Poliovirus replication

Poliomyelitis is a highly contagious disease that is often asymptomatic however, approximately 1 in every 100 to 1000 cases will develop a rapidly progressive paralytic disease. Polio is caused by poliovirus which has three serotypes type 1 is most frequently associated with paralytic disease. Poliovirus replicates in the oropharynx and intestinal tract and is excreted in oral secretions and feces, which can infect others. As a result, more than 90% of unvaccinated individuals will become infected with poliovirus following household exposure to wild-type poliovirus. Since the introduction of the first poliovirus vaccine, there has been a significant reduction in the number of polio cases. Today, polio caused by wild-type poliovirus has been eradicated from the Western Hemisphere with the goal of eradicating it from the world.11... 

It was reported that VPg is linked to each nascent strand present within the poliovirus replicative intermediate form (20, 21). Flanegan et (2l) find that the amount of VPg-pUp/unit weight arising from nuclease digestion of the replicative intermediate ERA is the same as that obtained from virion ERA. The intermediate has a mass about four times that of the virion ERA (consisting of a (-)-strand ERA and 6 nascent chains, on average half-completed (8). If one molecule of VPg is attached to the (-)-strand template (see below), then the remainder must be attached to the nascent (+)-strands. 

YOGO, Y. and WIMMER, E. Sequence studies of poliovirus ERA. III. Polyuridylic acid and polyadenylic acid as components of the purified poliovirus replicative intermediate. J. Mol. Biol. (1975), 2i, 467-477. 

Merryman, P., Jaffe, I., and Ehrenfeld, E., 1974, Effect of D-penicillamine on poliovirus replication in HeLa cells, J. Virol. 13 881. 

Gliotoxin, an inhibitor of poliovirus replication (Miller, Milstrey and Trown, 1968), interferes with complex formation between RNA and methyl-... 

Oppermann, H., Koch, G. Kinetics of poliovirus replication in HeLa Cells infected by isolated RNA, BBRC 52, 635-640 (1973). 

Inoculation of these mice with poliovirus resulted in viral replication in the central nervous system and in the development of a disease analogous to paralytic poliomyelitis. 

MV Davies, J Pelletier, K Meerovitch, N Sonenberg, RJ Kaufman. The effect of poliovirus proteinase 2Apro expression on cellular metabolism. Inhibition of DNA replication, RNA polymerase II transcription, and translation. J Biol Chem 266 14714-14720, 1991. 

Infection of a cell by a virus has two outcomes, depending on the nature of the virus and the particular cell type. Some viruses go into a lytic cycle, which results in the replication of the virus and the lysis of the cell. This is the case with viruses such as poliovirus and vaccinia virus, both of which are used in vaccination. The use of live viruses expressing protein antigens in vaccination has been discussed in Chapter 3. In vaccination, the goal is the transient replication of viruses for a period sufficient to raise antibody response. Thus, the use of lytic viruses leading to transient, self-limiting lytic infection is acceptable or even desirable. 

Despite some uncertainties as to the overall role of PVR in vivo, several studies link the importance of this receptor to the virus life cycle. Kaplan et al. showed that exposure of poliovirus to soluble PVR converted the 160S particle to the 135S form and that this was associated with reduced infectivity (Kaplan et al., 1990). Other investigators showed that antibody-coated poliovirus was unable to enter nonpermissive GHO cells bearing Fc receptors, whereas, in contrast, foot-and-mouth disease virus (FMDV) was able to utilize this alternative entry pathway (Mason et al, 1994). Thus, PVR selectively mediates conformational changes in the poliovirus particle that are associated with cell entry and confers virus infection of cultured cells. Further studies will be necessary to explain why the broad distribution of this receptor does not allow virus replication in many cell types in vivo. 

Molecular studies of poliovirus isolates have suggested that viral replication of vaccine-related pohoviruses may have persisted for as long as 7 years in a patient with vaccine-associated paraljdic pohomyehtis, in whom common variable immunodeficiency syndrome had previously been diagnosed (SEDA-21, 336). 

This is a Syrian hamster cell line derived from the kidneys of 1-day-old hamsters. The cells have a fibroblast-like morphology and are used for viral replication studies, including poliovirus, rabies (Pay et al, 1985), rubella, foot and mouth disease virus (Radlett et al, 1985), VSV, HSV, adenovirus (Ad) 25 and arbovirus. Successful cultivation at scales up to 80001 has been achieved with maximum cell density attained by minimum air sparging sufficient to satisfy the oxygen demand of the cells. 

