model of the Poliovirus Sabin-to-Mahoney transition. This code simulates a cell-to-cell model of Poliovirus replication. The model tracks genotypes (virus genomes) as they are replicated in cells, and as the cells burst and release particles into the medium of a culture dish. An inoculum is then taken from the pool of virions and is used to inoculate cells on a new dish. This process repeats. The Sabin genotype comprises the initial inoculum. Nucleotide positions that match the Sabin1 (vaccine strain) and Mahoney (wild type) genotypes, as well as the neurovirulent phenotype (from the literature) are enumerated as constants.

  18. PER.C6(®) cells as a serum-free suspension cell platform for the production of high titer poliovirus: a potential low cost of goods option for world supply of inactivated poliovirus vaccine.

    PubMed

    Sanders, Barbara P; Edo-Matas, Diana; Custers, Jerome H H V; Koldijk, Martin H; Klaren, Vincent; Turk, Marije; Luitjens, Alfred; Bakker, Wilfried A M; Uytdehaag, Fons; Goudsmit, Jaap; Lewis, John A; Schuitemaker, Hanneke

    2013-01-21

    There are two highly efficacious poliovirus vaccines: Sabin's live-attenuated oral polio vaccine (OPV) and Salk's inactivated polio vaccine (IPV). OPV can be made at low costs per dose and is easily administrated. However, the major drawback is the frequent reversion of the OPV vaccine strains to virulent poliovirus strains which can result in Vaccine Associated Paralytic Poliomyelitis (VAPP) in vaccinees. Furthermore, some OPV revertants with high transmissibility can circulate in the population as circulating Vaccine Derived Polioviruses (cVDPVs). IPV does not convey VAPP and cVDPVs but the high costs per dose and insufficient supply have rendered IPV an unfavorable option for low and middle-income countries. Here, we explored whether the human PER.C6(®) cell-line, which has the unique capability to grow at high density in suspension, under serum-free conditions, could be used as a platform for high yield production of poliovirus. PER.C6(®) cells supported replication of all three poliovirus serotypes with virus titers ranging from 9.4 log(10) to 11.1 log(10)TCID(50)/ml irrespective of the volume scale (10 ml in shaker flasks to 2 L in bioreactors). This production yield was 10-30 fold higher than in Vero cell cultures performed here, and even 100-fold higher than what has been reported for Vero cell cultures in literature [38]. In agreement, the D-antigen content per volume PER.C6(®)-derived poliovirus was on average 30-fold higher than Vero-derived poliovirus. Interestingly, PER.C6(®) cells produced on average 2.5-fold more D-antigen units per cell than Vero cells. Based on our findings, we are exploring PER.C6(®) as an interesting platform for large-scale production of poliovirus at low costs, potentially providing the basis for global supply of an affordable IPV. PMID:23123018

  19. Development of a multiplex RT-PCR assay for the identification of recombination types at different genomic regions of vaccine-derived polioviruses.

    PubMed

    Dimitriou, T G; Kyriakopoulou, Z; Tsakogiannis, D; Fikatas, A; Gartzonika, C; Levidiotou-Stefanou, S; Markoulatos, P

    2016-08-01

    Polioviruses (PVs) are the causal agents of acute paralytic poliomyelitis. Since the 1960s, poliomyelitis has been effectively controlled by the use of two vaccines containing all three serotypes of PVs, the inactivated poliovirus vaccine and the live attenuated oral poliovirus vaccine (OPV). Despite the success of OPV in polio eradication programme, a significant disadvantage was revealed: the emergence of vaccine-associated paralytic poliomyelitis (VAPP). VAPP is the result of accumulated mutations and putative recombination events located at the genome of attenuated vaccine Sabin strains. In the present study, ten Sabin isolates derived from OPV vaccinees and environmental samples were studied in order to identify recombination types located from VP1 to 3D genomic regions of virus genome. The experimental procedure that was followed was virus RNA extraction, reverse transcription to convert the virus genome into cDNA, PCR and multiplex-PCR using specific designed primers able to localize and identify each recombination following agarose gel electrophoresis. This multiplex RT-PCR assay allows for the immediate detection and identification of multiple recombination types located at the viral genome of OPV derivatives. After the eradication of wild PVs, the remaining sources of poliovirus infection worldwide would be the OPV derivatives. As a consequence, the immediate detection and molecular characterization of recombinant derivatives are important to avoid epidemics due to the circulation of neurovirulent viral strains. PMID:27098645

  20. Sabin-to-Mahoney Transition Model of Quasispecies Replication

    Energy Science and Technology Software Center (ESTSC)

    2009-05-31

    Qspp is an agent-based stochastic simulation model of the Poliovirus Sabin-to-Mahoney transition. This code simulates a cell-to-cell model of Poliovirus replication. The model tracks genotypes (virus genomes) as they are replicated in cells, and as the cells burst and release particles into the medium of a culture dish. An inoculum is then taken from the pool of virions and is used to inoculate cells on a new dish. This process repeats. The Sabin genotype comprisesmore » the initial inoculum. Nucleotide positions that match the Sabin1 (vaccine strain) and Mahoney (wild type) genotypes, as well as the neurovirulent phenotype (from the literature) are enumerated as constants.« less

  1. Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses.

    PubMed

    Muller, David A; Pearson, Frances E; Fernando, Germain J P; Agyei-Yeboah, Christiana; Owens, Nick S; Corrie, Simon R; Crichton, Michael L; Wei, Jonathan C J; Weldon, William C; Oberste, M Steven; Young, Paul R; Kendall, Mark A F

    2016-01-01

    Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns. PMID:26911254

  2. Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses

    PubMed Central

    Muller, David A.; Pearson, Frances E.; Fernando, Germain J.P.; Agyei-Yeboah, Christiana; Owens, Nick S.; Corrie, Simon R.; Crichton, Michael L.; Wei, Jonathan C.J.; Weldon, William C.; Oberste, M. Steven; Young, Paul R.; Kendall, Mark A. F.

    2016-01-01

    Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns. PMID:26911254

  3. Molecular Properties of Poliovirus Isolates: Nucleotide Sequence Analysis, Typing by PCR and Real-Time RT-PCR.

    PubMed

    Burns, Cara C; Kilpatrick, David R; Iber, Jane C; Chen, Qi; Kew, Olen M

    2016-01-01

    Virologic surveillance is essential to the success of the World Health Organization initiative to eradicate poliomyelitis. Molecular methods have been used to detect polioviruses in tissue culture isolates derived from stool samples obtained through surveillance for acute flaccid paralysis. This chapter describes the use of realtime PCR assays to identify and serotype polioviruses. In particular, a degenerate, inosine-containing, panpoliovirus (panPV) PCR primer set is used to distinguish polioviruses from NPEVs. The high degree of nucleotide sequence diversity among polioviruses presents a challenge to the systematic design of nucleic acid-based reagents. To accommodate the wide variability and rapid evolution of poliovirus genomes, degenerate codon positions on the template were matched to mixed-base or deoxyinosine residues on both the primers and the TaqMan™ probes. Additional assays distinguish between Sabin vaccine strains and non-Sabin strains. This chapter also describes the use of generic poliovirus specific primers, along with degenerate and inosine-containing primers, for routine VP1 sequencing of poliovirus isolates. These primers, along with nondegenerate serotype-specific Sabin primers, can also be used to sequence individual polioviruses in mixtures. PMID:26983735

  4. Notes from the Field: Circulating Vaccine-Derived Poliovirus Outbreaks - Five Countries, 2014-2015.

    PubMed

    Morales, Michelle; Nnadi, Chimeremma D; Tangermann, Rudolf H; Wassilak, Steven G F

    2016-02-12

    In 2015, wild poliovirus (WPV) transmission was identified in only Afghanistan and Pakistan (1). The widespread use of live, attenuated oral poliovirus vaccine (OPV) has been key in polio eradication efforts. However, OPV use, particularly in areas with low vaccination coverage, is associated with the low risk for emergence of vaccine-derived polioviruses (VDPV), which can cause paralysis (2). VDPVs vary genetically from vaccine viruses and can cause outbreaks in areas with low vaccination coverage. Circulating VDPVs (cVDPVs) are VDPVs in confirmed outbreaks. Single VDPVs for which the origin cannot be determined are classified as ambiguous (aVDPVs), which can also cause paralysis. Among the three types of WPV, type 2 has been declared to be eradicated. More than 90% of cVDPV cases have been caused by type 2 cVDPVs (cVDPV2). Therefore, in April 2016, all OPV-using countries of the world are discontinuing use of type 2 Sabin vaccine by simultaneously switching from trivalent OPV (types 1, 2, and 3) to bivalent OPV (types 1 and 3) for routine and supplementary immunization. The World Health Organization recently broadened the definition of cVDPVs to include any VDPV with genetic evidence of prolonged transmission (i.e., >1.5 years) and indicated that any single VDPV2 event (a case of paralysis caused by a VDPV or isolation of a VDPV from an environmental specimen) should elicit a detailed outbreak investigation and local immunization response. A confirmed cVDPV2 detection should elicit a full poliovirus outbreak response that includes multiple supplemental immunization activities (SIAs); an aVDPV designation should be made only after investigation and response (3). Since 2005, there have been 1-8 cVDPV outbreaks and 3-12 aVDPV events per year. There are currently five active cVDPV outbreaks in Guinea, Laos, Madagascar, Myanmar, and Ukraine, and four other active VDPV events. PMID:26866942

  5. Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence.

    PubMed Central

    Horie, H; Koike, S; Kurata, T; Sato-Yoshida, Y; Ise, I; Ota, Y; Abe, S; Hioki, K; Kato, H; Taya, C

    1994-01-01

    Recombinant viruses between the virulent Mahoney and attenuated Sabin 1 strains of poliovirus type 1 were subjected to neurovirulence tests using a transgenic (Tg) mouse line, ICR-PVRTg1, that carried the human poliovirus receptor gene. The Tg mice were inoculated intracerebrally with these recombinant viruses and observed for clinical signs, histopathological lesions, and viral antigens as parameters of neurovirulence of the viruses. These parameters observed in the Tg mice were different for different inoculated viruses. Dose-dependent incidences of paralysis and of death were observed in the Tg mice inoculated with any viruses used. This indicates that values of 50% lethal dose are useful to score a wide range of neurovirulence of poliovirus. The neurovirulence of individual viruses estimated by the Tg mouse model had a strong correlation with those estimated by monkey model. Consequently, the mouse tests identified the neurovirulence determinants on the genome of poliovirus that had been identified by monkey tests. In addition, the mouse tests revealed new neurovirulence determinants, that is, different nucleotides between the two strains at positions 189 and 21 and/or 935 in the 5'-proximal 1,122 nucleotides. The Tg mice used in this study may be suitable for replacing monkeys for investigating poliovirus neurovirulence. Images PMID:8289371

  6. Annual report of the Australian National Poliovirus Reference Laboratory, 2009.

    PubMed

    Roberts, Jason A; Hobday, Linda; Polychronopoulos, Sophie; Ibrahim, Aishah; Thorley, Bruce R

    2010-09-01

    The Australian National Poliovirus Reference Laboratory (NPRL) is accredited by the World Health Organization (WHO) for the testing of faecal specimens from acute flaccid paralysis (AFP) cases and operates as a regional poliovirus reference laboratory for the Western Pacific Region. The NPRL, in collaboration with the Australian Paediatric Surveillance Unit, co-ordinates surveillance for cases of AFP in children in Australia, according to criteria recommended by the WHO. Specimens are referred from AFP cases in children and suspected cases of poliomyelitis in persons of any age. The WHO AFP surveillance performance indicator is 1 non-polio AFP case per 100,000 children less than 15 years of age. In 2009, the Polio Expert Committee classified 48 cases as non-polio AFP, a rate of 1.17 cases per 100,000 children less than 15 years of age. An additional WHO AFP surveillance performance indicator is that more than 80% of notified AFP cases have 2 faecal samples collected 24 hours apart and within 14 days of onset of paralysis. Adequate faecal samples were received from 16 (33.3%) of the 48 classified cases. A poliovirus was referred via the Enterovirus Reference Laboratory Network of Australia from a non-AFP case and was determined to be Sabin-like. This case most likely represents an importation event, the source of which was not identified, as Australia ceased using Sabin oral polio vaccine in 2005. The last report of a wild poliovirus importation in Australia was from Pakistan in 2007. In 2009, 1,604 wild poliovirus cases were reported in 23 countries with Afghanistan, India, Nigeria and Pakistan remaining endemic for poliomyelitis. PMID:21090182

  7. Impaired binding of standard initiation factors eIF3b, eIF4G and eIF4B to domain V of the live-attenuated coxsackievirus B3 Sabin3-like IRES - alternatives for 5′UTR-related cardiovirulence mechanisms

    PubMed Central

    2013-01-01

    Abstract Internal ribosome entry site (IRES) elements fold into highly organized conserved secondary and probably tertiary structures that guide the ribosome to an internal site of the RNA at the IRES 3′end. The composition of the cellular proteome is under the control of multiple processes, one of the most important being translation initiation. In each poliovirus Sabin vaccine strain, a single point mutation in the IRES secondary-structure domain V is a major determinant of neurovirulence and translation attenuation. Here we are extrapolating poliovirus findings to a genomic related virus named coxsackievirus B3 CVB3); a causative agent of viral myocarditis. We have previously reported that Sabin3-like mutation (U473 → C) introduced in the domain V sequence of the CVB3 IRES led to a defective mutant with a serious reduction in translation efficiency and ribosomal initiation complex assembly, besides an impaired RNA-protein binding pattern. With the aim to identify proteins interacting with both CVB3 wild-type and Sabin3-like domain V RNAs and to assess the effect of the Sabin3-like mutation on these potential interactions, we have used a proteomic approach. This procedure allowed the identification of three RNA-binding proteins interacting with the domain V: eIF4G (p220), eIF3b (p116) and eIF4B (p80). Moreover, we report that this single-nucleotide exchange impairs the interaction pattern and the binding affinity of these standard translation initiation factors within the IRES domain V of the mutant strain. Taken together, these data indicate how this decisive Sabin3-like mutation mediates viral translation attenuation; playing a key role in the understanding of the cardiovirulence attenuation within this construct. Hence, these data provide further evidence for the crucial role of RNA structure for the IRES activity, and reinforce the idea of a distribution of function between the different IRES structural domains. Virtual slide The virtual slide(s) for

  8. Environmental Surveillance of Polioviruses in Rio de Janeiro, Brazil, in Support to the Activities of Global Polio Eradication Initiative.

    PubMed

    de Oliveira Pereira, Joseane Simone; da Silva, Lidiane Rodrigues; de Meireles Nunes, Amanda; de Souza Oliveira, Silas; da Costa, Eliane Veiga; da Silva, Edson Elias

    2016-03-01

    Wild polioviruses still remain endemic in three countries (Afghanistan, Pakistan, and Nigeria) and re-emergency of wild polio has been reported in previously polio-free countries. Environmental surveillance has been used as a supplementary tool in monitoring the circulation of wild poliovirus (PVs) and/or vaccine-derived PVs even in the absence of acute flaccid paralysis cases. This study aimed to monitor the presence of polioviruses in wastewater samples collected at one wastewater treatment plant located in the municipality of Rio de Janeiro, Brazil. From December 2011 to June 2012 and from September to December 2012, 31 samples were collected and processed. RD and L20B cell cultures were able to isolate PVs and non-polio enteroviruses in 27/31 samples. Polioviruses were isolated in eight samples (type 1 Sabin = 1, type 2 Sabin = 5, and type 3 Sabin = 2). Vaccine-derived polioviruses were not detected nor evidence of recombination with other PVs or non-polio enterovirus serotypes were observed among the isolates. The Sabin-related serotypes 2 and 3 presented nucleotide substitutions in positions associated with the neurovirulent phenotype at the 5'-UTR. Changes in important Amino acid residues at VP1 were also observed in the serotypes 2 and 3. Environmental surveillance has been used successfully in monitoring the circulation of PVs and non-polio enteroviruses and it is of crucial importance in the final stages of the WHO global polio eradication initiative. Our results show the continuous circulation of Sabin-like PVs and non-polio enteroviruses in the analyzed area during the study period. PMID:26538420

  9. An Introduction to Poliovirus: Pathogenesis, Vaccination, and the Endgame for Global Eradication.

    PubMed

    Minor, Philip D

    2016-01-01

    Poliomyelitis is caused by poliovirus, which is a positive strand non-enveloped virus that occurs in three distinct serotypes (1, 2, and 3). Infection is mainly by the fecal-oral route and can be confined to the gut by antibodies induced either by vaccine, previous infection or maternally acquired. Vaccines include the live attenuated strains developed by Sabin and the inactivated vaccines developed by Salk; the live attenuated vaccine (Oral Polio Vaccine or OPV) has been the main tool in the Global Program of Polio eradication of the World Health Organisation. Wild type 2 virus has not caused a case since 1999 and type 3 since 2012 and eradication seems near. However most infections are entirely silent so that sophisticated environmental surveillance may be needed to ensure that the virus has been eradicated, and the live vaccine can sometimes revert to virulent circulating forms under conditions that are not wholly understood. Cessation of vaccination is therefore an increasingly important issue and inactivated polio vaccine (IPV) is playing a larger part in the end game. PMID:26983727

  10. Immunity status of adults and children against poliomyelitis virus type 1 strains CHAT and Sabin (LSc-2ab) in Germany

    PubMed Central

    2010-01-01

    Background In October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab) presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV) containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV) containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster. Methods Neutralisation poliovirus antibodies against CHAT and Sabin 1 were measured in sera of 41 adults vaccinated with OPV. Additionally, sera from 28 children less than 10 years of age and immunised with IPV only were analysed. The neutralisation assay against poliovirus was performed according to WHO guidelines. Results The neutralisation activity against CHAT in adults with OPV vaccination history was significantly lower than against Sabin poliovirus type 1 strains (Wilcoxon signed-rank test P < 0.025). In eight sera, the antibody titres measured against CHAT were less than 8, although the titre against Sabin 1 varied between 8 and 64. Following IPV booster, anti-CHAT antibodies increased rapidly in sera of CHAT-negative adults with OPV history. Sera from children with IPV history neutralised CHAT and Sabin 1 strains equally. Conclusion The lack of neutralising antibodies against the CHAT strain in persons vaccinated with OPV might be associated with an increased risk of reinfection with the CHAT polio virus type 1, and this implies a putative risk of transmission of the virus to polio-free communities. We

  11. Registration of 'Sabine' Dallisgrass

    Technology Transfer Automated Retrieval System (TEKTRAN)

    'Sabine' dallisgrass (Paspalum dilatatum Poir.) (Reg. No. CV-2; PI 655527) was released by the USDA-Agricultural Research Service, Louisiana State University Agricultural Center, and Texas AgriLife Research on 2 September 2008. This cultivar is phenotypically and cytologically different from common...

  12. High resolution identity testing of inactivated poliovirus vaccines

    PubMed Central

    Mee, Edward T.; Minor, Philip D.; Martin, Javier

    2015-01-01

    Background Definitive identification of poliovirus strains in vaccines is essential for quality control, particularly where multiple wild-type and Sabin strains are produced in the same facility. Sequence-based identification provides the ultimate in identity testing and would offer several advantages over serological methods. Methods We employed random RT-PCR and high throughput sequencing to recover full-length genome sequences from monovalent and trivalent poliovirus vaccine products at various stages of the manufacturing process. Results All expected strains were detected in previously characterised products and the method permitted identification of strains comprising as little as 0.1% of sequence reads. Highly similar Mahoney and Sabin 1 strains were readily discriminated on the basis of specific variant positions. Analysis of a product known to contain incorrect strains demonstrated that the method correctly identified the contaminants. Conclusion Random RT-PCR and shotgun sequencing provided high resolution identification of vaccine components. In addition to the recovery of full-length genome sequences, the method could also be easily adapted to the characterisation of minor variant frequencies and distinction of closely related products on the basis of distinguishing consensus and low frequency polymorphisms. PMID:26049003

  13. 75 FR 29695 - Security Zones; Sabine Bank Channel, Sabine Pass Channel and Sabine-Neches Waterway, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... Federal Register (73 FR 3316). Public Meeting At this time, we do not plan to hold a public meeting, but... and Sabine-Neches Waterway, TX AGENCY: Coast Guard, DHS. ] ACTION: Notice of proposed rulemaking... waters through Sabine Bank Channel, Sabine Pass Channel and the Sabine-Neches Waterway, extending...

  14. Fractional-Dose Inactivated Poliovirus Vaccine Immunization Campaign - Telangana State, India, June 2016.

    PubMed

    Bahl, Sunil; Verma, Harish; Bhatnagar, Pankaj; Haldar, Pradeep; Satapathy, Asish; Kumar, K N Arun; Horton, Jennifer; Estivariz, Concepcion F; Anand, Abhijeet; Sutter, Roland

    2016-01-01

    Wild poliovirus type 2 was declared eradicated in September 2015 (1). In April 2016, India, switched from use of trivalent oral poliovirus vaccine (tOPV; containing types 1, 2, and 3 polio vaccine viruses), to bivalent OPV (bOPV; containing types 1 and 3), as part of a globally synchronized initiative to withdraw Sabin poliovirus type 2 vaccine. Concurrently, inactivated poliovirus vaccine (IPV) was introduced into India's routine immunization program to maintain an immunity base that would mitigate the number of paralytic cases in the event of epidemic transmission of poliovirus type 2 (2,3). After cessation of use of type 2 Sabin vaccine, any reported isolation of vaccine-derived poliovirus type 2 (VDPV2) would be treated as a public health emergency and might need outbreak response with monovalent type 2 oral vaccine, IPV, or both (4). In response to identification of a VDPV2 isolate from a sewage sample collected in the southern state of Telangana in May 2016, India conducted a mass vaccination campaign in June 2016 using an intradermal fractional dose (0.1 ml) of IPV (fIPV). Because of a global IPV supply shortage, fIPV, which uses one fifth of regular intramuscular (IM) dose administered intradermally, has been recommended as a response strategy for VDPV2 (5). Clinical trials have demonstrated that fIPV is highly immunogenic (6,7). During the 6-day campaign, 311,064 children aged 6 weeks-3 years were vaccinated, achieving an estimated coverage of 94%. With appropriate preparation, an emergency fIPV response can be promptly and successfully implemented. Lessons learned from this campaign can be applied to successful implementation of future outbreak responses using fIPV. PMID:27559683

  15. Vaccine-derived polioviruses.

    PubMed

    Burns, Cara C; Diop, Ousmane M; Sutter, Roland W; Kew, Olen M

    2014-11-01

    The attenuated oral poliovirus vaccine (OPV) has many properties favoring its use in polio eradication: ease of administration, efficient induction of intestinal immunity, induction of durable humoral immunity, and low cost. Despite these advantages, OPV has the disadvantage of genetic instability, resulting in rare and sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) and the emergence of genetically divergent vaccine-derived polioviruses (VDPVs). Whereas VAPP is an adverse event following exposure to OPV, VDPVs are polioviruses whose genetic properties indicate prolonged replication or transmission. Three categories of VDPVs are recognized: (1) circulating VDPVs (cVDPVs) from outbreaks in settings of low OPV coverage, (2) immunodeficiency-associated VDPVs (iVDPVs) from individuals with primary immunodeficiencies, and (3) ambiguous VDPVs (aVDPVs), which cannot be definitively assigned to either of the first 2 categories. Because most VDPVs are type 2, the World Health Organization's plans call for coordinated worldwide replacement of trivalent OPV with bivalent OPV containing poliovirus types 1 and 3. PMID:25316847

  16. Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study.

    PubMed Central

    Dragunsky, Eugenia; Nomura, Tatsuji; Karpinski, Kazimir; Furesz, John; Wood, David J.; Pervikov, Yuri; Abe, Shinobu; Kurata, Takeshi; Vanloocke, Olivier; Karganova, Galina; Taffs, Rolf; Heath, Alan; Ivshina, Anna; Levenbook, Inessa

    2003-01-01

    OBJECTIVE: Extensive WHO collaborative studies were performed to evaluate the suitability of transgenic mice susceptible to poliovirus (TgPVR mice, strain 21, bred and provided by the Central Institute for Experimental Animals, Japan) as an alternative to monkeys in the neurovirulence test (NVT) of oral poliovirus vaccine (OPV). METHODS: Nine laboratories participated in the collaborative study on testing neurovirulence of 94 preparations of OPV and vaccine derivatives of all three serotypes in TgPVR21 mice. FINDINGS: Statistical analysis of the data demonstrated that the TgPVR21 mouse NVT was of comparable sensitivity and reproducibility to the conventional WHO NVT in simians. A statistical model for acceptance/rejection of OPV lots in the mouse test was developed, validated, and shown to be suitable for all three vaccine types. The assessment of the transgenic mouse NVT is based on clinical evaluation of paralysed mice. Unlike the monkey NVT, histological examination of central nervous system tissue of each mouse offered no advantage over careful and detailed clinical observation. CONCLUSIONS: Based on data from the collaborative studies the WHO Expert Committee for Biological Standardization approved the mouse NVT as an alternative to the monkey test for all three OPV types and defined a standard implementation process for laboratories that wish to use the test. This represents the first successful introduction of transgenic animals into control of biologicals. PMID:12764491

  17. Cessation of Trivalent Oral Poliovirus Vaccine and Introduction of Inactivated Poliovirus Vaccine - Worldwide, 2016.

    PubMed

    Hampton, Lee M; Farrell, Margaret; Ramirez-Gonzalez, Alejandro; Menning, Lisa; Shendale, Stephanie; Lewis, Ian; Rubin, Jennifer; Garon, Julie; Harris, Jennifer; Hyde, Terri; Wassilak, Steven; Patel, Manish; Nandy, Robin; Chang-Blanc, Diana

    2016-01-01

    Since the 1988 World Health Assembly resolution to eradicate poliomyelitis, transmission of the three types of wild poliovirus (WPV) has been sharply reduced (1). WPV type 2 (WPV2) has not been detected since 1999 and was declared eradicated in September 2015. Because WPV type 3 has not been detected since November 2012, WPV type 1 (WPV1) is likely the only WPV that remains in circulation (1). This marked progress has been achieved through widespread use of oral poliovirus vaccines (OPVs), most commonly trivalent OPV (tOPV), which contains types 1, 2, and 3 live, attenuated polioviruses and has been a mainstay of efforts to prevent polio since the early 1960s. However, attenuated polioviruses in OPV can undergo genetic changes during replication, and in communities with low vaccination coverage, can result in vaccine-derived polioviruses (VDPVs) that can cause paralytic polio indistinguishable from the disease caused by WPVs (2). Among the 721 polio cases caused by circulating VDPVs (cVDPVs*) detected during January 2006-May 2016, type 2 cVDPVs (cVDPV2s) accounted for >94% (2). Eliminating the risk for polio caused by VDPVs will require stopping all OPV use. The first stage of OPV withdrawal involved a global, synchronized replacement of tOPV with bivalent OPV (bOPV) containing only types 1 and 3 attenuated polioviruses, planned for April 18-May 1, 2016, thereby withdrawing OPV type 2 from all immunization activities (3). Complementing the switch from tOPV to bOPV, introduction of at least 1 dose of injectable, trivalent inactivated poliovirus vaccine (IPV) into childhood immunization schedules reduces risks from and facilitates responses to cVDPV2 outbreaks. All 155 countries and territories that were still using OPV in immunization schedules in 2015 have reported that they had ceased use of tOPV by mid-May 2016.(†) As of August 31, 2016, 173 (89%) of 194 World Health Organization (WHO) countries included IPV in their immunization schedules.(§) The cessation of

  18. Importation and circulation of poliovirus in Bulgaria in 2001.

    PubMed Central

    Kojouharova, Mira; Zuber, Patrick L. F.; Gyurova, Snejana; Fiore, Lucia; Buttinelli, Gabriele; Kunchev, Angel; Vladimirova, Nadejda; Korsun, Neli; Filipova, Radosveta; Boneva, Roumiana; Gavrilin, Eugene; Deshpande, Jagadish M.; Oblapenko, George; Wassilak, Steven G.

    2003-01-01

    OBJECTIVE: To characterize the circumstances in which poliomyelitis occurred among three children in Bulgaria during 2001 and to describe the public health response. METHODS: Bulgarian authorities investigated the three cases of polio and their contacts, conducted faecal and serological screening of children from high-risk groups, implemented enhanced surveillance for acute flaccid paralysis, and conducted supplemental immunization activities. FINDINGS: The three cases of polio studied had not been vaccinated and lived in socioeconomically deprived areas of two cities. Four Roma children from the Bourgas district had antibody titres to serotype 1 poliovirus only, and wild type 1 virus was isolated from the faeces of two asymptomatic Roma children in the Bourgas and Sofia districts. Poliovirus isolates were related genetically and represented a single evolutionary lineage; genomic sequences were less than 90% identical to poliovirus strains isolated previously in Europe, but 98.3% similar to a strain isolated in India in 2000. No cases or wild virus isolates were found after supplemental immunization activities were launched in May 2001. CONCLUSIONS: In Bulgaria, an imported poliovirus was able to circulate for two to five months among minority populations. Surveillance data strongly suggest that wild poliovirus circulation ceased shortly after supplemental immunization activities with oral poliovirus vaccine were conducted. PMID:12973639

  19. 33 CFR 165.819 - Security Zone; Sabine Bank Channel, Sabine Pass Channel and Sabine-Neches Waterway, TX.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Sabine-Neches Waterway, TX. (a) Location. (1) The following LNG facility mooring basins are designated as fixed security zones whenever LNG carriers are moored within them: (i) Golden Pass LNG, Sabine TX: All...°45′50″ N, 093°55′17″ W. (ii) Sabine Pass LNG, Cameron Parish, LA: All mooring basin waters north of...

