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Cara C Burns,
Jing Shaw,
Jaume Jorba,
David Bukbuk,
Festus Adu,
Nicksy Gumede,
Muhammed Ali Pate,
Emmanuel Ade Abanida,
Alex Gasasira,
Jane Iber, [......],
Hiroyuki Shimizu,
Marycelin Baba,
Adekunle Adeniji,
A J Williams,
David R Kilpatrick,
M Steven Oberste,
Steven G Wassilak,
Oyewale Tomori,
Mark A Pallansch, Olen Kew
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ABSTRACT: 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 2005-2011 resolved the outbreak into 23 independent VDPV2 emergences, at least seven of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over six 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 OPV strain (A(481) in the 5' -untranslated region [5' -UTR] and VP1-Ile(143)) had been replaced in all VDPV2 isolates; most A(481) 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 neuronal-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: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 country settings.
Journal of Virology 02/2013; · 5.40 Impact Factor
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Steven Wassilak,
Muhammad Ali Pate,
Kathleen Wannemuehler,
Julie Jenks,
Cara Burns,
Paul Chenoweth,
Emmanuel Ade Abanida,
Festus Adu,
Marycelin Baba,
Alex Gasasira,
Jane Iber,
Pascal Mkanda,
A J Williams,
Jing Shaw,
Mark Pallansch, Olen Kew
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ABSTRACT: Wild poliovirus has remained endemic in northern Nigeria because of low coverage achieved in the routine immunization program and in supplementary immunization activities (SIAs). An outbreak of infection involving 315 cases of type 2 circulating vaccine-derived poliovirus (cVDPV2; >1% divergent from Sabin 2) occurred during July 2005-June 2010, a period when 23 of 34 SIAs used monovalent or bivalent oral poliovirus vaccine (OPV) lacking Sabin 2. In addition, 21 "pre-VDPV2" (0.5%-1.0% divergent) cases occurred during this period. Both cVDPV and pre-VDPV cases were clinically indistinguishable from cases due to wild poliovirus. The monthly incidence of cases increased sharply in early 2009, as more children aged without trivalent OPV SIAs. Cumulative state incidence of pre-VDPV2/cVDPV2 was correlated with low childhood immunization against poliovirus type 2 assessed by various means. Strengthened routine immunization programs in countries with suboptimal coverage and balanced use of OPV formulations in SIAs are necessary to minimize risks of VDPV emergence and circulation.
The Journal of Infectious Diseases 04/2011; 203(7):898-909. · 6.41 Impact Factor
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David R Kilpatrick,
Jane C Iber,
Qi Chen,
Karen Ching,
Su-Ju Yang,
Lina De,
Mark D Mandelbaum,
Brian Emery,
Ray Campagnoli,
Cara C Burns, Olen Kew
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ABSTRACT: The Global Polio Laboratory Network routinely uses poliovirus-specific PCR primers and probes to determine the serotype and genotype of poliovirus isolates obtained as part of global poliovirus surveillance. To provide detailed molecular epidemiologic information, poliovirus isolates are further characterized by sequencing the ~900-nucleotide region encoding the major capsid protein, VP1. It is difficult to obtain quality sequence information when clinical or environmental samples contain poliovirus mixtures. As an alternative to conventional methods for resolving poliovirus mixtures, sets of serotype-specific primers were developed for amplifying and sequencing the VP1 regions of individual components of mixed populations of vaccine-vaccine, vaccine-wild, and wild-wild polioviruses.
