Bacteriophage MS2

Genome The MS2 genome is one of the smallest known, consisting of 3569 nucleotides of single-stranded RNA. It consists of one copy of the maturation protein and 180 copies of the coat protein (organized as 90 dimers) arranged into an icosahedral shell with triangulation number T=3, protecting the genomic RNA inside. The virion has an isoelectric point (pI) of 3.9. The structure of the coat protein is a five-stranded β-sheet with two α-helices and a hairpin. When the capsid is assembled, the helices and hairpin face the exterior of the particle, while the β-sheet faces the interior. Life cycle MS2 infects enteric bacteria carrying the fertility (F) factor, a plasmid that allows cells to serve as DNA donors in bacterial conjugation. Genes on the F plasmid specifies the proteins of the F pilus, which includes the F-pilin protein that serves as the viral receptor. MS2 attaches to the F-pilin on the side of the pilus using its single maturation protein. Once the viral RNA has entered the cell, it begins to function as a messenger RNA for the production of phage proteins. The gene for the most abundant protein, the coat protein, can be immediately translated. The translation start of the replicase gene is normally hidden within RNA secondary structure, but can be transiently opened as ribosomes pass through the coat protein gene. Replicase translation is also shut down once large amounts of coat protein have been made; coat protein dimers bind and stabilize the RNA "operator hairpin", blocking the replicase start. The start of the maturation protein gene is accessible in RNA being replicated but hidden within RNA secondary structure in the completed MS2 RNA; this ensures translation of only a very few copies of maturation protein per RNA. Finally, the lysis protein gene can only be initiated by ribosomes that have completed translation of the coat protein gene and "slip back" to the start of the lysis protein gene, at about a 5% frequency. in fact, the complex of maturation protein and RNA is infectious. The assembly of the icosahedral shell or capsid from coat proteins can occur in the absence of RNA; however, capsid assembly is nucleated by coat protein dimer binding to the operator hairpin, and assembly occurs at much lower concentrations of coat protein when MS2 RNA is present. A LS dipeptide motif on the L protein is found throughout the genus Levivirus and appears to be essential to the lysis activity, although their different locations suggest that they have evolved independently. ==MS2 in History of Science and Use==

In 1961, MS2 was isolated by Alvin John Clark and recognized as an RNA-containing phage very similar to bacteriophage f2. In 1976, the MS2 genome was the first genome to be completely sequenced. This was accomplished by Walter Fiers and his team, building upon their earlier milestone in 1972 of the first gene to be completely sequenced, the MS2 coat protein. These sequences were determined at the RNA level. The first effort at a statistical analysis of the MS2 genome was a search for patterns in the nucleotide sequence. Several non-coding sequences were identified, however at the time of this investigation (1979), the functions of the non-coding patterns were unknown. Since 1998, the MS2 operator hairpin and coat protein have found utility in the detection of RNA in living cells (see MS2 tagging). MS2 and other viral capsids are also currently under investigation as agents in drug delivery, tumor imaging, and light harvesting applications. MS2, due to its structural similarities to noroviruses, its similar optimum proliferation conditions, and non-pathogenicity to humans, has been used as substitute for noroviruses in studies of disease transmission. == See also ==