  20. 77 FR 45329 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-31

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Forest Service Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Sabine Resource Advisory Committee will meet in ] Hemphill, Texas. The committee...

  1. 33 CFR 117.981 - Sabine River.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sabine River. 117.981 Section 117.981 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.981 Sabine River. See § 117.493, Sabine...

  2. 33 CFR 117.981 - Sabine River.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Sabine River. 117.981 Section 117.981 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.981 Sabine River. See § 117.493, Sabine...

  3. 33 CFR 117.981 - Sabine River.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Sabine River. 117.981 Section 117.981 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.981 Sabine River. See § 117.493, Sabine...

  4. 33 CFR 117.981 - Sabine River.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Sabine River. 117.981 Section 117.981 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.981 Sabine River. See § 117.493, Sabine...

  5. 33 CFR 117.981 - Sabine River.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Sabine River. 117.981 Section 117.981 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.981 Sabine River. See § 117.493, Sabine...

  6. Serial Recombination during Circulation of Type 1 Wild-Vaccine Recombinant Polioviruses in China

    PubMed Central

    Liu, Hong-Mei; Zheng, Du-Ping; Zhang, Li-Bi; Oberste, M. Steven; Kew, Olen M.; Pallansch, Mark A.

    2003-01-01

    Type 1 wild-vaccine recombinant polioviruses sharing a 367-nucleotide (nt) block of Sabin 1-derived sequence spanning the VP1 and 2A genes circulated widely in China from 1991 to 1993. We surveyed the sequence relationships among 34 wild-vaccine recombinants by comparing six genomic intervals: the conserved 5′-untranslated region (5′-UTR) (nt 186 to 639), the hypervariable portion of the 5′-UTR (nt 640 to 742), the VP4 and partial VP2 genes (nt 743 to 1176), the VP1 gene (nt 2480 to 3385), the 2A gene (nt 3386 to 3832), and the partial 3D gene (nt 6011 to 6544). The 5′-UTR, capsid (VP4-VP2 and VP1), and 2A sequence intervals had similar phylogenies. By contrast, the partial 3D sequences could be distributed into five divergent genetic classes. Most (25 of 34) of the wild-vaccine recombinant isolates showed no evidence of additional recombination beyond the initial wild-Sabin recombination event. Eight isolates from 1992 to 1993, however, appear to be derived from three independent additional recombination events, and one 1993 isolate was derived from two consecutive events. Complete genomic sequences of a representative isolate for each 3D sequence class demonstrated that these exchanges had occurred in the 2B, 2C, and 3D genes. The 3D gene sequences were not closely related to those of the Sabin strains or 53 diverse contemporary wild poliovirus isolates from China, but all were related to the 3D genes of species C enteroviruses. The appearance within approximately 2.5 years of five recombinant classes derived from a single ancestral infection illustrates the rapid emergence of new recombinants among circulating wild polioviruses. PMID:14512548

  7. Limited and localized outbreak of newly emergent type 2 vaccine-derived poliovirus in Sichuan, China.

    PubMed

    Yan, Dongmei; Zhang, Yong; Zhu, Shuangli; Chen, Na; Li, Xiaolei; Wang, Dongyan; Ma, Xiaozhen; Zhu, Hui; Tong, Wenbin; Xu, Wenbo

    2014-07-01

    From August 2011 to February 2012, an outbreak caused by type 2 circulating vaccine-derived poliovirus (cVDPV) occurred in Aba County, Sichuan, China. During the outbreak, four type 2 VDPVs (≥0.6% nucleotide divergence in the VP1 region relative to the Sabin 2 strain) were isolated from 3 patients with acute flaccid paralysis (AFP) and one close contact. In addition, a type 2 pre-VDPV (0.3% to 0.5% divergence from Sabin 2) that was genetically related to these type 2 VDPVs was isolated from another AFP patient. These 4 patients were all unimmunized children 0.7 to 1.1 years old. Nucleotide sequencing revealed that the 4 VDPV isolates differed from Sabin 2 by 0.7% to 1.2% in nucleotides in the VP1 region and shared 5 nucleotide substitutions with the pre-VDPV. All 5 isolates were closely related, and all were S2/S3/S2/S3 recombinants sharing common recombination crossover sites. Although the two major determinants of attenuation and temperature sensitivity phenotype of Sabin 2 (A481 in the 5' untranslated region and Ile143 in the VP1 protein) had reverted in all 5 isolates, one VDPV (strain CHN16017) still retained the temperature sensitivity phenotype. Phylogenetic analysis of the third coding position of the complete P1 coding region suggested that the cVDPVs circulated locally for about 7 months following the initiating oral poliovirus vaccine (OPV) dose. Our findings reinforce the point that cVDPVs can emerge and spread in isolated communities with immunity gaps and highlight the emergence risks of type 2 cVDPVs accompanying the trivalent OPV used. To solve this issue, it is recommended that type 2 OPV be removed from the trivalent OPV or that inactivated polio vaccine (IPV) be used instead. PMID:24850620

  8. Managing population immunity to reduce or eliminate the risks of circulation following the importation of polioviruses.

    PubMed

    Thompson, Kimberly M; Kalkowska, Dominika A; Duintjer Tebbens, Radboud J

    2015-03-24

    Poliovirus importations into polio-free countries represent a major concern during the final phases of global eradication of wild polioviruses (WPVs). We extend dynamic transmission models to demonstrate the dynamics of population immunity out through 2020 for three countries that only used inactivated poliovirus vaccine (IPV) for routine immunization: the US, Israel, and The Netherlands. For each country, we explore the vulnerability to re-established transmission following an importation for each poliovirus serotype, including the impact of immunization choices following the serotype 1 WPV importation that occurred in 2013 in Israel. As population immunity declines below the threshold required to prevent transmission, countries become at risk for re-established transmission. Although importations represent stochastic events that countries cannot fully control because people cross borders and polioviruses mainly cause asymptomatic infections, countries can ensure that any importations die out. Our results suggest that the general US population will remain above the threshold for transmission through 2020. In contrast, Israel became vulnerable to re-established transmission of importations of live polioviruses by the late 2000s. In Israel, the recent WPV importation and outbreak response use of bivalent oral poliovirus vaccine (bOPV) eliminated the vulnerability to an importation of poliovirus serotypes 1 and 3 for several years, but not serotype 2. The Netherlands experienced a serotype 1 WPV outbreak in 1992-1993 and became vulnerable to re-established transmission in religious communities with low vaccine acceptance around the year 2000, although the general population remains well-protected from widespread transmission. All countries should invest in active management of population immunity to avoid the potential circulation of imported live polioviruses. IPV-using countries may wish to consider prevention opportunities and/or ensure preparedness for response

  9. 78 FR 66909 - Sabine Pass Liquefaction, LLC; Sabine Pass LNG, L.P.; Notice of Application to Amend...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... Energy Regulatory Commission Sabine Pass Liquefaction, LLC; Sabine Pass LNG, L.P.; Notice of Application... Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P. (collectively, Sabine Pass), 700 Milam Street... authorizations granted on April 16, 2012 in Docket No. CP11-72-000 (Liquefaction Project), as amended in...

  10. 76 FR 14647 - Sabine National Forest Resource Advisory Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-17

    ...; ] DEPARTMENT OF AGRICULTURE Sabine National Forest Resource Advisory Committee Meeting AGENCY: Forest Service, USDA. ACTION: Notice of Public Meeting, Sabine National Forest Resource Advisory Committee. SUMMARY: In.... Department of Agriculture, Forest Service, Sabine National Forest Resource Advisory Committee (RAC)...

  11. S2M: A Stochastic Simulation Model of Poliovirus Genetic State Transition

    PubMed Central

    Ecale Zhou, Carol L.

    2016-01-01

    Modeling the molecular mechanisms that govern genetic variation can be useful in understanding the dynamics that drive genetic state transition in quasispecies viruses. For example, there is considerable interest in understanding how the relatively benign vaccine strains of poliovirus eventually revert to forms that confer neurovirulence and cause disease (ie, vaccine-derived poliovirus). This report describes a stochastic simulation model, S2M, which can be used to generate hypothetical outcomes based on known mechanisms of genetic diversity. S2M begins with predefined genotypes based on the Sabin-1 and Mahoney wild-type sequences, constructs a set of independent cell-based populations, and performs in-cell replication and cell-to-cell infection cycles while quantifying genetic changes that track the transition from Sabin-1 toward Mahoney. Realism is incorporated into the model by assigning defaults for variables that constrain mechanisms of genetic variability based roughly on metrics reported in the literature, yet these values can be modified at the command line in order to generate hypothetical outcomes driven by these parameters. To demonstrate the utility of S2M, simulations were performed to examine the effects of the rates of replication error and recombination and the presence or absence of defective interfering particles, upon reaching the end states of Mahoney resemblance (semblance of a vaccine-derived state), neurovirulence, genome fitness, and cloud diversity. Simulations provide insight into how modeled biological features may drive hypothetical outcomes, independently or in combination, in ways that are not always intuitively obvious. PMID:27385911

  12. Phylogenetic Analysis of Poliovirus Sequences.

    PubMed

    Jorba, Jaume

    2016-01-01

    Comparative genomic sequencing is a major surveillance tool in the Polio Laboratory Network. Due to the rapid evolution of polioviruses (~1 % per year), pathways of virus transmission can be reconstructed from the pathways of genomic evolution. Here, we describe three main phylogenetic methods; estimation of genetic distances, reconstruction of a maximum-likelihood (ML) tree, and estimation of substitution rates using Bayesian Markov chain Monte Carlo (MCMC). The data set used consists of complete capsid sequences from a survey of poliovirus sequences available in GenBank. PMID:26983737

  13. 76 FR 62342 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Forest Service Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Sabine Resource Advisory Committee will meet in Hemphill, Texas. The committee is...

  14. 76 FR 44574 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-26

    ... etaylor@fs.fed.us or via facsimile to 409-625-1953. Dated: July 20, 2011.FR William E. Taylor, Jr... Forest Service Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Sabine Resource Advisory Committee will meet in Hemphill, Texas. The committee is...

  15. 76 FR 34962 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF AGRICULTURE Forest Service Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Sabine Resource Advisory Committee will meet in Hemphill, Texas. The committee is...

  16. 76 FR 28950 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Sabine Resource Advisory Committee will meet in Hemphill, Texas. The committee is authorized under...

  17. 77 FR 53842 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Forest Service Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Sabine Resource Advisory Committee will meet in Hemphill, Texas. The committee is...

  18. 76 FR 66033 - Sabine Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Forest Service Sabine Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting cancellation. SUMMARY: The Sabine-Angelina Resource Advisory Committee was scheduled to meet October 20,...

  19. 33 CFR 117.493 - Sabine River.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Sabine River. 117.493 Section 117.493 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.493 Sabine River. (a) The draw of the...

  20. 33 CFR 117.493 - Sabine River.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sabine River. 117.493 Section 117.493 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.493 Sabine River. (a) The draw of the...

  1. 33 CFR 117.493 - Sabine River.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Sabine River. 117.493 Section 117.493 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.493 Sabine River. (a) The draw of the...

  2. 33 CFR 117.493 - Sabine River.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Sabine River. 117.493 Section 117.493 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.493 Sabine River. (a) The draw of the...

  3. 33 CFR 117.493 - Sabine River.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Sabine River. 117.493 Section 117.493 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.493 Sabine River. (a) The draw of the...

  4. 33 CFR 117.979 - Sabine Lake.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sabine Lake. 117.979 Section 117.979 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.979 Sabine Lake. The draw of the S82 bridge, mile...

  5. 33 CFR 117.979 - Sabine Lake.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Sabine Lake. 117.979 Section 117.979 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.979 Sabine Lake. The draw of the S82 bridge, mile...

  6. 33 CFR 117.979 - Sabine Lake.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Sabine Lake. 117.979 Section 117.979 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.979 Sabine Lake. The draw of the S82 bridge, mile...

  7. 33 CFR 117.979 - Sabine Lake.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Sabine Lake. 117.979 Section 117.979 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.979 Sabine Lake. The draw of the S82 bridge, mile...

  8. 33 CFR 117.979 - Sabine Lake.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Sabine Lake. 117.979 Section 117.979 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Texas § 117.979 Sabine Lake. The draw of the S82 bridge, mile...

  9. Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

    PubMed Central

    Shaw, Jing; Jorba, Jaume; Bukbuk, David; Adu, Festus; Gumede, Nicksy; Pate, Muhammed Ali; Abanida, Emmanuel Ade; Gasasira, Alex; Iber, Jane; Chen, Qi; Vincent, Annelet; Chenoweth, Paul; Henderson, Elizabeth; Wannemuehler, Kathleen; Naeem, Asif; Umami, Rifqiyah Nur; Nishimura, Yorihiro; Shimizu, Hiroyuki; Baba, Marycelin; Adeniji, Adekunle; Williams, A. J.; Kilpatrick, David R.; Oberste, M. Steven; Wassilak, Steven G.; Tomori, Oyewale; Pallansch, Mark A.; Kew, Olen

    2013-01-01

    Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A481 in the 5′-untranslated region [5′-UTR] and VP1-Ile143) had been replaced in all VDPV2 isolates; most A481 5′-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that ∼700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries. PMID:23408630

  10. 77 FR 65546 - Sabine Pass Liquefaction, LLC; Sabine Pass LNG, L.P.; Notice of Petition To Amend Authorizations...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-29

    ... Energy Regulatory Commission Sabine Pass Liquefaction, LLC; Sabine Pass LNG, L.P.; Notice of Petition To... Pass Liquefaction, LLC and Sabine Pass LNG, L.P. (collectively, Sabine Pass), 700 Milam Street, Suite... authorizations granted on April 16, 2012 in Docket No. CP11-72-000 (Liquefaction Project) in order to...

  11. 78 FR 25432 - Sabine Pass LNG, L.P., Sabine Pass Liquefaction, LLC; Notice of Availability of the Environmental...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-01

    ... Energy Regulatory Commission Sabine Pass LNG, L.P., Sabine Pass Liquefaction, LLC; Notice of Availability of the Environmental Assessment for the Proposed Sabine Pass Liquefaction Project Modification The... assessment (EA) for the Sabine Pass Liquefaction Project Modification (Modification Project), proposed...

  12. 76 FR 9573 - Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-18

    ... Energy Regulatory Commission Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P.; Notice of Application Take notice that on January 31, 2011, Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P... the Commission's Regulations, to site, construct, and operate liquefaction and export...

  13. Rare natural type 3/type 2 intertypic capsid recombinant vaccine-related poliovirus isolated from a case of acute flaccid paralysis in Brazil, 2015.

    PubMed

    Cassemiro, Klécia M S M; Burlandy, Fernanda M; da Silva, Edson E

    2016-07-01

    A natural type 3/type 2 intertypic capsid recombinant vaccine-related poliovirus was isolated from an acute flaccid paralytic case in Brazil. Genome sequencing revealed the uncommon location of the crossover site in the VP1 coding region (nucleotides 3251-3258 of Sabin 3 genome). The Sabin 2 donor sequence replaced the last 118 nt of VP1, resulting in the substitution of the complete antigenic site IIIa by PV2-specific amino acids. The low overall number of nucleotide substitutions in P1 region indicated that the predicted replication time of the isolate was about 8-9 weeks. Two of the principal determinants of attenuation in Sabin 3 genomes were mutated (U472C and C2493U), but the temperature-sensitive phenotype of the isolate was preserved. Our results support the theory that there exists a PV3/PV2 recombination hotspot site in the tail region of the VP1 capsid protein and that the recombination may occur soon after oral poliovirus vaccine administration. PMID:27082658

  14. Molecular and Phenotypic Characterization of a Highly Evolved Type 2 Vaccine-Derived Poliovirus Isolated from Seawater in Brazil, 2014

    PubMed Central

    Cassemiro, Klécia Marília S. de Melo; Burlandy, Fernanda M.; Barbosa, Mikaela R. F.; Chen, Qi; Jorba, Jaume; Hachich, Elayse M.; Sato, Maria I. Z.; Burns, Cara C.; da Silva, Edson E.

    2016-01-01

    A type 2 vaccine-derived poliovirus (VDPV), differing from the Sabin 2 strain at 8.6% (78/903) of VP1 nucleotide positions, was isolated from seawater collected from a seaport in São Paulo State, Brazil. The P1/capsid region is related to the Sabin 2 strain, but sequences within the 5'-untranslated region and downstream of the P1 region were derived from recombination with other members of Human Enterovirus Species C (HEV-C). The two known attenuating mutations had reverted to wild-type (A481G in the 5'-UTR and Ile143Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype and had accumulated amino acid substitutions in neutralizing antigenic (NAg) sites 3a and 3b. The date of the initiating OPV dose, estimated from the number of synonymous substitutions in the capsid region, was approximately 8.5 years before seawater sampling, a finding consistent with a long time of virus replication and possible transmission among several individuals. Although no closely related type 2 VDPVs were detected in Brazil or elsewhere, this VDPV was found in an area with a mobile population, where conditions may favor both viral infection and spread. Environmental surveillance serves as an important tool for sensitive and early detection of circulating poliovirus in the final stages of global polio eradication. PMID:27019095

  15. H1PVAT is a novel and potent early-stage inhibitor of poliovirus replication that targets VP1.

    PubMed

    Tijsma, Aloys; Thibaut, Hendrik Jan; Spieser, Stéphane A H; De Palma, Armando; Koukni, Mohamed; Rhoden, Eric; Oberste, Steve; Pürstinger, Gerhard; Volny-Luraghi, Antonia; Martin, Javier; Marchand, Arnaud; Chaltin, Patrick; Neyts, Johan; Leyssen, Pieter

    2014-10-01

    A novel small molecule, H1PVAT, was identified as a potent and selective inhibitor of the in vitro replication of all three poliovirus serotypes, whereas no activity was observed against other enteroviruses. Time-of-drug-addition studies revealed that the compound interfered with an early stage of virus replication. Four independently-selected H1PVAT-resistant virus variants uniformly carried the single amino acid substitution I194F in the VP1 capsid protein. Poliovirus type 1 strain Sabin, reverse-engineered to contain this substitution, proved to be completely insensitive to the antiviral effect of H1PVAT and was cross-resistant to the capsid-binding inhibitors V-073 and pirodavir. The VP1 I194F mutant had a smaller plaque phenotype than wild-type virus, and the amino acid substitution rendered the virus more susceptible to heat inactivation. Both for the wild-type and VP1 I194F mutant virus, the presence of H1PVAT increased the temperature at which the virus was inactivated, providing evidence that the compound interacts with the viral capsid, and that capsid stabilization and antiviral activity are not necessarily correlated. Molecular modeling suggested that H1PVAT binds with high affinity in the pocket underneath the floor of the canyon that is involved in receptor binding. Introduction of the I194F substitution in the model of VP1 induced a slight concerted rearrangement of the core β-barrel in this pocket, which disfavors binding of the compound. Taken together, the compound scaffold, to which H1PVAT belongs, may represent another promising class of poliovirus capsid-binding inhibitors next to V-073 and pirodavir. Potent antivirals against poliovirus will be essential in the poliovirus eradication end-game. PMID:25043639

  16. 76 FR 52563 - Special Local Regulations; Sabine River, Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ...) entitled Special Local Regulations; Sabine River, Orange, TX in the Federal Register (76 FR 103). We... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations; Sabine River, Orange, TX... temporary Special Local Regulation on the Sabine River within the Port Arthur, TX Captain of the Port...

  17. [Genetic Characteristics of Type 2 Vaccine-derived Poliovirus in Shanxi Province (China) in 2014].

    PubMed

    Yan, Dongrei; Li, Xiaolei; Zhang, Yong; Yang, Jianfang; Zhu, Shuangli; Wang, Dongyan; Zhang, Chuangye; Zhu, Hui; Xu, Wenbo

    2015-03-01

    The World Health Organization redefined the type 2 vaccine-derived poliovirus (VDPV) in 2010. To study the genetic characteristics and evolution of type 2 VDPV under this new definition, we conducted genome sequencing and analyses of type 2 VDPVs isolated from one patient with acute flaccid paralysis in Shanxi province (China) in 2014. Nucleotide sequencing revealed that the full-length of type 2 VDPV is 7439 bases encoding 2207 amino acids with no insertion or deletion of nucleotides compared with Sabin2. One nucleotide substitution identified as a key determinant of the attenuated phenotype of the Sabin 2 strain (A-G reversion at nucleotide nt 481 in the 5-end of the untranslated region) had reverted in the Shanxi type 2 VDPV. The other known key determinant of the attenuated phenotype of the Sabin 2 strain (U-->C reversion at nt2909 in the VP1 coding region that caused a Ile143Thr substitution in VP1) had not reverted in the Shanxi VDPV. The Shanxi type 2 VDPV was S2/S1 recombinant, the crossover site of which mapped to the 3-end of the 3D region (between nt 6247 and nt 6281). A phylogentic tree based on the VP1 coding region showed that evolution of the Shanxi type 2 VDPV was independent of other type 2 VDPVs detected worldwide. We estimated that the strain circulated for approximately = 11 months in the population according to the known evolution rate. The present study confirmed that the Chinese Polio Laboratory Network could discover the VDPV promptly and that it played an important part in maintenance of a polio-free China. PMID:26164941

  18. 77 FR 277 - Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P; Notice of Availability of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P; Notice of Availability of the Environmental Assessment for the Proposed Sabine Pass Liquefaction Project The staff of the Federal Energy Regulatory Commission...

  19. New Generation of Inactivated Poliovirus Vaccines for Universal Immunization After Eradication of Poliomyelitis

    PubMed Central

    Chumakov, Konstantin; Ehrenfeld, Ellie

    2008-01-01

    Twenty years of global polio eradication efforts may soon eliminate wild-type poliovirus transmission. However, new information about poliovirus learned during this campaign, as well as the political realities of a modern world demand that universal immunity against poliomyelitis be maintained even after wild poliovirus is eradicated. Although two excellent vaccines have proven highly effective in the past, neither the live nor current inactivated products are optimal for use in the post-eradication setting. Therefore, concerted efforts are urgently needed to develop a new generation of vaccine that is risk-free and affordable and can be produced on a global scale. Here we discuss the desired properties and ways to create a new polio vaccine. PMID:18990066

  20. Inhibition of poliovirus RNA synthesis by brefeldin A.

    PubMed Central

    Maynell, L A; Kirkegaard, K; Klymkowsky, M W

    1992-01-01

    Brefeldin A (BFA), a fungal metabolite that blocks transport of newly synthesized proteins from the endoplasmic reticulum, was found to inhibit poliovirus replication 10(5)- to 10(6)-fold. BFA does not inhibit entry of poliovirus into the cell or translation of viral RNA. Poliovirus RNA synthesis, however, is completely inhibited by BFA. A specific class of membranous vesicles, with which the poliovirus replication complex is physically associated, is known to proliferate in poliovirus-infected cells. BFA may inhibit poliovirus replication by preventing the formation of these vesicles. Images PMID:1312615

  1. Will containment of wild poliovirus in laboratories and inactivated poliovirus vaccine production sites be effective for global certification?

    PubMed Central

    Dowdle, Walter R.; Wolff, Christopher; Sanders, Raymond; Lambert, Scott; Best, Maureen

    2004-01-01

    The absolute laboratory containment of any virus cannot be guaranteed, but a wealth of experience indicates that effective containment of wild poliovirus materials for global certification is technically and operationally feasible. Effective containment is based on the principles of minimal wild poliovirus infectious and potentially infectious materials in laboratories; minimal risks of operations in laboratories and inactivated poliovirus vaccine production facilities; minimal susceptibility of workers to wild poliovirus infection and shedding; and minimal susceptibility of populations to wild poliovirus spread. Each principle alone is imperfect, but collectively they greatly minimize the risks of transmitting wild poliovirus from the laboratory to the community. PMID:15106302

  2. Examination of poliovirus vaccine preparations for SV40 sequences.

    PubMed

    Sangar, D; Pipkin, P A; Wood, D J; Minor, P D

    1999-03-01

    Oral poliovaccines derived from the strains developed by Sabin have been the basis of vaccination against poliomyelitis in the U.K. since 1962. Contamination of earlier materials with the monkey virus SV40, particularly inactivated Salk type poliovaccines, is well documented. Precautions have been in place for more than 30 years to prevent SV40 contamination of oral poliovaccines based on screening of donor animals and tests for SV40 infectivity. PCR was applied to examine all archived samples of oral poliovaccines available to us dating from 1966 to the present, including all vaccines used in the U.K. since 1980, for the presence of SV40 sequences. Of 132 materials examined, 118 were negative on initial testing and fourteen gave reactions which on further examination were attributed either to cross contamination during handling in the laboratory at National Institute for Biological Standards and Control (NIBSC) or to non-specific amplification. It was concluded that none of the samples contained SV40 sequences. The materials included 69 separate monovalent bulks of poliovirus type 1, 2 or 3 grown on monkey kidney cells from four different manufacturers and 74 bulks grown on human diploid cells from two manufacturers. One additional seed material from 1962 contained low levels of unique and characteristic SV40 sequences. The seed had been treated by the manufacturer to inactivate DNA viruses and tests by the manufacturer and at NIBSC failed to demonstrate the presence of infectious SV40 virus. Monovalent bulks prepared by the manufacturer from this seed were negative for SV40 sequences by PCR. The PCR studies provide no evidence of contamination of oral poliovaccines used in the UK with infectious SV40 and suggest that the steps taken to ensure the absence of infectious SV40 are satisfactory. PMID:10441397

  3. 78 FR 62344 - Sabine Pass Liquefaction Expansion, LLC, Sabine Pass Liquefaction, LLC, and Sabine Pass LNG, L.P...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-18

    ... Sabine Pass LNG, L.P., Cheniere Creole Trail Pipeline, L.P.; Notice of Application Take notice that on... Commission an application under section 3(a) of the Natural Gas Act (NGA) for authorization to site...) filed, in the same application, a request under section 7(c) of the NGA, for authorization to...

  4. 76 FR 1519 - Security Zones; Sabine Bank Channel, Sabine Pass Channel and Sabine-Neches Waterway, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-11

    ... and Sabine-Neches Waterway, TX in the Federal Register (75 FR 29695). We received one comment on the... recommendation from that one comment and requesting further comments (75 FR 65232). No public meeting was... preamble, the Coast Guard adopts the interim rule amending 33 CFR part 165 that was published at 75...

  5. 75 FR 65232 - Security Zones; Sabine Bank Channel, Sabine Pass Channel and Sabine-Neches Waterway, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ...-Neches Waterway, TX'' in the Federal Register (75 FR 29695). We received one comment on the proposed rule... public dockets in the January 17, 2008, issue of the Federal Register (73 FR 3316). Public Meeting We do... and Sabine-Neches Waterway, TX AGENCY: Coast Guard, DHS. ACTION: Interim rule with request...

  6. Identification and Manipulation of the Molecular Determinants Influencing Poliovirus Recombination

    PubMed Central

    Runckel, Charles; Westesson, Oscar; Andino, Raul; DeRisi, Joseph L.

    2013-01-01

    The control and prevention of communicable disease is directly impacted by the genetic mutability of the underlying etiological agents. In the case of RNA viruses, genetic recombination may impact public health by facilitating the generation of new viral strains with altered phenotypes and by compromising the genetic stability of live attenuated vaccines. The landscape of homologous recombination within a given RNA viral genome is thought to be influenced by several factors; however, a complete understanding of the genetic determinants of recombination is lacking. Here, we utilize gene synthesis and deep sequencing to create a detailed recombination map of the poliovirus 1 coding region. We identified over 50 thousand breakpoints throughout the genome, and we show the majority of breakpoints to be concentrated in a small number of specific “hotspots,” including those associated with known or predicted RNA secondary structures. Nucleotide base composition was also found to be associated with recombination frequency, suggesting that recombination is modulated across the genome by predictable and alterable motifs. We tested the predictive utility of the nucleotide base composition association by generating an artificial hotspot in the poliovirus genome. Our results imply that modification of these motifs could be extended to whole genome re-designs for the development of recombination-deficient, genetically stable live vaccine strains. PMID:23408891

  7. The late early Miocene Sabine River

    SciTech Connect

    Manning, E. )

    1990-09-01

    Work on a new late early Miocene vertebrate fossil site, in a paleochannel deposit of the upper Carnahan Bayou Member of the lower Fleming Formation, has revealed unexpected data on the course and nature of the Sabine River of that time. Screen washing for smaller vertebrate remains at the site, just west of the Sabine River in Newton County, central eastern Texas, has resulted in the recovery of early Permian, Early Cretaceous, Late Cretaceous (Maestrichtian), Paleocene/Eocene, late Eocene, and Oligocene/Miocene fossils, in addition to the main early Miocene fauna. The reworked fossils, as well as distinctive mineral grains, show that the late early Miocene Sabine River was connected to the Texas/Oklahoma/Arkansas boundary section of the Red River, as well as to rivers draining the southern Ouachita Mountains. These rivers must have joined the Texas/Louisiana boundary section of the Sabine River somewhere in northwest Louisiana at that time. This suggests that the Louisiana section of the present Red River pirated the Texas/Oklahoma/Arkansas boundary section of the river some time after the early Miocene. The preservation of recognizable fossils transported hundreds of miles in a large river itself requires explanation. It is speculated here that the late early Miocene Sabine River incorporated a large amount of the then recently deposited volcanic ash from the Trans-Pecos Volcanic Field. Montmorillonite clay from the altered volcanic ash would have made the river very turbid, which could have allowed coarse sand-sized particles to be carried in the suspended load of the river, rather than in its bed load (where they would have been destroyed by the rolling chert gravel). Additional evidence for such long-distance fossil transport in the late early Miocene rivers of the western Gulf Coastal Plain comes from the abundant Cretaceous fossils of the upper Oakville Formation of southeast Texas and the Siphonina davisi zone of the southeast Texas subsurface.