Journal of virological methods 03/2011; 174(1-2):128-30. · 2.13 Impact Factor
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Yong Zhang,
Dongmei Yan,
Shuangli Zhu,
Ning Wen,
Li Li,
Haiyan Wang,
Jianfeng Liu,
Xufang Ye,
Zhengrong Ding,
Dongyan Wang,
Hui Zhu,
Li Chen,
Xiaohui Hou,
Hongqiu An,
Xiaofeng Liang,
Huiming Luo, Olen Kew,
Wenbo Xu
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ABSTRACT: In China, 5 patients with acute flaccid paralysis (AFP) associated with type 2 vaccine-derived poliovirus (VDPV) were identified by an AFP surveillance system from 1996 through 2009. A maximum-likelihood tree shows that all 5 Chinese VDPVs were independent. These 5 VDPVs were 100-216 d old according to the number of synonymous substitutions per synonymous site and 176-292 d old according to the number of substitutions per site. This result indicates limited virus replication since the administration of the initiating oral polio vaccine (OPV) dose, which is consistent with the rapid evolution rate of poliovirus genomes. The above-mentioned VDPVs have important implications in the global polio eradication initiative. Localized, limited, and transient circulation may be typical of OPVs; hence, independent VDPVs could be found because of the large population and excellent surveillance system, which permitted early detection and response, but sustained transmission was limited because of high population immunity.
The Journal of Infectious Diseases 11/2010; 202(12):1780-8. · 6.41 Impact Factor
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Dongmei Yan,
Li Li,
Shuangli Zhu,
Yong Zhang,
Junjing An,
Dongyan Wang,
Ning Wen,
Jaume Jorba,
Wei Liu,
Ge Zhong,
Lin Huang, Olen Kew,
Xiaofeng Liang,
Wenbo Xu
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ABSTRACT: From March to May 2006, type 1 circulating vaccine-derived poliovirus (cVDPV) was isolated from one case patient with acute flaccid paralysis (AFP) and six unimmunized healthy contacts in isolated mountain villages in Guangxi, China. We conducted epidemiological investigations in the affected communities and nucleotide sequence analyses of the cVDPV isolates. The results of the investigations showed that the AFP patient, an unimmunized 10-year-old boy, and five laboratory-confirmed contacts lived in the same village; one contact lived in a neighboring village. Only approximately 27% of children 5 to 10 years of age in the affected villages had received three or more doses of the trivalent oral poliovirus vaccine (OPV). Nucleotide sequence analyses revealed that the cVDPV isolates differed from the Sabin 1 (S1) isolate at 1.4 to 2.2% of VP1 nucleotide positions and shared 12 nucleotide substitutions within VP1. All isolates were S1/S2/S1/S3 recombinants sharing common recombination junctions. Key determinants of attenuation were replaced. Phylogenetic analysis suggested that the cVDPV circulated locally for approximately 12 months following the initiating OPV dose. No VDPVs were found after mass OPV immunizations, conducted from May to June 2006, that targeted all children <12 years of age. Our findings reinforce the point that VDPVs can emerge and spread in isolated communities with immunity gaps. Maintenance of sensitive AFP and poliovirus surveillance is essential to permit early detection and a rapid response to VDPV circulation.
Journal of clinical microbiology 09/2010; 48(9):3274-80. · 4.16 Impact Factor
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Yong Zhang,
Shuangli Zhu,
Dongmei Yan,
Guiyan Liu,
Ruyin Bai,
Dongyan Wang,
Li Chen,
Hui Zhu,
Hongqiu An, Olen Kew,
Wenbo Xu
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ABSTRACT: Ten uncommon natural type 3/type 2 intertypic poliovirus recombinants were isolated from stool specimens from nine acute flaccid paralysis case patients and one healthy vaccinee in China from 2001 to 2008.
Complete genomic sequences revealed their vaccine-related genomic features and showed that their first crossover sites were randomly distributed in the 3' end of the VP1 coding region. The length of donor Sabin 2 sequences ranged from 55 to 136 nucleotides, which is the longest donor sequence reported in the literature for this type of poliovirus recombination. The recombination resulted in the introduction of Sabin 2 neutralizing antigenic site 3a (NAg3a) into a Sabin 3 genomic background in the VP1 coding region, which may have been altered by some of the type 3-specific antigenic properties, but had not acquired any type 2-specific characterizations. NAg3a of the Sabin 3 strain seems atypical; other wild-type poliovirus isolates that have circulated in recent years have sequences of NAg3a more like the Sabin 2 strain.
