Poliovirus mechanism

The structure/activity relationships for the methisazone, 3a, derivatives against adenoviruses and poxviruses have been shown to be similar [78]. Pearson and Zimmerman [79] demonstrated that all three types of polioviruses are inhibited by 2-acetylpyridine JV-dibutylthiosemicarbazone, which is similar to 3a, by blocking viral RNA synthesis. A 3-substituted triazinoindole derivative of isatin was effective against several strains of rhinovirus in tissue culture the mechanism of action is unknown [80]. 

The higher than normal serum IgA in many children with protein calorie malnutrition may be related to increased synthesis of IgA by the intestinal lamina propria in resjionse to increased antigenic stimuli from bacteria and virus. This is probably supported by the observation that children with kwashiorkor were found to maintain their polio antibodies during malnutrition, and their immune mechanism seemed to be quite capable of inhibiting poliovirus infection, indicating that the intestinal receptor cell for poliovirus operates normally in kwashiorkor (B8). It is now known that polio antiliodies are mainly associated with IgA. 

Ward RL (1980) Mechanisms of poliovirus inactivation by the direct and indirect effects of ionizing radiation. Radiat Res 83 330-344... 

ME Clark, T Hammerle, E Wimmer, A Dasgupta. Poliovirus proteinase 3C converts an active form of transcription factor IIIC to an inactive form a mechanism for inhibition of host cell polymerase III transcription by poliovirus. EMBO J 10 2941-2947, 1991. 

There is evidence that some antibodies neutralize in a manner not easily explained by the previous mechanisms. For example, it has been shovm that antibodies to Sindbis virus [8, 9] and poliovirus [10, 11] can eliminate infection or progression of infection even when added to cells hours after infection. In the case of Sindbis virus, the exact mechanism of this viral clearance is unknovm, but appears to be related to antibody cross-linking [9]. Similarly, the postadsorption neutralization properties of at least some of the antibodies to poliovirus appeared to be related to binding valency as well [11]. Therefore, antibodies, or antibodies interacting with viral components, may be triggering some unknown defensive mechanism within the infected cell. 

Mandel, B. (1976). Neutralization of poliovirus A hypothesis to explain the mechanism and the one-hit character of the neutralization reaction. Virology 69, 500-510. 

Studies on the mechanism of action, suggested that hypericin antiviral effect is directed towards enveloped viruses, while non enveloped viruses, such as adenovirus and poliovirus, are unaffected [4], Hypericin virucidal effect is increased by light, however its antiviral properties against selected viruses [7] have also been documented in the dark. 

Adsorption of enteric viruses on mineral surfaces in soil and aquatic environments is well recognized as an important mechanism controlling virus dissemination in natural systems. The adsorption of poliovirus type 1, strain LSc2ab, on oxide surfaces was studied from the standpoint of equilibrium thermodynamics. Mass-action free energies are found to agree with potentials evaluated from the DLVO-Lifshitz theory of colloid stability, the sum of electrodynamic van der Waals potentials and electrostatic double-layer interactions. The effects of pH and ionic strength as well as electrokinetic and dielectric properties of system components are developed from the model in the context of virus adsorption in extra-host systems. 

In collaboration with Eckard Wimmer (State University of New York, Stony Brook, New York) a breakthrough in our understanding of the replication mechanism of the poliovirus was achieved. Key to this study proved to be the accessibility of homogeneous uridylylated oligopeptide fragments. In itself, the chemical synthesis of peptide nucleic acid fragments of the complexity required for these studies, with the many synthetic hurdles that are caused by the incompatibility of standard peptide synthesis and nucleic acid synthesis protocols, represents a milestone in the oeuvre of Jacques van Boom and a hallmark in bioorganic chemistry. 

The VSY genome codes for only five proteins (33), and soon after infection the five YSY proteins represent the only translation products of the infected cell, since this virus also inhibits cellular protein synthesis (34) The five YSY monocistronic mRNAs serving as templates for these proteins have been relatively well characterized (35) and thus this system lends itself to studies on the mechanism of superinfection. Ehrenfeld and Lund (36) examined the consequences of superinfecting YSY infected HeLA cells at two hours after infection with poliovirus. By I.5 to 2 hours after poliovirus superinfection, virtually all YSY polysomes disaggregated. The pattern of protein synthesis as shown on polyacrylamide gels changed from YSY specific to poliovirus specific within 2.5 hours after infection. All five of the YSY proteins were inhibited to the same extent. 

