Poliovirus - Replication Cycle

Replication Cycle

Poliovirus infects human cells by binding to an immunoglobulin-like receptor, CD155, (also known as the poliovirus receptor (PVR)) on the cell surface. Interaction of poliovirus and CD155 facilitates an irreversible conformational change of the viral particle necessary for viral entry. The precise mechanism poliovirus uses to enter the host cell has not been firmly established. Attached to the host cell membrane, entry of the viral nucleic acid was thought to occur one of two ways: via the formation of a pore in the plasma membrane through which the RNA is then “injected” into the host cell cytoplasm, or that the virus is taken up by receptor-mediated endocytosis. Recent experimental evidence supports the latter hypothesis and suggests that poliovirus binds to CD155 and is taken up via endocytosis. Immediately after internalization of the particle, the viral RNA is released. However, any mechanism by which poliovirus enters the cell is very inefficient; as an infection is initiated only about 1% of the time.

Poliovirus is a positive stranded RNA virus. Thus the genome enclosed within the viral particle can be used as messenger RNA and immediately translated by the host cell. On entry the virus hijacks the cell's translation machinery; causing inhibition of cellular protein synthesis in favor of virus–specific protein production. Unlike the host cell's mRNAs the 5' end of poliovirus RNA is extremely long—over 700 nucleotides—and is highly structured. This region of the viral genome is called internal ribosome entry site (IRES) and it directs translation of the viral RNA. Genetic mutations in this region prevent viral protein production.

Poliovirus mRNA is translated as one long polypeptide. This polypeptide is then auto-cleaved by internal proteases into approximately 10 individual viral proteins, including:

• 3Dpol, an RNA dependent RNA polymerase whose function is to copy and multiply the viral RNA genome.
• 2Apro and 3Cpro/3CDpro, proteases which cleave the viral polypeptide.
• VPg (3B), a small protein that binds viral RNA and is necessary for synthesis of viral positive and negative strand RNA.
• 2BC, 2B, 2C, 3AB, 3A, 3B proteins which comprise the protein complex needed for virus replication.
• VP0, VP1, VP2, VP3, VP4 proteins of the viral capsid.

The assembly of new virus particles, (i.e. the packaging of progeny genome into a capsid which can survive outside the host cell) is not fully understood. Fully assembled poliovirus leaves the confines of its host cell 4 to 6 hours following initiation of infection in cultured mammalian cells. The mechanism of viral release from the cell is unclear, but each dying cell can release up to 10,000 polio virions.