Poliovirus and its Eradication

By Marina Artemiou

Recently, the African Regional Certification Commission certified the World Health Organisation (WHO) African Region as wild-polio free, following four years without any new registered poliomyelitis cases. This historic milestone, where five out of the six WHO regions representing approximately 90% of the world’s population are classed as polio-free, has brought the world one step closer towards achieving global polio eradication. Currently, only two countries globally, Pakistan and Afghanistan, continue to register new polio cases. (WHO, 2020)

Poliovirus is the causative agent of poliomyelitis, a life-threatening disease that often leads to irreversible paralysis, meningitis or paraesthesia due to the virus’ effect on the central nervous system, and is regarded as one of the simplest major viruses. Its viral particles are composed only of a positive-sense RNA genome, approximately 7500 nucleotides long and a protein capsid that contains 60 copies each of the four viral peptides; VP1, VP2, VP3 and VP4 (Immunopaedia, n.d). 

The virus is transmitted between humans via the oral-faecal route. Consequently, viral replication occurs upon entry in the gut where viral particles bind to immunoglobulin-like receptor CD155, also known as poliovirus receptor (PVR). PVR is a glycoprotein consisting of an N-terminal sequence made up of three extracellular immunoglobulin-like domains, a transmembrane domain and a cytoplasmic tail. Binding to the receptor facilitates an irreversible conformational change to the virion. This altered form becomes known as the A particle and bears some distinct differences from the virions in their native state, i.e. the sedimentation coefficient of the A particle is 135S and more sensitive to detergents compared to 160S in their native state. Upon attachment to the host cell membrane, the viral genome can enter the cell in one of two ways. This can occur by the “injection” the genome through a pore in the plasma membrane and into the host cell cytoplasm or the uptake of the viral particle via receptor-mediated endocytosis. Recent evidence, however, supports the latter hypothesis (CDC, 2019).

Viral RNA is translated via an IRES-mediated mechanism into a long polypeptide, which is then cleaved to yield 10 mature viral proteins. The positive-sense RNA also serves as a template for complementary negative-strand synthesis to form a double-stranded replicative form RNA. Furthermore, the negative-sense stand serves as a template for additional positive-sense strand synthesis. The newly synthesized positive-sense RNA molecules subsequently operate as templates for translation of further viral peptides or can be enclosed in a capsid to generate immature virions. Lysis of the infected cell results in release of infectious immature virions (CDC, 2019).

There are two types of polio vaccines used to date; one version is administered orally (OPV) and consists of attenuated strains of the virus whilst the other is administered by injection (IPV) and consists of inactivated strains (CHP, 2020).

OPV comprises of all three attenuated strains of the virus. As the virus in the vaccine is not inactivated, viral particles can possibly revert back to wild-type polio, however, because of their weakened internal critical ribosomal entry site (IRES) and capsid genes, virions do not tend to disseminate to the blood and subsequently the nervous system. Following OPV administration, the attenuated viruses induce both the cell-mediated and humoral responses which leave behind a pool of memory cells and antibodies in the intestines for all three poliovirus strains, providing rapid secondary immune response upon re-infection, preventing the development of poliomyelitis. This particular mode of vaccination is routinely given at birth and 6 weeks of age to infants in the South African region since it is more economical and much easier to administer (Immunopaedia, n.d).

Unlike OPV, IPV consists of inactivated viral strains, hence the possibility of virions reverting back to their natural state and becoming pathogenic is zero. The vaccine is administered intramuscularly or subcutaneously and, similarly to OPV, elicits both the cell-mediated and humoral response in the bloodstream, leaving a collection of antibodies and memory cells to provide rapid secondary immune responses upon re-infection. However, in contrast to OPV which provides a primary line of defence against virions upon entry into the gut, IPV provides a secondary line of defence against infection in the bloodstream. The efficacy of both vaccines is extremely high, however, IPV is more commonly used, despite its higher price, as there is no risk of acquiring poliomyelitis (CHP, 2020).

WHO recommendation to achieve global eradication of poliomyelitis consists of four major strategies. These involve high routine immunization coverage, where at least 90% of infants must be immunized by the age of 1 to achieve herd immunity, mass immunization campaigns, such as national immunization days in tropical and subtropical regions, and acute flaccid paralysis surveillance, such that potential cases of polio can be detected, the cause of infection investigated and chain of transmission broken. The final strategy involves the use of “mopping up” campaigns in targeted areas where there are poliovirus transmission chains. The purpose of these campaigns is to immunize all children younger than 5, regardless of their prior immunization status, to hopefully interrupt the spread (Hull et al, 1997). 

With the world now closer to eradicating this deadly and highly contagious virus, it would be useful to take note of the strategies used globally and implement them as soon as possible, such that the current Coronavirus pandemic can be effectively eliminated.

References:

World Health Organisation (WHO). (2020) Global polio eradication initiative applauds WHO African region for wild polio-free certification. Available from: https://www.who.int/news-room/detail/25-08-2020-global-polio-eradication-initiative-applauds-who-african-region-for-wild-polio-free-certification [Accessed 8th September 2020].

Children’s Hospital of Philadelphia (CHP). (2020) A Look at Each Vaccine: Polio Vaccine. Available from: https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-details/polio-vaccine  [Accessed 1st September 2020].

Immunopaedia. (n.d) Vaccine Associated Paralytic Polio. Available from: https://www.immunopaedia.org.za/immunology/archive/neonatal-immunity-2/intestinal-mucosa/b-cell-humoral-immunity/vaccine-associated-paralytic-polio/ [Accessed 2nd September 2020]

Hull HF, Birmingham ME, Melgaard B, et al. (1997) Journal of Infectious Disease. Progress toward —global polio eradication. 175 (1): S4-S9. Available from: doi: 10.1093/infdis/175.supplement_1.s4.

Centers for Disease Control and Prevention (CDC). (2019) Global Immunization: What is Polio. Available from: https://www.cdc.gov/polio/what-is-polio/index.htm [Accessed 2nd September 2020]

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