10 natural type 3/type 2 intertypic VP1 capsid-recombinant polioviruses, in which the first crossover sites were found to be in the VP1 coding region, were isolated and characterized. In spite of the complete replacement of NAg3a by type 2-specific amino acids, the serotypes of the recombinants were not altered, and they were totally neutralized by polyclonal type 3 antisera but not at all by type 2 antisera. It is possible that recent type 3 wild poliovirus isolates may be a recombinant having NAg3a sequences derived from another strain during between 1967 and 1980, and the type 3/type 2 recombination events in the 3' end of the VP1 coding region may result in a higher fitness.
PLoS ONE 01/2010; 5(12):e15300. · 4.09 Impact Factor
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ABSTRACT: Immunodeficient persons with persistent vaccine-related poliovirus infection may serve as a potential reservoir for reintroduction of polioviruses after wild poliovirus eradication, posing a risk of their further circulation in inadequately immunized populations.
To estimate the potential for vaccine-related poliovirus persistence among HIV-infected persons, we studied poliovirus excretion following vaccination among children at an orphanage in Kenya. For 12 months after national immunization days, we collected serial stool specimens from orphanage residents aged <5 years at enrollment and recorded their HIV status and demographic, clinical, immunological, and immunization data. To detect and characterize isolated polioviruses and non-polio enteroviruses (NPEV), we used viral culture, typing and intratypic differentiation of isolates by PCR, ELISA, and nucleic acid sequencing. Long-term persistence was defined as shedding for >or= 6 months.
Twenty-four children (15 HIV-infected, 9 HIV-uninfected) were enrolled, and 255 specimens (170 from HIV-infected, 85 from HIV-uninfected) were collected. All HIV-infected children had mildly or moderately symptomatic HIV-disease and moderate-to-severe immunosuppression. Fifteen participants shed vaccine-related polioviruses, and 22 shed NPEV at some point during the study period. Of 46 poliovirus-positive specimens, 31 were from HIV-infected, and 15 from HIV-uninfected children. No participant shed polioviruses for >or= 6 months. Genomic sequencing of poliovirus isolates did not reveal any genetic evidence of long-term shedding. There was no long-term shedding of NPEV.
The results indicate that mildly to moderately symptomatic HIV-infected children retain the ability to clear enteroviruses, including vaccine-related poliovirus. Larger studies are needed to confirm and generalize these findings.
BMC Infectious Diseases 08/2009; 9:136. · 3.12 Impact Factor
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ABSTRACT: Replicative fitness of poliovirus can be modulated systematically by replacement of preferred capsid region codons with synonymous unpreferred codons. To determine the key genetic contributors to fitness reduction, we introduced different sets of synonymous codons into the capsid coding region of an infectious clone derived from the type 2 prototype strain MEF-1. Replicative fitness in HeLa cells, measured by plaque areas and virus yields in single-step growth experiments, decreased sharply with increased frequencies of the dinucleotides CpG (suppressed in higher eukaryotes and most RNA viruses) and UpA (suppressed nearly universally). Replacement of MEF-1 capsid codons with the corresponding codons from another type 2 prototype strain (Lansing), a randomization of MEF-1 synonymous codons, increased the %G+C without increasing CpG, and reductions in the effective number of codons used had much smaller individual effects on fitness. Poliovirus fitness was reduced to the threshold of viability when CpG and UpA dinucleotides were saturated within and across synonymous codons of a capsid region interval representing only approximately 9% of the total genome. Codon replacements were associated with moderate decreases in total virion production but large decreases in the specific infectivities of intact poliovirions and viral RNAs. Replication of codon replacement viruses, but not MEF-1, was temperature sensitive at 39.5 degrees C. Synthesis and processing of viral intracellular proteins were largely unaltered in most codon replacement constructs. Replacement of natural codons with synonymous codons with increased frequencies of CpG and UpA dinucleotides may offer a general approach to the development of attenuated vaccines with well-defined antigenicities and very high genetic stabilities.