In this review I have outlined several theories that have been proposed to explain the mechanism by which picornaviruses inhibit cellular protein synthesis. Some theories seem less likely than others. Inhibition by ds ENA, for example, is no longer thought to be a likely possibility. In cell-free extracts ds ENA inhibits both cellular and viral mRNA translation (61). The inhibitor of cellular protein synthesis would be expected to be selective in its inhibitory activity. It is also apparent that picornavirus infection does not result in the degradation or alteration of cellular mENA (9> 27, 29 51). So,.too, experiments demonstrating that protein synthesis inhibition takes place in the absence of significant viral ENA synthesis (I4) tend to weaken the argument that protein synthesis inhibition results from direct competition of viral mENA with cellular ENA for initiation factor eIE-4D (47) As mentioned earlier, superinfection with poliovirus of cells infected with VSV prevents VSY mENA translation (J2, 56). In lysates from uninfected HeLa cells, however, 7SY mENA translation is favored over poliovirus mENA translation when both mENA species are present in equimolar saturating concentrations (55) If competition were a major cause of cellular protein synthesis inhibition, one would have expected poliovirus mENA to out-compete VSV mENA in cell-free translation, not the contrary. 

WILLEMS, M. and PENMAN, S. The mechanism of host cell protein synthesis inhibition by poliovirus. Virology, (I966), 30<... 

The competition between viral and host mMAs was, therefore, localized at the level of a specific protein and, probably, offered the most satisfactory explanation for the molecular mechanism of the shut-off. It was also suggested that eIE-4B was specifically inactivated in poliovirus-infected cells (10). This was not in contrast with the results of the experiments mentioned above on the effect of eIF-4B on vitro translation and with the high affinity of EMC EITA for this initiation factor. However it has not definitely been established whether in infected cells eIP-4B is... 

A tight coupling of poliovirus MA sjmthesis to viral protein synthesis exists throughout the infectious cycle even though the sites of translation and replication are physically separated (6). Our model may offer an explanation for this control mechanism. 

COLE, C.N. and BALTIMORE, D. Defective interfering particles of poliovirus. IV. Mechanisms of enrichment, J. Virol. 0975)>... 

Evers DL, Chao CE, Wemg X et eil (2005) Human cytomegalovirus-inhibitory flavonoids studies on antivirtil activity and mechanism of action. Antiviial Res 68 124-134 Felipe AM, Rincao VP, Benati FJ et al (2006) Antiviral effect of Guazuma ulmifolia and Stryphnodendron adstringens on poliovirus and bovine herpesvirus. Biol Pharm Bull 29 1092-1095... 

Salvati AL, De Dominicis A, Tail S et al (2004) Mechanism of action at the molecular level of the antiviral drug 3(2H)- isoflavene against type 2 poliovirus. Antimicrob Agents Chemother 48 2233-2243... 

Bablanian, R., Eggers, H. J., and Tamm, I., 1965a, Studies on the mechanism of poliovirus-induced cell damage. I. The relation between poliovirus-induced metabolic and morphological alterations in cultured cells. Virology 26 100. 

A mechanism that may be restricted more specifically to certain viruses is the inactivation of cap-binding proteins accompanying, for example, the shut-off of host protein synthesis by poliovirus (see Chapter by E. Ehrenfeld in this volume). Lee and Sonenberg (1982) have demonstrated that the ability of five polypeptides, associated with the CBP II complex, to be crosslinked to the cap is reduced in extracts of poliovirus-infected cells. This reduction correlates with... 

Infection of cultured cells with many lytic viruses results in a marked decrease in the rate of cellular protein synthesis. Usually, this decrease is accompanied by increasing rates of viral protein synthesis, marked cytopathic effects, and ultimately cell death. In most cases, it is not known whether the shut-off of host cell protein synthesis results from an active process induced by the virus evolved for that (or some other) purpose, or whether it is merely a passive result of another viral function, such as production of large quantities of viral mRNA which compete effectively with their cellular counterparts. In the case of poliovirus, however, three types of studies suggested that the former, active type of mechanism was at work. Kinetic analysis of the rate of protein synthesis in cells synchronously infected with high multiplicities of virus showed that cellular protein synthesis could be virtually completely inhibited prior to the synthesis of significant quantities of viral RNA and protein (Summers et ai, 1965). In addition, infection in the presence of 1-3 mM guanidine, which prevents detectable replication of viral RNA, nevertheless results in viral inhibition of host cell protein synthesis (Holland, 1%4 ... 

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