Polio virus replication

A rather distantly related analogue incorporating a 3-di-carbonyl moiety as a bioisosteric replacement for a carboxyl, aril done (55), blocks the uncoating of polio virus and herpes simplex virus type I and thus inhibits infection of cells and l.he early stages of virus replication. Thus effective therapy would require careful timing as it does with amantidine. 

Perhaps surprisingly, all of the most successful attenuated viral vaccine strains in current use were produced by empirical methods long before the genetic basis of pathogenesis by the specific pathogen was understood. Thus, attenuated strains of polio virus for use as a live, oral vaccine (Sabin) were selected by growth of viruses isolated from human cases under cultural conditions that did not permit replication of neuropathogenic virus. Comparable procedures were used to select the attenuated virus strains that are currently used in live measles, mumps, rubella and yellow fever vaccines. 

The flow of information in all cells is from DNA to RNA to protein, which is known as the central dogma of molecular biology it was formulated by Francis Crick shortly after the discovery of the structure of DNA. Information also can flow from DNA to DNA in both cells and among viruses that infect cells. Information also flows from RNA to RNA during the replication of RNA viruses such as the polio virus. The final permitted information transfer is from RNA to DNA, which only occurs in the case of retroviruses such as human immunodeficiency virus (HIV). The only information transfer that is prohibited by the central dogma is from protein to RNA or to DNA. The permitted information transfers in cells (infected or uninfected) is summarized below. 

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. 

A brief comment about size is in order, since viruses range from the minute, like polio viruses, rhinoviruses and hepatitis A (all around 25 nm), to the comparatively massive pox viruses, which are 10 times larger and just about visible under the light microscope. Whatever their size and shape, the one common feature of all viruses is their use of host-cell biochemistry to help with their reproductive cycle - their replication. It is usual to identify six stages in the life cycle of viruses ... 

Formaldehyde is useful in the production of killed virus vaccines. A deadly virus, such as polio virus, can be treated with heat and formaldehyde. Formaldehyde reacts with the genetic information (RNA) of the virus, damaging it irreparably. It also reacts with the virus proteins but does not change their shape. Thus when you are injected with the Salk killed polio vacdne, the virus can t replicate and harm you. Flowever, it will be recognized by your immune system, which wiU produce antibodies that will protect you against poUo virus infection. 

Flavonoids also showed, to some extent, some antifungal and antiviral activity. In this case, there is an important structure-activity relationship. The flavonol quercetin and the flavanone hesperidin exhibit inhibition activity towards the infective capacity and/or replication of herpes simplex type viruses and polio viruses, while the flavanone naringenin totally lacks this ability [124]. For researchers the impossibility to dissociate, the viruses from the flavonol quercetin after 1 hour of interaction, either by dialysis or ultracentrifugation suggests the formation of quercetin-virus complexes, which may have lost the ability to induce infection. With respect to the antiviral activity of the methoxylated flavones, this is strongly related to a substitution pattern based on... 

These compounds show a wide variety of biological activities (18). At concentrations of 10 to 20 yg/ml they can suppress, enhance or have no effect on the replication of Polio Virus type I, a L RNA virus, but none of the polymers tested have any activity toward L929 (mouse) of HeLa (human) tumor cells at these concentrations. At concentrations of 30 yg/ml and greater all of the polymers tested inhibit both L929 and HeLa tumor cells. Further mice tolerate a dose of 400 yg of a methylthio pyrimidine containing polymer with no apparent ill effects (highest dosage tested). Thus the polymers show specific, differential activity in the yg/ml level. 

AZATHIOPRINE VACCINES i effectiveness of vaccines, t risk of adverse/toxic effects of live vaccines (e.g. measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, TY21a typhoid), e.g. vaccinal infections Disseminated infection due to enhanced replication of vaccine virus in the presence of diminished immunocompetence Do not vaccinate when patients are on immunosuppressants. Vaccination should be deferred for at least 3 months after discontinuing immunosuppressants/myelosuppres-sants. If an individual has been recently vaccinated, do not initiate therapy for at least 2 weeks after vaccination... 

Excess replication of a live vaccine can lead to disease and can be the result of an immune deficient individual, or due to the selectirai of a too virulent strain, or because of reversion of a live strain to wUd-type. The development of aseptic meningitis as a result of administering the live mumps vaccine is one example of this. In the case of the polio vaccine where both live and inactivated vaccines are available, there is a 1 750,000 risk of the development of polio as a result of reversion of the live virus strain. The inactivated vaccine does not carry this risk, but it is not as effective as the live vaccine. 

Other vectors including polio (32), retrovirus (33), bacteria (34), and autonomous parvovirus (35) are all potential oncolytic vectors under development. Autonomous parvovirus is a nonenveloped, single- stranded DNA virus that replicates in cells in the cytoplasm of dividing and nondividing tumor cells. Its envelope can be modified, similar to retroviruses, to contain ligand moieties to target cell surfece receptors. It has been used in vaccine production where it showed low toxicity in human applications (11). Currently, the H-1 strain is being evaluated in the clinic (4). 

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