  8. Poliovirus Adsorption by 34 Minerals and Soils

    PubMed Central

    Moore, Rebecca S.; Taylor, Dene H.; Sturman, Lawrence S.; Reddy, Michael M.; Fuhs, G. Wolfgang

    1981-01-01

    The adsorption of radiolabeled infectious poliovirus type 2 by 34 well-defined soils and mineral substrates was analyzed in a synthetic freshwater medium containing 1 mM CaCl2 and 1.25 mM NaHCO3 at pH 7. In a model system, adsorption of poliovirus by Ottawa sand was rapid and reached equilibrium within 1 h at 4°C. Near saturation, the adsorption could be described by the Langmuir equation; the apparent surface saturation was 2.5 × 106 plaque-forming units of poliovirus per mg of Ottawa sand. At low surface coverage, adsorption was described by the Freundlich equation. The soils and minerals used ranged from acidic to basic and from high in organic content to organic free. The available negative surface charge on each substrate was measured by the adsorption of a cationic polyelectrolyte, polydiallyldimethylammonium chloride. Most of the substrates adsorbed more than 95% of the virus. In general, soils, in comparison with minerals, were weak adsorbents. Among the soils, muck and Genesee silt loam were the poorest adsorbents; among the minerals, montmorillonite, glauconite, and bituminous shale were the least effective. The most effective adsorbents were magnetite sand and hematite, which are predominantly oxides of iron. Correlation coefficients for substrate properties and virus adsorption revealed that the elemental composition of the adsorbents had little effect on poliovirus uptake. Substrate surface area and pH, by themselves, were not significantly correlated with poliovirus uptake. A strong negative correlation was found between poliovirus adsorption and both the contents of organic matter and the available negative surface charge on the substrates as determined by their capacities for adsorbing the cationic polyelectrolyte, polydiallyldimethylammonium chloride. PMID:6274259

  9. [Investigation of a Patient with Pre-vaccine-derived Poliovirus in Shandong Province, China].

    PubMed

    Lin, Xiaojuan; Liu, Yao; Wang, Suting; Zhang Xiao; Song, Lizhi; Tao, Zexin; Ji, Feng; Xiong, Ping; Xu, Aiqiang

    2015-09-01

    To analyze the genetic characteristics of a polio-I highly variant vaccine recombinant virus in Shandong Province (China) in 2011 and to identify isolates from healthy contacts, two stool specimens from one patient with acute flaccid paralysis (AFP) and 40 stool specimens from his contacts were collected for virus isolation. The complete genome of poliovirus and VP1 coding region of the non-polio enterovirus were sequenced. Homologous comparison and phylogenetic analyses based on VP1 sequences were undertaken among coxsackievirus (CV) B1, CV-B3 isolates, and those in GenBank. One poliovirus (P1/11186), CV-A4 and CV-A8 were isolated from the AFP patient; one CV-A2, Echovirus 3 (E-3), E-12 and E-14, ten CV-B1, and five CV-B3 strains were isolated from his contacts. These results led us to believe that there may be a human enterovirus epidemic in this area, and that surveillance must be enhanced. P1/11186 was a type-1 vaccine-related poliovirus; it combined with type-2 and type-3 polioviruses in 2A and 3A regions, respectively. There were 25 nucleotide mutations with 9 amino-acid alterations in the entire genome. There were 8 nucleotide mutations with 5 amino-acid alterations in the VP1 region compared with the corresponding Sabin strains. Homology analyses suggested that the ten CV-B1 isolates had 97.0%-100% nucleotide and 98.9%-100% amino-acid identities with each other, as well as 92.6%-100% nucleotide and 99.2%-100% amino-acid identities among the five CV-B3 isolates. Phylogenetic analyses on the complete sequences of VP1 among CV-B1 and CV-B3 isolates showed that Shandong strains, together with strains from other provinces in China, had a close relationship and belonged to the same group. PMID:26738293

  10. Poliovirus: Generation and Characterization of Mutants

    PubMed Central

    Burrill, Cecily P.; Strings, Vanessa R.; Schulte, Michael B.; Andino, Raul

    2016-01-01

    Poliovirus (PV) is the prototypical picornavirus. It is a non-enveloped RNA virus with a small (~7.5 kb) genome of positive polarity. cDNA clones of several strains are available, and infectious virus can be produced by the transfection of in vitro transcribed viral genomes into an appropriate host cell. The ease of genetic studies in poliovirus is a primary reason that it has long served as a model to study RNA virus biology, pathogenesis, and evolution. Protocols for the generation and characterization of PV mutants are presented. A separate unit concerning the production, propagation, quantification, and purification of PV will also be presented. PMID:23686829

  11. A severe case of co-infection with Enterovirus 71 and vaccine-derived Poliovirus type II.

    PubMed

    Ma, Shaohui; Du, Zengqing; Feng, Min; Che, Yanchun; Li, Qihan

    2015-11-01

    Enterovirus 71 (EV71) is often identified as the primary pathogen that directly leads to severe cases of HFMD, whereas the association between other enteroviruses and EV71 infection remains largely unclear. Here we report a rare case of a 5-year-old boy co-infected with EV71 and vaccine-derived Poliovirus (VDPV) type II, which were identified based on PCR and sequence analysis results and clinical symptoms and were characterized on CT. We determined that the EV71 strain belongs to the C4 subtype, and the VDPV II strain was closely genetically related to the reference Sabin type II strain. This report may improved our understanding of the clinical significance of the associations between clinical signs and the infectious properties of the involved pathogens. PMID:26361010

  12. Update on Vaccine-Derived Polioviruses - Worldwide, January 2015-May 2016.

    PubMed

    Jorba, Jaume; Diop, Ousmane M; Iber, Jane; Sutter, Roland W; Wassilak, Steven G; Burns, Cara C

    2016-01-01

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide (1). One of the main tools used in polio eradication efforts has been the live, attenuated, oral poliovirus vaccine (OPV) (2), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but provides long-term protection against paralytic disease. Through effective use of OPV, the Global Polio Eradication Initiative (GPEI) has brought wild polioviruses to the threshold of eradication (1). However, OPV use, particularly in areas with low routine vaccination coverage, is associated with the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (3). VDPVs can emerge among immunologically normal vaccine recipients and their contacts as well as among persons with primary immunodeficiencies (PIDs). Immunodeficiency-associated VDPVs (iVDPVs) can replicate for years in some persons with PIDs. In addition, circulating vaccine-derived polioviruses (cVDPVs) (3) can emerge in areas with low OPV coverage and can cause outbreaks of paralytic polio. This report updates previous summaries regarding VDPVs (4). PMID:27491079

  13. Poliovirus Laboratory Based Surveillance: An Overview.

    PubMed

    Zaidi, Syed Sohail Zahoor; Asghar, Humayun; Sharif, Salmaan; Alam, Muhammad Masroor

    2016-01-01

    World Health Assembly (WHA) in 1988 encouraged the member states to launch Global Polio Eradication Initiative (GPEI) (resolution WHA41.28) against "the Crippler" called poliovirus, through strong routine immunization program and intensified surveillance systems. Since its launch, global incidence of poliomyelitis has been reduced by more than 99 % and the disease squeezed to only three endemic countries (Afghanistan, Pakistan, and Nigeria) out of 125. Today, poliomyelitis is on the verge of eradication, and their etiological agents, the three poliovirus serotypes, are on the brink of extinction from the natural environment. The last case of poliomyelitis due to wild type 2 strain occurred in 1999 in Uttar Pradesh, India whereas the last paralytic case due to wild poliovirus type 3 (WPV3) was seen in November, 2012 in Yobe, Nigeria. Despite this progress, undetected circulation cannot fully rule out the eradication as most of the poliovirus infections are entirely subclinical; hence sophisticated environmental surveillance is needed to ensure the complete eradication of virus. Moreover, the vaccine virus in under-immunized communities can sometimes revert and attain wild type characteristics posing a big challenge to the program. PMID:26983728

  14. An Outbreak of Type Π Vaccine-Derived Poliovirus in Sichuan Province, China: Emergence and Circulation in an Under-Immunized Population

    PubMed Central

    Fan, Chun-Xiang; Liu, Qing-Lian; Hao, Li-Xin; Liu, Yu; Zheng, Jing-Shan; Qin, Zhi-Ying; Xia, Wei; Zhang, Shi-Yue; Yin, Zun-Dong; Jing, Qiong; Zhang, Yan-Xia; Huang, Rong-Na; Yang, Ru-Pei; Tong, Wen-Bin; Qi, Qi; Guan, Xu-Jing; Jing, Yu-Lin; Ma, Qian-Li; Wang, Jin; Ma, Xiao-Zhen; Chen, Na; Zheng, Hong-Ru; Li, Yin-Qiao; Ma, Chao; Su, Qi-Ru; Reilly, Kathleen H.; Luo, Hui-Ming; Wu, Xian-Ping; Wen, Ning; Yang, Wei-Zhong

    2014-01-01

    Background During August 2011–February 2012, an outbreak of type Π circulating vaccine-derived poliovirus (cVDPVs) occurred in Sichuan Province, China. Methods A field investigation of the outbreak was conducted to characterize outbreak isolates and to guide emergency response. Sequence analysis of poliovirus capsid protein VP1 was performed to determine the viral propagation, and a coverage survey was carried out for risk assessment. Results One clinical compatible polio case and three VDPV cases were determined in Ngawa County, Ngawa Tibetan and Qiang Autonomous Prefecture, Sichuan Province. Case patients were unimmunized children, 0.8–1 years old. Genetic sequencing showed that the isolates diverged from the VP1 region of the type Π Sabin strain by 5–12 nucleotides (nt) and shared the same 5 nt VP1 substitutions, which indicate single lineage of cVDPVs. Of the 7 acute flaccid paralysis cases (all>6 months) reported in Ngawa Prefecture in 2011, 4 (57.1%) cases (including 2 polio cases) did not receive oral attenuated poliovirus vaccine. Supplementary immunization activities (SIAs) were conducted in February–May, 2012, and the strain has not been isolated since. Conclusion High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Risk assessments should be conducted regularly to pinpoint high risk areas or subpopulations, with SIAs developed if necessary. PMID:25503964

  15. 75 FR 55968 - Special Local Regulations, Sabine River; Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-15

    ... (NPRM) entitled Special Local Regulations; Sabine River, Orange, TX in the Federal Register (75 FR 41119... published in 75 FR 41119. Regulatory Analyses We developed this rule after considering numerous statutes and... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations, Sabine River; Orange,...

  16. 75 FR 74029 - Sabine Pass LNG, L.P.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... Energy Regulatory Commission Sabine Pass LNG, L.P.; Notice of Application November 22, 2010. Take notice that on November 12, 2010, Sabine Pass LNG, L.P. (Sabine Pass), 700 Milam Street, Suite 800, Houston... directed to Patricia Outtrim, Sabine Pass LNG, L.P., 700 Milam Street, Suite 800, Houston, Texas 77002,...

  17. Update on vaccine-derived polioviruses - worldwide, July 2012-December 2013.

    PubMed

    Diop, Ousmane M; Burns, Cara C; Wassilak, Steven G; Kew, Olen M

    2014-03-21

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide. One of the main tools used in polio eradication efforts has been live, attenuated oral poliovirus vaccine (OPV), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but then it provides long-term protection against paralytic disease through durable humoral immunity. Rare cases of vaccine-associated paralytic poliomyelitis can occur among immunologically normal OPV recipients, their contacts, and persons who are immunodeficient. In addition, vaccine-derived polioviruses (VDPVs) can emerge in areas with low OPV coverage to cause polio outbreaks and can replicate for years in persons who have primary, B-cell immunodeficiencies. This report updates previous surveillance summaries and describes VDPVs detected worldwide during July 2012-December 2013. Those include a new circulating VDPV (cVDPV) outbreak identified in Pakistan in 2012, with spread to Afghanistan; an outbreak in Afghanistan previously identified in 2009 that continued into 2013; a new outbreak in Chad that spread to Cameroon, Niger, and northeastern Nigeria; and an outbreak that began in Somalia in 2008 that continued and spread to Kenya in 2013. A large outbreak in Nigeria that was identified in 2005 was nearly stopped by the end of 2013. Additionally, 10 newly identified persons in eight countries were found to excrete immunodeficiency-associated VDPVs (iVDPVs), and VDPVs were found among immunocompetent persons and environmental samples in 13 countries. Because the majority of VDPV isolates are type 2, the World Health Organization has developed a plan for coordinated worldwide replacement of trivalent OPV (tOPV) with bivalent OPV (bOPV; types 1 and 3) by 2016, preceded by introduction of at least 1 dose of inactivated poliovirus vaccine (IPV) containing all three poliovirus serotypes into routine immunization schedules worldwide to ensure high population

  18. 76 FR 63914 - Sabine River Authority of Texas and Sabine River Authority, State of Louisiana; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Sabine River Authority of Texas and Sabine River Authority, State of Louisiana; Notice of Application Tendered for Filing With the Commission and Establishing Procedural Schedule for Licensing and Deadline for...

  19. Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative

    PubMed Central

    Dunn, Glynis; Klapsa, Dimitra; Wilton, Thomas; Stone, Lindsay; Minor, Philip D.; Martin, Javier

    2015-01-01

    There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era. PMID:26313548

  20. [Circulating vaccine-derived poliovirus type 2 outbreak in Democratic Republic of Congo 2011-2012].

    PubMed

    Bazira, L; Coulibaly, T; Mayenga, M; Ncharre, C; Yogolelo, R; Mbule, A; Moudzeo, H; Lwamba, P; Mulumba, A W; Cabore, J

    2015-10-01

    According to the WHO records of 2013, the incidence of poliomyelitis was reduced by more than 99%, the number of endemic countries decreased from 125 in 1988 to 3 in 2013 and over 10 million cases were prevented from poliomyelitis thanks to the intensive use of Oral polio vaccine (OPV). However, the emergence of circulating vaccine-derived poliovirus strains (cVDPV), causing serious epidemics like the wild poliovirus, is a major challenge on the final straight towards the goal of eradication and OPV cessation. This paper describes the cVDPVoutbreak that occurred in the Democratic Republic of Congo (DRC) from November 2011 to April 2012. All children under 15 years of age with acute flaccid paralysis (AFP) and confirmed presence of cVDPV in the stool samples were included. Thirty (30) children, all from the administrative territories of Bukama and Malemba Nkulu in the Katanga Province (south-east DRC), were reported. The virus responsible was the cVDPV type 2 (0.7% -3.5% divergent from the reference Sabin 2 strain) in 29 children (97%) and the ambiguous vaccine-derived poliovirus strain (0.7% divergent) was confirmed in one case (3%), a boy seventeen months old and already vaccinated four times with OPV. Twentyfive children (83%) were protected by any of the routine EPI vaccines and 3 children (10%) had never received any dose of OPV. In reaction, DRC has conducted five local campaigns over a period of 10 months (from January to October 2012) and the epidemic was stopped after the second round performed in March 2012. As elsewhere in similar conditions, low immunization coverage, poor sanitation conditions and the stop of the use of OPV2 have favoured the emergence of the third cVDPV epidemic in DRC. The implementation of the Strategic Plan for Polio eradication and endgame strategic plan 2013-2018 will prevent the emergence of cVDPV and set up the conditions for a coordinated OPV phase out. PMID:26288132

  1. WHO collaborative studies on poliovirus type 3 strains isolated during the 1968 poliomyelitis epidemic in Poland.

    PubMed

    Melnick, J L; Berencsi, G; Biberi-Moroeanu, S; Combiescu, A A; Furesz, J; Kantoch, M; Kostrzewski, J; Magrath, D I; Perkins, F T; Vonka, V; Cockburn, W C; Dömök, I; Assaad, F A

    1972-01-01

    In 1968 in Poland an extensive outbreak of poliomyelitis, caused by type 3 poliovirus, began about four months after small vaccine trials with the Leon 12a(1)b (Sabin) and USOL-D bac vaccine strains had been carried out. Because of the temporal association, and because the first cases appeared in the province in which the USOL-D vaccine trial was carried out, a detailed investigation of the strains isolated from cases in the epidemic was made in four laboratories in an attempt to determine whether they were related to the two vaccine strains or to a "wild" strain. All the studies were made under code. The rct marker was of no help in determining the relationship of the epidemic strains to the vaccine strains. The McBride test and the elution marker test clearly separated the Leon 12a(1)b strains from those from the cases, but were incapable of detecting whether the epidemic strains were related to the USOL-D bac strain or to wild type 3 strains. Thus the studies did not provide valid information on the origin of the epidemic. PMID:4346582

  2. Environmental Isolation of Circulating Vaccine-Derived Poliovirus After Interruption of Wild Poliovirus Transmission - Nigeria, 2016.

    PubMed

    Etsano, Andrew; Damisa, Eunice; Shuaib, Faisal; Nganda, Gatei Wa; Enemaku, Ogu; Usman, Samuel; Adeniji, Adekunle; Jorba, Jaume; Iber, Jane; Ohuabunwo, Chima; Nnadi, Chimeremma; Wiesen, Eric

    2016-01-01

    In September 2015, more than 1 year after reporting its last wild poliovirus (WPV) case in July 2014 (1), Nigeria was removed from the list of countries with endemic poliovirus transmission,* leaving Afghanistan and Pakistan as the only remaining countries with endemic WPV. However, on April 29, 2016, a laboratory-confirmed, circulating vaccine-derived poliovirus type 2 (cVDPV2) isolate was reported from an environmental sample collected in March from a sewage effluent site in Maiduguri Municipal Council, Borno State, a security-compromised area in northeastern Nigeria. VDPVs are genetic variants of the vaccine viruses with the potential to cause paralysis and can circulate in areas with low population immunity. The Nigeria National Polio Emergency Operations Center initiated emergency response activities, including administration of at least 2 doses of oral poliovirus vaccine (OPV) to all children aged <5 years through mass campaigns; retroactive searches for missed cases of acute flaccid paralysis (AFP), and enhanced environmental surveillance. Approximately 1 million children were vaccinated in the first OPV round. Thirteen previously unreported AFP cases were identified. Enhanced environmental surveillance has not resulted in detection of additional VDPV isolates. The detection of persistent circulation of VDPV2 in Borno State highlights the low population immunity, surveillance limitations, and risk for international spread of cVDPVs associated with insurgency-related insecurity. Increasing vaccination coverage with additional targeted supplemental immunization activities and reestablishment of effective routine immunization activities in newly secured and difficult-to-reach areas in Borno is urgently needed. PMID:27490081

  3. Battle against poliovirus in Pakistan.

    PubMed

    Fatima, Kaneez; Qadri, Ishtiaq

    2013-11-01

    On 22 Feb 2013, the Polio Monitoring Cell of Pakistan announced that the 2012-2013 polio campaign ended, and that 1.6 million children could not be vaccinated due to security concerns in several regions where polio workers had been killed. Those who could not be vaccinated included 50,000 children from the Federally Administrated Tribal Area (FATA), 150,000 form Khyber Pakhtoon Khao, 400,000 from a Quetta, 400,000 from Karachi, and a small number from the Rawalpindi District. These statistics are worrying, as several districts in the large metropolitan cities of Karachi and Quetta were also excluded. The fear of advanced medicine, ideas, or complex devices is a new phenomenon in many conservative and poor countries such as Pakistan, Afghanistan, Sudan, and Somalia. To safeguard the safety of the rest of the world, the failure in the implementation of WHO guidelines for vaccination must be regulated by the UN. There are a number of reasons for the phobias surrounding vaccination, but as technology continues to evolve at such a rapid rate, those with self-determined ideologies cannot cope with such advances. They become vocal to gain popularity and prevent the use of these technologies and medicine by creating and spreading rumors and propaganda of expediency. The struggle to vaccinate children is not easily understood by anyone living in the developed world. The irrational fear of vaccines and the lack of vaccination pose a serious global health risk and must be curbed through a wide variety of pro-vaccination media and religious campaigns. PMID:24240051

  4. Circulating vaccine-derived polioviruses: current state of knowledge.

    PubMed Central

    Kew, Olen M.; Wright, Peter F.; Agol, Vadim I.; Delpeyroux, Francis; Shimizu, Hiroyuki; Nathanson, Neal; Pallansch, Mark A.

    2004-01-01

    Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence. PMID:15106296

  5. NCI’s Douglas R. Lowy and John T. Schiller awarded Sabin Medal

    Cancer.gov

    NCI scientists whose discovery provided the technology for commercially developed HPV vaccines were honored with the prestigious Albert B. Sabin Gold Medal Award at a ceremony held at the Sabin Vaccine Institute, May 18, 2011.

  6. Concentration and purification of poliovirus by ultrafiltration and isopycnic centrifugation.

    PubMed

    Guskey, L E; Wolff, D A

    1972-07-01

    A method is described by which poliovirus can be rapidly and simply concentrated by the use of a Diaflo XM-50 ultrafilter membrane. Freon-extracted ultrafilter concentrates banded in CsCl provided a 1,724-fold volumetric concentration of poliovirus. During concentration, trypsin-digested cellular material can pass through the ultrafilter membrane, thus providing a versatile means of degrading and eliminating extraneous contaminating proteins. The ultrafilter concentration system is compared with the CsCl cushion system of poliovirus concentration, and both systems are further compared by banding virus and virus capsid material in CsCl by use of isopycnic centrifugation. PMID:4341520

  7. Seroimmunity to polioviruses in U.S. Army recruits.

    PubMed

    Burke, D S; Gaydos, J C; Hodder, R A; Bancroft, W H

    1979-02-01

    Titers of neutralizing antibody to poliovirus types 1, 2, and 3 were determined for serum specimens obtained from 268 U.S. Army recruits. Among those tested, 20.9% lacked neutralizing antibody to one or more types of poliovirus, and 1.1% lacked antibody to all three types. An analysis of demographic data showed that age of less than 18 years, schooling for less than 10 years, and residence in the northeastern United States were associated with higher percentages of recruits lacking neutralizing antibodies to polioviruses in serum. PMID:220335

  8. 75 FR 33803 - Sabine Pipe Line LLC; Notice of Request Under Blanket Authorization

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ... Energy Regulatory Commission Sabine Pipe Line LLC; Notice of Request Under Blanket Authorization June 8, 2010. Take notice that on June 1, 2010, Sabine Pipe Line LLC (Sabine), 4800 Fournace Place, Bellaire... L. Kirk, Regulatory Specialist, Chevron Pipe Line Company, 4800 Fournace Place, Bellaire,...

  9. Kinetics of poliovirus shedding following oral vaccination as measured by quantitative reverse transcription-PCR versus culture.

    PubMed

    Taniuchi, Mami; Begum, Sharmin; Uddin, Md Jashim; Platts-Mills, James A; Liu, Jie; Kirkpatrick, Beth D; Chowdhury, Anwarul H; Jamil, Khondoker M; Haque, Rashidul; Petri, William A; Houpt, Eric R

    2015-01-01

    Amid polio eradication efforts, detection of oral polio vaccine (OPV) virus in stool samples can provide information about rates of mucosal immunity and allow estimation of the poliovirus reservoir. We developed a multiplex one-step quantitative reverse transcription-PCR (qRT-PCR) assay for detection of OPV Sabin strains 1, 2, and 3 directly in stool samples with an external control to normalize samples for viral quantity and compared its performance with that of viral culture. We applied the assay to samples from infants in Dhaka, Bangladesh, after the administration of trivalent OPV (tOPV) at weeks 14 and 52 of life (on days 0 [pre-OPV], +4, +11, +18, and +25 relative to vaccination). When 1,350 stool samples were tested, the sensitivity and specificity of the quantitative PCR (qPCR) assay were 89 and 91% compared with culture. A quantitative relationship between culture(+)/qPCR(+) and culture(-)/qPCR(+) stool samples was observed. The kinetics of shedding revealed by qPCR and culture were similar. qPCR quantitative cutoffs based on the day +11 or +18 stool samples could be used to identify the culture-positive shedders, as well as the long-duration or high-frequency shedders. Interestingly, qPCR revealed that a small minority (7%) of infants contributed the vast majority (93 to 100%) of the total estimated viral excretion across all subtypes at each time point. This qPCR assay for OPV can simply and quantitatively detect all three Sabin strains directly in stool samples to approximate shedding both qualitatively and quantitatively. PMID:25378579

  10. Construction and characterization of poliovirus subgenomic replicons.

    PubMed

    Kaplan, G; Racaniello, V R

    1988-05-01

    Poliovirus RNAs containing in-frame deletions within the capsid-coding region were produced by in vitro transcription of altered poliovirus type 1 cDNA by using bacteriophage T7 RNA polymerase. Three RNAs were transcribed that contained deletions of 2,317 nucleotides (bases 747 to 3064), 1,781 nucleotides (bases 1,175 to 2,956), and 1,295 nucleotides (bases 1,175 to 2,470). All three subgenomic RNAs replicated after transfection into HeLa cells, demonstrating that sequences encoding the capsid polypeptides are not essential for viral RNA replication in vivo. Viral RNA containing the largest deletion (R1) replicated approximately three times better than full-length RNA produced in vitro. Northern blot (RNA blot) hybridization analysis of total cellular RNA from HeLa cells at different times after transfection with R1 demonstrated the presence of increasing amounts of the expected 5.1-kilobase subgenomic RNA. Analysis by immunoprecipitation of viral proteins induced after transfection of R1 RNA into HeLa cells revealed the presence of proteins 2Apro, 2C, and 3Dpol and its precursors, suggesting that the polyprotein cleavages are similar to those occurring in virus-infected cells. Replication of P2/Lansing virion RNA was inhibited by cotransfection with the R1 replicon, as demonstrated by hybridization analysis with a serotype-specific oligonucleotide probe. A higher level of inhibition of RNA replication was observed when P2/Lansing RNA was cotransfected into HeLa cells with truncated R1 transcripts (R1-PvuII) that were missing 395 3' nucleotides and a poly(A) tail. These internally and terminally deleted RNAs inhibited the replication of subgenomic replicons R1, R2, and R3 and caused a reduction in plaque size when cotransfected with P1/Mahoney or P2/Lansing viral RNA, suggesting that individual cells had received both RNAs. No inhibition of plaque size was observed when replicon RNAs were used that were missing 1,384 or 1,839 3' nucleotides or contained plasmid

  11. Exploring the fitness landscape of poliovirus

    NASA Astrophysics Data System (ADS)

    Bianco, Simone; Acevedo, Ashely; Andino, Raul; Tang, Chao

    2012-02-01

    RNA viruses are known to display extraordinary adaptation capabilities to different environments, due to high mutation rates. Their very dynamical evolution is captured by the quasispecies concept, according to which the viral population forms a swarm of genetic variants linked through mutation, which cooperatively interact at a functional level and collectively contribute to the characteristics of the population. The description of the viral fitness landscape becomes paramount towards a more thorough understanding of the virus evolution and spread. The high mutation rate, together with the cooperative nature of the quasispecies, makes it particularly challenging to explore its fitness landscape. I will present an investigation of the dynamical properties of poliovirus fitness landscape, through both the adoption of new experimental techniques and theoretical models.

  12. Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame.

    PubMed

    Pons-Salort, Margarita; Burns, Cara C; Lyons, Hil; Blake, Isobel M; Jafari, Hamid; Oberste, M Steven; Kew, Olen M; Grassly, Nicholas C

    2016-07-01

    Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently "missed" groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004-2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55-0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity above the

  13. Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame

    PubMed Central

    Burns, Cara C.; Lyons, Hil; Blake, Isobel M.; Oberste, M. Steven; Kew, Olen M.; Grassly, Nicholas C.

    2016-01-01

    Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently “missed” groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004−2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55−0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity

  14. Development and consideration of global policies for managing the future risks of poliovirus outbreaks: insights and lessons learned through modeling.

    PubMed

    Thompson, Kimberly M; Duintjer Tebbens, Radboud J; Pallansch, Mark A; Kew, Olen M; Sutter, Roland W; Aylward, R Bruce; Watkins, Margaret; Gary, Howard; Alexander, James P; Venczel, Linda; Johnson, Denise; Cáceres, Victor M; Sangrujee, Nalinee; Jafari, Hamid; Cochi, Stephen L

    2006-12-01

    The success of the Global Polio Eradication Initiative promises to bring large benefits, including sustained improvements in quality of life (i.e., cases of paralytic disease and deaths avoided) and costs saved from cessation of vaccination. Obtaining and maintaining these benefits requires that policymakers manage the transition from the current massive use of oral poliovirus vaccine (OPV) to a world without OPV and free of the risks of potential future reintroductions of live polioviruses. This article describes the analytical journey that began in 2001 with a retrospective case study on polio risk management and led to development of dynamic integrated risk, economic, and decision analysis tools to inform global policies for managing the risks of polio. This analytical journey has provided several key insights and lessons learned that will be useful to future analysts involved in similar complex decision-making processes. PMID:17184398

  15. 75 FR 41119 - Special Local Regulations; Sabine River, Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ..., 2008, issue of the Federal Register (73 FR 3316). Public Meeting We do not now plan to hold a public... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations; Sabine River, Orange, TX... River, Orange, Texas. This Special Local Regulation is intended to restrict vessels from portions of...

