# Nisa Tezcan **Polioviruses**-"Essential Human Virology by Jennifer Louten (2016)." Chapter 14 P:257-272.
Resource link: https://www.sciencedirect.com/book/9780128009475/essential-human-virology


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# What is Poliovirus?
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Poliomyelitis, often called “polio,” is a disease caused by poliovirus, which is transmitted through the fecal–oral route. The word “poliomyelitis” stems
from the Greek words polios and myelos, meaning “gray marrow,” in reference to the gray matter of the spinal cord
that becomes inflamed and can cause paralysis (referred to as paralytic poliomyelitis.Because the disease afflicted mainly children, poliomyelitis was also known as "infantile paralysis".
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# THE STRUCTURE OF POLIOVIRUS

**Figure 1** Poliovirus Structure

The poliovirus capsid contains 60 copies each of the four viral polypeptides VP1, VP2, VP3, and VP4. The arrangement of proteins in the capsid creates icosahedral symmetry. The virion surface is covered with star-shaped mesas at its fivefold axes surrounded by deep canyons and three-bladed propellers.These are situated at threefold axes separated by saddle depressions straddling twofold axes. Capsid proteins VP1, VP2, and VP3 all have an eight-stranded β-barrel fold, but have different shaped loops on their N- and C-terminal extensions.

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# Clinical Course of Infection
Poliovirus is in the Picornaviridae family, within the Picornavirales order that was created in 2008. Poliovirus infects anterior horn cells, the motor neurons of the spinal cord, or the part of the brain stem known as the medulla oblongata. It should be noted that infection of nervous tissue is not required for continued transmission of the virus but may be due to an increase in virulence or a lack of adequate immune responses.
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There are two forms of disease that can occur upon infection of the central nervous system: nonparalytic aseptic meningitis (also referred to as nonparalytic poliomyelitis)
and paralytic poliomyelitis.
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<img src="https://i.imgur.com/V6JXXXb.png" height="400"/>

**Figure 2** Paralytic Poliomyelitis

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**Figure 3** Nonparalytic Poliomyelitis

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**FIGURE 4** Paralytic poliomyelitis. Paralysis caused by poliovirus is usually asymmetrical and appears 7–21 days following infection. Without normal stimulation, the affected muscles atrophy, as shown in this image of a child with permanent paralysis due to polio infection.

**FIGURE 5** Poliovirus damage to the central nervous system.
(A)Spinal poliomyelitis occurs when poliovirus affects anterior horn cells, the motor neurons that control movement of muscles. (B) Bulbar poliomyelitis results from the destruction of the bulbar region of the brain stem, more commonly referred to as the medulla oblongata. Bulbospinal poliomyelitis indicates both sites have sustained damage from poliovirus replication.

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# POLIOVIRUS REPLICATION
<img src="https://i.imgur.com/9sOij9f.png" height="400"/>

**Figure 6** Poliovirus Replication

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POLIOVIRUS VIRION

**Figure 7** Poliovirus Virion
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(A) Icosahedral poliovirus virions. Figure courtesy of the CDC, Dr. Fred Murphy, and Sylvia Whitfield. (B) The poliovirus capsid, composed of structural units containing VP1, VP2, and VP3. VP4 associates with these proteins on the underside of the capsid. (C) The 3D structure of the poliovirus capsid, showing the star-shaped plateau formed by VP1 and the canyon in which CD155 binds
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# POLIOVIRUS GENOME AND TRANSLATION PRODUCTS

**Figure 8** Poliovirus Genome And Translation Products
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(A) The +ssRNA poliovirus genome possesses a 5′-NTR that contains an IRES, followed by a single open reading frame that encodes the polyprotein. The 3′-NTR is polyadenylated.
(B) The translated polyprotein is cleaved several times by both viral and host proteinases into 11 distinct proteins. Intermediate cleavage products also have important functions. The colored scissors indicate sites of cleavage: orange by 2Apro, black by 3Cpro or 3CDpro, and green by an unidentified cellular proteas
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**Table 1**: Function of Poliovirus Proteins


