Identification of a Cellular Host Factor Required for Human Sapovirus Infection

Kei Haga, Kitasato University

Kei Haga1, Miyabi Arai1, Reiko Todaka1, Yuya Fukuda2, Ryoka Ishiyama1, Kazuhiko Katayama1 1: Kitasato University, 2: Sapporo Medical University School of Medicine

Entry and Replication

We established an efficient Caco-2 cell-based culture system for human sapovirus (HuSaV) propagation by isolating highly susceptible clones, designated as Caco-2 MC and ME cells. In these clones, more than 90% of the cell population was infected and expressed the viral capsid protein. In contrast, we also isolated unsusceptible clones, named PG and PJ, and compared their transcriptomic profiles with those of the susceptible clones. This analysis identified 775 genes that were significantly upregulated (by more than 2-fold) and 508 genes that were significantly downregulated (by more than 2-fold) in MC and ME cells. We focused on the upregulated genes in the susceptible clones and investigated their potential roles in HuSaV replication. Using MC cells, we applied the CRISPR/Cas9 system to knock out these candidate genes and assessed their impact on HuSaV susceptibility. Notably, knockout of one particular gene significantly impaired HuSaV replication—including genogroups GI, GII, and GV—in MC cells. Furthermore, ectopic expression of this gene in unsusceptible cell lines enhanced their susceptibility to HuSaV infection.
In this presentation, we will reveal the identity of this key gene and further elucidate its role in HuSaV replication.