  16. 76 FR 30890 - Special Local Regulations; Sabine River, Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-27

    ... Federal Register (73 FR 3316). Public Meeting We do not now plan to hold a public meeting. But you may... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations; Sabine River, Orange, TX... River, Orange, Texas on September 24-25, 2011. This Special Local Regulation is intended to...

  17. Seroepidemiology of Polioviruses among University Students in Northern Italy

    PubMed Central

    Baldo, Vincenzo; Cocchio, Silvia; Lazzari, Roberta; Saracino, Elena; Bertoncello, Chiara; Buja, Alessandra; Trevisan, Andrea

    2012-01-01

    The widespread use of poliovirus vaccination schemes has led to a marked decline in the incidence of paralytic poliomyelitis worldwide, but wild poliovirus is still endemic in some developing countries, and in 2009 a total of 23 countries reported at least 1 case of poliomyelitis caused by wild-strain polio viruses. A serological survey was thus conducted on the immunological status against polioviruses of 318 young adults, classified by their country of origin. Immunity to poliomyelitis was assessed by neutralizing antibody titration in tissues cultured on microplates. The rate of seronegativity (≤1:8) in the study population was 26.7% for poliovirus type 1, 7.2% for type 2, and 22.6% for type 3. In our sample of 318 individuals, 219 (68.9%) were Italian and 99 (31.1%) were from outside the European Union (EU). The proportion of cases found seropositive to polioviruses 1 and 3 decreased significantly with older age; this age-related decrease was more evident in the Italian group than among the non-EU subjects. Any risk of the wild virus recurring and causing paralytic poliomyelitis must be prevented, keeping Europe polio free by means of appropriate immunological protection, until polio has been conclusively eradicated all over the world. Judging from our findings, it may be worth considering administering a fifth dose of polio vaccine to adolescents. PMID:22739695

  18. Seroepidemiology of polioviruses among university students in northern Italy.

    PubMed

    Baldo, Vincenzo; Baldovin, Tatjana; Cocchio, Silvia; Lazzari, Roberta; Saracino, Elena; Bertoncello, Chiara; Buja, Alessandra; Trevisan, Andrea

    2012-08-01

    The widespread use of poliovirus vaccination schemes has led to a marked decline in the incidence of paralytic poliomyelitis worldwide, but wild poliovirus is still endemic in some developing countries, and in 2009 a total of 23 countries reported at least 1 case of poliomyelitis caused by wild-strain polio viruses. A serological survey was thus conducted on the immunological status against polioviruses of 318 young adults, classified by their country of origin. Immunity to poliomyelitis was assessed by neutralizing antibody titration in tissues cultured on microplates. The rate of seronegativity (≤ 1:8) in the study population was 26.7% for poliovirus type 1, 7.2% for type 2, and 22.6% for type 3. In our sample of 318 individuals, 219 (68.9%) were Italian and 99 (31.1%) were from outside the European Union (EU). The proportion of cases found seropositive to polioviruses 1 and 3 decreased significantly with older age; this age-related decrease was more evident in the Italian group than among the non-EU subjects. Any risk of the wild virus recurring and causing paralytic poliomyelitis must be prevented, keeping Europe polio free by means of appropriate immunological protection, until polio has been conclusively eradicated all over the world. Judging from our findings, it may be worth considering administering a fifth dose of polio vaccine to adolescents. PMID:22739695

  19. 78 FR 1851 - Sabine Pass Liquefaction, LLC and Sabine Pass LNG, L.P.; Notice of Intent To Prepare an...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... facility; condensate storage, metering and send-out facilities; four gas pipeline meter stations... HRU, condensate storage, and metering facilities would be located within the existing Sabine Pass LNG... wetlands; Cultural resources; Vegetation and wildlife; Air quality and noise; Endangered and...

  20. Cellular origin and ultrastructure of membranes induced during poliovirus infection.

    PubMed Central

    Schlegel, A; Giddings, T H; Ladinsky, M S; Kirkegaard, K

    1996-01-01

    Poliovirus RNA replicative complexes are associated with cytoplasmic membranous structures that accumulate during viral infection. These membranes were immunoisolated by using a monoclonal antibody against the viral nonstructural protein 2C. Biochemical analysis of the isolated membranes revealed that several organelles of the host cell (lysosomes, trans-Golgi stack and trans-Golgi network, and endoplasmic reticulum) contributed to the virus-induced membranous structures. Electron microscopy of infected cells preserved by high-pressure freezing revealed that the virus-induced membranes contain double lipid bilayers that surround apparently cytosolic material. Immunolabeling experiments showed that poliovirus proteins 2C and 3D were localized to the same membranes as the cellular markers tested. The morphological and biochemical data are consistent with the hypothesis that autophagy or a similar host process is involved in the formation of the poliovirus-induced membranes. PMID:8794292

  1. Poliovirus protein 2C has ATPase and GTPase activities.

    PubMed

    Rodríguez, P L; Carrasco, L

    1993-04-15

    Poliovirus protein 2C belongs to an expanding group of proteins containing a nucleotide binding motif in their sequence. We present evidence that poliovirus 2C has nucleoside triphosphatase (NTPase) activity and binds to RNA. Poliovirus 2C was expressed in Escherichia coli cells as a fusion protein with the maltose binding protein (MBP). The fusion protein MBP-2C is efficiently cut by protease Xa within the 2C region. Thus, the fusion protein as such was used to assay for the putative activities of poliovirus 2C. Deletion mutants were constructed which lacked different portions of the 2C carboxyl terminus: mutant 2C delta 1 lacked the last 169 amino acids, whereas mutant 2C delta 2 had the last 74 amino acids deleted. The fusion proteins MBP-2C, MBP-2BC, and the mutant MBP-2C delta 2 that contained the first 255 amino acids of 2C had NTPase activity. Both ATPase and GTPase activities are inhibited by antibodies directed against the MBP-2C protein. Analysis of the ability of the different proteins to bind to labeled RNA indicates that MBP-2C and MBP-2BC form a complex, whereas none of the mutants interacted with RNA, indicating that the RNA binding domain lies beyond amino acid 255. None of the fusion proteins had detectable helicase activity. We suggest that poliovirus protein 2C shows similarities to the GTPases group involved in vesicular traffic and transports the viral RNA replication complexes. These results provide the first experimental evidence that poliovirus protein 2C is an NTPase and that this protein has affinity for nucleic acids. PMID:8385138

  2. Annual report of the Australian National Poliovirus Reference Laboratory, 2008.

    PubMed

    Roberts, Jason A; Grant, Kristina A; Yoon, Yeon Kyung; Polychronopoulos, Sophie; Ibrahim, Aishah; Thorley, Bruce R

    2009-09-01

    The Australian National Poliovirus Reference Laboratory (NPRL) is accredited by the World Health Organization (WHO) for the testing of stool specimens from cases of acute flaccid paralysis (AFP), a major clinical presentation of poliovirus infection. The NPRL, in collaboration with the Australian Paediatric Surveillance Unit, co-ordinates surveillance for cases of AFP in children in Australia, according to criteria recommended by the WHO. Clinical specimens are referred from AFP cases in children and suspected case of poliomyelitis in persons of any age. The WHO AFP surveillance performance indicator for a polio-free country such as Australia, is 1 non-polio AFP case per 100,000 children less than 15 years of age. In 2008, the Polio Expert Committee (PEC) classified 62 cases as non-polio AFP, or 1.51 non-polio AFP cases per 100,000 children aged less than 15 years. Poliovirus infection is confirmed by virus culture of stool specimens from AFP cases as other conditions that present with acute paralysis can mimic polio. While no poliovirus was reported in Australia from any source in 2008, the non-polio enteroviruses echovirus 25, coxsackievirus B2 and echovirus 11 were isolated from stool specimens of AFP cases. The last report of a wild poliovirus in Australia was due to an importation from Pakistan in 2007. With 4 countries remaining endemic for poliomyelitis--Afghanistan, India, Nigeria and Pakistan--and more than 1,600 confirmed cases of wild poliovirus infection in 18 countries in 2008, Australia continues to be at risk of further importation events. PMID:20043599

  3. Modification of RNA polymerase IIO subspecies after poliovirus infection.

    PubMed Central

    Rangel, L M; Fernandez-Tomas, C; Dahmus, M E; Gariglio, P

    1987-01-01

    Infection of HeLa cells with poliovirus results in a shutdown of host transcription. In an effort to understand the mechanism(s) that underlies this process, we analyzed the distribution of RNA polymerase IIO before and after viral infection. Analysis of free and chromatin-bound enzyme indicated that there is a significant reduction in RNA polymerase IIO following infection. This observation, together with increasing evidence that transcription is catalyzed by RNA polymerase IIO, supports the hypothesis that poliovirus-induced inhibition of host transcription occurs at the level of RNA chain initiation and involves the direct modification of RNA polymerase II. Images PMID:3029396

  4. Defective Interfering Particles of Poliovirus I. Isolation and Physical Properties

    PubMed Central

    Cole, Charles N.; Smoler, Donna; Wimmer, Eckard; Baltimore, David

    1971-01-01

    A class of defective interfering (DI) poliovirus particles has been identified. The first was found as a contaminant of a viral stock; others have been isolated by serial passage at a high multiplicity of infection. The DI particles are less dense than standard virus and sediment more slowly. Their ribonucleic acid (RNA) sediments more slowly than standard RNA and has a higher electrophoretic mobility. Competition hybridization experiments with double-stranded viral RNA indicate that DI RNA is 80 to 90% of the length of standard RNA. The proteins of DI particles are indistinguishable from those of standard poliovirus. PMID:4329564

  5. Update on Vaccine-Derived Polioviruses - Worldwide, January 2014-March 2015.

    PubMed

    Diop, Ousmane M; Burns, Cara C; Sutter, Roland W; Wassilak, Steven G; Kew, Olen M

    2015-06-19

    Since the World Health Assembly's 1988 resolution to eradicate poliomyelitis, one of the main tools of the World Health Organization (WHO) Global Polio Eradication Initiative (GPEI) has been the live, attenuated oral poliovirus vaccine (OPV). OPV might require several doses to induce immunity but provides long-term protection against paralytic disease. Through effective use of OPV, GPEI has brought polio to the threshold of eradication. Wild poliovirus type 2 (WPV2) was eliminated in 1999, WPV3 has not been detected since November 2012, and WPV1 circulation appears to be restricted to parts of Pakistan and Afghanistan. However, continued use of OPV carries two key risks. The first, vaccine-associated paralytic poliomyelitis (VAPP) has been recognized since the early 1960s. VAPP is a very rare event that occurs sporadically when an administered dose of OPV reverts to neurovirulence and causes paralysis in the vaccine recipient or a nonimmune contact. VAPP can occur among immunologically normal vaccine recipients and their contacts as well as among persons who have primary immunodeficiencies (PIDs) manifested by defects in antibody production; it is not associated with outbreaks. The second, the emergence of genetically divergent, neurovirulent vaccine-derived polioviruses (VDPVs) was recognized more recently. Circulating VDPVs (cVDPVs) resemble WPVs and, in areas with low OPV coverage, can cause polio outbreaks. Immunodeficiency-associated VDPVs (iVDPVs) can replicate and be excreted for years in some persons with PIDs; GPEI maintains a registry of iVDPV cases. Ambiguous VDPVs (aVDPVs) are isolates that cannot be classified definitively. This report updates previous surveillance summaries and describes VDPVs detected worldwide during January 2014-March 2015. Those include new cVDPV outbreaks in Madagascar and South Sudan, and sharply reduced type 2 cVDPV (cVDPV2) circulation in Nigeria and Pakistan during the latter half of 2014. Eight newly identified persons in

  6. Multiple Poliovirus Proteins Repress Cytoplasmic RNA Granules

    PubMed Central

    Dougherty, Jonathan D.; Tsai, Wei-Chih; Lloyd, Richard E.

    2015-01-01

    We have previously shown that poliovirus (PV) infection induces stress granule (SG) formation early in infection and then inhibits the formation of SG and disperses processing bodies (PBs) by the mid-phase of infection. Loss of SG was linked to cleavage of G3BP1 by viral 3C proteinase (3Cpro), however dispersal of PBs was not strongly linked to cleavage of specific factors by viral proteinases, suggesting other viral proteins may play roles in inhibition of SG or PB formation. Here we have screened all viral proteins for roles in inducing or inhibiting the formation of RNA granules by creating fusions with mCherry and expressing them individually in cells. Expression of viral proteins separately revealed that the capsid region P1, 2Apro, 3A, 3Cpro, the protease precursor 3CD and 3D polymerase all affect RNA granules to varying extents, whereas 2BC does not. 2Apro, which cleaves eIF4GI, induced SGs as expected, and entered novel foci containing the SG nucleating protein G3BP1. Of the two forms of G3BP, only G3BP1 is cleaved by a virus proteinase, 3Cpro, whereas G3BP2 is not cleaved by 3Cpro or 2Apro. Surprisingly, 3CD, which contains proteinase activity, differentially repressed PBs but not SGs. Further, both 2Apro and 3Cpro expression dispersed PBs, however molecular targets were different since PB dispersal due to 2Apro and heat shock protein (Hsp)90 inhibition but not 3Cpro, could be rescued by application of oxidative stress to cells. The data indicate that PV repression of SGs and PBs is multifactorial, though protease function is dominant. PMID:26610553

  7. Poliovirus receptor CD155–targeted oncolysis of glioma1

    PubMed Central

    Merrill, Melinda K.; Bernhardt, Guenter; Sampson, John H.; Wikstrand, Carol J.; Bigner, Darell D.; Gromeier, Matthias

    2004-01-01

    Cell adhesion molecules of the immunoglobulin superfamily are aberrantly expressed in malignant glioma. Amongst these, the human poliovirus receptor CD155 provides a molecular target for therapeutic intervention with oncolytic poliovirus recombinants. Poliovirus has been genetically modified through insertion of regulatory sequences derived from human rhinovirus type 2 to selectively replicate within and destroy cancerous cells. Efficacious oncolysis mediated by poliovirus derivatives depends on the presence of CD155 in targeted tumors. To prepare oncolytic polioviruses for clinical application, we have developed a series of assays in high-grade malignant glioma (HGL) to characterize CD155 expression levels and susceptibility to oncolytic poliovirus recombinants. Analysis of 6 HGL cases indicates that CD155 is expressed in these tumors and in primary cell lines derived from these tumors. Upregulation of the molecular target CD155 rendered explant cultures of all studied tumors highly susceptible to a prototype oncolytic poliovirus recombinant. Our observations support the clinical application of such agents against HGL. PMID:15279713

  8. Polio eradication. Efficacy of inactivated poliovirus vaccine in India.

    PubMed

    Jafari, Hamid; Deshpande, Jagadish M; Sutter, Roland W; Bahl, Sunil; Verma, Harish; Ahmad, Mohammad; Kunwar, Abhishek; Vishwakarma, Rakesh; Agarwal, Ashutosh; Jain, Shilpi; Estivariz, Concepcion; Sethi, Raman; Molodecky, Natalie A; Grassly, Nicholas C; Pallansch, Mark A; Chatterjee, Arani; Aylward, R Bruce

    2014-08-22

    Inactivated poliovirus vaccine (IPV) is efficacious against paralytic disease, but its effect on mucosal immunity is debated. We assessed the efficacy of IPV in boosting mucosal immunity. Participants received IPV, bivalent 1 and 3 oral poliovirus vaccine (bOPV), or no vaccine. A bOPV challenge was administered 4 weeks later, and excretion was assessed 3, 7, and 14 days later. Nine hundred and fifty-four participants completed the study. Any fecal shedding of poliovirus type 1 was 8.8, 9.1, and 13.5% in the IPV group and 14.4, 24.1, and 52.4% in the control group by 6- to 11-month, 5-year, and 10-year groups, respectively (IPV versus control: Fisher's exact test P < 0.001). IPV reduced excretion for poliovirus types 1 and 3 between 38.9 and 74.2% and 52.8 and 75.7%, respectively. Thus, IPV in OPV-vaccinated individuals boosts intestinal mucosal immunity. PMID:25146288

  9. 21 CFR 866.3405 - Poliovirus serological reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405...

  10. 21 CFR 866.3405 - Poliovirus serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405...

  11. 21 CFR 866.3405 - Poliovirus serological reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405...

  12. 21 CFR 866.3405 - Poliovirus serological reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405...

  13. 21 CFR 866.3405 - Poliovirus serological reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405...

  14. POLIOVIRUS TYPE 1: NEUTRALIZATION BY PAPAIN-DIGESTED ANTIBODIES.

    PubMed

    VOGT, A; KOPP, R; MAASS, G; REICH, L

    1964-09-25

    Papain-digested rabbit antibody (Porter's fractions I and II) can neutralize poliovirus. Neutralizing capacity after digestion ranged from 35 to 45 percent of that of the undigested antibody. No definite dissociation of the antibody fragments from the virus was observed after the reaction mixture had been diluted in a neutral medium. PMID:14175107

  15. Analysis of Sabine river flow data using semiparametric spline modeling

    NASA Astrophysics Data System (ADS)

    Bandyopadhyay, Soutir; Maity, Arnab

    2011-03-01

    SummaryIn this article, a modeling approach for the mean annual flow in different segments of Sabine river, as released in the NHDPlus data in 2007, as a function of five predictor variables is described. Modeling flow is extremely complex and the deterministic flow models are widely used for that purpose. The justification for using these deterministic models comes from the fact that the flow is governed by some explicitly stated physical laws. In contrast, in this article, this complex issue is addressed from a completely statistical point of view. A semiparametric model is proposed to analyze the spatial distribution of the mean annual flow of Sabine river. Semiparametric additive models allow explicit consideration of the linear and nonlinear relations with relevant explanatory variables. We use a conditionally specified Gaussian model for the estimation of the univariate conditional distributions of flow to incorporate auxiliary information and this formulation does not require the target variable to be independent.

  16. 33 CFR 80.840 - Sabine Pass, TX to Galveston, TX.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sabine Pass, TX to Galveston, TX. 80.840 Section 80.840 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Eighth District § 80.840 Sabine Pass, TX to...

  17. 33 CFR 165.806 - Sabine Neches Waterway, Texas-regulated navigation area.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Sabine Neches Waterway, Texas... § 165.806 Sabine Neches Waterway, Texas—regulated navigation area. (a) The following is a regulated... thereto. (b) Unless otherwise authorized by the Captain of the Port, Port Arthur, Texas, tows on a...

  18. 33 CFR 165.806 - Sabine Neches Waterway, Texas-regulated navigation area.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Sabine Neches Waterway, Texas... § 165.806 Sabine Neches Waterway, Texas—regulated navigation area. (a) The following is a regulated... thereto. (b) Unless otherwise authorized by the Captain of the Port, Port Arthur, Texas, tows on a...

  19. 33 CFR 165.806 - Sabine Neches Waterway, Texas-regulated navigation area.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Sabine Neches Waterway, Texas... § 165.806 Sabine Neches Waterway, Texas—regulated navigation area. (a) The following is a regulated... thereto. (b) Unless otherwise authorized by the Captain of the Port, Port Arthur, Texas, tows on a...

  20. 33 CFR 165.806 - Sabine Neches Waterway, Texas-regulated navigation area.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Sabine Neches Waterway, Texas... § 165.806 Sabine Neches Waterway, Texas—regulated navigation area. (a) The following is a regulated... thereto. (b) Unless otherwise authorized by the Captain of the Port, Port Arthur, Texas, tows on a...

  1. Interim CDC guidance for polio vaccination for travel to and from countries affected by wild poliovirus.

    PubMed

    Wallace, Gregory S; Seward, Jane F; Pallansch, Mark A

    2014-07-11

    In the prevaccine era, infection with wild poliovirus (WPV) was common worldwide, with seasonal peaks and epidemics in the summer and fall in temperate areas. The incidence of poliomyelitis in the United States declined rapidly after the licensure of inactivated polio vaccine (IPV) in 1955 and live oral polio vaccine (OPV) in the 1960s. The last cases of indigenously acquired WPV in the United States occurred in 1979, the last WPV case in a U.S. resident traveling abroad occurred in 1986, and the last WPV imported case was in 1993. Since 2000, the United States has exclusively used IPV, resulting in prevention of 8-10 vaccine-associated paralytic poliomyelitis cases annually. In 2005, an unvaccinated U.S. adult traveling abroad acquired vaccine-associated paralytic poliomyelitis after contact with an infant recently vaccinated with OPV. PMID:25006826

  2. National choices related to inactivated poliovirus vaccine, innovation and the endgame of global polio eradication.

    PubMed

    Thompson, Kimberly M; Duintjer Tebbens, Radboud J

    2014-02-01

    Achieving the goal of a world free of poliomyelitis still requires significant effort. Although polio immunization represents a mature area, the polio endgame will require new tools and strategies, particularly as national and global health leaders coordinate the cessation of all three serotypes of oral poliovirus vaccine and increasingly adopt inactivated poliovirus vaccine (IPV). Poliovirus epidemiology and the global options for managing polioviruses continue to evolve, along with our understanding and appreciation of the resources needed and the risks that require management. Based on insights from modeling, we offer some perspective on the current status of plans and opportunities to achieve and maintain a world free of wild polioviruses and to successfully implement oral poliovirus vaccine cessation. IPV costs and potential wastage will represent an important consideration for national policy makers. Innovations may reduce future IPV costs, but the world urgently needs lower-cost IPV options. PMID:24308581

  3. Albert Sabin and the Coalition to Eliminate Polio From the Americas

    PubMed Central

    2009-01-01

    Albert B. Sabin, MD, developer of the oral polio vaccine, was also a major proponent of its use in annual vaccination campaigns aimed at the elimination of polio. Sabin argued that administering his vaccine simultaneously to every child in a country would break polio's chains of transmission. Although he was already promoting mass vaccination by the 1960s, Sabin's efforts expanded considerably when he became an adviser to groups fighting polio in the Americas in the 1980s. Sabin's experiences provide a window into both the formation of the coalition that eliminated poliomyelitis from the Western Hemisphere and what can happen when biomedical researchers become public health policy advisers. Although the polio elimination coalition succeeded in part because member groups often accommodated each other's priorities, Sabin was often limited by his indifference to the interests of those he was advising and to the shortcomings of his vaccine. PMID:19008524

  4. Chlorine resistance of poliovirus isolants recovered from drinking water.

    PubMed Central

    Shaffer, P T; Metcalf, T G; Sproul, O J

    1980-01-01

    Poliovirus 1 isolants were recovered from finished drinking water produced by a modern, well-operated water treatment plant. These waters contained free chlorine residuals in excess of 1 mg/liter. The chlorine inactivation of purified high-titer preparations of two such isolants was compared with the inactivation behavior of two stock strains of poliovirus 1, LSc and Mahoney. The surviving fraction of virus derived from the two natural isolants was shown to be orders of magnitude greater than that of the standard strains. These results raise the question whether indirect drinking water standards based on free chlorine residuals are adequate public health measures, or whether direct standards based on virus determinations might be necessary. Images PMID:6257162

  5. Surface for Catalysis by Poliovirus RNA-Dependent RNA Polymerase

    PubMed Central

    Wang, Jing; Lyle, John M.; Bullitt, Esther

    2013-01-01

    The poliovirus RNA-dependent RNA polymerase, 3Dpol, replicates the viral genomic RNA on the surface of virus-induced intracellular membranes. Macromolecular assemblies of 3Dpol form linear array of subunits that propagate along a strong protein-protein interaction called interface-I, as was observed in the crystal structure of wild-type poliovirus polymerase. These “filaments” recur with slight modifications in planar sheets and, with additional modifications that accommodate curvature, in helical tubes of the polymerase, by packing filaments together via a second set of interactions. Periodic variations of subunit orientations within 3Dpol tubes give rise to “ghost reflections” in diffraction patterns computed from electron cryomicrographs of helical arrays. The ghost reflections reveal that polymerase tubes are formed by bundles of 4–6 interface-I filaments, which are then connected to the next bundle of filaments with a perturbation of interface interactions between bundles. While enzymatically inactive polymerase is also capable of oligomerization, much thinner tubes are formed that lack interface-I interactions between adjacent subunits, suggesting that long-range allostery produces conformational changes that extend from the active site to the protein-protein interface. Macromolecular assemblies of poliovirus polymerase show repeated use of flexible interface interactions for polymerase lattice formation, suggesting that adaptability of polymerase-polymerase interactions facilitates RNA replication. In addition, the presence of a positively charged groove identified in polymerase arrays may help position and stabilize the RNA template during replication. PMID:23583774

  6. INFECTIVITY OF HISTONE-POLIOVIRUS RIBONUCLEIC ACID PREPARATIONS.

    PubMed

    LUDWIG, E H; SMULL, C E

    1963-06-01

    Ludwig, Ernest H. (The Pennsylvania State University, University Park) and Christine E. Smull. Infectivity of histone-poliovirus ribonucleic acid preparations. J. Bacteriol. 85:1334-1338. 1963.-Some properties of histone-poliovirus ribonucleic acid (RNA) preparations, as relate to infectivity for HeLa cell monolayers, were investigated. The histone-RNA preparations were found to lose their infectivity rapidly at room temperature. They were considerably more stable at ice-bath temperature. Dilution of a histone-RNA preparation in a diluent containing an appropriate amount of histone yielded a plaque count which was proportional to the dilution factor, and which regressed linearly through the point of origin. Dilution of a histone-RNA preparation in a diluent containing no histone resulted in a rapidly decreasing plaque count which was not proportional to the dilution factor. The ability of histone to enhance the infectivity of poliovirus RNA was found to be dependent upon the presence of a low concentration of a monovalent salt in the histone-RNA preparations. Histone-RNA preparations containing approximately isotonic levels of NaCl exhibited a high degree of infectivity. When concentrations of NaCl outside this range were used, a great loss in infectivity of the histone-RNA preparations occurred. The NaCl could be replaced by KCl but not by CaCl(2), MgCl(2), or MgSO(4). PMID:14047226

  7. An Insight into Recombination with Enterovirus Species C and Nucleotide G-480 Reversion from the Viewpoint of Neurovirulence of Vaccine-Derived Polioviruses

    PubMed Central

    Zhang, Yong; Yan, Dongmei; Zhu, Shuangli; Nishimura, Yorihiro; Ye, Xufang; Wang, Dongyan; Jorba, Jaume; Zhu, Hui; An, Hongqiu; Shimizu, Hiroyuki; Kew, Olen; Xu, Wenbo

    2015-01-01

    A poliomyelitis outbreak caused by type 1 circulating vaccine-derived polioviruses (cVDPVs) was identified in China in 2004. Six independent cVDPVs (eight isolates) could be grouped into a single cluster with pathways of divergence different from a single cVDPV progenitor, which circulated and evolved into both a highly neurovirulent lineage and a less neurovirulent lineage. They were as neurovirulent as the wild type 1 Mahoney strain, recombination was absent, and their nucleotide 480-G was identical to that of the Sabin strain. The Guizhou/China cVDPV strains shared 4 amino acid replacements in the NAg sites: 3 located at the BC loop, which may underlie the aberrant results of the ELISA intratypic differentiation (ITD) test. The complete ORF tree diverged into two main branches from a common ancestral infection estimated to have occurred in about mid-September 2003, nine months before the appearance of the VDPV case, which indicated recently evolved VDPV. Further, recombination with species C enteroviruses may indicate the presence and density of these enteroviruses in the population and prolonged virus circulation in the community. The aforementioned cVDPVs has important implications in the global initiative to eradicate polio: high quality surveillance permitted earliest detection and response. PMID:26603565

  8. Co-Circulation and Evolution of Polioviruses and Species C Enteroviruses in a District of Madagascar

    PubMed Central

    Rakoto-Andrianarivelo, Mala; Guillot, Sophie; Iber, Jane; Balanant, Jean; Blondel, Bruno; Riquet, Franck; Martin, Javier; Kew, Olen; Randriamanalina, Bakolalao; Razafinimpiasa, Lalatiana; Rousset, Dominique; Delpeyroux, Francis

    2007-01-01

    Between October 2001 and April 2002, five cases of acute flaccid paralysis (AFP) associated with type 2 vaccine-derived polioviruses (VDPVs) were reported in the southern province of the Republic of Madagascar. To determine viral factors that favor the emergence of these pathogenic VDPVs, we analyzed in detail their genomic and phenotypic characteristics and compared them with co-circulating enteroviruses. These VDPVs appeared to belong to two independent recombinant lineages with sequences from the type 2 strain of the oral poliovaccine (OPV) in the 5′-half of the genome and sequences derived from unidentified species C enteroviruses (HEV-C) in the 3′-half. VDPV strains showed characteristics similar to those of wild neurovirulent viruses including neurovirulence in poliovirus-receptor transgenic mice. We looked for other VDPVs and for circulating enteroviruses in 316 stools collected from healthy children living in the small area where most of the AFP cases occurred. We found vaccine PVs, two VDPVs similar to those found in AFP cases, some echoviruses, and above all, many serotypes of coxsackie A viruses belonging to HEV-C, with substantial genetic diversity. Several coxsackie viruses A17 and A13 carried nucleotide sequences closely related to the 2C and the 3Dpol coding regions of the VDPVs, respectively. There was also evidence of multiple genetic recombination events among the HEV-C resulting in numerous recombinant genotypes. This indicates that co-circulation of HEV-C and OPV strains is associated with evolution by recombination, resulting in unexpectedly extensive viral diversity in small human populations in some tropical regions. This probably contributed to the emergence of recombinant VDPVs. These findings give further insight into viral ecosystems and the evolutionary processes that shape viral biodiversity. PMID:18085822

  9. Assessment of cell culture and polymerase chain reaction procedures for the detection of polioviruses in wastewater.

    PubMed Central

    Grabow, W. O.; Botma, K. L.; de Villiers, J. C.; Clay, C. G.; Erasmus, B.

