A cylindrical arrangement of proteins protects a long strand of RNA in TMV

Tobacco mosaic virus, with the RNA genome in red. Download high quality TIFF image

Tobacco mosaic virus (TMV) has been at the center of virus research since its discovery over a hundred years ago. TMV was the first virus to be discovered. Late in the 19th century, researchers found that a tiny infectious agent, too small to be a bacterium, was the cause of a disease of tobacco plants. It then took 30 years of work before the nature of this mysterious agent became apparent. In a Nobel-prize-winning study, Wendell Stanley coaxed the virus to form crystals, and discovered that it was composed primarily of protein. Others quickly discovered that there was also RNA in the virus. Then, many prominent structural researchers (including J. D. Bernal, Rosalind Franklin, Ken Holmes, Aaron Klug, Don Caspar, and Gerald Stubbs) used X-ray diffraction and electron microscopy to probe the structure of the virus.

A Helical Virus

2tmv 2om3 Several structures of the whole tobacco mosaic virus are available in the PDB, including the ground-breaking one solved by X-ray fiber diffraction (shown here from PDB entry), and a recent structure solved by analysis of many electron micrographs (PDB entry). The virus is composed of one strand of RNA (shown in red) wrapped inside a sheath of protein (shown in blue). The protein coat is composed of about 2130 copies of a small protein, which stack like bricks in a cylindrical chimney. The RNA strand encodes four proteins, which together orchestrate the life cycle of the virus. These include two proteins that replicate the viral RNA, a protein that transports the RNA from cell to cell, spreading the infection, and the capsid protein seen in the PDB structures.

TMV Infection

Tobacco mosaic virus is very stable, so stable that it can survive for years in cigars and cigarettes made from infected leaves. The viral RNA is infectious by itself, but the addition of a protein coat protects the RNA from enzymes that would destroy it. The protein coat poses a problem, however: it must be removed once the virus gets inside a cell. TMV uses two tricks to release its RNA. As with many viruses, TMV has a chemical switch that causes the protein to change when the environment changes. The capsid protein has several clusters of acidic amino acids that are stable outside of cells, where calcium levels are high, but repel one another in the low-calcium conditions inside cells. This is enough to loosen the first few capsid proteins, releasing the end of the RNA. TMV then uses ribosomes as the engines to finish the job. As the ribosomes move down the strand, creating the first set of virus proteins, they displace the remaining capsid proteins.