关键词： oral poliovirus vaccine   poliomyelitis   primary immunodeficiencies   tissue injury   vaccine-associated paralytic poliomyelitis  

关键词： Poliovirus   Recombination   RNA   Secondary structure  

摘要： In order to test the hypothesis that RNA structural elements promote the distribution of certain types of recombination junctions in each one of the 2C and 3D poliovirus genomic regions (Sabin 3/Sabin 2 or Sabin 1 in 2C and Sabin 2/Sabin 1 or Sabin 3 in 3D), we searched in 2C and 3D regions of reference Sabin strains for high probability RNA structural elements that could promote recombination. Recombination junctions that were identified in clinical strains of this study, as well as in clinical strains of previous studies, were superimposed on RNA secondary structure models of 2C and 3D genomic regions. Furthermore, we created an in vitro model, based on double infection of cell-culture with two poliovirus strains, for the production and identification of recombinant Sabin strains in 2C and 3D regions. Our intention was to compare the results that refer to the correlation of recombination junctions and RNA secondary structures in 2C and 3D regions of clinical strains, with the respective results of the in vitro model. Most of the recombination junctions of the clinical strains were correlated with RNA secondary structure elements, which were identical between recombining Sabin strains, and also presented high predictive value. In consensus were, the respective results originated from the in vitro model. We propose that the distribution of specific types of recombination junctions in certain regions of Sabin strains is not fortuitous and is correlated with RNA secondary structure elements identical to both recombination partners. Furthermore, results of this study highlight an important role for the stem region of the RNA structure elements in promoting recombination.

关键词： Oral poliovirus vaccine (OPV)   Vaccine-associated paralytic poliomyelitis (VAPP)   Perianal abscess   Infant  

摘要： We describe a case of vaccine-associated paralytic poliomyelitis (VAPP) in a 7-month-old infant with perianal abscesses. The infant had suffered from perianal abscesses from 3 weeks after birth. The abscesses repeatedly developed and spontaneously drained through the orifice. Twenty-seven days before admission, a live attenuated oral poliovirus vaccine (OPV) was given to the infant for the first time for routine immunization. His body temperature rose to 38A degrees C 19 days after receiving the OPV and fell 4 days later. Flaccid paralysis of the right leg appeared 26 days after receipt of the OPV. A Sabin type 3 poliovirus was isolated from a stool obtained at admission. The DNA sequences of the VP1 region of the isolated virus were more than 99% identical with those of the vaccine strain. Mild muscle atrophy with moderate motor impairment in the right leg persisted at 18 months of age. One VAPP case provoked by a perianal abscess has been reported from the United Kingdom. Database search revealed that one of nine VAPP cases reported during 2003-2008 in Japan had a perianal abscess. Taken together, these reports and our case imply that we should give OPV with caution to infants with a perianal abscess.

关键词： USO1 gene   N-Terminus   Virus Replication   GBF1 gene   Poliovirus  

摘要： P>Viruses are intracellular parasites whose reproduction relies on factors provided by the host. The cellular protein GBF1 is critical for poliovirus replication. Here we show that the contribution of GBF1 to virus replication is different from its known activities in uninfected cells. Normally GBF1 activates the ADP-ribosylation factor (Arf) GTPases necessary for formation of COPI transport vesicles. GBF1 function is modulated by p115 and Rab1b. However, in polio-infected cells, p115 is degraded and neither p115 nor Rab1b knock-down affects virus replication. Poliovirus infection is very sensitive to brefeldin A (BFA), an inhibitor of Arf activation by GBF1. BFA targets the catalytic Sec7 domain of GBF1. Nevertheless the BFA block of polio replication is rescued by expression of only the N-terminal region of GBF1 lacking the Sec7 domain. Replication of BFA-resistant poliovirus in the presence of BFA is uncoupled from Arf activation but is dependent on GBF1. Thus the function(s) of this protein essential for viral replication can be separated from those required for cellular metabolism.

关键词： mRNA   viral capsid protein: expression   9-aminoacridine derivative   DNA: replication   inhibition   RNA: replication   transcription   p53 transcript   quinacrine: 83-89-6   enzyme inhibitor-drug   antiprotozoal-drug   antiviral-drug   antipar   asitic-drug   antiinfective-drug   virus replication   Antiviral Agents   RNA replication   Virus Replication   Quality Control   Diethazine Hydrochloride   DNA Replication   Encephalomyocarditis virus   Inclusion complexes   Quinacrine   aminoacridine derivative  

摘要： The 9-aminoacridine (9AA) derivative quinacrine (QC) has a long history of safe human use as an anti-protozoal and antirheumatic agent. QC intercalates into DNA and RNA and can inhibit DNA replication, RNA transcription, and protein synthesis. The extent of QC intercalation into RNA depends on the complexity of its secondary and tertiary structure. Internal ribosome entry sites (IRESs) that are required for initiation of translation of some viral and cellular mRNAs typically have complex structures. Recent work has shown that some intercalating drugs, including QC, are capable of inhibiting hepatitis C virus IRES-mediated translation in a cell-free system. Here, we show that QC suppresses translation directed by the encephalomyocarditis virus (EMCV) and poliovirus IRESs in a cell-free system and in virus-infected HeLa cells. In contrast, IRESs present in the mammalian p53 transcript that are predicted to have less-complex structures were not sensitive to QC. Inhibition of IRES-mediated translation by QC correlated with the affinity of binding between QC and the particular IRES. Expression of viral capsid proteins, replication of viral RNAs, and production of virus were all strongly inhibited by QC (and 9AA). These results suggest that QC and similar intercalating drugs could potentially be used for treatment of viral infections.