    1999-01-01

    WHO considers that environmental surveillance for wild-type polioviruses is potentially important for surveillance for acute flaccid paralysis as a means of confirming eradication of poliomyelitis. The present study investigated methods for detecting polioviruses in a variety of water environments in South Africa. Most polioviruses were isolated on L20B mouse cells, which, however, were not selective: 16 reoviruses and 8 enteroviruses, apparently animal strains, were also isolated on these cells. Vaccine strains of polioviruses were isolated from surface waters during and shortly after two rounds of mass vaccination of children in an informal settlement where there was no sewerage. The results demonstrated the feasibility of poliovirus surveillance in such settlements. It was also evident that neither poliovirus vaccine strains nor other viruses were likely to interfere significantly with the detection of wild-type polioviruses. Optimal isolation of polioviruses was accomplished by parallel inoculation of L20B mouse cells and at least the PLC/PRF/5 human liver and buffalo green monkey (BGM) kidney cell lines. Analysis of cell cultures using the polymerase chain reaction revealed that 319 test samples contained at least 263 human enteroviruses that failed to produce a cytopathogenic effect. This type of analysis thus significantly increased the sensitivity of enterovirus detection. PMID:10680244

  10. Evidence of presence of poliovirus genomic sequences in cerebrospinal fluid from patients with postpolio syndrome.

    PubMed

    Leparc-Goffart, I; Julien, J; Fuchs, F; Janatova, I; Aymard, M; Kopecka, H

    1996-08-01

    The postpolio syndrome (PPS) is characterized by new neuromuscular symptoms occurring 30 to 40 years after the acute episode of poliomyelitis paralysis. The presence of the poliovirus RNA genome in the cerebrospinal fluid from 10 patients with PPS and from 23 control patients was sought by using reverse transcription and a PCR specific for polioviruses and/or other enteroviruses. Poliovirus-specific genomic sequences in the 5' untranslated region and in the capsid region (VP1) were detected by reverse transcription PCR in 5 of 10 patients with PPS but in none of the control patients. Sequencing confirmed the presence of mutated poliovirus sequences. This finding suggests persistent viral infection in the central nervous system related to the presence of poliovirus genomes. PMID:8818905

  11. Immunogenicity of poliovirus vaccines in chronically malnourished infants: A randomized controlled trial in Pakistan

    PubMed Central

    Saleem, Ali Faisal; Mach, Ondrej; Quadri, Farheen; Khan, Asia; Bhatti, Zaid; Rehman, Najeeb ur; Zaidi, Sohail; Weldon, William C.; Oberste, Steven M.; Salama, Maha; Sutter, Roland W.; Zaidi, Anita K.M.

    2015-01-01

    Reaching high population immunity against polioviruses (PV) is essential to achieving global polio eradication. Efficacy of oral poliovirus vaccine (OPV) varies and is lower among children living in tropical areas with impoverished environments. Malnutrition found as a risk factor for lower serological protection against PV. We compared whether inactivated polio vaccine (IPV) can be used to rapidly close the immunity gap among chronically malnourished (stunted) infants in Pakistan who will not be eligible for the 14 week IPV dose in routine EPI schedule. A phase 3, multicenter 4-arm randomized controlled trial conducted at five Primary Health Care (PHC) centers in Karachi, Pakistan. Infants, 9–12 months were stratified by length for age Z score into chronically malnourished and normally nourished. Infants were randomized to receive one dose of either bivalent OPV (bOPV) alone or bOPV + IPV. Baseline seroprevalence of PV antibodies and serum immune response to study vaccine dose were assessed by neutralization assay. Vaccine PV shedding in stool was evaluated 7 days after a bOPV challenge dose. Sera and stool were analyzed from 852/928 (92%) enrolled children. At baseline, the seroprevalence was 85.6% (n = 386), 73.6% (n = 332), and 70.7% (n = 319) in malnourished children against PV types 1, 2 and 3 respectively; and 94.1% (n = 448), 87.0% (n = 441) and 83.6% (n = 397) in the normally nourished group (p < 0.05). Children had previously received 9–10 doses of bOPV (80%) or tOPV (20%). One dose of IPV + bOPV given to malnourished children increased their serological protection (PV1, n = 201, 97.6%; PV2, n = 198, 96.1% and PV3, n = 189, 91.7%) to parity with normally nourished children who had not received IPV (p = <0.001). Seroconversion and boosting for all three serotypes was significantly more frequent in children who received IPV + bOPV than in those with bOPV only (p < 0.001) in both strata. Shedding of polioviruses in stool did

  12. 76 FR 14052 - Notice of Inventory Completion: Sabine River Authority of Texas, Quitman, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-15

    ... above are reasonably believed to have been placed with or near individual human remains at the time of death or later as part of the death rite or ceremony. Lastly, officials of the Sabine River Authority...

  13. Sit Down with Sabin: Henrik Scheller: Customizing plants for biofuels. (LBNL Summer Lecture Series)

    ScienceCinema

    Sabin, Russell; Scheller, Henrik

    2014-05-06

    Henrik Scheller from the JBEI appeared on August 3rd, 2011 for this installment of "Sit Down with Sabin," a conversation in which former reporter Sabin Russell chats with Lab staff about innovative science. They will discuss "Customizing plants for biofuels." During this series of conversations, Russell and Lab staff will explore the ups and downs of pioneering science, all without the aid of PowerPoints.

  14. Sit Down With Sabin: Merrian Fuller: Efficiency for sale. Who's buying? (LBNL Summer Lecture Series)

    SciTech Connect

    Fuller, Merrian; Russell, Sabin

    2011-07-26

    Merrian Fuller from the Environmental Energy Technologies Division appeared on July 26th, 2011 for this installment of "Sit Down with Sabin," a conversation in which former reporter Sabin Russell chats with Lab staff about innovative science. They will discuss "Efficiency for Sale. Who's Buying?" During this series of conversations, Russell and Lab staff will explore the ups and downs of pioneering science, all without the aid of PowerPoints.

  15. Sit Down with Sabin: Venkat Srinivasan: The Future of Batteries (LBNL Summer Lecture Series)

    SciTech Connect

    Russell, Sabin; Srinivasan, Venkat

    2011-06-29

    Lawrence Berkeley National Laboratory battery scientist Venkat Srinivasan appears June 29, 2011 on "Sit Down with Sabin," a weekly conversation in which former reporter Sabin Russell chats with Berkeley Lab staff about innovative science. Over the course of several conversations held at noon in the Building 50 auditorium, Russell and Lab staff will explore the ups and downs of pioneering science — all without the aid of PowerPoints. Brought to you by Berkeley Lab Public Affairs.

  16. Analysis of Sabine and Eyring equations and their application to concert hall audience and chair absorption.

    PubMed

    Beranek, Leo L

    2006-09-01

    Historically, two equations have been used for predicting reverberation times, Sabine and Eyring. A precise means is presented for determining Eyring absorption coefficients alpha(eyring) when the Sabine coefficients alpha(sabine) are known, and vice versa. Thus, either formula can be used provided the absorption coefficients for the Sabine formula are allowed to exceed 1.0. The Sabine formula is not an approximation to the Eyring equation and is not a shortcoming. Given low reverberation times, the ratio of alpha(sabine) to alpha(eyring) may become greater than 2.0. It is vital that, for correct prediction of reverberation times, the absorption coefficients used in either formula must have been determined in spaces similar in size and shape, with similar locations of high absorption (audience) areas, and with similar reverberation times. For concert halls, it is found that, when the audience area (fully occupied) and midfrequency reverberation time are postulated, the hall volume is directly proportional to the audience absorption coefficient. Approximately 6% greater room volumes are needed when choosing nonrectangular versus classical-rectangular shaped halls and approximately 10% greater volumes when choosing heavily upholstered versus medium upholstered chairs. Determinations of audience sound absorption coefficients are presented, based on published acoustical and architectural data for 20 halls. PMID:17004464

  17. Cross-neutralizing human anti-poliovirus antibodies bind the recognition site for cellular receptor

    PubMed Central

    Chen, Zhaochun; Fischer, Elizabeth R.; Kouiavskaia, Diana; Hansen, Bryan T.; Ludtke, Steven J.; Bidzhieva, Bella; Makiya, Michelle; Agulto, Liane; Purcell, Robert H.; Chumakov, Konstantin

    2013-01-01

    Most structural information about poliovirus interaction with neutralizing antibodies was obtained in the 1980s in studies of mouse monoclonal antibodies. Recently we have isolated a number of human/chimpanzee anti-poliovirus antibodies and demonstrated that one of them, MAb A12, could neutralize polioviruses of both serotypes 1 and 2. This communication presents data on isolation of an additional cross-neutralizing antibody (F12) and identification of a previously unknown epitope on the surface of poliovirus virions. Epitope mapping was performed by sequencing of antibody-resistant mutants and by cryo-EM of complexes of virions with Fab fragments. The results have demonstrated that both cross-neutralizing antibodies bind the site located at the bottom of the canyon surrounding the fivefold axis of symmetry that was previously shown to interact with cellular poliovirus receptor CD155. However, the same antibody binds to serotypes 1 and 2 through different specific interactions. It was also shown to interact with type 3 poliovirus, albeit with about 10-fold lower affinity, insufficient for effective neutralization. Antibody interaction with the binding site of the cellular receptor may explain its broad reactivity and suggest that further screening or antibody engineering could lead to a universal antibody capable of neutralizing all three serotypes of poliovirus. PMID:24277851

  18. Poliovirus Proteins Induce Membrane Association of GTPase ADP-Ribosylation Factor

    PubMed Central

    Belov, George A.; Fogg, Mark H.; Ehrenfeld, Ellie

    2005-01-01

    Poliovirus infection results in the disintegration of intracellular membrane structures and formation of specific vesicles that serve as sites for replication of viral RNA. The mechanism of membrane rearrangement has not been clearly defined. Replication of poliovirus is sensitive to brefeldin A (BFA), a fungal metabolite known to prevent normal function of the ADP-ribosylation factor (ARF) family of small GTPases. During normal membrane trafficking in uninfected cells, ARFs are involved in vesicle formation from different intracellular sites through interaction with numerous regulatory and coat proteins as well as in regulation of phospholipase D activity and cytoskeleton modifications. We demonstrate here that ARFs 3 and 5, but not ARF6, are translocated to membranes in HeLa cell extracts that are engaged in translation of poliovirus RNA. The accumulation of ARFs on membranes correlates with active replication of poliovirus RNA in vitro, whereas ARF translocation to membranes does not occur in the presence of BFA. ARF translocation can be induced independently by synthesis of poliovirus 3A or 3CD proteins, and we describe mutations that abolished this activity. In infected HeLa cells, an ARF1-enhanced green fluorescent protein fusion redistributes from Golgi stacks to the perinuclear region, where poliovirus RNA replication occurs. Taken together, the data suggest an involvement of ARF in poliovirus RNA replication. PMID:15890959

  19. Poliovirus concentration from tap water with electropositive adsorbent filters.

    PubMed

    Sobsey, M D; Glass, J S

    1980-08-01

    Simple, reliable, and efficient concentration of poliovirus from tap water was obtained with two types of electropositive filter media, one of which is available in the form of a pleated cartridge filter (Virozorb 1MDS). Virus adsorption from tap water between pH 3.5 and 7.5 was more efficient with electropositive filters than with Filterite filters. Elution of adsorbed viruses was more efficient with beef extract in glycine, pH 9.5, than with glycine-NaOH, pH 11.0. In paired comparative studies, electropositive filters, with adsorption at pH 7.5 and no added polyvalent cation salts, gave less variable virus concentration efficiencies than did Filterite filters with adsorption at pH 3.5 plus added MgCl2. Recovery of poliovirus from 1,000-liter tap water volumes was approximately 30% efficient with both Virozorb 1MDS and Filterite pleated cartridge filters, but the former were much simpler to use. The virus adsorption behavior of these filters appears to be related to their surface charge properties, with more electropositive filters giving more efficient virus adsorption from tap water at higher pH levels. PMID:6258472

  20. A transcriptionally active form of TFIIIC is modified in poliovirus-infected HeLa cells.

    PubMed Central

    Clark, M E; Dasgupta, A

    1990-01-01

    In HeLa cells, RNA polymerase III (pol III)-mediated transcription is severely inhibited by poliovirus infection. This inhibition is due primarily to the reduction in transcriptional activity of the pol III transcription factor TFIIIC in poliovirus-infected cells. However, the specific binding of TFIIIC to the VAI gene B-box sequence, as assayed by DNase I footprinting, is not altered by poliovirus infection. We have used gel retardation analysis to analyze TFIIIC-DNA complexes formed in nuclear extracts prepared from mock- and poliovirus-infected cells. In mock-infected cell extracts, two closely migrating TFIIIC-containing complexes, complexes I and II, were detected in the gel retardation assay. The slower migrating complex, complex I, was absent in poliovirus-infected cell extracts, and an increase occurred in the intensity of the faster-migrating complex (complex II). Also, in poliovirus-infected cell extracts, a new, rapidly migrating complex, complex III, was formed. Complex III may have been the result of limited proteolysis of complex I or II. These changes in TFIIIC-containing complexes in poliovirus-infected cell extracts correlated kinetically with the decrease in TFIIIC transcriptional activity. Complexes I, II, and III were chromatographically separated; only complex I was transcriptionally active and specifically restored pol III transcription when added to poliovirus-infected cell extracts. Acid phosphatase treatment partially converted complex I to complex II but did not affect the binding of complex II or III. Dephosphorylation and limited proteolysis of TFIIIC are discussed as possible mechanisms for the inhibition of pol III-mediated transcription by poliovirus. Images PMID:2204807

  1. Concentration and Purification of Poliovirus by Ultrafiltration and Isopycnic Centrifugation1

    PubMed Central

    Guskey, Louis E.; Wolff, David A.

    1972-01-01

    A method is described by which poliovirus can be rapidly and simply concentrated by the use of a Diaflo XM-50 ultrafilter membrane. Freon-extracted ultrafilter concentrates banded in CsCl provided a 1,724-fold volumetric concentration of poliovirus. During concentration, trypsin-digested cellular material can pass through the ultrafilter membrane, thus providing a versatile means of degrading and eliminating extraneous contaminating proteins. The ultrafilter concentration system is compared with the CsCl cushion system of poliovirus concentration, and both systems are further compared by banding virus and virus capsid material in CsCl by use of isopycnic centrifugation. Images PMID:4341520

  2. Human Circulating Antibody-Producing B Cell as a Predictive Measure of Mucosal Immunity to Poliovirus

    PubMed Central

    Verma, Harish; Sharma, Prashant; Yang, Jae Seung; Saletti, Giulietta; Ahmad, Mohammad; Bahl, Sunil K.; Wierzba, Thomas F.; Nandy, Ranjan K.; Deshpande, Jagadish M.; Sutter, Roland W.; Czerkinsky, Cecil

    2016-01-01

    Background The “gold standard” for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine. Methods 199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4β7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation. Results An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, α4β7+ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive α4β7+ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4β7+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for

  3. Oral and Inactivated Poliovirus Vaccines in the Newborn: A review

    PubMed Central

    Mateen, Farrah J.; Shinohara, Russell T.; Sutter, Roland W.

    2015-01-01

    Background Oral poliovirus vaccine (OPV) remains the vaccine-of-choice for routine immunization and supplemental immunization activities (SIAs) to eradicate poliomyelitis globally. Recent data from India suggested lowerthanexpected immunogenicity of an OPV birth dose, prompting a review of the immunogenicity of OPV or inactivated poliovirus vaccine (IPV) when administered at birth. Methods We evaluated the seroconversion and reported adverse events among infants given a single birth dose (given ≤7 days of life) of OPV or IPV through a systematic review of published articles and conference abstracts from 1959-2011 in any language found on PubMed, Google Scholar, or reference lists of selected articles. Results 25 articles from 13 countries published between1959 and 2011 documented seroconversion rates in newborns following an OPV dose given within the first seven days of life. There were 10 studies that measured seroconversion rates between 4 and 8 weeks of a single birth dose of TOPV, using an umbilical cord blood draw at the time of birth to establish baseline antibody levels. The percentage of newborns who seroconverted at 8 weeks range 6-42% for poliovirus type 1, 2-63% for type 2, and 1-35% for type 3). For mOPV type 1, seroconversion ranged from 10-76%; mOPV type 3, the range was 12-58%; and for the one study reporting bOPV, it was 20% for type 1 and 7% for type 3. There were four studies of IPV in newborns with a seroconversion rate of 8-100% for serotype 1, 15-100% for serotype 2, and 15-94% for serotype 3, measured at 4-6 weeks of life. No serious adverse events related to newborn OPV or IPV dosing were reported, including no cases of acute flaccid paralysis. Conclusions There is great variability of the immunogenicity of a birth dose of OPV for reasons largely unknown. Our review confirms the utility of a birth dose of OPV, particularly in countries where early induction of polio immunity is imperative. IPV has higher seroconversion rates in newborns and

  4. Survival of poliovirus within organic solids during chlorination.

    PubMed Central

    Hejkal, T W; Wellings, F M; LaRock, P A; Lewis, A L

    1979-01-01

    Poliovirus in fecal homogenates was used to determine the protection against inactivation by chlorination afforded virus that was occluded within particulates. Virus that was closely associated with or occluded within small fecal particulates was protected. A fourfold increase in combined residual chlorine was required to achieve the same degree of inactivation for occluded virus as for free or secondarily adsorbed virus. A combined chlorine residual of 6.6 mg/liter was necessary to achieve 50% inactivation in 15 min at pH 8.0 and 22 degrees C in a particulate suspension containing occluded virus compared to 1.4 mg/liter for free virus. These differences were found to be relatively small compared to differences due to the presence of dissolved organics or between free and combined chlorine residuals. The results suggest different mechanisms of protection due to adsorption and occlusion. PMID:225993

  5. Postpolio syndrome: poliovirus persistence is involved in the pathogenesis.

    PubMed

    Julien, J; Leparc-Goffart, I; Lina, B; Fuchs, F; Foray, S; Janatova, I; Aymard, M; Kopecka, H

    1999-06-01

    The pathogenesis of the postpolio syndrome (PPS) remains unclear. In this study we looked for poliovirus (PV) persistence in the CSF of 20 patients with PPS, in a control group including 20 patients with unrelated neurological diseases, and in 7 patients with stable poliomyelitis sequelae. CSF samples and sera were examined using reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of PV or other enterovirus genomes; this assay allows the detection from as little as 1 fg viral RNA. Sequencing of amplified products from 5 patients was performed. PV genomic sequences were detected in the CSF of 11 of 20 patients with PPS and in none of the control group. Sequencing in the 5' untranslated region confirmed the presence of mutated PV sequences. These findings suggest that PPS is related to the persistence of PV in the central nervous system. PMID:10431774

  6. Cytotoxic and immunogenic mechanisms of recombinant oncolytic poliovirus.

    PubMed

    Brown, Michael C; Gromeier, Matthias

    2015-08-01

    An oncolytic virus (OV) based on poliovirus (PV), the highly attenuated polio/rhinovirus recombinant PVSRIPO, may deliver targeted inflammatory cancer cell killing; a principle that is showing promise in clinical trials for recurrent glioblastoma (GBM). The two decisive factors in PVSRIPO anti-tumor efficacy are selective cytotoxicity and its in situ immunogenic imprint. While our work is focused on what constitutes PVSRIPO cancer cytotoxicity, we are also studying how this engenders host immune responses that are vital to tumor regression. We hypothesize that PVSRIPO cytotoxicity and immunogenicity are inextricably linked in essential, complimentary roles that define the anti-neoplastic response. Herein we delineate mechanisms we unraveled to decipher the basis for PVSRIPO cytotoxicity and its immunotherapeutic potential. PMID:26083317

  7. A survey for neutralizing antibodies to the three types of poliovirus among children in Maiduguri, Nigeria.

    PubMed

    Baba, M M; Haruna, B A; Ogunmola, O; Ambe, J P; Shidali, N N; Oderinde, B; Marcello, A; Talle, M

    2012-04-01

    The milestone in polio eradication program is to protect effectively children aged 0-5 years against the three serotypes of poliovirus. It became necessary to measure the level of neutralizing antibodies to the three poliovirus types in an endemic State in Nigeria. Neutralizing antibodies to the poliovirus types among children aged 0-5 years was estimated using micro neutralization assay. Of 129 children, 99 (76.8%), 95 (73.6%), and 95 (73.6%) had neutralizing antibodies with the geometric mean titer of 42.7, 31.3, and 33.2 for the poliovirus type 1, 2, and 3, respectively. Fifty-three percent of the children were protected against the three types of poliovirus. Combination of poliovirus types 1 and 2, 1 and 3, and 2 and 3 were neutralized by 62.8, 58.9, and 61.2% of the children studied, respectively. Only poliovirus type 1 induced antibody titres ≥1:1,024. The number of children with neutralizing antibodies after receiving three doses was significantly higher than those who received one or two doses of oral polio vaccine (P ≤ 0.05). However, those who received more than three doses of oral polio vaccine showed no significant difference in their antibody response. The existence of immunity gap poses a risk of re-emergence of the paralytic poliovirus. The existence of unimmunized and unprotected children along with high birth rate could impede the success of polio vaccination in Nigeria. Elimination of non-compliance to polio vaccine, promotion of health education and documented evidence of vaccination of each child with the parents may facilitate the success of polio eradication program in Nigeria. PMID:22337311

  8. Sit Down with Sabin: Margaret Torn: The Carbon Cycle Like You've Never Seen It (LBNL Summer Lecture Series)

    SciTech Connect

    Russell, Sabin; Torn, Margaret

    2011-07-06

    Lawrence Berkeley National Laboratory soil scientist Margaret Torn appears July 6, 2011 on "Sit Down with Sabin," a weekly conversation in which former reporter Sabin Russell chats with Berkeley Lab staff about innovative science. Torn discusses how she travels the world to learn more about soil's huge role in the global carbon cycle. Brought to you by Berkeley Lab Public Affairs.

  9. Complex Dynamic Development of Poliovirus Membranous Replication Complexes

    PubMed Central

    Nair, Vinod; Hansen, Bryan T.; Hoyt, Forrest H.; Fischer, Elizabeth R.; Ehrenfeld, Ellie

    2012-01-01

    Replication of all positive-strand RNA viruses is intimately associated with membranes. Here we utilize electron tomography and other methods to investigate the remodeling of membranes in poliovirus-infected cells. We found that the viral replication structures previously described as “vesicles” are in fact convoluted, branching chambers with complex and dynamic morphology. They are likely to originate from cis-Golgi membranes and are represented during the early stages of infection by single-walled connecting and branching tubular compartments. These early viral organelles gradually transform into double-membrane structures by extension of membranous walls and/or collapsing of the luminal cavity of the single-membrane structures. As the double-membrane regions develop, they enclose cytoplasmic material. At this stage, a continuous membranous structure may have double- and single-walled membrane morphology at adjacent cross-sections. In the late stages of the replication cycle, the structures are represented mostly by double-membrane vesicles. Viral replication proteins, double-stranded RNA species, and actively replicating RNA are associated with both double- and single-membrane structures. However, the exponential phase of viral RNA synthesis occurs when single-membrane formations are predominant in the cell. It has been shown previously that replication complexes of some other positive-strand RNA viruses form on membrane invaginations, which result from negative membrane curvature. Our data show that the remodeling of cellular membranes in poliovirus-infected cells produces structures with positive curvature of membranes. Thus, it is likely that there is a fundamental divergence in the requirements for the supporting cellular membrane-shaping machinery among different groups of positive-strand RNA viruses. PMID:22072780

  10. Analysis of mutations in oral poliovirus vaccine by hybridization with generic oligonucleotide microchips.

    SciTech Connect

    Proudnikov, D.; Kirillov, E.; Chumakov, K.; Donion, J.; Rezapkin, G.; Mirzabekov, A.; Biochip Technology Center; Engelhardt Inst. of Molecular Biology; Center for Biologics Evaluation and Research

    2000-01-01

    This paper describes use of a new technology of hybridization with a micro-array of immobilized oligonucleotides for detection and quantification of neurovirulent mutants in Oral Poliovirus Vaccine (OPV). We used a micro-array consisting of three-dimensional gel-elements containing all possible hexamers (total of 4096 probes). Hybridization of fluorescently labelled viral cDNA samples with such microchips resulted in a pattern of spots that was registered and quantified by a computer-linked CCD camera, so that the sequence of the original cDNA could be deduced. The method could reliably identify single point mutations, since each of them affected fluorescence intensity of 12 micro-array elements. Micro-array hybridization of DNA mixtures with varying contents of point mutants demonstrated that the method can detect as little as 10% of revertants in a population of vaccine virus. This new technology should be useful for quality control of live viral vaccines, as well as for other applications requiring identification and quantification of point mutations.

  11. Contribution of Environmental Surveillance Toward Interruption of Poliovirus Transmission in Nigeria, 2012–2015

    PubMed Central

    Johnson Muluh, Ticha; Hamisu, Abdullahi Walla; Craig, Kehinde; Mkanda, Pascal; Andrew, Etsano; Adeniji, Johnson; Akande, Adefunke; Musa, Audu; Ayodeji, Isiaka; Nicksy, Gumede; Banda, Richard; Tegegne, Sisay G.; Nsubuga, Peter; Oyetunji, Ajiboye; Diop, Ousmane; Vaz, Rui G.; Muhammad, Ado J. G.

    2016-01-01

    Background. Cases of paralysis caused by poliovirus have decreased by >99% since the 1988 World Health Assembly's resolution to eradicate polio. The World Health Organization identified environmental surveillance (ES) of poliovirus in the poliomyelitis eradication strategic plan as an activity that can complement acute flaccid paralysis (AFP) surveillance. This article summarizes key public health interventions that followed the isolation of polioviruses from ES between 2012 and 2015. Methods. The grap method was used to collect 1.75 L of raw flowing sewage every 2–4 weeks. Once collected, samples were shipped at 4°C to a polio laboratory for concentration. ES data were then used to guide program implementation. Results. From 2012 to 2015, ES reported 97 circulating vaccine-derived polioviruses (cVDPV2) and 14 wild polioviruses. In 2014 alone, 54 cVDPV type 2 cases and 1 WPV type 1 case were reported. In Sokoto State, 58 cases of AFP were found from a search of 9426 households. A total of 2 252 059 inactivated polio vaccine and 2 460 124 oral polio vaccine doses were administered to children aged <5 year in Borno and Yobe states. Conclusions. This article is among the first from Africa that relates ES findings to key public health interventions (mass immunization campaigns, inactivated polio vaccine introduction, and strengthening of AFP surveillance) that have contributed to the interruption of poliovirus transmission in Nigeria. PMID:26908747

  12. Framework for evaluating the risks of paralytic poliomyelitis after global interruption of wild poliovirus transmission.

    PubMed Central

    Aylward, R. Bruce; Cochi, Stephen L.

    2004-01-01

    With the interruption of wild poliovirus transmission globally, the need for new policies to deal with the post-certification era will rapidly arise. New policies will be required in four areas: detection and notification of circulating polioviruses; biocontainment of wild, vaccine-derived and attenuated strains of poliovirus; vaccine stockpiles and response mechanisms; and routine immunization against polioviruses. A common understanding of the potential risks of paralytic poliomyelitis in the post-certification period is essential to the development of these policies. Since 2000, there has been increasing international consensus that the risks of paralytic poliomyelitis in the post-certification era fall into two categories: those due to the continued use of the oral poliovirus vaccine (OPV) and those due to future improper handling of wild polioviruses. The specific risks within both categories have now been defined, and an understanding of the frequency and potential burden of disease associated with each is rapidly improving. This knowledge and clarity have provided a framework that is already proving valuable for identifying research priorities and discussing potential policy options with national authorities. However, this framework must be regarded as a dynamic tool, requiring regular updating as additional information on these risks becomes available through further scientific research, programmatic work, and policy decisions. PMID:15106299

  13. Current polio global eradication and control policy options: perspectives from modeling and prerequisites for oral poliovirus vaccine cessation.

