Polio virus

Poliovirus, the causative agent of polio (also known as poliomyelitis), is a member virus of Enterovirus C, in the family of Picornaviridae. Poliovirus, the causative agent of polio (also known as poliomyelitis), is a member virus of Enterovirus C, in the family of Picornaviridae. Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is about 30 nm in diameter with icosahedral symmetry. Because of its short genome and its simple composition—only RNA and a nonenveloped icosahedral protein coat that encapsulates it, poliovirus is widely regarded as the simplest significant virus. Poliovirus was first isolated in 1909 by Karl Landsteiner and Erwin Popper. In 1981, the poliovirus genome was published by two different teams of researchers: by Vincent Racaniello and David Baltimore at MIT and by Naomi Kitamura and Eckard Wimmer at Stony Brook University. Poliovirus is one of the most well-characterized viruses, and has become a useful model system for understanding the biology of RNA viruses. Poliovirus infects human cells by binding to an immunoglobulin-like receptor, CD155 (also known as the poliovirus receptor or PVR) on the cell surface. Interaction of poliovirus and CD155 facilitates an irreversible conformational change of the viral particle necessary for viral entry. 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 by endocytosis. Immediately after internalization of the particle, the viral RNA is released. 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 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. The first IRES to be discovered was found in poliovirus RNA. Poliovirus mRNA is translated as one long polypeptide. This polypeptide is then autocleaved by internal proteases into about 10 individual viral proteins. Not all cleavages occur with the same efficiency. Therefore, the amounts of proteins produced by the polypeptide cleavage vary: for example, smaller amounts of 3Dpol are produced than those of capsid proteins, VP1–4. These individual viral proteins are: After translation, transcription and genome replication which involve a single process (synthesis of (+) RNA) is realized. For the infecting (+) RNA to be replicated, multiple copies of (−) RNA must be transcribed and then used as templates for (+) RNA synthesis. Replicative intermediates (RIs) which are an association of RNA molecules consisting of a template RNA and several growing RNAs of varying length, are seen in both the replication complexes for (−) RNAs and (+) RNAs. The primer for both (+) and (−) strand synthesis is the small protein VPg, which is uridylylated at the hydroxyl group of a tyrosine residue by the poliovirus RNA polymerase at a cis-acting replication element located in a stem-loop in the virus genome. Some of the (+) RNA molecules are used as templates for further (−) RNA synthesis, some function as mRNA, and some are destined to be the genomes of progeny virions. In the assembly of new virus particles (i.e. the packaging of progeny genome into a procapsid which can survive outside the host cell), including, respectively: Fully assembled poliovirus leaves the confines of its host cell by lysis 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.