Autophagy Inhibition Mediated By Human Cytomegalovirus Infection In The Context Of Epithelial Renal Cells

LOPEZ GIULIANI, A.C.; ESCLATINE, A.; COLOMBO, MARÍA I.; ANA CLARA GARCÍA SAMARTINO; DELGUI, LAURA R.

Simposio; II Simposio Internacional de Medicina Traslacional; 2019

Autophagy is a tightly regulated catabolic process involved in numerous physiological and physiopathological mechanisms. In the context of in our collaborative work, we demonstrated that Human Cytomegalovirus (HCMV) modulates autophagy with a beneficial role for the virus replication. HCMV is a ubiquitous herpesvirus that commonly infects people. However, it is also the most common agent responsible for congenital infections and represents the most important viral infection complicating solid organ transplantations, especially kidney grafts, causing a great impact in the health area.In order to connect our previous observations to the physiopathology of HCMV infections in vivo, we decided to particularly focus on renal infections, since HCMV causes life-threatening diseases after kidney transplantation, by far the most frequently carried out transplantation globally. We developed a model of infection of HK-2 cells, a cell line derived from human proximal tubule, by using an HCMV strain named TB40E, known to more efficiently infect epithelial cells than the classical laboratory strain AD169. We showed that HK-2 cells are infected by HCMV, express different viral proteins but we did not observe any infectious viral particle in the extracellular compartment. Concordantly with the HCMV name, coming from the appearance of its cytopathic effect in cell culture (from the Greek, ?cyto? means ?cell,? and ?megalo? refers to ?giant? size), HCMV-infected HK-2 cells became significantly bigger than the non-infected ones. Furthermore, data obtained by us suggest that autophagy is inhibited by HCMV in HK-2 cells whereas ciliogenesis (primary cilium biogenesis) is not modified.Our results suggest that autophagy inhibition induced by HCMV in renal epithelial cells leads to deregulation of cellular volume and, consequently, loss of function of renal cells. Our further findings could provide in vitro evidence for a pathogenic mechanism that explains the clinical association between HCMV infection, autophagy inhibition, and adverse renal allograft outcome.