To complete the replication cycle, the viral components are assembled into the mature viral particle, or yirioit. Fur simple, noncnvelopcd viruses (e.g.. the picomavirus poliovirus). the genome and only a few enzymes are encased b) capsid proteins to complete the virion. Other, more coniplet viru.scs are enveloped by one or more membranes containinc carbohydrate and lipopnitein components derived Irani the ho.st cell membrane. 

The way in which the viral genome is replicated depends entirely on the nature of the nucleic acid carried by the virus. Positive strand RNA viruses (e.g. poliovirus) can use the parent RNA directly as mRNA, after the acquisition from the host cell of a terminal sequence enabling immediate translation. With negative strand RNA viruses (e.g. influenza virus), a positive RNA strand complementary in base sequence to the parent RNA has to be transcribed using an RNA-dependent RNA polymerase carried by the virus, as eukaryotic cells do not possess such enzymes. 

Selected polyamines were tested for their ability to alter the normal replication cycle of two representative RNA viruses Ence-phalomyocardltls (EMC strain MM) and Poliovirus Type I. Mono-layers of L929 and HeLa cells were treated with solutions containing specified polyamines. After Incubation the cultures were washed and then Infected with the RNA virus. After a 24 hours Incubation period, the supernatant fluids were collected and assayed for virus (pfu) content. 

The data given In Tables 5 and 6 are offered to Illustrate the variety of results. Thus for Poliovirus, platinum polyamines can effect an Increase or decrease In the growth of the virus or exhibit no effect at concentrations below that where the HeLa cells are affected. Similar results are found for the polyamines In L929 cells Infected with EMC strain MM. Thus with treatment for 24 hours, polymers 9,11 and 12 suppressed viral replication (Table 6). With the exception of polymer 6, all of the polymers suppressed EMC viral replication when treatment was extended to 48 hours. Again viral replication was affected at polyamlne concentrations well below that necessary to Inhibit the L929 cells. 

Table 5. Effects of Platinum Coiqpounds on the Viral Replication of Poliovirus in HeLa Cells. Compound ...

Poliomyelitis is a contagious viral infection that usually causes asymptomatic infection but in its serious form causes acute flaccid paralysis. Poliovirus is spread via the fecal-oral route. The virus replicates in the upper respiratory tract, gastrointestinal tract, and local lymphatics. The vast majority of polio infections are subclinical and asymptomatic. Indigenous polio has been absent from the United States since 1979, and the last case in the Americas was reported in 1991. Global eradication efforts are entering the final stages, and the eradication of polio should be accomplished in the next few years. 

Replication of the poliovirus genome. The poliovirus replicase utilizes the VPg priming protein to initiate synthesis of (-)-strand RNA, which becomes the template... 

Poliovirus is an RNA-RNA virus that redirects the host-cell protein synthesis machinery toward translation of its own RNA genome. The poliovirus polypeptide is cleaved into active subunits by the proteolytic action of virally encoded proteases. Poliovirus RNA replication utilizes a novel protein-uridine primer to initiate RNA synthesis using its own RNA-dependent RNA polymerase. 

Natural quinones also exert antiviral activity against other viruses, such as the Epstein-Barr virus and poliovirus type 2 and 3 [163-165], For example, chrysophanic acid (l,8-dihydroxy-3-methylanthraquinone) isolated from the Australian Aboriginal medicinal plant Dianella longifolia Street has been found to inhibit the replication of poliovirus type 2 and 3 in vitro. Four structurally-related anthraquinones (rhein, Fig. (5), 1,8-... 

Poliomyelitis is not the scourge that it once was, thanks to improved hygienic practices which have effectively blocked the spread of wild-type polioviruses, especially in developed countries, and thanks to the widespread use of vaccines. The viruses, like other enteroviruses, are transmitted by the fecal-oral route, following ingestion, they replicate in various cell types in the pharynx and small intestine (they are quite stable to stomach acids) and gain access to the circulation. From there, they disseminate and occasionally gain access to the central nervous system, where they may produce the characteristic lesions leading to poliomyelitis. 

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