TY - JOUR
T1 - Mortalin restricts porcine epidemic diarrhea virus entry by downregulating clathrin-mediated endocytosis
AU - Fan, Baochao
AU - Zhu, Lin
AU - Chang, Xinjian
AU - Zhou, Jinzhu
AU - Guo, Rongli
AU - Zhao, Yongxiang
AU - Shi, Danyi
AU - Niu, Beibei
AU - Gu, Jun
AU - Yu, Zhengyu
AU - Song, Tao
AU - Luo, Chuping
AU - Ma, Zengjun
AU - Bai, Juan
AU - Zhou, Bin
AU - Ding, Siyuan
AU - He, Kongwang
AU - Li, Bin
N1 - Funding Information:
This work was supported by National Key Research and Development Program ( 2016YFD0500101 ), the Jiangsu province Natural Sciences Foundation ( BK20190003 ), National Natural Science Foundation of China ( 31872481 and 31802167 ), Jiangsu Agricultural Science and Technology Innovation Fund ( CX (19) 2020 ), Six talent peaks in jiangsu province ( NY-045 ) and Jiangsu Provincial Key Construction Laboratory of Probiotics Preparation ( JSYSZJ2017004 ).
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - CLTC
KW - Clathrin-mediated endocytosis
KW - Mortalin
KW - PEDV
UR - http://www.scopus.com/inward/record.url?scp=85073280419&partnerID=8YFLogxK
U2 - 10.1016/j.vetmic.2019.108455
DO - 10.1016/j.vetmic.2019.108455
M3 - Article
C2 - 31767073
AN - SCOPUS:85073280419
SN - 0378-1135
VL - 239
JO - Veterinary Microbiology
JF - Veterinary Microbiology
M1 - 108455
ER -