关键词： Sindbis replicon   picornavirus IRES   poliovirus 2A   eIF4G   regulation of translation  

摘要： Alphavirus replicons are very useful for analyzing different aspects of viral molecular biology. They are also useful tools in the development of new vaccines and highly efficient expression of heterologous genes. We have investigated the translatability of Sindbis virus (SV) subgenomic mRNA bearing different 5'-untranslated regions, including several viral internal ribosome entry sites (IRESs) from picornaviruses, hepatitis C virus, and cricket paralysis virus. Our findings indicate that all these IRES-containing mRNAs are initially translated in culture cells transfected with the corresponding SV replicon but their translation is inhibited in the late phase of SV replication. Notably, co-expression of different poliovirus (PV) non-structural genes reveals that the protease 2A (2A(pro)) is able to increase translation of subgenomic mRNAs containing the PV or encephalomyocarditis virus IRESs but not of those of hepatitis C virus or cricket paralysis virus. A PV 2A(pro) variant deficient in eukaryotic initiation factor (eIF) 4GI cleavage or PV protease 3C, neither of which cleaves eIF4GI, does not increase picornavirus IRES-driven translation, whereas L protease from foot-and-mouth disease virus also rescues translation. These findings suggest that the replicative foci of SV-infected cells where translation takes place are deficient in components necessary to translate IRES-containing mRNAs. In the case of picornavirus IRESs, cleavage of eIF4GI accomplished by PV 2A(pro) or foot-and-mouth disease virus protease L rescues this inhibition. eIF4GI co-localizes with ribosomes both in cells electroporated with SV replicons bearing the picornavirus IRES and in cells co-electroporated with replicons that express PV 2A(pro). These findings support the idea that eIF4GI cleavage is necessary to rescue the translation driven by picornavirus IRESs in baby hamster kidney cells that express SV replicons. (C) 2010 Elsevier Ltd. All rights reserved.

关键词： Rotavirus   Rotavirus vaccine   Oral poliovirus vaccine   South Africa  

摘要： A double-blind, placebo-controlled phase II trial (e-Track 444563-014/NCT00346892) was conducted in South Africa to evaluate the co-administration of RIX4414 (live-attenuated human G1P[8] rotavirus vaccine) and oral poliovirus vaccine (OPV) administered simultaneously. Healthy infants (n = 450) were randomized into three groups (RIX4414 + OPV, RIX4414 + IPV or Placebo + OPV) to receive two oral doses of RIX4414/placebo with OPV or IPV using two vaccination schedules (6-10 weeks and 10-14 weeks). Serum anti-rotavirus IgA antibodies (ELISA) and neutralizing antibodies (micro-neutralization assay) to poliovirus serotypes 1, 2 and 3 were measured. Co-administration of RIX4414 with OPV did not result in a decrease in the high sero-protection rates against poliovirus serotypes 1, 2 and 3 detected after the third OPV dose (98-100%). The anti-rotavirus IgA antibody sero-conversion rates were higher for the 10-14 weeks schedule (55-61%) compared to the 6-10 weeks schedule (36-43%). Solicited symptoms were reported at similar rates between RIX4414 and placebo groups and no serious adverse events related to RIX4414 were reported. This study provided evidence that RIX4414 can be co-administered with routine EPI immunizations including OPV and that two doses of RIX4414 were well tolerated and immunogenic in South African infants. (C) 2010 Published by Elsevier Ltd.

关键词： 疫苗相关麻痹型脊髓灰质炎   疑似病例   调查分析  

摘要： 2005年1月菏泽市郓城县发生1例疫苗相关麻痹型脊髓灰质炎疑似病例,现调查分析如下.

关键词： Regimen   Prophylactic vaccination   Mouth   Seroconversion   Placebos   Poliovirus Vaccines   RIX4414 vaccine   Immunoglobulin A   immunogenicity   Rotavirus Vaccines  

摘要： Background. A phase II, randomized, double-blind, placebo-controlled study was conducted in South Africa during 2003-2004 to evaluate the safety, reactogenicity, and immunogenicity of 2 regimens of the live attenuated oral human rotavirus vaccine RIX4414 when coadministered with the Expanded Program on Immunization childhood vaccines, including oral polio vaccine. Methods. Healthy infants were randomized (2:2:1) to receive either 2 doses of RIX4414 (n = 190;at 10 and 14 weeks, with placebo at 6 weeks), 3 doses of RIX4414 (n = 189;at 6, 10, and 14 weeks), or 3 doses of placebo (n = 96), all with concomitant routine vaccinations. The antirotavirus IgA seroconversion rate was assessed using enzyme-linked immunosorbent assay at 2 months after the last dose of RIX4414 or placebo. Antipolio types 1, 2, and 3 antibodies were measured using a virus neutralization assay. Solicited symptoms were recorded for 15 days after each dose. Results. The antirotavirus IgA seroconversion rates were similar in the RIX4414 2- and 3-dose groups (44.3% and 44.4%, respectively;P = .544, by 1-sided Fisher exact test) and antirotavirus IgA geometric mean concentrations were also comparable. Seroprotection rates for antipolio types 1, 2, and 3 antibodies were high (93%-100%) and were not significantly different among groups. Solicited symptoms reported within 15 days after vaccination were similar in all groups. Conclusions. The immune seroconversion response to the RIX4414 vaccine with 3 doses was not superior to the 2-dose regimen. There was no interference by either regimen with antibody response to oral polio vaccine, and RIX4414 was well tolerated when given with routine vaccinations.