Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity

ABSTRACT The route taken by papillomaviruses from the cell surface to the nucleus during infection is incompletely understood. Here, we developed a novel human papillomavirus 16 (HPV16) pseudovirus in which the carboxy terminus of the minor capsid protein L2 is exposed on the exterior of the intact...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wei Zhang, Teymur Kazakov, Andreea Popa, Daniel DiMaio
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8d04ebcfd83442be8aae0219556ef21e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8d04ebcfd83442be8aae0219556ef21e
record_format	dspace
spelling	oai:doaj.org-article:8d04ebcfd83442be8aae0219556ef21e2021-11-15T15:45:55ZVesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity10.1128/mBio.01777-142150-7511https://doaj.org/article/8d04ebcfd83442be8aae0219556ef21e2014-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01777-14https://doaj.org/toc/2150-7511ABSTRACT The route taken by papillomaviruses from the cell surface to the nucleus during infection is incompletely understood. Here, we developed a novel human papillomavirus 16 (HPV16) pseudovirus in which the carboxy terminus of the minor capsid protein L2 is exposed on the exterior of the intact capsid prior to cell binding. With this pseudovirus, we used the proximity ligation assay immune detection technique to demonstrate that during entry HPV16 L2 traffics into and out of the early endosome prior to Golgi localization, and we demonstrated that L2 enters the endoplasmic reticulum during entry. The cellular membrane-associated protease, γ-secretase, is required for infection by HPV16 pseudovirus and authentic HPV16. We also showed that inhibition of γ-secretase does not interfere substantively with virus internalization, initiation of capsid disassembly, entry into the early endosome, or exit from this compartment, but γ-secretase is required for localization of L2 and viral DNA to the Golgi apparatus and the endoplasmic reticulum. These results show that incoming HPV16 traffics sequentially from the cell surface to the endosome and then to the Golgi apparatus and the endoplasmic reticulum prior to nuclear entry. IMPORTANCE The human papillomaviruses are small nonenveloped DNA viruses responsible for approximately 5% of all human cancer deaths, but little is known about the process by which these viruses transit from the cell surface to the nucleus. Here we show that incoming HPV16, the most common high-risk HPV, traffics though a series of vesicular compartments during infectious entry, including the endosome, Golgi apparatus, and endoplasmic reticulum. Furthermore, we show that γ-secretase, a cellular membrane-associated protease, is required for entry of the L2 minor capsid protein and viral DNA into the Golgi apparatus and endoplasmic reticulum. These studies reveal a new pathway of cell entry by DNA viruses and suggest that components of this pathway are candidate antiviral targets.Wei ZhangTeymur KazakovAndreea PopaDaniel DiMaioAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 5 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Wei Zhang Teymur Kazakov Andreea Popa Daniel DiMaio Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity
description	ABSTRACT The route taken by papillomaviruses from the cell surface to the nucleus during infection is incompletely understood. Here, we developed a novel human papillomavirus 16 (HPV16) pseudovirus in which the carboxy terminus of the minor capsid protein L2 is exposed on the exterior of the intact capsid prior to cell binding. With this pseudovirus, we used the proximity ligation assay immune detection technique to demonstrate that during entry HPV16 L2 traffics into and out of the early endosome prior to Golgi localization, and we demonstrated that L2 enters the endoplasmic reticulum during entry. The cellular membrane-associated protease, γ-secretase, is required for infection by HPV16 pseudovirus and authentic HPV16. We also showed that inhibition of γ-secretase does not interfere substantively with virus internalization, initiation of capsid disassembly, entry into the early endosome, or exit from this compartment, but γ-secretase is required for localization of L2 and viral DNA to the Golgi apparatus and the endoplasmic reticulum. These results show that incoming HPV16 traffics sequentially from the cell surface to the endosome and then to the Golgi apparatus and the endoplasmic reticulum prior to nuclear entry. IMPORTANCE The human papillomaviruses are small nonenveloped DNA viruses responsible for approximately 5% of all human cancer deaths, but little is known about the process by which these viruses transit from the cell surface to the nucleus. Here we show that incoming HPV16, the most common high-risk HPV, traffics though a series of vesicular compartments during infectious entry, including the endosome, Golgi apparatus, and endoplasmic reticulum. Furthermore, we show that γ-secretase, a cellular membrane-associated protease, is required for entry of the L2 minor capsid protein and viral DNA into the Golgi apparatus and endoplasmic reticulum. These studies reveal a new pathway of cell entry by DNA viruses and suggest that components of this pathway are candidate antiviral targets.
format	article
author	Wei Zhang Teymur Kazakov Andreea Popa Daniel DiMaio
author_facet	Wei Zhang Teymur Kazakov Andreea Popa Daniel DiMaio
author_sort	Wei Zhang
title	Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity
title_short	Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity
title_full	Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity
title_fullStr	Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity
title_full_unstemmed	Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity
title_sort	vesicular trafficking of incoming human papillomavirus 16 to the golgi apparatus and endoplasmic reticulum requires γ-secretase activity
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/8d04ebcfd83442be8aae0219556ef21e
work_keys_str_mv	AT weizhang vesiculartraffickingofincominghumanpapillomavirus16tothegolgiapparatusandendoplasmicreticulumrequiresgsecretaseactivity AT teymurkazakov vesiculartraffickingofincominghumanpapillomavirus16tothegolgiapparatusandendoplasmicreticulumrequiresgsecretaseactivity AT andreeapopa vesiculartraffickingofincominghumanpapillomavirus16tothegolgiapparatusandendoplasmicreticulumrequiresgsecretaseactivity AT danieldimaio vesiculartraffickingofincominghumanpapillomavirus16tothegolgiapparatusandendoplasmicreticulumrequiresgsecretaseactivity
_version_	1718427530406395904

Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity

Ejemplares similares