Scientists at Cancer Research UK's London Research Institute (now part of the Francis Crick Institute) have found an unexpected role for a protein that helps viruses to invade host cells. They've discovered that the protein, clathrin, also enables virus particles that are leaving the cell to spread.
The team was led by Michael Way: "Many groups have shown that clathrin plays a role in entry of viruses into cells, but this is the first time clathrin has been shown to be involved in promoting the spread of a virus in this way."
The researchers used molecular biology methods to study a virus called vaccinia. The virus is part of the pox virus family and was used to create a vaccine to eradicate smallpox in the 1960s and 70s. Today, vaccinia virus is widely studied by scientists and used as a tool to deliver genes into cells.
Dr Way explained: "Like many pathogens, vaccinia virus hijacks the cellular processes of its host to assist the spread of infection. An important stage in this is its ability to form an 'actin tail' - a protein tail that acts to push virus particles onto neighbouring cells."
A cell membrane is a thin layer around the cell that keeps everything inside it separate from the outside environment and other cells - however certain proteins and other molecules are able to pass through the membrane.
The scientists found that the presence of clathrin helps to cluster proteins from the virus within the host cell's membrane. This kick-starts the process of an actin tail forming to propel the virus from one host cell to another.
The study also showed that if clathrin recruitment is blocked (meaning the protein isn't present at the host cell's membrane), the actin tail takes longer to form and is less stable, and the virus doesn't spread as well or as widely.
Dr Way added: "Our work has identified a new way in which viruses exploit clathrin for their own gain. The formation of actin structures is a common mechanism used by many pathogens to promote cell to cell spread, and therefore this work sets a precedent for future studies examining whether the exploitation of clathrin in this role is also widespread.
"Nonetheless, the ability of different viruses to take advantage of clathrin in different ways means it is an important avenue for future research aimed at stopping the spread of unwanted viruses."
The paper, Clathrin potentiates vaccinia-induced actin polymerisation to facilitate viral spread, was published in Cell Host and Microbe.