    PubMed

    Thompson, Kimberly M; Tebbens, Radboud J Duintjer

    2012-04-01

    As the Global Polio Eradication Initiative progresses toward the eradication of wild polioviruses, national and global health leaders must still actively consider options for managing poliovirus risks, including risks associated with using oral poliovirus vaccine. Oral poliovirus vaccine continues to represent a highly effective tool, but its use causes noticeable, rare cases of vaccine-associated paralytic polio and with low coverage it can evolve to become circulating vaccine-derived polioviruse that causes outbreaks. National leaders face a wide range of options, but their choices depend in part on global policies. This article explores the current set of global options for poliovirus eradication or control, discusses constraints and prerequisites for their implementation and offers some insights based on dynamic modeling to inform discussions and frame future economic analyses. PMID:22551030

  14. Sit Down with Sabin: David Schlegel: Hunting Dark Energy (LBNL Summer Lecture Series)

    SciTech Connect

    Russell, Sabin; Schlegel, David

    2011-06-22

    Lawrence Berkeley National Laboratory physicist and dark energy hunter David Schlegel chats with Sabin Russell, former San Francisco Chronicle reporter turned Berkeley Lab science writer, June 22, 2011. Their conversation is the first installment of "Sit Down With Sabin," a weekly conversation hosted by Russell. Over the course of five conversations with Berkeley Lab staff this summer, Russell will explore the ups and downs of innovative science — all without the aid of PowerPoint slides. Brought to you by Berkeley Lab Public Affairs.

  15. Effect of Enzymes on the Interaction of Enteroviruses with Living HeLa Cells1

    PubMed Central

    Zajac, Ihor; Crowell, Richard L.

    1965-01-01

    Zajac, Ihor (Hahnemann Medical College, Philadelphia, Pa.), and Richard L. Crowell. Effect of enzymes on the interaction of enteroviruses with living HeLa cells. J. Bacteriol. 89:574–582. 1965.—Eight crude enzyme preparations and two crystalline enzymes were tested for ability to inactivate coxsackie group B and poliovirus receptors on living HeLa cells. Receptor-destroying enzyme, erepsin, lysozyme, collagenase, proteinase, and cobra venom did not alter attachment of coxsackie B3 or poliovirus T1 to cells, whereas elastase prevented attachment of both viruses tested. Treatment of live cells with pancreatin or chymotrypsin rendered cells unable to attach group B coxsackie viruses, whereas cells treated with trypsin failed to attach poliovirus T1. In addition, chymotrypsin was found to release coxsackie B3 and poliovirus T1 from cell surfaces, whereas trypsin was unable to dissociate virus-cell union. These results indicate that cellular receptors for polioviruses differ from those for group B coxsackie-viruses. The finding that 1% solutions of enzymes will inactivate differentially the enteroviral receptors of HeLa cells, without altering cell viability, provides a useful approach for study of enterovirus receptors of live host cells. PMID:14273631

  16. Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine.

    PubMed

    Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V

    2015-10-13

    Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents. PMID:26362098

  17. EFFECT OF ENDOTOXIN ON CELLS AND ON THEIR RESPONSE TO INFECTION BY POLIOVIRUSES1

    PubMed Central

    Murphy, William H.; Wisner, Carolyn

    1962-01-01

    Murphy, W. H. (The University of Michigan, Ann Arbor) and C. Wisner. Effect of endotoxin on cells and on their response to infection by polioviruses. J. Bacteriol. 83:649–662. 1962.—The effect of lipopolysaccharide on HeLa-S3, HeLa-Gey, Chang-liver, Maben, and L strain mouse fibroblasts was studied. The liminal dose of endotoxin for the human epithelial cell strains was approximately 250 μg/ml, and their order of sensitivity to endotoxin was: Chang-liver, HeLa-Gey, HeLa-S3, and Maben, the latter being the most resistant. Endotoxin at concentrations exceeding 100 μg/ml was cytotoxic to the L strain of mouse fibroblasts and caused them to markedly agglutinate. Cytotoxic response of cells to endotoxin was not characterized by cell lysis, but by distinctive nuclear changes. In an attempt to demonstrate the metabolic induction of the latent infection of cell cultures by a noncytopathic variant of poliovirus, endotoxin was added at maximal subliminal concentration to cell cultures totally, partially, or fully susceptible to virus. Endotoxin caused a slight but consistent accelerative cytopathic response of cells to infection by cytopathic poliovirus, but failed to induce cytopathic response to infection by submoderate (noncytopathic) poliovirus. Although endotoxin slightly suppressed yields of poliovirus from cells, it did not affect the plating efficiency of virus on cell monolayers. Images PMID:14477444

  18. Poliovirus neutralization epitopes: analysis and localization with neutralizing monoclonal antibodies.

    PubMed Central

    Emini, E A; Jameson, B A; Lewis, A J; Larsen, G R; Wimmer, E

    1982-01-01

    Two hybridomas (H3 and D3) secreting monoclonal neutralizing antibody to intact poliovirus type 1 (Mahoney strain) were established. Each antibody bound to a site qualitatively different from that to which the other antibody bound. The H3 site was located on intact virions and, to a lesser extent, on 80S naturally occurring empty capsids and 14S precursor subunits. The D3 site was found only on virions and empty capsids. Neither site was expressed on 80S heat-treated virions. The antibodies did not react with free denatured or undenatured viral structural proteins. Viral variants which were no longer capable of being neutralized by either one or the other antibody were obtained. Such variants arose during normal cell culture passage of wild-type virus and were present in the progeny viral population on the order of 10(-4) variant per wild-type virus PFU. Toluene-2,4-diisocyanate, a heterobifunctional covalent cross-linking reagent, was used to irreversibly bind the F(ab) fragments of the two antibodies to their respective binding sites. In this way, VP1 was identified as the structural protein containing both sites. PMID:6183443

  19. 78 FR 38672 - Ocean Dumping; Sabine-Neches Waterway (SNWW) Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-27

    ...The EPA is proposing to designate four new Ocean Dredged Material Disposal Site(s) (ODMDS) located offshore of Texas for the disposal of dredged material from the Sabine-Neches Waterway (SNWW), pursuant to the Marine Protection, Research and Sanctuaries Act, as amended (MPRSA). The new sites are needed for the disposal of additional dredged material associated with the SNWW Channel Improvement......

  20. 77 FR 47519 - Annual Marine Events in the Eighth Coast Guard District, Sabine River; Orange, TX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-09

    ... SECURITY Coast Guard 33 CFR Part 100 Annual Marine Events in the Eighth Coast Guard District, Sabine River; Orange, TX AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast..., call or email Mr. Scott Whalen. U.S. Coast Guard Marine Safety Unit Port Arthur, TX; telephone...

  1. Time of travel of solutes in the Sabine River basin, Texas, August-November 1996

    USGS Publications Warehouse

    Raines, Timothy H.

    1997-01-01

    The U.S. Geological Survey (USGS), in cooperation with the Sabine River Authority, did a time-of-travel study in the Sabine River Basin during low flow from August to November 1996. The study was done to provide accurate estimates of the time-of-travel and dispersion characteristics for solutes during low flow in a 1.8-mile (mi) reach of Grace Creek, a 23.9-mi reach of the mainstem Sabine River, a 3.4-mi reach of Hawkins Creek, and a 1.9-mi reach of Rocky Creek. This report explains the approach and documents the results of the study. The results of the study will be used by the Texas Natural Resource Conservation Commission in a water-quality model to determine waste-load allocation in Segment 0505 of the Sabine River Basin. The time-of-travel and dispersion characteristics also provide useful information on the probable behavior of soluble contaminants that might be introduced into the streams measured in this study.

  2. Progress in the development of poliovirus antiviral agents and their essential role in reducing risks that threaten eradication.

    PubMed

    McKinlay, Mark A; Collett, Marc S; Hincks, Jeffrey R; Oberste, M Steven; Pallansch, Mark A; Okayasu, Hiromasa; Sutter, Roland W; Modlin, John F; Dowdle, Walter R

    2014-11-01

    Chronic prolonged excretion of vaccine-derived polioviruses by immunodeficient persons (iVDPV) presents a personal risk of poliomyelitis to the patient as well as a programmatic risk of delayed global eradication. Poliovirus antiviral drugs offer the only mitigation of these risks. Antiviral agents may also have a potential role in the management of accidental exposures and in certain outbreak scenarios. Efforts to discover and develop poliovirus antiviral agents have been ongoing in earnest since the formation in 2007 of the Poliovirus Antivirals Initiative. The most advanced antiviral, pocapavir (V-073), is a capsid inhibitor that has recently demonstrated activity in an oral poliovirus vaccine human challenge model. Additional antiviral candidates with differing mechanisms of action continue to be profiled and evaluated preclinically with the goal of having 2 antivirals available for use in combination to treat iVDPV excreters. PMID:25316866

  3. Development of a poliovirus neutralization test with poliovirus pseudovirus for measurement of neutralizing antibody titer in human serum.

    PubMed

    Arita, Minetaro; Iwai, Masae; Wakita, Takaji; Shimizu, Hiroyuki

    2011-11-01

    In the Global Polio Eradication Initiative, laboratory diagnosis plays a critical role by isolating and identifying poliovirus (PV) from the stool samples from acute flaccid paralysis (AFP) cases. In recent years, reestablishment of PV circulation in countries where PV was previously eliminated has occurred because of decreased herd immunity, possibly due to poor vaccination coverage. To monitor the vulnerability of countries to PV circulation, surveillance of neutralizing-antibody titers against PV in susceptible populations is essential in the end game of the polio eradication program. In this study, we have developed a PV neutralization test with type 1, 2, and 3 PV pseudoviruses to determine the neutralizing-antibody titer against PV in human serum samples. With this test, the neutralizing-antibody titer against PV could be determined within 2 days by automated interpretation of luciferase signals without using infectious PV strains. We validated the pseudovirus PV neutralization test with 131 human serum samples collected from a wide range of age groups (ages 1 to >60 years) by comparison with a conventional neutralization test. We found good correlation in the neutralizing-antibody titers determined by these tests. These results suggest that a pseudovirus PV neutralization test would serve as a safe and simple procedure for the measurement of the neutralizing-antibody titer against PV. PMID:21880850

  4. The recent outbreaks and reemergence of poliovirus in war and conflict-affected areas

    PubMed Central

    Akil, Luma; Ahmad, H. Anwar

    2016-01-01

    SUMMARY Background Poliomyelitis is a highly infectious disease caused by poliovirus, which becomes difficult to manage/eradicate in politically unstable areas. The objectives of this study were to determine the movement and management of such polio outbreaks in endemic countries and countries with reoccurring cases of polio and to determine the effect of political instability on polio eradication. Methods In this study, the extent of polio outbreaks was examined and modeled using statistical methodologies and mapped with GIS software. Data on polio cases and immunization were collected for countries with polio cases for the period 2011 to 2014. Weekly data from the Global Polio Eradication Initiative were collected for selected countries. The recent virus origin and current movement was mapped using GIS. Correlations between immunization rates, the Global Peace Index (GPI), and other indicators of a country’s political stability with polio outbreaks were determined. Data were analyzed using SAS 9.4 and ArcGIS 10. Results For several reasons, Pakistan remains highly vulnerable to new incidences of polio (306 cases in 2014). Overall immunization rates showed a steady decline over time in selected countries. Countries with polio cases were shown to have high rates of infant mortality, and their GPI ranked between 2.0 and 3.3; displaced populations, level of violent crime rating, and political instability also were ranked high for several countries. Conclusion Polio was shown to be high in areas with increased conflict and instability. Displaced populations living in hard-to-reach areas may lack access to proper vaccination and health care. Wars and conflict have also resulted in the reemergence of polio in otherwise polio-free countries. PMID:27237735

  5. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine

    PubMed Central

    Sanders, Barbara P.; de los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G.; Song, Yutong; Cooper, Gillian; Crawt, Laura E.; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H. H. V.; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2016-01-01

    The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4–9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive

  6. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine.

    PubMed

    Sanders, Barbara P; de Los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G; Song, Yutong; Cooper, Gillian; Crawt, Laura E; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2016-03-01

    The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4-9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive

  7. Septage treatments to reduce the numbers of bacteria and polioviruses.

    PubMed Central

    Stramer, S L; Cliver, D O

    1984-01-01

    Disposal of the pumped contents of septic tanks (septage) represents a possible means of dissemination of enteric pathogens including viruses, since persistence of enteroviruses in septic tank sludge for greater than 100 days has been demonstrated. The risk of exposure to potentially infectious agents can be reduced by disinfecting septages before their disposal. Of the septage disinfectants examined (technical and analytical grade glutaraldehyde, hydrogen peroxide, heat treatments, and a combination of heat and hydrogen peroxide), the treatment including hydrogen peroxide (5 mg, plus 0.33 mg of trichloroacetic acid, per ml of septage) and 55 degrees C killed virtually all the bacteria in septage within 1 h, whereas 55 degrees C alone inactivated inoculated polioviruses within 30 min. Virus was the most sensitive to heat, whereas fecal coliforms appeared to be the most sensitive to all chemical treatments. The responses of fecal streptococci and virus to both grades of glutaraldehyde (each at 1 mg/ml) were similar. Virus was more resistant than either fecal streptococci or total bacteria to low concentrations of hydrogen peroxide (1 to 5 mg/ml); however, virus and fecal streptococci were more labile than total bacteria to the highest peroxide concentration (10 mg/ml) examined. It is possible that the treatment combining heat and hydrogen peroxide was the most effective in reducing the concentrations of all bacteria, because catalase and peroxidases as well as other enzymes were heat inactivated, although catalase seems the most likely cause of damage. However, this most effective treatment does not appear to be practical for on-site use as performed, so further work on septage disinfection is recommended. PMID:6093691

  8. Synthesis of immunogenic, but non-infectious, poliovirus particles in insect cells by a baculovirus expression vector.

    PubMed

    Urakawa, T; Ferguson, M; Minor, P D; Cooper, J; Sullivan, M; Almond, J W; Bishop, D H

    1989-06-01

    A baculovirus expression vector (AcLeon) derived from Autographa californica nuclear polyhedrosis virus (AcNPV) was prepared containing the complete 6.6 kb coding region of the P3/Leon/37 strain of poliovirus type 3 placed under the control of the AcNPV polyhedrin promoter. The recombinant virus was used to infect Spodoptera frugiperda insect cells. As demonstrated by use of the appropriate antibodies, infected insect cells made poliovirus proteins that included the structural proteins VP0, VP1 and VP3. Poliovirus particles were recovered from extracts of the infected cells and demonstrated to be free from detectable levels of RNA and to be non-infectious in tissue culture. After particle purification by CsCl gradient centrifugation and immunization of outbred mice, antibodies to the structural proteins, including neutralizing antibodies, were obtained. Other recombinant baculoviruses, containing the majority of the capsid coding region of P3/Leon/37 (e.g. AcCAP21, nucleotide residues 742 to 3318), made an unprocessed precursor to the poliovirus structural proteins. These data suggested that processing of the poliovirus gene product by the AcLeon construct was catalysed by the poliovirus-encoded proteases. The results demonstrated that antigenic and immunogenic poliovirus proteins and empty particles can be made in insect cells by recombinant baculoviruses. PMID:2543785

  9. CONCENTRATION OF POLIOVIRUS FROM TAP WATER USING POSITIVELY CHARGED MICROPOROUS FILTERS

    EPA Science Inventory

    Microporous filters that are more electropositive than the negatively charged filters currently used for virus concentration from water by filter adsorption-elution methods were evaluated for poliovirus recovery from tap water. Zeta Plus filters composed of diatomaceous earth-cel...

  10. Concentration of poliovirus from tap water using positively charged microporous filters.

    PubMed Central

    Sobsey, M D; Jones, B L

    1979-01-01

    Microporous filters that are more electropositive than the negatively charged filters currently used for virus concentrations from water by filter adsorption-elution methods were evaluated for poliovirus recovery from tap water. Zeta Plus filters composed of diatomaceous earth-cellulose-"charge-modified" resin mixtures and having a net positive charge of up to pH 5 to 6 efficiently adsorbed poliovirus from tap water at ambient pH levels 7.0 to 7.5 without added multivalent cation salts. The adsorbed virus were eluted with glycine-NaOH, pH 9.5 to 11.5. Electropositive asbestos-cellulose filters efficiently adsorbed poliovirus from tap water without added multivalent cation salts between pH 3.5 and 9.0, and the absorbed viruses could be eluted with 3% beef extract, pH 9, but not with pH 9.5 to 11.5 glycine-NaOH. Under water quality conditions in which poliovirus recoveries from large volumes of water were less than 5% with conventional negatively charged filters and standard methods, recoveries with Zeta Plus filters averaged 64 and 22.5% for one- and two-stage concentration procedures, respectively. Electropositive filters appear to offer distinct advantages over conventional negatively charged filters for concentrating enteric viruses from water, and their behavior tends to confirm the importance of electrostatic forces in virus recovery from water by microporous filter adsorption-elution methods. PMID:36844

  11. Differential depuration of poliovirus, Escherichia coli, and a coliphage by the common mussel, Mytilus edulis

    SciTech Connect

    Power, U.F.; Collins, J.K. )

    1989-06-01

    The elimination of sewage effluent-associated poliovirus, Escherichia coli, and a 22-nm icosahedral coliphage by the common mussel, Mytilus edulis, was studied. Both laboratory-and commercial-scale recirculating, UV depuration systems were used in this study. In the laboratory system, the logarithms of the poliovirus, E. coli, and coliphage levels were reduced by 1.86, 2.9, and 2.16, respectively, within 52 h of depuration. The relative patterns and rates of elimination of the three organisms suggest that they are eliminated from mussels by different mechanisms during depuration under suitable conditions. Poliovirus was not included in experiments undertaken in the commercial-scale depuration system. The differences in the relative rates and patterns of elimination were maintained for E. coli and coliphage in this system, with the logarithm of the E. coli levels being reduced by 3.18 and the logarithm of the coliphage levels being reduced by 0.87. The results from both depuration systems suggest that E. coli is an inappropriate indicator of the efficiency of virus elimination during depuration. The coliphage used appears to be a more representative indicator. Depuration under stressful conditions appeared to have a negligible affect on poliovirus and coliphage elimination rates from mussels. However, the rate and pattern of E. coli elimination were dramatically affected by these conditions. Therefore, monitoring E. coli counts might prove useful in ensuring that mussels are functioning well during depuration.

  12. Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease

    SciTech Connect

    Alvarez, Enrique; Castello, Alfredo; Carrasco, Luis; Izquierdo, Jose M.

    2011-10-14

    Highlights: {yields} Novel role for poliovirus 2A protease as splicing modulator. {yields} Poliovirus 2A protease inhibits the alternative splicing of pre-mRNAs. {yields} Poliovirus 2A protease blocks the second catalytic step of splicing. -- Abstract: Viruses have developed multiple strategies to interfere with the gene expression of host cells at different stages to ensure their own survival. Here we report a new role for poliovirus 2A{sup pro} modulating the alternative splicing of pre-mRNAs. Expression of 2A{sup pro} potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A{sup pro} abrogate Fas exon 6 skipping, whereas higher levels of protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA using nuclear extracts is also strongly inhibited by 2A{sup pro}, leading to accumulation of the first exon and the lariat product containing the unspliced second exon. These findings reveal that the mechanism of action of 2A{sup pro} on splicing is to selectively block the second catalytic step.

  13. EFFECTS OF BENTONITE CLAY SOLIDS ON POLIOVIRUS CONCENTRATION FROM WATER BY MICROPOROUS FILTER METHODS

    EPA Science Inventory

    In order to determine if suspended solids interfere with enteric virus recovery from water by microporous filter methods, the effects of bentonite clay solids at a concentration of 10 NTU on the recovery of poliovirus type 1 from seeded, activated carbon-treated, filtered tap wat...

  14. Capped mRNAs with reduced secondary structure can function in extracts from poliovirus-infected cells

    SciTech Connect

    Sonenberg, N.; Guertin, D.; Lee, K.A.W.

    1982-12-01

    Extracts form poliovirus-infected HeLa cells were used to study ribosome binding of native and denatured reovirus mRNAs and translation of capped mRNAs with different degrees of secondary structure. Here, the authors demonstrate that ribosomes in extracts from poliovirus-infected cells could form initiation complexes with denatured reovirus mRNA, in contrast to their inability to bind native reovirus mRNA. Furthermore, the capped alfalfa mosiac virus 4 RNA, which is most probable devoid of stable secondary structure at its 5' end, could be translated at much higher efficiency than could other capped mRNAs in extracts from poliovirus-infected cells.

  15. Mathematical model for simulating discharges on the Sabine River between Tatum and Ruliff, Texas

    USGS Publications Warehouse

    Neely, Braxtel L.

    1979-01-01

    A mathematical model for simulating discharges on the Sabine River between Tatum and Ruliff, TX., was developed to evaluate the effects of release schedules on discharges from the Toledo Bend Reservoir compared to discharges under natural conditions. Using the discharge at Tatum, TX., the rainfall over the basin, and the discharge release schedule for the reservoir, discharge hydrographs for the natural and reservoir-controlled conditions can be computed. (Woodard-USGS)

  16. Effects of hydrostatic pressure on the stability and thermostability of poliovirus: a new method for vaccine preservation.

    PubMed

    Ferreira, Evanilce; Mendes, Ygara S; Silva, Jerson L; Galler, Ricardo; Oliveira, Andréa C; Freire, Marcos S; Gaspar, Luciane P

    2009-08-27

    Viruses are a structurally diverse group of infectious agents that differ widely in their sensitivities to high hydrostatic pressure (HHP). Studies on picornaviruses have demonstrated that these viruses are extremely resistant to HHP treatments, with poliovirus appearing to be the most resistant. Here, the three attenuated poliovirus serotypes were compared with regard to pressure and thermal resistance. We found that HHP does not inactivate any of the three serotypes studied (1-3). Rather, HHP treatment was found to stabilize poliovirus by increasing viral thermal resistance at 37 degrees C. Identification of new methods that stabilize poliovirus against heat inactivation would aid in the design of a more heat-stable vaccine, circumventing the problems associated with refrigeration during storage and transport of the vaccine prior to use. PMID:19616496

  17. 33 CFR 334.790 - Sabine River at Orange, Tex.; restricted area in vicinity of the Naval and Marine Corps Reserve...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Sabine River at Orange, Tex... RESTRICTED AREA REGULATIONS § 334.790 Sabine River at Orange, Tex.; restricted area in vicinity of the Naval.... Government or those duly authorized by the Commanding Officer, Naval and Marine Corps Reserve Center,...

  18. 33 CFR 334.790 - Sabine River at Orange, Tex.; restricted area in vicinity of the Naval and Marine Corps Reserve...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Sabine River at Orange, Tex... RESTRICTED AREA REGULATIONS § 334.790 Sabine River at Orange, Tex.; restricted area in vicinity of the Naval.... Government or those duly authorized by the Commanding Officer, Naval and Marine Corps Reserve Center,...

  19. 33 CFR 334.790 - Sabine River at Orange, Tex.; restricted area in vicinity of the Naval and Marine Corps Reserve...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Sabine River at Orange, Tex... RESTRICTED AREA REGULATIONS § 334.790 Sabine River at Orange, Tex.; restricted area in vicinity of the Naval.... Government or those duly authorized by the Commanding Officer, Naval and Marine Corps Reserve Center,...

  20. 33 CFR 334.790 - Sabine River at Orange, Tex.; restricted area in vicinity of the Naval and Marine Corps Reserve...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Sabine River at Orange, Tex... RESTRICTED AREA REGULATIONS § 334.790 Sabine River at Orange, Tex.; restricted area in vicinity of the Naval.... Government or those duly authorized by the Commanding Officer, Naval and Marine Corps Reserve Center,...

  1. 33 CFR 334.790 - Sabine River at Orange, Tex.; restricted area in vicinity of the Naval and Marine Corps Reserve...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Sabine River at Orange, Tex... RESTRICTED AREA REGULATIONS § 334.790 Sabine River at Orange, Tex.; restricted area in vicinity of the Naval.... Government or those duly authorized by the Commanding Officer, Naval and Marine Corps Reserve Center,...

  2. Nectin-Like Interactions between Poliovirus and Its Receptor Trigger Conformational Changes Associated with Cell Entry

    PubMed Central

    Strauss, Mike; Filman, David J.; Belnap, David M.; Cheng, Naiqian; Noel, Roane T.

    2015-01-01

    ABSTRACT Poliovirus infection is initiated by attachment to a receptor on the cell surface called Pvr or CD155. At physiological temperatures, the receptor catalyzes an irreversible expansion of the virus to form an expanded form of the capsid called the 135S particle. This expansion results in the externalization of the myristoylated capsid protein VP4 and the N-terminal extension of the capsid protein VP1, both of which become inserted into the cell membrane. Structures of the expanded forms of poliovirus and of several related viruses have recently been reported. However, until now, it has been unclear how receptor binding triggers viral expansion at physiological temperature. Here, we report poliovirus in complex with an enzymatically partially deglycosylated form of the 3-domain ectodomain of Pvr at a 4-Å resolution, as determined by cryo-electron microscopy. The interaction of the receptor with the virus in this structure is reminiscent of the interactions of Pvr with its natural ligands. At a low temperature, the receptor induces very few changes in the structure of the virus, with the largest changes occurring within the footprint of the receptor, and in a loop of the internal protein VP4. Changes in the vicinity of the receptor include the displacement of a natural lipid ligand (called “pocket factor”), demonstrating that the loss of this ligand, alone, is not sufficient to induce particle expansion. Finally, analogies with naturally occurring ligand binding in the nectin family suggest which specific structural rearrangements in the virus-receptor complex could help to trigger the irreversible expansion of the capsid. IMPORTANCE The cell-surface receptor (Pvr) catalyzes a large structural change in the virus that exposes membrane-binding protein chains. We fitted known atomic models of the virus and Pvr into three-dimensional experimental maps of the receptor-virus complex. The molecular interactions we see between poliovirus and its receptor are

  3. Improved genotyping vaccine and wild-type poliovirus strains by restriction fragment length polymorphism analysis: clinical diagnostic implications.

    PubMed

    Georgopoulou, A; Markoulatos, P; Spyrou, N; Vamvakopoulos, N C

    2000-12-01

    The combination of preventive vaccination and diagnostic typing of viral isolates from patients with clinical poliomyelitis constitutes our main protective shield against polioviruses. The restriction fragment length polymorphism (RFLP) adaptation of the reverse transcriptase (RT)-PCR methodology has advanced diagnostic genotyping of polioviruses, although further improvements are definitely needed. We report here on an improved RFLP procedure for the genotyping of polioviruses. A highly conserved segment within the 5' noncoding region of polioviruses was selected for RT-PCR amplification by the UC(53)-UG(52) primer pair with the hope that it would be most resistant to the inescapable genetic alteration-drift experienced by the other segments of the viral genome. Complete inter- and intratypic genotyping of polioviruses by the present RFLP method was accomplished with a minimum set of four restriction endonucleases (HaeIII, DdeI, NcoI, and AvaI). To compensate for potential genetic drift within the recognition sites of HaeIII, DdeI, or NcoI in atypical clinical samples, the RFLP patterns generated with HpaII and StyI as replacements were analyzed. The specificity of the method was also successfully assessed by RFLP analysis of 55 reference nonpoliovirus enterovirus controls. The concerted implementation of these conditional protocols for diagnostic inter- and intratypic genotyping of polioviruses was evaluated with 21 clinical samples with absolute success. PMID:11101561

  4. Improved Genotyping Vaccine and Wild-Type Poliovirus Strains by Restriction Fragment Length Polymorphism Analysis: Clinical Diagnostic Implications

    PubMed Central

    Georgopoulou, Amalia; Markoulatos, Panayotis; Spyrou, Niki; Vamvakopoulos, Nicholas C.

    2000-01-01

    The combination of preventive vaccination and diagnostic typing of viral isolates from patients with clinical poliomyelitis constitutes our main protective shield against polioviruses. The restriction fragment length polymorphism (RFLP) adaptation of the reverse transcriptase (RT)-PCR methodology has advanced diagnostic genotyping of polioviruses, although further improvements are definitely needed. We report here on an improved RFLP procedure for the genotyping of polioviruses. A highly conserved segment within the 5′ noncoding region of polioviruses was selected for RT-PCR amplification by the UC53-UG52 primer pair with the hope that it would be most resistant to the inescapable genetic alteration-drift experienced by the other segments of the viral genome. Complete inter- and intratypic genotyping of polioviruses by the present RFLP method was accomplished with a minimum set of four restriction endonucleases (HaeIII, DdeI, NcoI, and AvaI). To compensate for potential genetic drift within the recognition sites of HaeIII, DdeI, or NcoI in atypical clinical samples, the RFLP patterns generated with HpaII and StyI as replacements were analyzed. The specificity of the method was also successfully assessed by RFLP analysis of 55 reference nonpoliovirus enterovirus controls. The concerted implementation of these conditional protocols for diagnostic inter- and intratypic genotyping of polioviruses was evaluated with 21 clinical samples with absolute success. PMID:11101561

  5. The poliovirus receptor protein is produced both as membrane-bound and secreted forms.

    PubMed Central

    Koike, S; Horie, H; Ise, I; Okitsu, A; Yoshida, M; Iizuka, N; Takeuchi, K; Takegami, T; Nomoto, A

    1990-01-01

    Both genomic and complementary DNA clones encoding poliovirus receptors were isolated from genomic and complementary DNA libraries prepared from HeLa S3 cells, respectively. Nucleotide sequence analysis of these cloned DNAs revealed that the poliovirus receptor gene is approximately 20 kb long and contains seven introns in the coding region, and that at least four mRNA isoforms referring to the coding sequence are generated by alternative splicing and appear to encode four different molecules, that is, PVR alpha, PVR beta, PVR gamma and PVR delta. The predicted amino acid sequences indicate that PVR alpha and PVR delta, corresponding to the previously described cDNA clones H20A and H20B, respectively, are integral membrane proteins while the other two molecules described here for the first time lack a putative transmembrane domain. Mouse cell transformants carrying PVR alpha were permissive for poliovirus infection, but those carrying PVR beta were hardly permissive. In contrast to PVR alpha, PVR beta was not detected on the surface of the mouse cell transformants but was detected in the culture fluid by an immunological method using a monoclonal antibody against poliovirus receptor. Three types of splicing products for PVR alpha, PVR beta and PVR gamma were detected by polymerase chain reactions using appropriate primers in poly(A)+ RNAs of the brain, leukocyte, liver, lung and placenta of humans; the choice of primers used did not permit detection of PVR delta. In situ hybridization using a cDNA fragment as a probe demonstrated that the PVR gene is located at the band q13.1----13.2 of human chromosome 19. Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:2170108

  6. Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

    NASA Technical Reports Server (NTRS)

    Butel, J. S.

