9 research outputs found
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Genomic analysis of recombinant Sabin clinical isolates
Recombination in Poliovirus vaccine strains is a very frequent phenomenon. In this report 23 polio/Sabin strains isolated from healthy vaccinees or from VAPP patients after OPV administration, were investigated in order to identify recombination sites from 2C to 3D regions of the poliovirus genome. RT-PCR, followed by Restriction Fragment Length Polymorphism (RFLP) screening analysis were applied in four distant genomic regions (5' UTR, VP1, 2C and 3C-3D) in order to detect any putative recombinant. The detected recombinants were sequenced from 2C to the end of the genome (3' UTR) and the exact recombination sites were determined with computational analysis. Five of the 23 isolated strains were recombinant in one genomic region, two of them in 2C, isolates EP16:S3/S2, EP23:S3/S1, two in 3D isolates EP6:S2/S1, EP12:S2/S1 and one in 3A isolate EP9:S2/Sl. Point mutations were found in strains EP3, EP6, EP9 and EP12. Recombination specific types and sites re-occurrence along with point mutations are discussed concerning the polioviruses evolution
Recombinant Sabin environmental isolates in Greece and Cyprus
Aims: Twenty-one polioviruses (PVs) Sabin strains were isolated from sewage treatment plants from Metamorphosis, Athens, Greece during the time period from May to October 1996, and from two other sites located at Nicosia and Limassol in Cyprus between April and December 2003 were retrospectively investigated for the detection of recombinant PVs. Methods and Results: Three PVs isolates were found as tripartite recombinants, S3/S2/S1 in the 2C genomic viral region. The first recombination site S3/S2 was located close to the 5' end of 2C while the second recombination site S2/S1 was located towards the 3' end of 2C .Such recombination is a rare event producing a tripartite hybrid 2C protein. Three more PVs isolates were characterized as bipartite S2/S1 recombinants and one as S2/S3 bipartite recombinant. Conclusions: Detection of recombinant circulating vaccine-derived PVs (cVDPVs) is crucial, since increased transmissibility over that of the parental Sabin strains has been proposed to be the result of recombination events. Significance and Impact of the Study: Importation of recombinant cVDPVs evolved derivatives pose a serious threat to public health and environmental surveillance should be implemented during and after PVs eradication
Search For Poliovirus Carriers Among People With Primary Immune Deficiency Diseases In The United States, Mexico, Brazil, And The United Kingdom
Objective: To estimate the rate of long-term poliovirus excretors in people known to have B-cell immune deficiency disorders. Methods: An active search for chronic excretors was conducted among 306 persons known to have immunoglobulin G (IgG) deficiency in the United States, Mexico, Brazil, and the United Kingdom, and 40 people with IgA deficiency in the United States. Written informed consent or assent was obtained from the participants or their legal guardians, and the studies were formally approved. Stool samples were collected from participants and cultured for polioviruses. Calculation of the confidence interval for the proportion of participants with persistent poliovirus excretion was based on the binomial distribution. Findings: No individuals with long-term excretion of polioviruses were identified. Most participants had received oral poliovirus vaccine (OPV) and almost all had been exposed to household contacts who had received OPV. Polioviruses of recent vaccine origin were transiently found in four individuals in Mexico and Brazil, where OPV is recommended for all children. Conclusion: Although chronic poliovirus excretion can occur in immunodeficient persons, it appears to be rare.82138Benyesh-Melnick, M., Melnick, J.L., Rawls, W.E., Wimberly, I., Oro, J.B., Ben-Porath, E., Studies of the immunogenicity, communicability and genetic stability of oral poliovaccine administered during the winter (1967) American Journal of Epidemiology, 86, pp. 112-136Melnick, J.L., Benyesh-Melnick, M., Brennan, J.C., Studies on live poliovirus vaccines. 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Detection of unusual mutation within the VP1 region of different re-isolates of poliovirus Sabin vaccine
In the present study, a genomic analysis of full VP1 sequence region of 15 clinical re-isolates (14 healthy vaccinees and one bone marrow tumor patient) was conducted, aiming to the identification of mutations and to the assessment of their impact on virus fitness, providing also insights relevant with the natural evolution of Sabin strains. Clinical re-isolates were analyzed by RT-PCR, sequencing and computational analysis. Some re-isolates were characterized by an unusual mutational pattern in which non-synonymous mutations outnumbered the synonymous ones. Furthermore, the majority of amino-acid substitutions were located in the capsid exterior, specifically in N-Ags, near N-Ags and in the north rim of the canyon. Also mutations, which are well-known determinants of attenuation, were identified. The results of this study propose that some re-isolates are characterized by an evolutionary pattern in which non-synonymous mutations with a direct phenotypic impact on viral fitness are fixed in viral genomes, in spite of synonymous ones with no phenotypic impact on viral fitness. Results of the present retrospective characterization of Sabin clinical re-isolates, based on the full VP1 sequence, suggest that vaccine-derived viruses may make their way through narrow breaches and may evolve into transmissible pathogens even in adequately immunized populations. For this reason increased poliovirus laboratory surveillance should be permanent and full VP1 sequence analysis should be conducted even in isolates originating from healthy vaccinees