Clathrin-mediated endocytosis is a mechanism used for the invasion of cells by a variety of viruses.
Mortalin protein is involved in a variety of cellular functions and plays a role in
viral infection. In this study, we found that
mortalin significantly inhibited the replication of porcine epidemic diarrhea virus (PEDV) through restricting virus entry. Mechanistically, a biochemical interaction between the carboxyl terminus of
mortalin and
clathrin heavy chain (CLTC) was been found, and
mortalin could induce CLTC degradation through the proteasomal pathway, thereby inhibiting the
clathrin-mediated endocytosis of PEDV into host cells. In addition, artificial changes in
mortalin expression affected the cell entry of
transferrin, further confirming the above results. Finally, we confirmed that this host-mounted
antiviral mechanism was broadly applicable to other viruses, such as
vesicular stomatitis virus (VSV), rotavirus (RV), and transmissible gastroenteritis virus (TGEV), which use the same
clathrin-mediated endocytic to entry. These results reveal a new function of
mortalin in inhibiting endocytosis, and provide a novel strategy for treating PEDV
infections.