    2000-01-01

    From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

  7. Massive outbreak of poliomyelitis caused by type-3 wild poliovirus in Angola in 1999.

    PubMed Central

    Valente, F.; Otten, M.; Balbina, F.; Van de Weerdt, R.; Chezzi, C.; Eriki, P.; Van-Dúnnen, J.; Bele, J. M.

    2000-01-01

    The largest outbreak of poliomyelitis ever recorded in Africa (1093 cases) occurred from 1 March to 28 May 1999 in Luanda, Angola, and in surrounding areas. The outbreak was caused primarily by a type-3 wild poliovirus, although type-1 wild poliovirus was circulating in the outbreak area at the same time. Infected individuals ranged in age from 2 months to 22 years; 788 individuals (72%) were younger than 3 years. Of the 590 individuals whose vaccination status was known, 23% had received no vaccine and 54% had received fewer than three doses of oral poliovirus vaccine (OPV). The major factors that contributed to this outbreak were as follows: massive displacement of unvaccinated persons to urban settings; low routine OPV coverage; inaccessible populations during the previous three national immunization days (NIDs); and inadequate sanitation. This outbreak indicates the urgent need to improve accessibility to all children during NIDs and the dramatic impact that war can have by displacing persons and impeding access to routine immunizations. The period immediately after an outbreak provides an enhanced opportunity to eradicate poliomyelitis. If continuous access in all districts for acute flaccid paralysis surveillance and supplemental immunizations cannot be assured, the current war in Angola may threaten global poliomyelitis eradication. PMID:10812730

  8. Strand-specific attachment of avidin-spheres to double-stranded poliovirus RNA.

    PubMed Central

    Richards, O C; Ehrenfeld, E; Manning, J

    1979-01-01

    Poliovirus-specific double-stranded RNA molecules containing covalently attached protein were coupled with a biotin ester through the protein moiety. Subsequent interaction of the RNA-biotin with avidin attached to electronopaque plastic spheres led to the formation of complexes that were easily visualized in the electron microscope. Avidinspheres were associated only with one end of the RNA-biotin molecules, as seen in the electron microscope. Avidin-sphere attachment to poliovirus double-stranded RNA is strand specific, as shown by molecular hybridization of strand-specific probes to the separated strands of denatured complexes. [3H]DNA complementary to polio virion RNA hybridized exclusively to the strands bearing associated spheres [(+) strands] whereas 125I-labeled virion RNA hybridized predominantly with strands without spheres [(-)strands]. This biotin-avidin labeling technique provides a means for the isolation of full-length poliovirus (-) strands and may provide a general means for isolation of double-stranded polynucleotides containing tightly attached protein. Images PMID:218216

  9. Identification of terminal adenylyl transferase activity of the poliovirus polymerase 3Dpol.

    PubMed Central

    Neufeld, K L; Galarza, J M; Richards, O C; Summers, D F; Ehrenfeld, E

    1994-01-01

    A terminal adenylyl transferase (TATase) activity has been identified in preparations of purified poliovirus RNA-dependent RNA polymerase (3Dpol). Highly purified 3Dpol is capable of adding [32P]AMP to the 3' ends of chemically synthesized 12-nucleotide (nt)-long RNAs. The purified 52-kDa polypeptide, isolated after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and renatured, retained the TATase activity. Two 3Dpol mutants, purified from Escherichia coli expression systems, displayed no detectable polymerase activity and were unable to catalyze TATase activity. Likewise, extracts from the parental E. coli strain that harbored no expression plasmid were unable to catalyze formation of the TATase products. With the RNA oligonucleotide 5'-CCUGCUUUUGCA-3' used as an acceptor, the products formed by wild-type 3Dpol were 9 and 18 nt longer than the 12-nt oligomer. GTP, CTP, and UTP did not serve as substrates for transfer to this RNA, either by themselves or when all deoxynucleoside triphosphates were present in the reaction. Results from kinetic and stoichiometric analyses suggest that the reaction is catalytic and shows substrate and enzyme dependence. The 3'-terminal 13 nt of poliovirus minus-strand RNA also served as an acceptor for TATase activity, raising the possibility that this activity functions in poliovirus RNA replication. The efficiency of utilization and the nature of the products formed during the reaction were dependent on the acceptor RNA. Images PMID:8057462

  10. Recovery of poliovirus from cut surface of stored fresh papaya fruit.

    PubMed

    Lee, A S; Yap, K L

    1999-06-01

    Poliovirus kept on the cut surfaces of fully ripe papaya cubes placed in an ice box showed a sharp and significant reduction in the recovery of infectious virus about 15 minutes after exposure. Thereafter, a very gradual decrease ensued and infectious residual virus was detected up to the end of the 6-hour exposure period. Papaya cubes washed or kept overnight before virus inoculation, and from less ripe fruits produced a similar survival pattern. A very small proportion of the inoculum was recovered from the mashed content of the inoculated papaya cubes thus suggesting that most of the non-recovered virus particles were inactivated. The results suggest that the importance of poliovirus-contaminated cut papayas as a transmission vehicle for the virus is greatly reduced by the rapid decline in the infectivity of a large proportion of the virus soon after contamination. Nevertheless, the potential to transmit remains as a small residual pool of infectious poliovirus is able to survive for a relatively long period. PMID:10774695

  11. Environmental surveillance of poliovirus and non-polio enterovirus in urban sewage in Dakar, Senegal (2007-2013)

    PubMed Central

    Ndiaye, Abdou Kader; Diop, Pape Amadou Mbathio; Diop, Ousmane Madiagne

    2014-01-01

    Introduction Global poliomyelitis eradication initiative relies on (i) laboratory based surveillance of acute flaccid surveillance (AFP) to monitor the circulation of wild poliovirus in a population, and (ii) vaccination to prevent its diffusion. However, as poliovirus can survive in the environment namely in sewage, environmental surveillance (ES) is of growing importance as the eradication target is close. This study aimed to assess polioviruses and non polio enteroviruses circulation in sewage drains covering a significant population of Dakar. Methods From April 2007 to May 2013, 271 specimens of raw sewage were collected using the grab method in 6 neighborhoods of Dakar. Samples were processed to extract and concentrate viruses using polyethylene glycol and Dextran (two-phase separation method). Isolation of enteroviruses was attempted in RD, L20B and Hep2 cell lines. Polioviruses were identified by RT-PCR and Elisa. Non Polio Enteroviruses (NPEVs) were identified by RT-PCR and microneutralisation tests. Results Polioviruses and NPEVs were respectively detected in 34,3% and 42,8% sewage samples. No wild poliovirus neither circulating vaccine-derived Poliovirus (cVDPV) was detected. Neutralization assays have identified 49 non polio enteroviruses that were subsequently classified in 13 serotypes belonging to HEV-A (22, 4%), HEV-B (12, 24%), HEV-C (26, 53%) and HEV-D (6, 12%) species. Conclusion This study is the first documentation of enteroviruses environmental detection in Senegal. It shows the usefulness of environmental surveillance for indirect monitoring of the circulation and distribution of enteroviruses in the community. PMID:25848458

  12. Predictive spatial risk model of poliovirus to aid prioritization and hasten eradication in Nigeria

    PubMed Central

    2014-01-01

    Background One of the challenges facing the Global Polio Eradication Initiative is efficiently directing limited resources, such as specially trained personnel, community outreach activities, and satellite vaccinator tracking, to the most at-risk areas to maximize the impact of interventions. A validated predictive model of wild poliovirus circulation would greatly inform prioritization efforts by accurately forecasting areas at greatest risk, thus enabling the greatest effect of program interventions. Methods Using Nigerian acute flaccid paralysis surveillance data from 2004-2013, we developed a spatial hierarchical Poisson hurdle model fitted within a Bayesian framework to study historical polio caseload patterns and forecast future circulation of type 1 and 3 wild poliovirus within districts in Nigeria. A Bayesian temporal smoothing model was applied to address data sparsity underlying estimates of covariates at the district level. Results We find that calculated vaccine-derived population immunity is significantly negatively associated with the probability and number of wild poliovirus case(s) within a district. Recent case information is significantly positively associated with probability of a case, but not the number of cases. We used lagged indicators and coefficients from the fitted models to forecast reported cases in the subsequent six-month periods. Over the past three years, the average predictive ability is 86 ± 2% and 85 ± 4% for wild poliovirus type 1 and 3, respectively. Interestingly, the predictive accuracy of historical transmission patterns alone is equivalent (86 ± 2% and 84 ± 4% for type 1 and 3, respectively). We calculate uncertainty in risk ranking to inform assessments of changes in rank between time periods. Conclusions The model developed in this study successfully predicts districts at risk for future wild poliovirus cases in Nigeria. The highest predicted district risk was 12.8 WPV1 cases in 2006, while the lowest district risk

  13. Isolation and characterization of HeLa cell lines blocked at different steps in the poliovirus life cycle.

    PubMed Central

    Kaplan, G; Levy, A; Racaniello, V R

    1989-01-01

    Cotransfection of poliovirus RNA and R1, a poliovirus subgenomic RNA containing a deletion of nearly all of the capsid region, resulted in surviving cells, in contrast to the complete cell death observed after transfection with viral RNA. Cells that survived the cotransfection grew into colonies, produced infectious poliovirus, and underwent cycles of cell lysis (crisis periods) where less than 1% of the cells survived, followed by periods of growth. Poliovirus evolved during the persistent infection as judged by changes in plaque size. After passage for 6 months, a stable line called SOFIA emerged that no longer produced infectious virus and did not contain viral proteins or viral RNA. Cells frozen in liquid N2 while still in crisis and recultured 4 months later (named SOFIA N2) were also stabilized. After infection with poliovirus, SOFIA N2 cells showed a delay in the development of cytopathic effect, viral production, and cellular death when compared with HeLa cells. In contrast, SOFIA cells did not develop cytopathic effect and produced 10,000 times less virus than SOFIA N2 or HeLa cells. Viral production was delayed in SOFIA and SOFIA N2 cells transfected with poliovirus RNA when compared with HeLa cells, suggesting the presence of an intracellular block to poliovirus replication. Analysis of the cellular receptor for poliovirus by virus binding, an enzyme-linked immunosorbent assay, and in situ rosette assays with an antireceptor monoclonal antibody showed that receptors were expressed in SOFIA N2 cells but not in SOFIA cells. Echovirus 6, an enterovirus which uses a different cellular receptor, formed small plaques on SOFIA cells. Vesicular stomatitis virus formed plaques of similar size on SOFIA and HeLa cells, suggesting that the intracellular block was specific for enteroviruses. Cotransfection of the subgenomic replicon R1 with poliovirion RNA therefore resulted in the selection of HeLa cell variants containing blocks to poliovirus replication at the

  14. A poliovirus hybrid expressing a neutralization epitope from the major outer membrane protein of Chlamydia trachomatis is highly immunogenic.

    PubMed Central

    Murdin, A D; Su, H; Manning, D S; Klein, M H; Parnell, M J; Caldwell, H D

    1993-01-01

    Trachoma and sexually transmitted diseases caused by Chlamydia trachomatis are major health problems worldwide. Epitopes on the major outer membrane protein (MOMP) of C. trachomatis have been identified as important targets for the development of vaccines. In order to examine the immunogenicity of a recombinant vector expressing a chlamydial epitope, a poliovirus hybrid was constructed in which part of neutralization antigenic site I of poliovirus type 1 Mahoney (PV1-M) was replaced by a sequence from variable domain I of the MOMP of C. trachomatis serovar A. The chlamydial sequence included the neutralization epitope VAGLEK. This hybrid was viable, grew very well compared with PV1-M, and expressed both poliovirus and chlamydial antigenic determinants. When inoculated into rabbits, this hybrid was highly immunogenic, inducing a strong response against both PV1-M and C. trachomatis serovar A. Antichlamydia titers were 10- to 100-fold higher than the titers induced by equimolar amounts of either purified MOMP or a synthetic peptide expressing the VAGLEK epitope. Furthermore, rabbit antisera raised against this hybrid neutralized chlamydial infectivity both in vitro, for hamster kidney cells, and passively in vivo, for conjunctival epithelia of cynomolgus monkeys. Because poliovirus infection induces a strong mucosal immune response in primates and humans, these results indicate that poliovirus-chlamydia hybrids could become powerful tools for the study of mucosal immunity to chlamydial infection and for the development of recombinant chlamydial vaccines. Images PMID:7691749

  15. Isolation of a soluble and template-dependent poliovirus RNA polymerase that copies virion RNA in vitro.

    PubMed Central

    Flanegan, J B; Van Dyke, T A

    1979-01-01

    A soluble RNA-dependent RNA polymerase was isolated from poliovirus-infected HeLa cells and was shown to copy poliovirus RNA in vitro. The enzyme was purified from a 200,000-X-g supernatant of a cytoplasmic extract of infected cells. The activity of the enzyme was measured throughout the purification by using a polyadenylic acid template and oligouridylic acid primer. The enzyme was partially purified by ammonium sulfate precipitation, glycerol gradient centrifugation, and phosphocellulose chromatography. The polymerase precipitated in a 35% saturated solution of ammonium sulfate, sedimented at about 7S on a glycerol gradient, and eluted from phosphocellulose with 0.15 M KC1. The polymerase was purified about 40-fold and was shown to be totally dependent on exogenous RNA for activity and relatively free of contaminating nuclease. The partially purified polymerase was able to use purified polio virion RNA as well as a template. Under the reaction conditions used, the polymerase required an oligouridylic acid primer and all four ribonucleside triphosphates for activity. The optimum ratio of oligouridylic acid molecules to poliovirus RNA molecules for priming activity was about 16:1. A nearest-neighbor analysis of the in vitro RNA product shows it to be heteropolymeric. Annealing the in vitro product with poliovirus RNA product shows it to be heteropolymeric. Annealing the in vitro product with poliovirus RNA rendered it resistant to RNase digestion, thus suggesting that the product RNA was complementary to the virion RNA template. PMID:232168

  16. Attenuation of Neurovirulence, Biodistribution, and Shedding of a Poliovirus:Rhinovirus Chimera after Intrathalamic Inoculation in Macaca fascicularis

    PubMed Central

    Dobrikova, Elena Y.; Goetz, Christian; Walters, Robert W.; Lawson, Sarah K.; Peggins, James O.; Muszynski, Karen; Ruppel, Sheryl; Poole, Karyol; Giardina, Steven L.; Vela, Eric M.; Estep, James E.

    2012-01-01

    A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation in Macaca fascicularis. These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied. PMID:22171271

  17. Gain-loss study along two streams in the upper Sabine River basin, Texas; August-September 1981

    USGS Publications Warehouse

    Myers, Dennis R.

    1983-01-01

    A gain-loss study was made August-September 1981 along the upper Sabine River from Lake Tawakoni to Farm Road 2517 near Carthage and along Lake Fork Creek from Lake Fork Reservoir to its junction (mouth) with the Sabine River. The hydrologic data collected during the gain-loss study indicated that during periods of low flow on the Sabine River, at least as much water as is released from Lake Tawakoni and from Lake Fork Reservoir will be available downstream at Farm Road 14 near Big Sandy and at Farm Road 2517 near Carthage. Gains from bank seepage and small tributary inflows compensate for losses due to evaporation, evapotranspiration, and loss of water into the alluvial aquifer. Dissolved solids concentrations in the Sabine River, estimated from specific conductance, increased from about 120 milligrams per liter near the upstream end of the reach to about 400 milligrams per liter near the downstream end of the reach. Water with these concentrations of dissolved solids generally is suitable for most uses.

  18. Efficiency of beef extract for the recovery of poliovirus from wastewater effluents.

    PubMed

    Landry, E F; Vaughn, J M; Thomas, M Z; Vicale, T J

    1978-10-01

    The efficiency of poliovirus elution from fiber glass cartridge filters (K27), epoxy-fiber glass-asbestos filters (M780), and pleated cartridge filters was assessed by using 3% beef extract (pH 9.0) or 0.1 M glycine (pH 11.5). Poliovirus type I, strain LSc, was seeded into 20- to 25-gallon (ca. 75.6- to 95.6-liter) samples of treated sewage effluent and concentrated by using a filter adsorption-elution technique. Virus elution was accomplished by using either two 600-ml portions of 3% beef extract (pH 9.0), or two 1-liter portions of 0.1 M glycine (pH 11.5). In all experiments, beef extract elution followed by organic flocculation was found to be superior, yielding a mean recovery efficiency of 85%, with recoveries ranging from 68 to 100%. Elution with 0.1 M glycine (pH 11.5) followed by inorganic flocculation resulted in a mean recovery efficiency of 36%. The variable range of recoveries with beef extract could not be significantly improved by varying the type of beef extract or by extending the elution time to 30 min. Second-step reconcentration of 1-liter seeded sewage effluent and renovated wastewater samples indicated that organic flocculation was a more efficient method for virus recovery than inorganic flocculation. Beef extract concentrations of less than 3% were found to be efficient in the recovery of poliovirus from renovated wastewater. PMID:30391

  19. Conditional poliovirus mutants made by random deletion mutagenesis of infectious cDNA.

    PubMed Central

    Kirkegaard, K; Nelsen, B

    1990-01-01

    Small deletions were introduced into DNA plasmids bearing cDNA copies of Mahoney type 1 poliovirus RNA. The procedure used was similar to that of P. Hearing and T. Shenk (J. Mol. Biol. 167:809-822, 1983), with modifications designed to introduce only one lesion randomly into each DNA molecule. Methods to map small deletions in either large DNA or RNA molecules were employed. Two poliovirus mutants, VP1-101 and VP1-102, were selected from mutagenized populations on the basis of their host range phenotype, showing a large reduction in the relative numbers of plaques on CV1 and HeLa cells compared with wild-type virus. The deletions borne by the mutant genomes were mapped to the region encoding the amino terminus of VP1. That these lesions were responsible for the mutant phenotypes was substantiated by reintroduction of the sequenced lesions into a wild-type poliovirus cDNA by deoxyoligonucleotide-directed mutagenesis. The deletion of nucleotides encoding amino acids 8 and 9 of VP1 was responsible for the VP1-101 phenotype; the VP1-102 defect was caused by the deletion of the sequences encoding the first four amino acids of VP1. The peptide sequence at the VP1-VP3 proteolytic cleavage site was altered from glutamine-glycine to glutamine-methionine in VP1-102; this apparently did not alter the proteolytic cleavage pattern. The biochemical defects resulting from these mutations are discussed in the accompanying report. Images PMID:2152811

  20. The human poliovirus receptor. Receptor-virus interaction and parameters of disease specificity.

    PubMed

    Gromeier, M; Lu, H H; Bernhardt, G; Harber, J J; Bibb, J A; Wimmer, E

    1995-05-25

    The host range of poliovirus is determined by the expression of the hPVR, a member of the immunoglobulin superfamily. We characterized hPVR proteins biochemically and found them to be complex-type glycoproteins. The outermost V-like domain of three extracellular domains harbors the PVR function. A panel of single or multiple amino acid exchanges were introduced throughout this domain in order to localize regions involved in virus-receptor interactions. Putative contact amino acids were found to reside in the C'C"D and DE regions. Binding and uptake of poliovirus paralleled virus replication in all mutants tested suggesting that virus binding was affected without abrogating the ability to mediate subsequent events in the infection. Although the primate PVR is essential in conferring susceptibility to poliovirus infection, certain strains can induce neurological disease in rodents. Mouse neurovirulent PV isolates of divergent serotypical origin each provoked a distinctive, characteristic neurological syndrome upon intracerebral infection of wild-type mice. We analyzed clinical and histopathological features of diffuse encephalomyelitis caused by these PV strains and compared the condition with poliomyelitis in mice transgenic for the hPVR. Diffuse PV encephalomyelitis in wild-type mice could be distinguished clinically and histopathologically from hPVR-mediated poliomyelitis in trangenic mice. We localized the determinants of mouse neurovirulence of PV1(LS-a), a derivative of PV1 (Mahoney), in a portion of the viral genome encompassing parts of the capsid protein VP1 as well as the nonstructural protein 2A. Mouse neuropathogenicity could possibly be conferred by reduced particle stability of PV1(LS-a) inasmuch as we found particles to be thermolabile. PMID:7611627

  1. In Vitro Synthesis of Poliovirus Ribonucleic Acid: Role of the Replicative Intermediate

    PubMed Central

    Girard, Marc

    1969-01-01

    Poliovirus ribonucleic acid (RNA) polymerase crude extracts could be stored frozen in liquid nitrogen without loss of activity or specificity. The major in vitro product of these extracts was viral single-stranded RNA. However, after short periods of incubation with radioactive nucleoside triphosphates, most of the incorporated label was found in replicative intermediate. When excess unlabeled nucleoside triphosphate was added, the label was displaced from the replicative intermediate and accumulated as viral RNA. It is concluded from this experiment that the replicative intermediate is the precursor to viral RNA. In addition, some of the label was chased into double-stranded RNA. The implications of this finding are discussed. PMID:4306193

  2. Calcium Flux between the Endoplasmic Reticulum and Mitochondrion Contributes to Poliovirus-Induced Apoptosis▿

    PubMed Central

    Brisac, Cynthia; Téoulé, François; Autret, Arnaud; Pelletier, Isabelle; Colbère-Garapin, Florence; Brenner, Catherine; Lemaire, Christophe; Blondel, Bruno

    2010-01-01

    We show that poliovirus (PV) infection induces an increase in cytosolic calcium (Ca2+) concentration in neuroblastoma IMR5 cells, at least partly through Ca2+ release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) channels. This leads to Ca2+ accumulation in mitochondria through the mitochondrial Ca2+ uniporter and the voltage-dependent anion channel (VDAC). This increase in mitochondrial Ca2+ concentration in PV-infected cells leads to mitochondrial dysfunction and apoptosis. PMID:20861253

  3. North Sabine Lake field: complex deposition and reservoir morphology of lower Hackberry (Oligocene), southwest Louisiana

    SciTech Connect

    Eubanks, L.G.

    1987-10-01

    Gas and condensate production at the North Sabine Lake field is from sands of the Hackberry wedge of the Oligocene Frio Formation. These lower Hackberry sands were deposited in a preexisting submarine canyon. Multiple sand bodies are present, and five patterns of sand deposition are recognized from SP logs: (1) incised channel fill, (2) braided fan channel, (3) intermediate suprafan, (4) proximal suprafan, and (5) overbank. Although three faults surround the field, the primary trapping mechanism is stratigraphic. The development and production history of the field indicate that many small sand lenses have coalesced to form a single large reservoir; however, differences in permeability have caused variations in water influx and in the levels of gas-water contacts. Sand lenses that are not connected to the larger reservoir are of limited size and have produced small amounts of hydrocarbon. Development of the field has been complicated by casing damage probably caused by reservoir compaction. 11 figures, 2 tables.

  4. Remodeling the Endoplasmic Reticulum by Poliovirus Infection and by Individual Viral Proteins: an Autophagy-Like Origin for Virus-Induced Vesicles

    PubMed Central

    Suhy, David A.; Giddings, Thomas H.; Kirkegaard, Karla

    2000-01-01

    All positive-strand RNA viruses of eukaryotes studied assemble RNA replication complexes on the surfaces of cytoplasmic membranes. Infection of mammalian cells with poliovirus and other picornaviruses results in the accumulation of dramatically rearranged and vesiculated membranes. Poliovirus-induced membranes did not cofractionate with endoplasmic reticulum (ER), lysosomes, mitochondria, or the majority of Golgi-derived or endosomal membranes in buoyant density gradients, although changes in ionic strength affected ER and virus-induced vesicles, but not other cellular organelles, similarly. When expressed in isolation, two viral proteins of the poliovirus RNA replication complex, 3A and 2C, cofractionated with ER membranes. However, in cells that expressed 2BC, a proteolytic precursor of the 2B and 2C proteins, membranes identical in buoyant density to those observed during poliovirus infection were formed. When coexpressed with 2BC, viral protein 3A was quantitatively incorporated into these fractions, and the membranes formed were ultrastructurally similar to those in poliovirus-infected cells. These data argue that poliovirus-induced vesicles derive from the ER by the action of viral proteins 2BC and 3A by a mechanism that excludes resident host proteins. The double-membraned morphology, cytosolic content, and apparent ER origin of poliovirus-induced membranes are all consistent with an autophagic origin for these membranes. PMID:10982339

  5. Modification of an adenovirus major late promoter-binding factor during poliovirus infection.

    PubMed Central

    Lazard, D; Fernández-Tomás, C; Gariglio, P; Weinmann, R

    1989-01-01

    To further characterize the mechanism involved in poliovirus-induced inhibition of HeLa cells mRNA synthesis, in vitro formation of DNA-protein complexes between nuclear upstream stimulatory transcription factor (USF) and the adenovirus type 2 major late promoter upstream promoter element (UPE; located between -45 and -65 base pairs) was studied. Using the gel shift assay, we found differences between the UPE-protein complex formed with partially purified nuclear extracts from poliovirus-infected HeLa cells and that obtained in the presence of mock-infected extracts. Formation of the modified UPE-USF complex coincided with virus-induced inhibition of host cell RNA synthesis in vivo and with a less efficient in vitro transcriptional activity of the nuclear extracts from infected cells. Furthermore, using a cross-linking protocol, we found that the host 46-kilodalton UPE-binding USF factor was severely diminished and that a virus-induced or -modified 50-kilodalton polypeptide appeared to be specifically bound to the UPE template. Images PMID:2474675

  6. Effect of Poliovirus on Deoxyribonucleic Acid Synthesis in HeLa Cells

    PubMed Central

    Ackermann, W. W.; Cox, D. C.; Kurtz, H.; Powers, C. D.; Davies, S. J.

    1966-01-01

    Ackermann, W. W. (University of Michigan, Ann Arbor), D. C. Cox, H. Kurtz, C. D. Powers, and S. J. Davies. Effect of poliovirus on deoxyribonucleic acid synthesis in HeLa cells. J. Bacteriol. 91:1943–1952. 1966.—Both poliovirus and arginine stimulated deoxyribonucleic acid (DNA) synthesis in cultures of HeLa cells which were preconditioned by incubation in a medium deficient in arginine. However, the number of cells producing DNA was unaffected. DNA synthesis in such preconditioned cells was 10 to 20% of the maximal value obtained with a full complement of amino acids. Inhibition of DNA synthesis was produced in these cultures either by increasing the multiplicity of exposure above 40 plaque-forming units of virus per cell or by increasing the concentration of the deficient amino acid at the time of virus addition. Inhibition of DNA synthesis resulted from a reduction in the fraction of cells producing DNA. The concentration of arginine required for viral inhibition of DNA synthesis is greater than that for viral multiplication. PMID:4287076

  7. Development of a novel bag-mediated filtration system for environmental recovery of poliovirus.

    PubMed

    Fagnant, Christine Susan; Beck, Nicola Koren; Yang, Ming-Fong; Barnes, Kilala Sayisha; Boyle, David S; Meschke, John Scott

    2014-12-01

    Poliovirus (PV) is on the verge of global eradication. Due to asymptomatic shedding, eradication certification requires environmental and clinical surveillance. Current environmental surveillance methods involve collection and processing of 400-mL to 1-L grab samples by a two-phase separation method, where sample volume limits detection sensitivity. Filtration of larger sample volumes facilitates increased detection sensitivity. This study describes development of a pumpless in-field filtration system for poliovirus recovery from environmental waters. Recovery of PV types 1, 2, and 3 were compared for glass wool, ViroCap, and NanoCeram (PV1 only) filters. Seeded experiments were performed using 10(5) plaque forming units of PV inoculated into 10-L volumes of secondary effluent, surface water, or a 50:50 mixture of each at pH 7.0. Filter eluates were plated onto buffalo green monkey kidney cells for virus enumeration by plaque assay. Across all water types, recovery from glass wool filters for PV1, PV2, and PV3 averaged 17%, 28%, and 6%, respectively. Recovery from ViroCaps for PV1, PV2, and PV3 averaged 44%, 70%, and 81%, respectively. 10-L samples of moderate turbidity water were processed through ViroCap filters in less than 30 minutes using a pumpless, bag-mediated filtration system. Bag-mediated filtration offers a simple, compact, and efficient method for enhanced environmental PV surveillance. PMID:25473984

  8. A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication

    PubMed Central

    Belov, George A.; Feng, Qian; Nikovics, Krisztina; Jackson, Catherine L.; Ehrenfeld, Ellie

    2008-01-01

    Replication of many RNA viruses is accompanied by extensive remodeling of intracellular membranes. In poliovirus-infected cells, ER and Golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral RNA synthesis. Virus replication is inhibited by brefeldin A (BFA), implicating some components(s) of the cellular secretory pathway in virus growth. Formation of characteristic vesicles induced by expression of viral proteins was not inhibited by BFA, but they were functionally deficient. GBF1, a guanine nucleotide exchange factor for the small cellular GTPases, Arf, is responsible for the sensitivity of virus infection to BFA, and is required for virus replication. Knockdown of GBF1 expression inhibited virus replication, which was rescued by catalytically active protein with an intact N-terminal sequence. We identified a mutation in GBF1 that allows growth of poliovirus in the presence of BFA. Interaction between GBF1 and viral protein 3A determined the outcome of infection in the presence of BFA. PMID:19023417

  9. All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution

    SciTech Connect

    Andoh, Y.; Yoshii, N.; Yamada, A.; Kojima, H.; Mizutani, K.; Okazaki, S.; Fujimoto, K.; Nakagawa, A.; Nomoto, A.

