Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry.
Rab GTPases play key roles in controlling intracellular vesicular transport. GTP-bound Rab proteins support vesicle trafficking. Here, we report that, unlike cellular protein cargos, retromer-mediated delivery of human papillomaviruses (HPV) into the retrograde transport pathway during virus entry i...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2023-09-01
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Series: | PLoS Pathogens |
Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011648&type=printable |
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author | Jeongjoon Choi Daniel DiMaio |
author_facet | Jeongjoon Choi Daniel DiMaio |
author_sort | Jeongjoon Choi |
collection | DOAJ |
description | Rab GTPases play key roles in controlling intracellular vesicular transport. GTP-bound Rab proteins support vesicle trafficking. Here, we report that, unlike cellular protein cargos, retromer-mediated delivery of human papillomaviruses (HPV) into the retrograde transport pathway during virus entry is inhibited by Rab9a in its GTP-bound form. Knockdown of Rab9a inhibits HPV entry by modulating the HPV-retromer interaction and impairing retromer-mediated endosome-to-Golgi transport of the incoming virus, resulting in the accumulation of HPV in the endosome. Rab9a is in proximity to HPV as early as 3.5 h post-infection, prior to the Rab7-HPV interaction, and HPV displays increased association with retromer in Rab9a knockdown cells, even in the presence of dominant negative Rab7. Thus, Rab9a can regulate HPV-retromer association independently of Rab7. Surprisingly, excess GTP-Rab9a impairs HPV entry, whereas excess GDP-Rab9a reduces association between L2 and Rab9a and stimulates entry. These findings reveal that HPV and cellular proteins utilize the Rab9a host trafficking machinery in distinct ways during intracellular trafficking. |
first_indexed | 2024-03-11T18:22:27Z |
format | Article |
id | doaj.art-af80c2fc32d941bd906360490a681007 |
institution | Directory Open Access Journal |
issn | 1553-7366 1553-7374 |
language | English |
last_indexed | 2024-03-11T18:22:27Z |
publishDate | 2023-09-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS Pathogens |
spelling | doaj.art-af80c2fc32d941bd906360490a6810072023-10-15T05:31:48ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-09-01199e101164810.1371/journal.ppat.1011648Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry.Jeongjoon ChoiDaniel DiMaioRab GTPases play key roles in controlling intracellular vesicular transport. GTP-bound Rab proteins support vesicle trafficking. Here, we report that, unlike cellular protein cargos, retromer-mediated delivery of human papillomaviruses (HPV) into the retrograde transport pathway during virus entry is inhibited by Rab9a in its GTP-bound form. Knockdown of Rab9a inhibits HPV entry by modulating the HPV-retromer interaction and impairing retromer-mediated endosome-to-Golgi transport of the incoming virus, resulting in the accumulation of HPV in the endosome. Rab9a is in proximity to HPV as early as 3.5 h post-infection, prior to the Rab7-HPV interaction, and HPV displays increased association with retromer in Rab9a knockdown cells, even in the presence of dominant negative Rab7. Thus, Rab9a can regulate HPV-retromer association independently of Rab7. Surprisingly, excess GTP-Rab9a impairs HPV entry, whereas excess GDP-Rab9a reduces association between L2 and Rab9a and stimulates entry. These findings reveal that HPV and cellular proteins utilize the Rab9a host trafficking machinery in distinct ways during intracellular trafficking.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011648&type=printable |
spellingShingle | Jeongjoon Choi Daniel DiMaio Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry. PLoS Pathogens |
title | Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry. |
title_full | Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry. |
title_fullStr | Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry. |
title_full_unstemmed | Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry. |
title_short | Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry. |
title_sort | noncanonical rab9a action supports retromer mediated endosomal exit of human papillomavirus during virus entry |
url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011648&type=printable |
work_keys_str_mv | AT jeongjoonchoi noncanonicalrab9aactionsupportsretromermediatedendosomalexitofhumanpapillomavirusduringvirusentry AT danieldimaio noncanonicalrab9aactionsupportsretromermediatedendosomalexitofhumanpapillomavirusduringvirusentry |