Journal of Virology 08/2009; 83(19):9957-69. · 5.40 Impact Factor
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Shohreh Shahmahmoodi,
Nima Parvaneh,
Cara Burns,
Humayun Asghar,
Setareh Mamishi,
Hamideh Tabatabaie,
Qi Chen,
Shahram Teimourian,
Mohammad Mehdi Gooya,
Abdol-Reza Esteghamati,
Taha Mousavi,
Maryam Yousefi,
Kobra Farrokhi,
Maryam Mashlool, Olen Kew,
Rakhshandeh Nategh
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ABSTRACT: Type 3 immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) were isolated from a 15-month-old Iranian boy with acute flaccid paralysis (AFP) who was subsequently diagnosed with X-linked agammaglobulinemia (XLA). VP1 nucleotide sequences of the two isolates differed from Sabin 3 by 2.0% and 2.1% and from each other by 0.6%. Although the key determinant of attenuation and temperature sensitivity in the 5'-untranslated region (U(472)-->C) had reverted, a second capsid-region determinant (VP3:Phe(091)) was unchanged, but a presumptive suppressor (VP1:Ala(054)-->Val) was found. The isolates were Sabin 3/Sabin 1 recombinants, sharing a single recombination breakpoint in the 2C region. Although the two isolates were antigenically distinct from Sabin 3, only one amino acid replacement was found in the neutralizing antigenic sites (VP3:Ser(059)-->Asn in site 3). The patient was placed on intravenous immunoglobulin (IVIG) therapy within 9 days of onset of AFP, and iVDPV excretion ceased thereafter, but the patient remained severely paralyzed until his death approximately 11 months after paralysis. No secondary AFP cases were found, and none of the seven tested contacts of the patient were found to be infected with poliovirus.
Virus Research 10/2008; 137(1):168-72. · 2.94 Impact Factor
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JAMA The Journal of the American Medical Association 09/2008; 300(7):839-41. · 30.03 Impact Factor
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ABSTRACT: We have calibrated five different molecular clocks for circulating poliovirus based upon the rates of fixation of total substitutions (K(t)), synonymous substitutions (K(s)), synonymous transitions (A(s)), synonymous transversions (B(s)), and nonsynonymous substitutions (K(a)) into the P1/capsid region (2,643 nucleotides). Rates were determined over a 10-year period by analysis of sequences of 31 wild poliovirus type 1 isolates representing a well-defined phylogeny derived from a common imported ancestor. Similar rates were obtained by linear regression, the maximum likelihood/single-rate dated-tip method, and Bayesian inference. The very rapid K(t) [(1.03 +/- 0.10) x 10(-2) substitutions/site/year] and K(s) [(1.00 +/- 0.08) x 10(-2)] clocks were driven primarily by the A(s) clock [(0.96 +/- 0.09) x 10(-2)], the B(s) clock was approximately 10-fold slower [(0.10 +/- 0.03) x 10(-2)], and the more stochastic K(a) clock was approximately 30-fold slower [(0.03 +/- 0.01) x 10(-2)]. Nonsynonymous substitutions at all P1/capsid sites, including the neutralizing antigenic sites, appeared to be constrained by purifying selection. Simulation of the evolution of third-codon positions suggested that saturation of synonymous transitions would be evident at 10 years and complete at approximately 65 years of independent transmission. Saturation of synonymous transversions was predicted to be minimal at 20 years and incomplete at 100 years. The rapid evolution of the K(t), K(s), and A(s) clocks can be used to estimate the dates of divergence of closely related viruses, whereas the slower B(s) and K(a) clocks may be used to explore deeper evolutionary relationships within and across poliovirus genotypes.