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# Assembly, Maturation, and Release
The 2Apro cleaves the single poliovirus polyprotein between P1 and P2 to release the P1 precursor, which contains all components of the capsid. The P1 precursor is cleaved by 3CDpro to release VP1 and VP3 proteins, along with VP0, an immature protein that will later be cleaved into VP2 and VP4 as part of the maturation process. VP1, VP3, and VP0 associate with each other to form the structural units, known as **protomers**. Five protomers spontaneously aggregate to form a pentamer, and twelve pentamers (for a total of 60 structural units) form the **procapsid**.

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The +ssRNA genome and covalently associated VPg are
packaged into the procapsid, or alternatively, the procapsid assembles around the genome. Virions undergo maturation into an infectious virion upon the cleavage of VP0 into VP2 and VP4 by what is thought to be a host protease.
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Poliovirus has been considered a lytic virus, although evidence has emerged recently that in certain conditions release can also occur in a nonlytic fashion through the release of virus
within vesicles that have been hijacked from those involved
in autophagy, a process that degrades and recycles damaged intracellular components, including organelles. The entire poliovirus replication cycle is depicted in **Figure 9**
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**Figure 9** Poliovirus replication: Poliovirus binds to CD155, which induces endocytosis. A conformational change in the capsid creates a pore
through which the genome is transported. Host ribosomes translate the genome into a polyprotein, which is cleaved into separate proteins by viral proteinases. The viral RdRp 3Dpol replicates the antigenome template and genomic RNA on replication complexes (not shown due to space constraints).
The genome is packaged into capsids composed of VP1,VP3, and VP0. In the process of maturation, VP0 is cleaved into VP2 and VP4 by an unidentified cellular protease. Release then occurs via lysis or exocytosis involving autophagosome vesicles.

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# EPIDEMIOLOGY AND WORLDWIDE ERADICATION EFFORTS

**Figure 10 (A) and (B): National Immunization Day:** All children within a country were immunized on National Immunization Days. (A) A clinic worker administers an oral polio vaccine to a child in Uttar Pradesh, India. (B) Scouts wearing their “no Polio” headbands as part of the India’s celebration of National Immunization Day in 2000.
**Figure 11 (right): The Global Polio Eradication Initiative** Health workers and volunteers paid individual visits to millions of houses in door-todoor immunization campaigns, which often took place by boat, bicycle, horse, or on foot.

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**Figure 12**: The eradication of poliovirus.

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The Global Polio Eradication Initiative was announced in 1988, when over 125 countries had
endemic wild poliovirus infections. By 2006, this number dropped to four countries—India, Nigeria, Pakistan, and Afghanistan. India and Nigeria
logged their last case in 2011 and 2012, respectively.
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By 1957, 2 years after the approval of the Salk vaccine, cases of polio had dropped to less than a
tenth of their usual numbers (Figure 13 A). The Salk and Sabin vaccines were viewed positively by parents who were anxious to prevent paralysis in their children (Figure 13 B and C). The last cases of paralytic poliomyelitis in the United States were in 1979, when poliovirus was imported from the Netherlands and infected unvaccinated individuals in Amish communities in several Midwestern states. In the following 20 years, 162 cases of paralytic
poliomyelitis were reported; 6 were imported from other countries, 154 were VAPP cases caused by the OPV, and 2 were of indeterminant origin. Poliovirus vaccination continues to occur, because outbreaks remain possible from imported cases until the virus is eliminated from every location in the world.

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**FIGURE 13** Vaccination efforts in the United States. Cases of paralytic poliomyelitis peaked in 1952, when over 21,000 people had mild to permanent paralysis. Cases dropped precipitously following the approval of the inactivated Salk vaccine in 1955.

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