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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Polio is a highly infectious disease caused by Poliovirus that invades the nervous system. Poliovirus are small (27–30 nm), nonenveloped viruses with capsids enclosing a single-stranded, positive-sense RNA genome about 7,500 nucleotides long. Person-to-person spread of poliovirus via the fecal-oral route is the most important route of transmission, although the oral-oral route may account for some cases.

Taxonomy

Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Picornavirales; Picornaviridae; Enterovirus; Poliovirus

Biology

A Transmission electron microscopy of poliovirus Image provided by the CDC Centers for Disease Control and Prevention

Poliovirus is a member of the genus enterovirus, family Picornaviridae. Enteroviruses are small, nonenveloped, positive stranded RNA viruses. Other members of the family include: Rhinovirus, Hepatovirus, Cardiovirus and Apthovirus. Poliovirus is a transient inhabitant of the gastrointestinal tract, stable at an acid pH. Enteroviruses in general do not cause disease, or are responsible for mild symptoms. Disease syndromes resulting from viral spread to other secondary regions are rare. Despite rare, these syndromes may lead to severe disease complications, seldom with fatal outcomes.

There are three poliovirus serotype (P1, P2, and P3) that replicate efficiently in the gastrointestinal tract. There is minimal heterotypic immunity between the three serotypes. That is, immunity to one serotype does not produce significant immunity to the other serotypes. The poliovirus is rapidly inactivated by heat, formaldehyde, chlorine, and ultraviolet light.

The characteristics of poliovirus make it a good model for viral study, specifically: high viral titers, stable capsid and ease of purification, along with a low bio-safety requirement.

Structure

The genome of poliovirus consists of a single positive-sense RNA molecule, of approximately 7740 nucleotides. At the 5' end of the RNA molecule are coded 88 nucleotides that interact to form a clover leaf structure, which is involved in the replication process. At the 3' end of the genome is encoded a poly Adenine sequence, which varies about 60 adenylate residues in length. The translation of the genome is initiated by the attachment of the host cell's ribosomes to the often called internal ribosomal entry site (IRES). This is a specific RNA segment in the 5' end region of the RNA (not translated), where the host cell's translational ribosomes first attach, in order to initiate viral genome replication. The understanding of this mechanism has led to the establishment of a new mechanism of protein synthesis in eukaryotes.

Tropism

Extra-Cellular Tissue Tropism

The cellular receptor for poliovirus was discovered after the transformation of mouse L-cells. These cells were altered with HeLa cell DNA, which led to susceptibility to poliovirus, of previously unsusceptible mice. The cDNA of the cellular receptor for poliovirus was later isolated and named CD155, or PVR. This receptor is a member of the immunoglobulin family, containing 3 Ig domains. CD155 is expressed in the following organs:

• Brain
• Spinal cord
• Heart
• Skeletal muscle
• Leukocytes
• Placenta
• Lung
• Ileum
• Liver
• Kidney

However, viral replication does not occur on all CD155-expressing cells. Possible explanations include:

• The detection method does not differentiate variants of the receptor. Some variants, despite detected, may not serve as receptor.
• Excess secretion of non-receptor isoforms of CD155 may compete for the virus, thereby inactivating the virus.
• Other ligands may compete with poliovirus for CD155.
• Physical barriers may block poliovirus access to CD155.
• Cytoplasm of certain cells may be inadequate for poliovirus replication.

CD155 positive tissues involved in the pathogenesis of the virus, include:

• Germinal centers of tonsils
• Germinal centers of Peyer's patches
• Epithelium of Peyer's patches
• Small intestine enterocytes
• Colon enterocytes

Intra-Cellular Tissue Tropism

Extra-cellular viral receptors are not the only determinants of tissue tropism. Genetic properties of the virus, which dictate the ability of poliovirus to replicate within a certain cell environment, are also an important contributor for tropism. Cellular host factors interact with the viral RNA, influencing replication. An example is polypyrimidine tract binding protein (PTB), which binds to IRES. This bound initiates a cap independent translation of the virus, and has also been implicated in alternative splicing mechanisms. Other factors within the host cell may alter the poliovirus replication cycle:

• Proteolytic processing of poliovirus proteins
• Lack of an host factor for viral replication
• Cease of protein synthesis within the host cell

Natural Reservoir

Humans are the only known reservoir of poliovirus, which is transmitted most frequently by persons with inapparent infections. There is no asymptomatic carrier state except in immune deficient persons.