The capsid protein of papillomavirus is used in vaccines that prevent cervical cancer.

Structures of papillomavirus capsid from cryoelectron microscopy. Capsomeres in orange are surrounded by five other capsomeres, and the ones in red are surrounded by six neighbors. The structure at the bottom is covered with many virus-specific antibodies (blue, only the Fab portion of the antibody is included in the structure). Download high quality TIFF image

Papillomaviruses are annoying pests that occasionally turn into deadly dangers. They attack cells in our skin and mucous membranes. When they infect cells, they ramp up the normal growth functions, often forming warts. Usually our defenses are able to get the infection under control, but in some exceptional cases, the virus persists and the unwanted growth can turn into cancer. Alarmingly, infection by a few particularly-virulent types of papillomavirus is the leading cause of cervical cancer. Fortunately, by studying these viruses, scientists have discovered highly effective ways to fight them.

A Tiny Danger

Papillomavirus is a small virus, with a simple capsid surrounding a circular DNA genome. The capsid (PDB entry 3j6r ) includes 360 copies of the major capsid chain, called L1. A second capsid chain, called L2, is found on the inside and may help with packaging the genome. The capsid structure, however, is not a typical quasisymmetrical virus . Instead, like simian virus 40 , the L1 chains form 72 pentameric “capsomeres”, which then interact with one another through long flexible tails.

VLPs and Vaccines

As soon as researchers discovered that these viruses cause cancer, they started looking for vaccines to fight them. Currently, the most effective approach is to create a “virus-like particle” that is composed of the L1 protein, but doesn’t include the DNA. The immune system builds defenses against these VLPs, but they are not infectious, so they are safe to use as a vaccine. PDB entry 6bt3 shows how antibodies coat the surface of the virus, making it unable to infect cells.

Perfecting Vaccines

Many types of papillomaviruses infect humans, and researchers have perfected several prophylactic vaccines to fight the most dangerous ones. The bivalent vaccine targets the two major types involved in cervical cancer, types 16 and 18. The quadrivalent vaccine adds types 6 and 11, which cause most genital warts, and the nonavalent vaccine adds an additional 5 oncogenic strains, giving it an even wider spectrum of activity. The capsids shown here are type 16 papillomavirus, the most common cause of cervical cancer worldwide.