Sphingomyelin synthase 1 supports two steps of rubella virus life cycle

Summary: Our knowledge of the regulatory mechanisms that govern the replication of the rubella virus (RV) in human cells is limited. To gain insight into the host-pathogen interaction, we conducted a loss-of-function screening using the CRISPR-Cas9 system in the human placenta-derived JAR cells. We...

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Main Authors: Mayuko Yagi, Minami Hama, Sayaka Ichii, Yurie Nakashima, Daiki Kanbayashi, Takako Kurata, Kosuke Yusa, Jun Komano
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223023441
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author Mayuko Yagi
Minami Hama
Sayaka Ichii
Yurie Nakashima
Daiki Kanbayashi
Takako Kurata
Kosuke Yusa
Jun Komano
author_facet Mayuko Yagi
Minami Hama
Sayaka Ichii
Yurie Nakashima
Daiki Kanbayashi
Takako Kurata
Kosuke Yusa
Jun Komano
author_sort Mayuko Yagi
collection DOAJ
description Summary: Our knowledge of the regulatory mechanisms that govern the replication of the rubella virus (RV) in human cells is limited. To gain insight into the host-pathogen interaction, we conducted a loss-of-function screening using the CRISPR-Cas9 system in the human placenta-derived JAR cells. We identified sphingomyelin synthase 1 (SGMS1 or SMS1) as a susceptibility factor for RV infection. Genetic knockout of SGMS1 rendered JAR cells resistant to infection by RV. The re-introduction of SGMS1 restored cellular susceptibility to RV infection. The restricted step of RV infection was post-endocytosis processes associated with the endosomal acidification. In the late phase of the RV replication cycle, the maintenance of viral persistence was disrupted, partly due to the attenuated viral gene expression. Our results shed light on the unique regulation of RV replication by a host factor during the early and late phases of viral life cycle.
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spelling doaj.art-00a52f3bb99047b380852346d0ab1f552023-11-04T04:18:42ZengElsevieriScience2589-00422023-11-012611108267Sphingomyelin synthase 1 supports two steps of rubella virus life cycleMayuko Yagi0Minami Hama1Sayaka Ichii2Yurie Nakashima3Daiki Kanbayashi4Takako Kurata5Kosuke Yusa6Jun Komano7Department of Microbiology and Infection Control, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki City, Osaka 569-1041, JapanDepartment of Microbiology and Infection Control, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki City, Osaka 569-1041, JapanDepartment of Microbiology and Infection Control, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki City, Osaka 569-1041, JapanDepartment of Microbiology and Infection Control, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki City, Osaka 569-1041, JapanOsaka Institute of Public Health, Morinomiya Center, 1-3-69, Nakamichi, Higashinari-ku, Osaka 537-0025, JapanOsaka Institute of Public Health, Morinomiya Center, 1-3-69, Nakamichi, Higashinari-ku, Osaka 537-0025, JapanStem Cell Genetics, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, JapanDepartment of Microbiology and Infection Control, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki City, Osaka 569-1041, Japan; Corresponding authorSummary: Our knowledge of the regulatory mechanisms that govern the replication of the rubella virus (RV) in human cells is limited. To gain insight into the host-pathogen interaction, we conducted a loss-of-function screening using the CRISPR-Cas9 system in the human placenta-derived JAR cells. We identified sphingomyelin synthase 1 (SGMS1 or SMS1) as a susceptibility factor for RV infection. Genetic knockout of SGMS1 rendered JAR cells resistant to infection by RV. The re-introduction of SGMS1 restored cellular susceptibility to RV infection. The restricted step of RV infection was post-endocytosis processes associated with the endosomal acidification. In the late phase of the RV replication cycle, the maintenance of viral persistence was disrupted, partly due to the attenuated viral gene expression. Our results shed light on the unique regulation of RV replication by a host factor during the early and late phases of viral life cycle.http://www.sciencedirect.com/science/article/pii/S2589004223023441VirologyMolecular biology
spellingShingle Mayuko Yagi
Minami Hama
Sayaka Ichii
Yurie Nakashima
Daiki Kanbayashi
Takako Kurata
Kosuke Yusa
Jun Komano
Sphingomyelin synthase 1 supports two steps of rubella virus life cycle
iScience
Virology
Molecular biology
title Sphingomyelin synthase 1 supports two steps of rubella virus life cycle
title_full Sphingomyelin synthase 1 supports two steps of rubella virus life cycle
title_fullStr Sphingomyelin synthase 1 supports two steps of rubella virus life cycle
title_full_unstemmed Sphingomyelin synthase 1 supports two steps of rubella virus life cycle
title_short Sphingomyelin synthase 1 supports two steps of rubella virus life cycle
title_sort sphingomyelin synthase 1 supports two steps of rubella virus life cycle
topic Virology
Molecular biology
url http://www.sciencedirect.com/science/article/pii/S2589004223023441
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