Journal of Virology 06/2008; 82(9):4429-40. · 5.40 Impact Factor
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Mala Rakoto-Andrianarivelo,
Sophie Guillot,
Jane Iber,
Jean Balanant,
Bruno Blondel,
Franck Riquet,
Javier Martin, Olen Kew,
Bakolalao Randriamanalina,
Lalatiana Razafinimpiasa,
Dominique Rousset,
Francis Delpeyroux
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ABSTRACT: 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 3D(pol) 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.
PLoS Pathogens 01/2008; 3(12):e191. · 9.13 Impact Factor
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Festus Adu,
Jane Iber,
David Bukbuk,
Nicksy Gumede,
Su-Ju Yang,
Jaume Jorba,
Ray Campagnoli,
Waidi Folorunso Sule,
Chen-Fu Yang,
Cara Burns,
Mark Pallansch,
Tekena Harry, Olen Kew
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ABSTRACT: A type 2 vaccine-derived poliovirus (VDPV), differing from Sabin 2 at 2.5% (22/903) of VP1 nucleotide (nt) positions, was isolated from an incompletely immunized 21-month-old Nigerian child who developed acute flaccid paralysis in 2002. Sequences upstream of nt position 620 (within the 5'-untranslated region [5'-UTR]) and downstream of nt position 5840 (in the 3C(pro) region) were derived from species C enteroviruses unrelated to the oral poliovirus vaccine (OPV) strains. The two substitutions associated with the attenuated phenotype had either recombined out (A(481)-->G in the 5'-UTR) or reverted (Ile(143)-->Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype of Sabin 2 and it was antigenically distinct from the parental OPV strain, having amino acid substitutions in or near neutralizing antigenic sites 1 and 3. The date of the initiating OPV dose, calculated from the number of synonymous substitutions in the capsid region, was estimated to be approximately 16 to 18 months before onset of paralysis, a finding inconsistent with the most recent mass OPV campaign (conducted 12 days before onset of paralysis) as being the source of infection. Although no related type 2 VDPVs were detected in Nigeria or elsewhere, the VDPV was found in an area where conditions favor VDPV emergence and spread.
Virus Research 07/2007; 127(1):17-25. · 2.94 Impact Factor
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ABSTRACT: The goal of the World Health Organization is to stop routine use of oral poliovirus vaccine shortly after interruption of wild poliovirus transmission. A key component of this goal is to minimize the risk of reintroduction by destruction of polioviruses except in an absolute minimum number of facilities that serve essential functions and implement effective containment. Effective containment begins with a complete facility risk assessment. This article focuses on characterizing the risks of exposure to polioviruses from the essential vaccine production, quality control, and international reference and research facilities that remain. We consider the potential exposure pathways that might lead to a poliovirus reintroduction, including para-occupational exposures and releases to the environment, and review the literature to provide available estimates and a qualitative assessment of containment risks. Minimizing the risk of poliovirus transmission from a poliovirus facility to increasingly susceptible communities is a crucial and ongoing effort requiring understanding and actively managing the potential exposure pathways.
Risk Analysis 01/2007; 26(6):1449-69. · 2.37 Impact Factor
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The Journal of Infectious Diseases 10/2006; 194(5):539-41. · 6.41 Impact Factor
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Aamir J Khan,
Hailemichael Gebreselassie,
Edwin J Asturias,
Mubina Agboatwalla,
Redda Teklehaimanot,
Stephen P Luby,
Berhane Beyene,
Berhane Bayene,
Claudia Chezzi,
Humayun Asghar,
Tariq Moatter,
Olga R Torres, Olen Kew,
Jerry Winkelstein,
Neal A Halsey
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ABSTRACT: Persons who have developed acute flaccid paralysis following infection with wild-type polioviruses or vaccine-associated paralytic poliomyelitis usually excrete polioviruses for only a few weeks. However, some patients with paralytic poliomyelitis have had prolonged excretion of polioviruses for periods of up to 10 years after onset of disease. Most prolonged excretors have been identified in industrialized countries. We studied 348 patients 2-28 years old in Ethiopia, Pakistan and Guatemala with residual paralytic poliomyelitis to determine if they had IgA or IgG deficiency or persistent poliomyelitis excretion at least 1 year after onset of disease. None of the 348 affected individuals had IgG deficiency or persistent poliovirus excretion. One child had borderline low serum IgA concentration. Since we did not study children under 2 years of age, persons born with IgG deficiency disorders may have died in developing countries where replacement immunoglobulin therapy is not readily available. Nevertheless, persistent poliovirus excretion among persons 2 years of age and older with residual paralytic poliomyelitis is uncommon in developing countries.
