Human papillomavirus (HPV), the virus that causes cervical cancer, enters the cells it infects inside a membrane-bound sac called the endosome, a new Yale study has found.
A team led by Daniel DiMaio, MD, PhD, deputy director of Yale Cancer Center and Waldemar Von Zedtwitz Professor of Genetics, and professor of molecular biophysics and biochemistry, and of therapeutic radiology, had previously found that the retromer protein shepherds HPV from the endosome to the nucleus by grabbing onto an HPV protein called L2. But it was unclear in what way the retromer, in the cytoplasm, could access L2, within the endosome.
In a study published Aug. 16 in Cell, DiMaio and his team reveal that a short portion of L2, a cell-penetrating peptide (CPP), protrudes from the endosome into the cytoplasm. When the CPP, which is next to L2’s retromer binding site, enters the cytoplasm, it brings along the retromer binding site and exposes it to the retromer, the researchers found. Drugs that target the CPP or retromer binding could potentially block HPV infection, DiMaio says, and his lab is testing that possibility.