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NMR solution structure of poliovirus uridylyated peptide linked to the genome (VPgpU).

Picornaviruses have a 22-24 amino acid peptide, VPg, bound covalently at the 5' end of their RNA, that is essential for replication. VPgs are uridylylated at a conserved tyrosine to form VPgpU, the primer of RNA synthesis by the viral polymerase. This first complete structure for any uridylylated VPg, of poliovirus type 1 (PV1)-VPgpU, shows that conserved amino acids in VPg stabilize the bound UMP, with the uridine atoms involved in base pairing and chain elongation projected outward. Comparing this structure to PV1-VPg and partial structures of VPg/VPgpU from other picornaviruses suggests tha…

Development of a particle agglutination method with soluble virus receptor for identification of poliovirus.

In the Global Polio Eradication Initiative, laboratory diagnosis plays a critical role by isolating and identifying poliovirus (PV) from the stool samples of patients with acute flaccid paralysis (AFP). In this study, we developed a particle agglutination (PA) method with a soluble human PV receptor (hPVR) in the form of an immunoadhesin (PVR-IgG2a) for the simple and rapid identification of PV. Sensitized gelatin particles with PVR-IgG2a showed specific agglutination with the culture fluid of PV-infected cells within 2 h of reaction in a one-step procedure. Detection limits for type 1, 2, and…

Receptor-dependent and -independent axonal retrograde transport of poliovirus in motor neurons.

Poliovirus (PV), when injected intramuscularly into the calf, is incorporated into the sciatic nerve and causes an initial paralysis of the inoculated limb in transgenic (Tg) mice carrying the human PV receptor (hPVR/CD155) gene. We have previously demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerves of hPVR-Tg mice and that intramuscularly inoculated PV causes paralytic disease in an hPVR-dependent manner. Here we showed that hPVR-independent axonal transport of PV was observed in hPVR-Tg and non-Tg mice, indicating that seve…

Role of simvastatin and methyl-beta-cyclodextrin [corrected] on inhibition of poliovirus infection.

Cells exposed to simvastatin or to methyl-beta-cyclodextrin show reduced poliovirus infection, without alteration in virus binding or on the kinetics of genome entry, suggesting that the steps which are altered are those post uncoating and genome entry. Reduction of infection by cyclodextrin is reversed by increasing MOI whereas that produced by simvastatin treatment is not, suggesting that the effects on infection are not due to a reduction in cholesterol. The differences in the characteristics of inhibition can be explained by the differential effects of the compounds. Cyclodextrin inhibits …

Characterization of different strains of poliovirus and influenza virus by differential scanning calorimetry.

Vaccines against poliomyelitis and influenza contain inactivated forms of poliovirus and influenza virus. These antigens are generated on an industrial scale from the purified active viruses that have been analysed in this study by DSC (differential scanning calorimetry). Multiple unfolding transitions are seen for influenza virus A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2) and B/Shangdong/7/97. These data, combined with previously reported data on other influenza viruses, indicates that each influenza virus strain has a characteristic unfolding behaviour. Only minor changes were see…

The alpha/beta interferon response controls tissue tropism and pathogenicity of poliovirus.

Poliovirus selectively replicates in neurons in the spinal cord and brainstem, although poliovirus receptor (PVR) expression is observed in both the target and nontarget tissues in humans and transgenic mice expressing human PVR (PVR-transgenic mice). We assessed the role of alpha/beta interferon (IFN) in determining tissue tropism by comparing the pathogenesis of the virulent Mahoney strain in PVR-transgenic mice and PVR-transgenic mice deficient in the alpha/beta IFN receptor gene (PVR-transgenic/Ifnar knockout mice). PVR-transgenic/Ifnar knockout mice showed increased susceptibility to poli…

Mutations in the 2C region of poliovirus responsible for altered sensitivity to benzimidazole derivatives.

MRL-1237, [1-(4-fluorophenyl)-2-(4-imino-1,4-dihydropyridin-1-yl) methylbenzimidazole hydrochloride], is a potent and selective inhibitor of the replication of enteroviruses. To reveal the target molecule of MRL-1237 in viral replication, we selected spontaneous MRL-1237-resistant poliovirus mutants. Of 15 MRL-1237-resistant mutants obtained, 14 were cross-resistant to guanidine hydrochloride (mrgr), while 1 was susceptible (mrgs). Sequence analysis of the 2C region revealed that the 14 mrgr mutants contained a single nucleotide substitution that altered an amino acid residue from Phe-164 to T…

[Circulation of the poliovirus in endemic zones with children vaccinated by the oral polio vaccine].

