Track topics on Twitter Track topics that are important to you
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.
This article was published in the following journal.
Name: The Journal of cell biology
Amyloid-β proteins deposition and aggregation occur in extracellular space and form neuritic plaques in Alzheimer's disease (AD) brain. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)/ ...
The President's Cancer Panel released a report in 2014 calling for communication strategies to promote the human papillomavirus vaccine among males and females. The purpose of this study was to (1) es...
Twenty years ago, Wolfe, Xia, and Selkoe identified two aspartate residues in Alzheimer's presenilin protein that constitute the active site of the γ-secretase complex. Mutations in the genes encodin...
Mitochondrial gene expression in Saccharomyces cerevisiae is responsible for the production of highly hydrophobic subunits of the oxidative phosphorylation system. Membrane insertion occurs co-transla...
Many staphylococcal bacteriophages encode a minor capsid protein between the genes for the portal and scaffolding proteins. In Staphylococcus aureus bacteriophage 80α, this protein, called gp44, is e...
RATIONALE: Vaccines made from human papillomavirus may help the body build an effective immune response to kill HIV cells. PURPOSE: This phase II trial is studying the side effects and ho...
A randomized, observer-blind non-inferiority trial to evaluate alternative human papillomavirus (HPV) vaccination schedules in young females in West Africa.
The purpose of the study is to determine the Human Papillomavirus (HPV) prevalence and HPV type distribution among women aged >= 18 years, attending out-patient health services for gynaeco...
The purpose of this study is to determine if maternal infection with human papillomavirus (HPV) is associated with pregnancy complications including spontaneous preterm delivery (sPTD), se...
The main risk factor for the development of cervical lesions is human papillomavirus (HPV) infection. Vaccination against human papillomavirus, which is offered to all girls aged 11 to 14,...
Vaccines or candidate vaccines used to prevent PAPILLOMAVIRUS INFECTIONS. Human vaccines are intended to reduce the incidence of UTERINE CERVICAL NEOPLASMS, so they are sometimes considered a type of CANCER VACCINES. They are often composed of CAPSID PROTEINS, especially L1 protein, from various types of ALPHAPAPILLOMAVIRUS.
A vaccine containing L1 capsid proteins from four types of HPV (ALPHAPAPILLOMAVIRUS), types 6, 11, 16 and 18 that is used to prevent infections from HUMAN PAPILLOMAVIRUSES of these subtypes.
A type of human papillomavirus especially associated with malignant tumors of the genital and RESPIRATORY MUCOSA.
Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PROTEIN precursors. PSEN2 mutations cause ALZHEIMER DISEASE type 4.
Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PROTEIN precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...