Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry.

Human papillomavirus (HPV) is a non-enveloped virus composed of a circular DNA genome and two capsid proteins, L1 and L2. Multiple interactions between its capsid proteins and host cellular proteins are required for infectious HPV entry, including cell attachment and internalization, intracellular t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yoshiyuki Ishii, Tomomi Nakahara, Michiyo Kataoka, Rika Kusumoto-Matsuo, Seiichiro Mori, Takamasa Takeuchi, Iwao Kukimoto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/64b62148c9c745b193927ffe803b4302
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:64b62148c9c745b193927ffe803b4302
record_format	dspace
spelling	oai:doaj.org-article:64b62148c9c745b193927ffe803b43022021-11-18T08:46:25ZIdentification of TRAPPC8 as a host factor required for human papillomavirus cell entry.1932-620310.1371/journal.pone.0080297https://doaj.org/article/64b62148c9c745b193927ffe803b43022013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244674/?tool=EBIhttps://doaj.org/toc/1932-6203Human papillomavirus (HPV) is a non-enveloped virus composed of a circular DNA genome and two capsid proteins, L1 and L2. Multiple interactions between its capsid proteins and host cellular proteins are required for infectious HPV entry, including cell attachment and internalization, intracellular trafficking and viral genome transfer into the nucleus. Using two variants of HPV type 51, the Ma and Nu strains, we have previously reported that MaL2 is required for efficient pseudovirus (PsV) transduction. However, the cellular factors that confer this L2 dependency have not yet been identified. Here we report that the transport protein particle complex subunit 8 (TRAPPC8) specifically interacts with MaL2. TRAPPC8 knockdown in HeLa cells yielded reduced levels of reporter gene expression when inoculated with HPV51Ma, HPV16, and HPV31 PsVs. TRAPPC8 knockdown in HaCaT cells also showed reduced susceptibility to infection with authentic HPV31 virions, indicating that TRAPPC8 plays a crucial role in native HPV infection. Immunofluorescence microscopy revealed that the central region of TRAPPC8 was exposed on the cell surface and colocalized with inoculated PsVs. The entry of Ma, Nu, and L2-lacking PsVs into cells was equally impaired in TRAPPC8 knockdown HeLa cells, suggesting that TRAPPC8-dependent endocytosis plays an important role in HPV entry that is independent of L2 interaction. Finally, expression of GFP-fused L2 that can also interact with TRAPPC8 induced dispersal of the Golgi stack structure in HeLa cells, a phenotype also observed by TRAPPC8 knockdown. These results suggest that during viral intracellular trafficking, binding of L2 to TRAPPC8 inhibits its function resulting in Golgi destabilization, a process that may assist HPV genome escape from the trans-Golgi network.Yoshiyuki IshiiTomomi NakaharaMichiyo KataokaRika Kusumoto-MatsuoSeiichiro MoriTakamasa TakeuchiIwao KukimotoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e80297 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshiyuki Ishii Tomomi Nakahara Michiyo Kataoka Rika Kusumoto-Matsuo Seiichiro Mori Takamasa Takeuchi Iwao Kukimoto Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry.
description	Human papillomavirus (HPV) is a non-enveloped virus composed of a circular DNA genome and two capsid proteins, L1 and L2. Multiple interactions between its capsid proteins and host cellular proteins are required for infectious HPV entry, including cell attachment and internalization, intracellular trafficking and viral genome transfer into the nucleus. Using two variants of HPV type 51, the Ma and Nu strains, we have previously reported that MaL2 is required for efficient pseudovirus (PsV) transduction. However, the cellular factors that confer this L2 dependency have not yet been identified. Here we report that the transport protein particle complex subunit 8 (TRAPPC8) specifically interacts with MaL2. TRAPPC8 knockdown in HeLa cells yielded reduced levels of reporter gene expression when inoculated with HPV51Ma, HPV16, and HPV31 PsVs. TRAPPC8 knockdown in HaCaT cells also showed reduced susceptibility to infection with authentic HPV31 virions, indicating that TRAPPC8 plays a crucial role in native HPV infection. Immunofluorescence microscopy revealed that the central region of TRAPPC8 was exposed on the cell surface and colocalized with inoculated PsVs. The entry of Ma, Nu, and L2-lacking PsVs into cells was equally impaired in TRAPPC8 knockdown HeLa cells, suggesting that TRAPPC8-dependent endocytosis plays an important role in HPV entry that is independent of L2 interaction. Finally, expression of GFP-fused L2 that can also interact with TRAPPC8 induced dispersal of the Golgi stack structure in HeLa cells, a phenotype also observed by TRAPPC8 knockdown. These results suggest that during viral intracellular trafficking, binding of L2 to TRAPPC8 inhibits its function resulting in Golgi destabilization, a process that may assist HPV genome escape from the trans-Golgi network.
format	article
author	Yoshiyuki Ishii Tomomi Nakahara Michiyo Kataoka Rika Kusumoto-Matsuo Seiichiro Mori Takamasa Takeuchi Iwao Kukimoto
author_facet	Yoshiyuki Ishii Tomomi Nakahara Michiyo Kataoka Rika Kusumoto-Matsuo Seiichiro Mori Takamasa Takeuchi Iwao Kukimoto
author_sort	Yoshiyuki Ishii
title	Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry.
title_short	Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry.
title_full	Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry.
title_fullStr	Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry.
title_full_unstemmed	Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry.
title_sort	identification of trappc8 as a host factor required for human papillomavirus cell entry.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/64b62148c9c745b193927ffe803b4302
work_keys_str_mv	AT yoshiyukiishii identificationoftrappc8asahostfactorrequiredforhumanpapillomaviruscellentry AT tomominakahara identificationoftrappc8asahostfactorrequiredforhumanpapillomaviruscellentry AT michiyokataoka identificationoftrappc8asahostfactorrequiredforhumanpapillomaviruscellentry AT rikakusumotomatsuo identificationoftrappc8asahostfactorrequiredforhumanpapillomaviruscellentry AT seiichiromori identificationoftrappc8asahostfactorrequiredforhumanpapillomaviruscellentry AT takamasatakeuchi identificationoftrappc8asahostfactorrequiredforhumanpapillomaviruscellentry AT iwaokukimoto identificationoftrappc8asahostfactorrequiredforhumanpapillomaviruscellentry
_version_	1718421324450234368

Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry.

Ejemplares similares