Identification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen

ABSTRACT BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant pati...

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Autores principales:	Linbo Zhao, Michael J. Imperiale
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	BKPyV NRZ complex Rab18 siRNA screen syntaxin 18 virus trafficking Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fe4a3ae4a9a349739d747e73c5fa1048
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spelling	oai:doaj.org-article:fe4a3ae4a9a349739d747e73c5fa10482021-11-15T15:22:04ZIdentification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen10.1128/mSphereDirect.00291-172379-5042https://doaj.org/article/fe4a3ae4a9a349739d747e73c5fa10482017-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00291-17https://doaj.org/toc/2379-5042ABSTRACT BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis. To establish a successful infection in host cells, BKPyV must travel in retrograde transport vesicles to reach the nucleus. To make this happen, BKPyV requires the cooperation of host cell proteins. To further identify host factors associated with BKPyV entry and intracellular trafficking, we performed a whole-genome small interfering RNA screen on BKPyV infection of primary human renal proximal tubule epithelial cells. The results revealed the importance of Ras-related protein Rab18 and syntaxin 18 for BKPyV infection. Our subsequent experiments implicated additional factors that interact with this pathway and suggest a more detailed model of the intracellular trafficking process, indicating that BKPyV reaches the endoplasmic reticulum (ER) lumen through a retrograde transport pathway between the late endosome and the ER. IMPORTANCE Polyomaviruses bind to a group of specific gangliosides on the plasma membrane of the cell prior to being endocytosed. They then follow a retrograde trafficking pathway to reach the endoplasmic reticulum (ER). The viruses begin to disassemble in the ER and then exit the ER and move to the nucleus. However, the details of intracellular trafficking between the endosome and the ER are largely unknown. By implementing a whole human genome small interfering RNA screen, we identified Rab18, syntaxin 18, and the NRZ complex as key components in endosome-ER trafficking of the human polyomavirus BKPyV. These results serve to further elucidate the route BKPyV takes from outside the cell to its site of replication in the nucleus.Linbo ZhaoMichael J. ImperialeAmerican Society for MicrobiologyarticleBKPyVNRZ complexRab18siRNA screensyntaxin 18virus traffickingMicrobiologyQR1-502ENmSphere, Vol 2, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	BKPyV NRZ complex Rab18 siRNA screen syntaxin 18 virus trafficking Microbiology QR1-502
spellingShingle	BKPyV NRZ complex Rab18 siRNA screen syntaxin 18 virus trafficking Microbiology QR1-502 Linbo Zhao Michael J. Imperiale Identification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen
description	ABSTRACT BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis. To establish a successful infection in host cells, BKPyV must travel in retrograde transport vesicles to reach the nucleus. To make this happen, BKPyV requires the cooperation of host cell proteins. To further identify host factors associated with BKPyV entry and intracellular trafficking, we performed a whole-genome small interfering RNA screen on BKPyV infection of primary human renal proximal tubule epithelial cells. The results revealed the importance of Ras-related protein Rab18 and syntaxin 18 for BKPyV infection. Our subsequent experiments implicated additional factors that interact with this pathway and suggest a more detailed model of the intracellular trafficking process, indicating that BKPyV reaches the endoplasmic reticulum (ER) lumen through a retrograde transport pathway between the late endosome and the ER. IMPORTANCE Polyomaviruses bind to a group of specific gangliosides on the plasma membrane of the cell prior to being endocytosed. They then follow a retrograde trafficking pathway to reach the endoplasmic reticulum (ER). The viruses begin to disassemble in the ER and then exit the ER and move to the nucleus. However, the details of intracellular trafficking between the endosome and the ER are largely unknown. By implementing a whole human genome small interfering RNA screen, we identified Rab18, syntaxin 18, and the NRZ complex as key components in endosome-ER trafficking of the human polyomavirus BKPyV. These results serve to further elucidate the route BKPyV takes from outside the cell to its site of replication in the nucleus.
format	article
author	Linbo Zhao Michael J. Imperiale
author_facet	Linbo Zhao Michael J. Imperiale
author_sort	Linbo Zhao
title	Identification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen
title_short	Identification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen
title_full	Identification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen
title_fullStr	Identification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen
title_full_unstemmed	Identification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen
title_sort	identification of rab18 as an essential host factor for bk polyomavirus infection using a whole-genome rna interference screen
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/fe4a3ae4a9a349739d747e73c5fa1048
work_keys_str_mv	AT linbozhao identificationofrab18asanessentialhostfactorforbkpolyomavirusinfectionusingawholegenomernainterferencescreen AT michaeljimperiale identificationofrab18asanessentialhostfactorforbkpolyomavirusinfectionusingawholegenomernainterferencescreen
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Identification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen

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