More effective treatments for cancer and viral diseases, better therapy for auto-immune conditions, and a deeper understanding of the body’s defences enabling the development of more tightly focused immunosuppressive drugs are some of the wide-ranging possibilities arising from research that has unravelled the molecular structure and function of the protein perforin, which is used by the body as a front-line weapon against viral infection. The focus of the work, published in Nature, can now switch to developing inhibitors and enhancers to regulate the molecule to medical advantage against cancer and other conditions such as cerebral malaria and juvenile diabetes.
Perforin is typically used by the immune system’s T-cells and natural killer cells to punch holes in the outer membranes of cells invaded by viruses. The immune system then uses these pores as access points for packages of toxic enzymes, or granzymes, which kill off the infected cells. The process prevents the replication and spread of virus particles within the body.
“This is a weapon of cleansing and death,” says Prof James Whisstock of Biochemistry and Molecular Biology at Monash University. “It’s the body’s key tool for killing off rogue cells.”
How these immune pore-forming proteins function has been a key question since the discovery of “haemolytic complement proteins” in the 1890s by...