In the late 1970s, scientists were divided on how viruses enter and infect host cells. Some investigators thought viruses were directly penetrating the cell membrane into the cytoplasm, while others argued the pathogens were first engulfed into clathrin-coated pits. As evidence, both sides used static electron microscopy images, which told different stories "depending on how you took the pictures," says Ari Helenius, a professor of biochemistry at the Swiss Federal Institute of Technology (ETH) in Zurich.
In 1980, Helenius, then at the European Molecular Biology Laboratory in Germany, and colleagues combined a storyboard of electron microscopy snapshots with in vivo and in vitro biochemical analyses to describe the complete infection pathway of the Semliki Forest Virus, a simple animal virus. It turns out the virus entered cells via endocytosis in clathrin-coated vesicles, then made its way into larger vacuoles, and released its genome into the cytoplasm, depending on pH. The ...