The molecular biology of poliovaccines

Minor, Philip D.

doi:10.1099/0022-1317-73-12-3065

Cited by 200 publications

(138 citation statements)

References 39 publications

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“…Enterovirus 71 (EV71) belongs to the genus Enterovirus but was classified into a different species from PV, Human enterovirus species A. EV71 is a causative agent of hand, foot and mouth disease and herpangina, but sometimes causes severe neurological diseases, such as brainstem encephalitis and poliomyelitis-like paralysis (Chumakov et al, 1979;McMinn, 2002;Wang et al, 2003). The case-severity rate of EV71 in an outbreak in Taiwan was ,0.3 % (Ho et al, 1999), suggesting a high neuropathogenicity of EV71 as well as PV, which causes poliomyelitis in 0.1-1.0 % of infected individuals (reviewed by Minor, 1992). EV71 causes fatal pulmonary oedema and/or pulmonary haemorrhage in young children by destruction of the vasomotor and respiratory centres in the brain stem Ho et al, 1999;Huang et al, 1999;Komatsu et al, 1999;Lum et al, 1998;Wang et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity

Arita

Wakita

Shimizu

2008

Journal of General Virology

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Poliovirus (PV) and enterovirus 71 (EV71) cause severe neurological symptoms in their infections of the central nervous system. To identify compounds with anti-PV and anti-EV71 activities that would not allow the emergence of resistant mutants, we performed drug screening by utilizing a pharmacologically active compound library targeting cellular factors with PV and EV71 pseudoviruses that encapsidated luciferase-encoding replicons. We have found that metrifudil (N-[2-methylphenyl]methyl)-adenosine) (an A2 adenosine receptor agonist), N 6 -benzyladenosine (an A1 adenosine receptor agonist) and NF449 (4,49,40,409-[carbonylbis[imino-5,1,3-benzenetriyl bis(carbonyl-imino)]] tetrakis (benzene-1,3-disulfonic acid) octasodium salt) (a Gs-a inhibitor) have anti-EV71 activity, and that GW5074 (3-(3, 5-dibromo-4-hydroxybenzylidine-5-iodo-1,3-dihydro-indol-2-one)) (a Raf-1 inhibitor) has both anti-PV and anti-EV71 activities. EV71 mutants resistant to metrifudil, N 6 -benzyladenosine and NF449 were isolated after passages in the presence of these compounds, but mutants resistant to GW5074 were not isolated for both PV and EV71. The inhibitory effect of GW5074 was not observed in Sendai virus infection and the treatment did not induce the expression of OAS1 and STAT1 mRNA. Small interfering RNA treatment against putative cellular targets of GW5074, including Raf-1, B-Raf, Pim-1, -2, and -3, HIPK2, GAK, MST2 and ATF-3, did not consistently suppress PV replication. Moreover, downregulation of Raf-1 and B-Raf did not affect the sensitivity of RD cells to the inhibitory effect of GW5074. These results suggest that GW5074 has strong and selective inhibitory effect against the replication of PV and EV71 by inhibiting conserved targets in the infection independently of the interferon response.

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Section: Introductionmentioning

confidence: 99%

Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity

Arita

Wakita

Shimizu

2008

Journal of General Virology

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“…If panels of neutralizing monoclonal antibodies are used, antigenic differences are observed between the strains of the three serotypes. However, these differences are invariably confined to the limits of each serotype (5,17,23). This has made possible the efficient prophylaxis of poliomyelitis using two vaccines: the inactivated poliovirus vaccine (IPV) and the oral poliovirus vaccine (OPV), both of which contain all three PV serotypes.…”

mentioning

confidence: 99%

Natural Genetic Exchanges between Vaccine and Wild Poliovirus Strains in Humans

Guillot

Caro

Cuervo

et al. 2000

J Virol

182

165

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In a previous study of poliovirus vaccine-derived strains isolated from patients with vaccine-associated paralytic poliomyelitis (VAPP) (9, 11), we reported that a high proportion (over 50%) of viruses had a recombinant genome. Most were intertypic vaccine/vaccine recombinants. However, some had restriction fragment length polymorphism (RFLP) profiles different from those of poliovirus vaccine strains. We demonstrate here that five such recombinants, of 88 VAPP strains examined, carried sequences of wild (nonvaccine) origin. To identify the parental wild donor of these sequences, we used RFLP profiles and nucleotide sequencing to look for similarity in the 3D polymerase-coding region of 61 wild, cocirculating poliovirus isolates (43 type 1, 16 type 2, and 2 type 3 isolates). In only one case was the donor identified, and it was a wild type 1 poliovirus. For the other four vaccine/wild recombinants, the wild parent could not be identified. The possibility that the wild sequences were of a non-poliovirus-enterovirus origin could not be excluded. Another vaccine/wild recombinant, isolated in Belarus from a VAPP case, indicated that the poliovirus vaccine/wild recombination is not an isolated phenomenon. We also found wild polioviruses (2 of 15) carrying vaccine-derived sequences in the 3 moiety of their genome. All these results suggest that genetic exchanges with wild poliovirus and perhaps with nonpoliovirus enteroviruses, are also a natural means of evolution for poliovirus vaccine strains.

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“…In contrast, fewer than 20% excreted vaccine strains after 5 weeks. Excretion of polio ranged from a few days to several months (Minor, 1992). The highest probability of detecting poliovirus positive stool samples was reported to be at 14 days after the onset of paralysis (Alexander et al, 1997;Dowdle and Birmingham, 1997) and is the basis of stool sample collection for diagnosis of polio by AFP surveillance (WHO, 2004).…”

Section: Poliomyelitis Vaccination and Eradication Updatementioning

confidence: 99%