Biologicals 07/2006; 34(2):113-6. · 1.70 Impact Factor
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ABSTRACT: We replaced degenerate codons for nine amino acids within the capsid region of the Sabin type 2 oral poliovirus vaccine strain with corresponding nonpreferred synonymous codons. Codon replacements were introduced into four contiguous intervals spanning 97% of the capsid region. In the capsid region of the most highly modified virus construct, the effective number of codons used (N(C)) fell from 56.2 to 29.8, the number of CG dinucleotides rose from 97 to 302, and the G+C content increased from 48.4% to 56.4%. Replicative fitness in HeLa cells, measured by plaque areas and virus yields in single-step growth experiments, decreased in proportion to the number of replacement codons. Plaque areas decreased over an approximately 10-fold range, and virus yields decreased over an approximately 65-fold range. Perhaps unexpectedly, the synthesis and processing of viral proteins appeared to be largely unaltered by the restriction in codon usage. In contrast, total yields of viral RNA in infected cells were reduced approximately 3-fold and specific infectivities of purified virions (measured by particle/PFU ratios) decreased approximately 18-fold in the most highly modified virus. The replicative fitness of both codon replacement viruses and unmodified viruses increased with the passage number in HeLa cells. After 25 serial passages (approximately 50 replication cycles), most codon replacements were retained, and the relative fitness of the modified viruses remained well below that of the unmodified virus. The increased replicative fitness of high-passage modified virus was associated with the elimination of several CG dinucleotides. Potential applications for the systematic modulation of poliovirus replicative fitness by deoptimization of codon usage are discussed.
Journal of Virology 05/2006; 80(7):3259-72. · 5.40 Impact Factor
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Chen-Fu Yang,
Hour-Young Chen,
Jaume Jorba,
Hui-Chih Sun,
Su-Ju Yang,
Hsiang-Chi Lee,
Yhu-Chering Huang,
Tzou-Yien Lin,
Pei-Jer Chen,
Hiroyuki Shimizu,
Yorihiro Nishimura,
Andi Utama,
Mark Pallansch,
Tatsuo Miyamura, Olen Kew,
Jyh-Yuan Yang
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ABSTRACT: We determined the complete genomic sequences of nine type 1 immunodeficient vaccine-derived poliovirus (iVDPV) isolates obtained over a 337-day period from a poliomyelitis patient from Taiwan with common variable immunodeficiency. The iVDPV isolates differed from the Sabin type 1 oral poliovirus vaccine (OPV) strain at 1.84% to 3.15% of total open reading frame positions and had diverged into at least five distinct lineages. Phylogenetic analysis suggested that the chronic infection was initiated by the fifth and last OPV dose, given 567 days before onset of paralysis, and that divergence of major lineages began very early in the chronic infection. Key determinants of attenuation in Sabin 1 had reverted in the iVDPV isolates, and representative isolates of each lineage showed increased neurovirulence for PVR-Tg21 transgenic mice. None of the isolates had retained the temperature-sensitive phenotype of Sabin 1. All isolates were antigenic variants of Sabin 1, having multiple amino acid substitutions within or near neutralizing antigenic sites 1, 2, and 3a. Antigenic divergence of the iVDPV variants from Sabin 1 followed two major independent evolutionary pathways. The emergence of distinct coreplicating lineages suggests that iVDPVs can replicate for many months at separate sites in the gastrointestinal tract. Some isolates had mosaic genome structures indicative of recombination across and within lineages. iVDPV excretion apparently ceased after 30 to 35 months of chronic infection. The appearance of a chronic VDPV excretor in a tropical, developing country has important implications for the strategy to stop OPV immunization after eradication of wild polioviruses.
