S phingomyelin synthase 1 supports two steps of rubella virus life cycle

Mayuko Yagi; Minami Hama; Sayaka Ichii; Yurie Nakashima; Daiki Kanbayashi; Takako Kurata; Kosuke Yusa; Jun Komano

doi:10.1016/j.isci.2023.108267

S phingomyelin synthase 1 supports two steps of rubella virus life cycle

iScience. 2023 Oct 26;26(11):108267. doi: 10.1016/j.isci.2023.108267. eCollection 2023 Nov 17.

Authors

Mayuko Yagi¹, Minami Hama¹, Sayaka Ichii¹, Yurie Nakashima¹, Daiki Kanbayashi², Takako Kurata², Kosuke Yusa³, Jun Komano¹

Affiliations

¹ Department of Microbiology and Infection Control, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki City, Osaka 569-1041, Japan.
² Osaka Institute of Public Health, Morinomiya Center, 1-3-69, Nakamichi, Higashinari-ku, Osaka 537-0025, Japan.
³ Stem Cell Genetics, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

Abstract

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.

Keywords: Molecular biology; Virology.