Characterization of immortalized human podocytes infected with lentivirus as an in vitro model of viral infection-associated podocytopathy

A large number of studies have shown the association of kidney disease with viral infections in the body. Viral infections cause kidney injury in two manners, the systemic inflammation (cytokine storm) and the direct infection of kidney cells. Concerning direct viral infection of podocytes, the mechanism underlying virus-induced podocyte injury remains largely unknown and requires effective experimental models to facilitate its study. Here, we performed molecular characterization of immortalized human podocyte cell line (HPC) infected with lentivirus by RNA-seq. Bioinformatics analysis revealed a strong innate immune response in the cells, including interferon production and signaling. Meanwhile, activations of ferroptosis pathway and TNF-alpha signaling were also found, consistent with an impaired viability of the cells. Lentiviral infection also upregulated expression of APOL1 as observed in patients with HIV associated nephropathy (HIVAN) and diabetic nephropathy (DN). Interestingly, when the lentiviral infected cells were treated with Adriamycin (ADR), the ADR-associated signaling pathways were not interfered and remained activated as that in the cells treated with ADR only, suggesting that the virus and ADR have distinct mechanisms in damaging podocytes. Thus, the lentivirus-infected HPC cells represent a useful in vitro model of viral infection-associated podocytopathy.