Journal of Virology 11/2005; 79(20):12623-34. · 5.40 Impact Factor
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Hiroyuki Shimizu,
Bruce Thorley,
Fem Julia Paladin,
Kerri Anne Brussen,
Vicki Stambos,
Lilly Yuen,
Andi Utama,
Yoshio Tano,
Minetaro Arita,
Hiromu Yoshida,
Tetsuo Yoneyama,
Agnes Benegas,
Sigrun Roesel,
Mark Pallansch, Olen Kew,
Tatsuo Miyamura
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ABSTRACT: In 2001, highly evolved type 1 circulating vaccine-derived poliovirus (cVDPV) was isolated from three acute flaccid paralysis patients and one contact from three separate communities in the Philippines. Complete genomic sequencing of these four cVDPV isolates revealed that the capsid region was derived from the Sabin 1 vaccine strain but most of the noncapsid region was derived from an unidentified enterovirus unrelated to the oral poliovirus vaccine (OPV) strains. The sequences of the cVDPV isolates were closely related to each other, and the isolates had a common recombination site. Most of the genetic and biological properties of the cVDPV isolates were indistinguishable from those of wild polioviruses. However, the most recently identified cVDPV isolate from a healthy contact retained the temperature sensitivity and partial attenuation phenotypes. The sequence relationships among the isolates and Sabin 1 suggested that cVDPV originated from an OPV dose given in 1998 to 1999 and that cVDPV circulated along a narrow chain of transmission. Type 1 cVDPV was last detected in the Philippines in September 2001, and population immunity to polio was raised by extensive OPV campaigns in late 2001 and early 2002.
Journal of Virology 01/2005; 78(24):13512-21. · 5.40 Impact Factor
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Jan Vinjé,
Nicole Gregoricus,
Javier Martin,
Howard E Gary,
Victor M Caceres,
Linda Venczel,
Andrew Macadam,
James G Dobbins,
Cara Burns,
Douglas Wait,
Gwangpyo Ko,
Mauricio Landaverde, Olen Kew,
Mark D Sobsey
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ABSTRACT: Twenty-one cases of acute flaccid paralysis (AFP) were reported on the island of Hispaniola in 2000. Laboratory analysis confirmed the presence of circulating vaccine-derived poliovirus (cVDPV) type 1 in stool samples obtained from patients. As a complement to the active search for cases of AFP, environmental sampling was conducted during November and December 2000, to test for cVDPV in sewage, streams, canals, and public latrines. Fifty-five environmental samples were obtained and analyzed for the presence of polioviruses by use of cell culture followed by neutralization and reverse-transcription polymerase chain reaction. Of the 23 positive samples, 10 tested positive for poliovirus type 1, 7 tested positive for poliovirus type 2, 5 tested positive for poliovirus type 3, and 1 tested positive for both poliovirus type 2 and type 3. By sequence analysis of the complete viral capsid gene 1 (VP1), a 2.1%-3.7% genetic sequence difference between 7 type 1 strains and Sabin type 1 vaccine strain was found. Phylogenetic analysis showed that these viruses are highly related to cVDPV isolated from clinical cases and form distinct subclusters related to geographic region. Our findings demonstrate a useful role for environmental surveillance of neurovirulent polioviruses in the overall polio eradication program.
The Journal of Infectious Diseases 05/2004; 189(7):1168-75. · 6.41 Impact Factor