    2014-10-28

    Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 10{sup 6} all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200 000) can leave the capsid and be replaced by water molecules from the outside in about 25 μs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

  10. All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution

    NASA Astrophysics Data System (ADS)

    Andoh, Y.; Yoshii, N.; Yamada, A.; Fujimoto, K.; Kojima, H.; Mizutani, K.; Nakagawa, A.; Nomoto, A.; Okazaki, S.

    2014-10-01

    Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 106 all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200 000) can leave the capsid and be replaced by water molecules from the outside in about 25 μs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

  11. The Role of Electron Microscopy in Studying the Continuum of Changes in Membranous Structures during Poliovirus Infection

    PubMed Central

    Rossignol, Evan D.; Yang, Jie E.; Bullitt, Esther

    2015-01-01

    Replication of the poliovirus genome is localized to cytoplasmic replication factories that are fashioned out of a mixture of viral proteins, scavenged cellular components, and new components that are synthesized within the cell due to viral manipulation/up-regulation of protein and phospholipid synthesis. These membranous replication factories are quite complex, and include markers from multiple cytoplasmic cellular organelles. This review focuses on the role of electron microscopy in advancing our understanding of poliovirus RNA replication factories. Structural data from the literature provide the basis for interpreting a wide range of biochemical studies that have been published on virus-induced lipid biosynthesis. In combination, structural and biochemical experiments elucidate the dramatic membrane remodeling that is a hallmark of poliovirus infection. Temporal and spatial membrane modifications throughout the infection cycle are discussed. Early electron microscopy studies of morphological changes following viral infection are re-considered in light of more recent data on viral manipulation of lipid and protein biosynthesis. These data suggest the existence of distinct subcellular vesicle populations, each of which serves specialized roles in poliovirus replication processes. PMID:26473912

  12. Viral precursor protein P3 and its processed products perform discrete and essential functions in the poliovirus RNA replication complex

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The differential use of protein precursors and their products is a key strategy used during poliovirus replication. To characterize the role of protein precursors during replication, we examined the complementation profiles of mutants that inhibited 3D polymerase or 3C-RNA binding activity. We showe...

  13. Isolation and Characterization of a Type 2 Vaccine-Derived Poliovirus from Environmental Surveillance in China, 2012

    PubMed Central

    Liu, Yao; Xu, Aiqiang; Lin, Xiaojuan; Yoshida, Hiromu; Xiong, Ping; Zhu, Shuangli; Wang, Suting; Yan, Dongmei; Song, Lizhi; Wang, Haiyan; Cui, Ning; Xu, Wenbo

    2013-01-01

    Environmental surveillance of poliovirus on sewage has been conducted in Shandong Province, China since 2008. A type 2 vaccine-derived poliovirus (VDPV) with 7 mutations in VP1 coding region was isolated from the sewage collected in the city of Jinan in December 2012. The complete genome sequencing analysis of this isolate revealed 25 nucleotide substitutions, 7 of which resulted in amino acid alteration. No evidence of recombination with other poliovirus serotypes was observed. The virus did not lose temperature sensitive phenotype at 40°C. An estimation based on the evolution rate of the P1 coding region suggested that evolution time of this strain might be 160–176 days. VP1 sequence analysis revealed that this VDPV strain is of no close relationship with other local type 2 polioviruses (n = 66) from sewage collected between May 2012 and June 2013, suggesting the lack of its circulation in the local population. The person who excreted the virus was not known and no closely related virus was isolated in local population via acute flaccid paralysis surveillance. By far this is the first report of VDPV isolated from sewage in China, and these results underscore the value of environmental surveillance in the polio surveillance system even in countries with high rates of OPV coverage. PMID:24386319

  14. The compatibility of inactivated-Enterovirus 71 vaccination with Coxsackievirus A16 and Poliovirus immunizations in humans and animals

    PubMed Central

    Mao, Qunying; Wang, Yiping; Shao, Jie; Ying, Zhifang; Gao, Fan; Yao, Xin; Li, Changgui; Ye, Qiang; Xu, Miao; Li, Rongcheng; Zhu, Fengcai; Liang, Zhenglun

    2015-01-01

    Enterovirus 71 (EV71) is the key pathogen for Hand, Foot, and Mouth Disease (HFMD) and can result in severe neurological complications and death among young children. Three inactivated-EV71 vaccines have gone through phase III clinical trials and have demonstrated good safety and efficacy. These vaccines will benefit young children under the threat of severe HFMD. However, the potential immunization-related compatibility for different enterovirus vaccines remains unclear, making it hard to include the EV71 vaccine in Expanded Program on Immunization (EPI). Here, we measured the neutralizing antibodies (NTAbs) against EV71, Coxsackievirus A16 (CA16) and Poliovirus from infants enrolled in those EV71 vaccine clinical trials. The results indicated that the levels of NTAb GMTs for EV71 increased significantly in all 3 vaccine groups (high, middle and low dosages, respectively) post-vaccination. Seroconversion ratios and Geometric mean fold increase were significantly higher in the vaccine groups (≥7/9 and 8.9~228.1) than in the placebo group (≤1/10 and 0.8~1.7, P < 0.05). But no similar NTAb response trends were found in CA16 and 3 types of Poliovirus. The decrease of 3 types of Poliovirus NTAb GMTs and an increase of CA16 GMTs post-EV71-vaccination were found in vaccine and placebo groups. Further animal study on CA16 and poliovirus vaccine co-immunization or pre-immunization with EV71 vaccine in mice indicated that there was no NTAb cross-activity between EV71 and CA16/Poliovirus. Our research showed that inactivated-EV71 vaccine has good specific-neutralizing capacity and can be included in EPI. PMID:25715318

  15. Poliovirus Polyuridylic Acid Polymerase and RNA Replicase Have the Same Viral Polypeptide

    PubMed Central

    Flanegan, James B.; Baltimore, David

    1979-01-01

    A poliovirus-specific polyuridylic acid [poly(U)] polymerase that copies a polyadenylic acid template complexed to an oligouridylic acid primer was isolated from the membrane fraction of infected HeLa cells and was found to sediment at 4 to 5S on a linear 5 to 20% glycerol gradient. When the poly(U) polymerase was isolated from cells labeled with [35S]methionine and was analyzed by glycerol gradient centrifugation and polyacrylamide gel electrophoresis, the position of only one viral protein was found to correlate with the location of enzyme activity. This protein had an apparent molecular weight of 62,500 based on its electrophoretic mobility relative to that of several molecular weight standards and was designated p63. When the poly(U) polymerase was isolated from the soluble fraction of a cytoplasmic extract, the activity was found to sediment at about 7S. In this case, however, both p63 and NCVP2 (77,000-dalton precursor of p63) cosedimented with the 7S activity peak. When the 7S polymerase activity was purified by phosphocellulose chromatography, both p63 and NCVP2 were found to co-chromatograph with poly(U) polymerase activity. The poliovirus replicase complexed with its endogenous RNA template was isolated from infected cells labeled with [35S]methionine and was centrifuged through a linear 15 to 30% glycerol gradient. The major viral polypeptide component in a 26S peak of replicase activity was p63, but small amounts of other poliovirus proteins were also present. When the replicase-template complex was treated with RNase T1 before centrifugation, a single peak of activity was found that sedimented at 20S and contained only labeled p63. Thus, p63 was found to be the only viral polypeptide in the replicase bound to its endogenous RNA template, and appears to be active as a poly(U) polymerase either as a monomer protein or as a 7S complex. Images PMID:219230

  16. Cell-Specific Establishment of Poliovirus Resistance to an Inhibitor Targeting a Cellular Protein

    PubMed Central

    Viktorova, Ekaterina G.; Nchoutmboube, Jules; Ford-Siltz, Lauren A.

    2015-01-01

    ABSTRACT It is hypothesized that targeting stable cellular factors involved in viral replication instead of virus-specific proteins may raise the barrier for development of resistant mutants, which is especially important for highly adaptable small (+)RNA viruses. However, contrary to this assumption, the accumulated evidence shows that these viruses easily generate mutants resistant to the inhibitors of cellular proteins at least in some systems. We investigated here the development of poliovirus resistance to brefeldin A (BFA), an inhibitor of the cellular protein GBF1, a guanine nucleotide exchange factor for the small cellular GTPase Arf1. We found that while resistant viruses can be easily selected in HeLa cells, they do not emerge in Vero cells, in spite that in the absence of the drug both cultures support robust virus replication. Our data show that the viral replication is much more resilient to BFA than functioning of the cellular secretory pathway, suggesting that the role of GBF1 in the viral replication is independent of its Arf activating function. We demonstrate that the level of recruitment of GBF1 to the replication complexes limits the establishment and expression of a BFA resistance phenotype in both HeLa and Vero cells. Moreover, the BFA resistance phenotype of poliovirus mutants is also cell type dependent in different cells of human origin and results in a fitness loss in the form of reduced efficiency of RNA replication in the absence of the drug. Thus, a rational approach to the development of host-targeting antivirals may overcome the superior adaptability of (+)RNA viruses. IMPORTANCE Compared to the number of viral diseases, the number of available vaccines is miniscule. For some viruses vaccine development has not been successful after multiple attempts, and for many others vaccination is not a viable option. Antiviral drugs are needed for clinical practice and public health emergencies. However, viruses are highly adaptable and can

  17. Host range of poliovirus is restricted to simians because of a rapid sequence change of the poliovirus receptor gene during evolution.

    PubMed

    Ida-Hosonuma, M; Sasaki, Y; Toyoda, H; Nomoto, A; Gotoh, O; Yonekawa, H; Koike, S

    2003-01-01

    The host range of most poliovirus (PV) strains is restricted to simians. This host range specificity is believed to be determined by the interaction between PV and its receptor molecule. To elucidate the molecular basis of this species-specific infection of PV, we cloned orthologs of the PV receptor (PVR) gene ( pvr) as well as those of PV receptor-related genes 1 and 2 ( prr1 and prr2) from various mammalian species. These three genes are widely present in mammalian genomes including those of non-susceptible species. Comparison of the deduced amino acid sequences of PVR orthologs revealed that the NH(2)-terminal immunoglobulin-like domain (domain 1), which is the virus binding site in the human PVR, is highly variable among species, whereas that of PRR1 is highly conserved. Domain 1 of the PVR orthologs for the ring-tailed lemur and rabbit, which are not susceptible to PV, show only 51 and 61% amino acid sequence identity to that of human PVR, respectively. Chimeric PVR proteins that have the domain 1 of the ring-tailed lemur and rabbit PVRs failed to serve as receptors for PV. These results suggest that rapid changes in the domain 1 sequence during mammalian evolution determined the host range restriction of PV. PMID:12536294

  18. Seroprevalence of poliovirus antibodies among 7-month-old infants after 4 doses of oral polio vaccine in Sistan-va-Baluchestan, Islamic Republic of Iran.

    PubMed

    Izadi, S; Shahmahmoodi, S; Zahraei, S M; Dorostkar, F; Majdzadeh, S-R

    2015-02-01

    Despite high coverage rates of polio vaccine in the Islamic Republic of Iran, the seroconversion rates of infants may be inadequate. This study measured seroprevalence of antibodies against poliovirus serotypes 1 to 3 (PV1, PV2 and PV3) in 7-month-old infants who had received at least 4 doses of trivalent oral polio vaccine. A serosurvey was conducted in 2010 in rural areas of Chabahar, Sistan-va-Baluchestan province. Using cluster sampling, 72 eligible infants were tested for antibody against the 3 poliovirus serotypes according to WHO guidelines. Antibody titres ≥ 1:10 were considered positive. The seropositive rates for antibody against PV1, PV2 and PV3 were 84.7%, 95.8% and 70.8% respectively. Only 63.9% of participants were seropositive for antibodies against all 3 poliovirus serotypes. Except for PV2, the seroprevalence of antibody against the other 2 poliovirus serotypes, especially PV3, was unsatisfactory. PMID:25876819

  19. Comparison of ozone inactivation, in flowing water, of hepatitis A virus, poliovirus 1, and indicator organisms

    SciTech Connect

    Herbold, K.; Flehmig, B.; Botzenhart, K. )

    1989-11-01

    In steadily flowing water at 20 degrees C and pH 7, five organisms had the following order of resistance to ozone (at constant levels of ozone): poliovirus 1 (PV1) less than Escherichia coli less than hepatitis A virus (HAV) less than Legionella pneumophila serogroup 6 less than Bacillus subtilis spores. The tests were repeated at 10 degrees C with HAV, PV1, and E. coli. Ozone inactivation of HAV and E. coli was faster at 10 degrees C than at 20 degrees C. At 20 degrees C, 0.25 to 0.38 mg of O3 per liter was required for complete inactivation of HAV but only 0.13 mg of O3 per liter was required for complete inactivation of PV1.

  20. Effects of actinomycin D on the cytopathology induced by poliovirus in HEp-2 cells.

    PubMed

    Guskey, L E; Wolff, D A

    1974-11-01

    One possible mechanism of virus-induced cell damage is that the redistributed (released) lysosomal enzymes produce the cytopathic effect during cytolytic types of infections such as poliovirus in HEp-2 cells. To determine if the lysosomal enzyme redistribution and cell damage are host-cell directed, we studied sensitivity of these events to the action of actinomycin D. By the use of actinomycin D at concentrations producing the least toxicity but maximal effectiveness in shuting down cell RNA synthesis, it was shown that the cytopathic effect and enzyme redistribution were not inhibited and, therefore, not directly controlled and induced by the cell genome in response to the virus infection. Evaluation of cytopathic effect by a phase contrast microscopy method detected changes earlier than the erythrocin B uptake method. PMID:4372396

  1. Effects of Actinomycin D on the Cytopathology Induced by Poliovirus in HEp-2 Cells

    PubMed Central

    Guskey, Louis E.; Wolff, David A.

    1974-01-01

    One possible mechanism of virus-induced cell damage is that the redistributed (released) lysosomal enzymes produce the cytopathic effect during cytolytic types of infections such as poliovirus in HEp-2 cells. To determine if the lysosomal enzyme redistribution and cell damage are host-cell directed, we studied sensitivity of these events to the action of actinomycin D. By the use of actinomycin D at concentrations producing the least toxicity but maximal effectiveness in shuting down cell RNA synthesis, it was shown that the cytopathic effect and enzyme redistribution were not inhibited and, therefore, not directly controlled and induced by the cell genome in response to the virus infection. Evaluation of cytopathic effect by a phase contrast microscopy method detected changes earlier than the erythrocin B uptake method. PMID:4372396

  2. Human-Mouse Hybrid Cell Lines and Susceptibility to Poliovirus 1

    PubMed Central

    Wang, Richard; Pollack, Robert; Kusano, Toshihisa; Green, Howard

    1970-01-01

    A number of human-mouse somatic hybrid cell lines have been prepared, containing from 3 to 12 human biarmed chromosomes. These lines were susceptible to poliovirus type 1, producing viral yields comparable to those of the human parental cells. A small proportion of the cells of these lines survived the polio infection, and their progeny were solidly resistant to reinfection with the virus. Both sensitive and resistant hybrids produced virus following infection with viral ribonucleic acid, indicating that the cytoplasm of the resistant hybrids was able to support viral multiplication. Viral adsorption studies carried out at 4 C showed that the resistant sublines had negligible ability to adsorb the virus. It was concluded that the hybrid cells became resistant to polio through loss of the human chromosome bearing the gene for the receptor substance. PMID:4317112

  3. Molecular Characterization and Phylogenetic Relationship of Wild Type 1 Poliovirus Strains Circulating across Pakistan and Afghanistan Bordering Areas during 2010–2012

    PubMed Central

    Shaukat, Shahzad; Angez, Mehar; Alam, Muhammad Masroor; Sharif, Salmaan; Khurshid, Adnan; Malik, Farzana; Rehman, Lubna; Zaidi, Syed Sohail Zahoor

    2014-01-01

    Pakistan and Afghanistan share a long uncontrolled border with extensive population movement on both sides. Wild poliovirus transmission has never been interrupted in this block due to war against terrorism, poor public health infrastructure, misconceptions about polio vaccines and inadequate immunization activities. All these issues complicate the eradication operations and reinforce the complexity of wiping out poliomyelitis from this region. This study illustrates the origins and routes of cross-border wild poliovirus type 1 (WPV1) transmission during 2010–2012 between Pakistan and Afghanistan. Sequence analyses were conducted based on complete VP1 capsid protein sequences for WPV1 study strains to determine the origin of poliovirus genetic lineages and their evolutionary relationships. Phylogenetic tree was constructed from VP1 gene sequences applying Maximum Likelihood method using Kimura 2- parameter model in MEGA program v 5.0. A total of 72 (14.3%) out of 502 wild-type 1 polioviruses were found circulating in border areas of both countries during 2010–2012. Molecular phylogenetic analysis classified these strains in to two sub-genotypes with four clusters and 18 lineages. Genetic data confirmed that the most of WPV1 lineages (12; 66.6%) were transmitted from Pakistan to Afghanistan. However, the genetic diversity was significantly reduced during 2012 as most of the lineages were completely eliminated. In conclusion, Pakistan-Afghanistan block has emerged as a single poliovirus reservoir sharing the multiple poliovirus lineages due to uncontrolled movement of people across the borders between two countries. If it is neglected, it can jeopardize the extensive global efforts done so-far to eradicate the poliovirus infection. Our data will be helpful to devise the preventive strategies for effective control of wild poliovirus transmission in this region. PMID:25229826

  4. Detection and quantification of poliovirus infection using FTIR spectroscopy and cell culture

    PubMed Central

    2011-01-01

    Background In a globalized word, prevention of infectious diseases is a major challenge. Rapid detection of viable virus particles in water and other environmental samples is essential to public health risk assessment, homeland security and environmental protection. Current virus detection methods, especially assessing viral infectivity, are complex and time-consuming, making point-of-care detection a challenge. Faster, more sensitive, highly specific methods are needed to quantify potentially hazardous viral pathogens and to determine if suspected materials contain viable viral particles. Fourier transform infrared (FTIR) spectroscopy combined with cellular-based sensing, may offer a precise way to detect specific viruses. This approach utilizes infrared light to monitor changes in molecular components of cells by tracking changes in absorbance patterns produced following virus infection. In this work poliovirus (PV1) was used to evaluate the utility of FTIR spectroscopy with cell culture for rapid detection of infective virus particles. Results Buffalo green monkey kidney (BGMK) cells infected with different virus titers were studied at 1 - 12 hours post-infection (h.p.i.). A partial least squares (PLS) regression method was used to analyze and model cellular responses to different infection titers and times post-infection. The model performs best at 8 h.p.i., resulting in an estimated root mean square error of cross validation (RMSECV) of 17 plaque forming units (PFU)/ml when using low titers of infection of 10 and 100 PFU/ml. Higher titers, from 103 to 106 PFU/ml, could also be reliably detected. Conclusions This approach to poliovirus detection and quantification using FTIR spectroscopy and cell culture could potentially be extended to compare biochemical cell responses to infection with different viruses. This virus detection method could feasibly be adapted to an automated scheme for use in areas such as water safety monitoring and medical diagnostics. PMID

  5. Characterization of Poliovirus Neutralization Escape Mutants of Single-Domain Antibody Fragments (VHHs)

    PubMed Central

    Schotte, Lise; Thys, Bert; Strauss, Mike; Filman, David J.; Rombaut, Bart

    2015-01-01

    To complete the eradication of poliovirus and to protect unvaccinated people subsequently, the development of one or more antiviral drugs will be necessary. A set of five single-domain antibody fragments (variable parts of the heavy chain of a heavy-chain antibody [VHHs]) with an in vitro neutralizing activity against poliovirus type 1 was developed previously (B. Thys, L. Schotte, S. Muyldermans, U. Wernery, G. Hassanzadeh-Ghassabeh, and B. Rombaut, Antiviral Res 87:257–264, 2010, http://dx.doi.org/10.1016/j.antiviral.2010.05.012), and their mechanisms of action have been studied (L. Schotte, M. Strauss, B. Thys, H. Halewyck, D. J. Filman, M. Bostina, J. M. Hogle, and B. Rombaut, J Virol 88:4403–4413, 2014, http://dx.doi.org/10.1128/JVI.03402-13). In this study, neutralization escape mutants were selected for each VHH. Sequencing of the P1 region of the genome showed that amino acid substitutions are found in the four viral proteins of the capsid and that they are located both in proximity to the binding sites of the VHHs and in regions further away from the canyon and hidden beneath the surface. Characterization of the mutants demonstrated that they have single-cycle replication kinetics that are similar to those of their parental strain and that they are all drug (VHH) independent. Their resistant phenotypes are stable, as they do not regain full susceptibility to the VHH after passage over HeLa cells in the absence of VHH. They are all at least as stable as the parental strain against heat inactivation at 44°C, and three of them are even significantly (P < 0.05) more resistant to heat inactivation. The resistant variants all still can be neutralized by at least two other VHHs and retain full susceptibility to pirodavir and 35-1F4. PMID:26014941

  6. Antiviral Activity of Trichilia catigua Bark Extracts for Herpesvirus and Poliovirus.

    PubMed

    Espada, Samantha F; Faccin-Galhardi, Ligia C; Rincao, Vinicius P; Bernardi, Ana L S; Lopes, Nayara; Longhini, Renata; de Mello, Joao C P; Linhares, Rosa E C; Nozawa, Carlos

    2015-01-01

    Herpesvirus and poliovirus are responsible for important diseases in human and animal. Trichilia catigua a Brazilian native plant known as catiguá has several medicinal properties among them antimicrobial for bacteria and protozoa, however, no antiviral activity has been reported yet. This study evaluated the antiviral activity of the crude extract (CE) and aqueous and ethyl acetate fractions (AF, EAF) obtained from T. catigua in the replication of the Herpes simplex virus (HSV-1), bovine herpesvirus (BoHV-1) and poliovirus (PV-1). The cytotoxicity was analyzed by MTT assay and the antiviral effect was determined by the addition of extracts (0.25 to 100.0 μg/ml), before (-2h and -1h), during (Oh) and after (1h and 2h) the viral infection, by plaque reduction assay, in HEp-2 cell culture. The virucidal activity and inhibition of viral adsorption were also evaluated. In addition, the combination index (CI) with Acyclovir (ACV - reference drug) was determined for HSV-1. CE, AF and EAF showed a low toxicity (CC(50) >400 µg/ml) and low inhibitory concentration (IC50), ranging from 2.44-34.25 µg/ml for herpesvirus and 0.67 to 1.8 µg/ml for PV-1, associated with high selectivity index. The tested compounds showed high virucidal effect and high ability to inhibit viral adsorption, for all virus. The CI demonstrated a synergic effect (CI<1) for AF and EAF comparatively to acyclovir (ACV). Our study demonstrated that the extract and fractions of T. catigua is promising for future antiviral drug design with economically feasible production. PMID:25941883

  7. Preliminary report on vaccination in Croatia against poliomyelitis with type 1 (CHAT) and type 3 (W-Fox) attenuated polioviruses of Koprowski

    PubMed Central

    Ikić, D.; Jančikić, B.; Lulić, V.; Ćuk, D.; Juzbašić, M.; Manhalter, T.; Sindik, A.

    1963-01-01

    The incidence of poliomyelitis in the People's Republic of Croatia has progressively increased since 1945, and in 1953 and 1960 there were serious epidemics. In order to protect the age-groups at greatest risk a mass vaccination campaign was carried out with Koprowski live-virus vaccine in the early spring of 1961, covering the entire population aged 3 months to 20 years. Altogether 1 339 244 persons were given type 1 (CHAT strain), and 1 287 909 received type 3 (W-Fox). Over 100 000 persons were estimated to possess no pre-existing antibody to any of the three types of poliovirus. Although no unvaccinated control group was set up, it is considered that the epidemiological and serological data indicate the safety and efficacy of the vaccination. The serological conversion rate was 91.5% for type 1 and 93.5% for type 3. No post-vaccinal reactions were observed. The usual summer peak in incidence did not occur in 1961, altogether 6 cases being recorded from June (when immunity is considered to have been established) to December. This is the lowest figure since 1945. PMID:20604139

  8. Channel adjustments to historical disturbances along the lower Brazos and Sabine Rivers, south-central USA

    NASA Astrophysics Data System (ADS)

    Heitmuller, Franklin T.

    2014-01-01

    Historical channel adjustments are documented and discussed in context with anthropogenic disturbances along two meandering, coastal plain rivers - the lower Brazos and Sabine Rivers in the south-central United States. Hard-copy streamflow-measurement notes of the U.S. Geological Survey were utilized to render historical cross sections (1925-2007) at nine gauging stations, which were complemented with repeat photographs and flood-frequency analysis to assess trajectories of channel change and interpret causative mechanisms. Downstream- and upstream-propagating disturbances caused episodes of channel-bed incision and aggradation at different locations for distinct time periods along both rivers. Incision associated with upstream dams is detected, but channels are compensated downstream with sediment inputs from lateral channel migration and tributaries. In one case, temporary aggradation along the Brazos River at Waco was likely caused by a combination of dam construction and regional soil erosion. Channel-bed incision on the lowermost Brazos River is unrelated to dams, but is associated with instream aggregate extraction, possibly in conjunction with downstream channelization. On the Sabine River, extensive aggradation during the 1930s might be associated with logging activities (1880s-1930s), but whether the cause is pervasive regional-scale hillslope erosion or local-scale mill-site activities is indeterminate. Following passage of this sediment, the river generally recovered to pre-disturbance conditions and has exhibited stability despite a mainstem reservoir. Translation of this sediment slug is attenuated by a transition to a flood-prone, distributary-dominated system downstream of the Holocene-Pleistocene terrace onlap position. Additional findings include cross-channel hingepoints separating thalweg incision from simultaneous point-bar or bank accretion at meander bends, which indicates channel adjustment occurs along non-cohesive beds in preference to

  9. The vaccine origin of the 1968 epidemic of type 3 poliomyelitis in Poland.

    PubMed

    Martín, J; Ferguson, G L; Wood, D J; Minor, P D

    2000-12-01

    A clear association was demonstrated between the use of USOL-D-bac type 3 poliovirus live-attenuated vaccine and the 1968 poliomyelitis epidemic in Poland. The epidemic followed small-scale trials with Sabin and USOL-D-bac type 3 vaccine strains carried out in seven countries including Poland. Factors that might have contributed to the genesis and development of the epidemic were the pattern of virus excretion from vaccinees, mutations found in viruses from the epidemic, and the particular vaccination policies in Poland during the previous years. These findings may provide essential insights into the strategies for stopping polio immunisation once wild poliovirus has been eradicated. PMID:11112479

  10. Associations between degraded benthic communities and contaminated sediments: Sabine Lake, Lake Pontchartrain, and Choctawhatchee Bay

    SciTech Connect

    Engle, V.D.; Summers, J.K.; Macauley, J.M.

    1994-12-31

    The Environmental Monitoring and Assessment Program for Estuaries (EMAP-E) in the Gulf of Mexico supplements its base sampling effort each year with localized, intensive spatial sampling in selected large estuarine systems. By selecting random locations within 70 km{sup 2} hexagonal areas, individual estuaries were sampled using EMAP methods but at four times the density as base sampling. In 1992, 19 sites were sampled in Lake Pontchartrain, Louisiana. In 1 993, 18 sites were sampled in Sabine Lake, Texas and 12 sites were sampled in Choctawhatchee Bay, Florida. At all sites, sediment grabs were taken and analyzed for benthic species composition and abundance, for toxicity to Ampelisca, and for organic and inorganic sediment contaminants. An indicator of biotic integrity, the benthic index, was calculated to represent the status of benthic communities. A series of statistical techniques, such as stepwise regression analysis, were employed to determine whether the variation in the benthic index could be associated with variation in sediment contaminants, sediment toxicity, or levels of dissolved oxygen. Spatial distributions of these parameters were examined to determine the geographical co-occurrence of degraded benthic communities and environmental stressors. In Lake Pontchartrain, for example, 85% of the variation in the benthic index was associated with decreased levels of dissolved oxygen, and increased concentrations of PCBs, alkanes, copper, tin, and zinc in the sediments.