Strategies aiming to eradicate the poliovirus and poliomyelitis seek primarily to eliminate wild strains associated with the disease, by means of world wide vaccination campaigns using the oral attenuated vaccine (OPV). OPV contains attenuated viral strains which retain their replicating capacity in the digestive tract and thus induce the development of an antiviral local intestinal immunity and limit the circulation of the virus. In such a context, poliomyelitis surveillance laboratories should study above all cases of acute flaccid paralysis (AFP), highlighting the circulation of wild strain…

Nationwide oral poliovirus vaccination campaign and the incidence of Guillain-Barré Syndrome.

A retrospective analysis of the incidence of Guillain-Barré syndrome (GBS) in Finland in 1981-1986 was carried out by careful examination of medical records identified from nationwide Hospital Discharge Register data based on a mean total population of 5 million people. Records from 247 patients fulfilled the accepted criteria of GBS corresponding to a mean annual incidence of 0.82 per 100,000 population. Monthly rates showed an increased incidence of GBS in March 1985, following by a few weeks the onset of the nationwide oral poliovirus vaccine campaign and partly overlapping it. Analysis of …

Prolonged replication of a type 1 vaccine-derived poliovirus in an immunodeficient patient.

VP1 sequences were determined for poliovirus type 1 isolates obtained over a 189-day period from a poliomyelitis patient with common variable immunodeficiency syndrome (a defect in antibody formation). The isolate from the first sample, taken 11 days after onset of paralysis, contained two poliovirus populations, differing from the Sabin 1 vaccine strain by approximately 10%, differing from diverse type 1 wild polioviruses by 19 to 24%, and differing from each other by 5.5% of nucleotides. Specimens taken after day 11 appeared to contain only one major poliovirus population. Evolution of VP1 s…

Molecular aspects of poliovirus biology with a special focus on the interactions with nerve cells.

Poliovirus (PV), the pathogenic agent of paralytic poliomyelitis, is the prototype of the picornavirus family. Although paralytic poliomyelitis has been nearly totally eradicated in most industrialized countries, PV continues to be an important public health problem in many developing countries. Moreover, in industrialized countries, two current concerns are the occurrence, albeit at a very low frequency, of vaccine-associated paralytic poliomyelitis, due to the genetic instability of the attenuated oral PV strains in vaccines, and the emergence of a neuro-muscular pathology in many survivors …

Approaches to the construction of new candidate poliovirus type 3 vaccine strains.

The World Health Organization has called for improvements to oral polio vaccines (OPV), particularly the type 3 component. Our improved understanding of the genetic basis of attenuation and antigenicity of this strain gives rise to possibilities for constructing new derivatives via mutagenesis of infectious cDNA. This article reviews progress made with various approaches to constructing a new type 3 candidate vaccine strain. These include the construction of antigen chimaeras of poliovirus based on the Sabin type 1 strain, the introduction of new genetically stable attenuation mutations into t…

Poliovirus spreads from muscle to the central nervous system by neural pathways.

A transgenic mouse model was used to address an unsolved question in the pathogenesis of poliomyelitis: how poliovirus invades the central nervous system (CNS). LD50 values for intramuscular and intracerebral inoculation of poliovirus in transgenic mice expressing poliovirus receptors (TgPVR mice) were similar. After intramuscular inoculation with poliovirus, paralysis was observed first in the inoculated limb. In contrast, localization of initial paralysis to the inoculated limb was not observed in normal mice inoculated intramuscularly with the mouse-adapted P2/Lansing poliovirus strain. Aft…

Трансгенные мыши выражают рецептор полиомиелитвируса: новая модель полиомиелита.

Для создания трансгенных мышей был использован ген полиомиелитвирусного рецептора человека (PVR), который экспрессирует PVR и связывает полиомиелитвирусы в самых различных тканях. В результате инфракрасной прививки трансгенных мышей PVR с полиомиелитвирусом типа 1, штаммом Махони в мозгу и спинном мозге и развития паралитического полиомиелита. P1/Mahoney не воспроизводила и не вызывала паралич в нетрансгенных мышах. PVR трансгенные мыши не смогли развить клиническую болезнь, когда они были привиты интрацибрально с живым слабительным штаммом вакцины Sabin типа 1. Эти результаты свидетельствуют

Совпадение в аннотации оригинала
A human poliovirus receptor (PVR) gene was used to generate transgenic mice that express PVR transcripts and poliovirus binding sites in a wide range of tissues. Intracerebral inoculation of PVR transgenic mice with poliovirus type 1, Mahoney strain, resulted in viral replication in the brain and spinal cord and development of paralytic poliomyelitis. P1/Mah…