γ-Secretase promotes membrane insertion of the human papillomavirus L2 capsid protein during virus infection
Year: 2018
Type: article
Abstract: Despite their importance as human pathogens, entry of human papillomaviruses (HPVs) into cells is poorly understood. The transmembrane protease γ-secretase executes a crucial function during the early stages of HPV infection, but the role of γ-secretase in infection and the identity of its critical substrate are unknown. Here we demonstrate that γ-secretase harbors a previously uncharacterized chaperone function, promoting low pH-dependent insertion of the HPV L2 capsid protein into endosomal membranes. Upon membrane insertion, L2 recruits the cytosolic retromer, which enables the L2 viral genome complex to enter the retrograde transport pathway and traffic to the Golgi en route for infection. Although a small fraction of membrane-inserted L2 is also cleaved by γ-secretase, this proteolytic event appears dispensable for HPV infection. Our findings demonstrate that γ-secretase is endowed with an activity that can promote membrane insertion of L2, thereby targeting the virus to the productive infectious pathway.
Source: The Journal of Cell Biology
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: The essential role of gamma-secretase in human papillomavirus infection, How polyomaviruses penetrate the ER membrane, Role of Retromer-mediated Retrograde Transport in HPV Entry, Molecular Basis of Cancer Virus Replication, Transformation, and Innate Defense, G8718966553, Mechanism of endosomal membrane penetration by Human Papillomavirus 16, A novel cytosolic chaperone complex in polyomavirus ER membrane transport, G9000132752
OpenAlex ID: W2883669998