Calmodulin-like 5 promotes PEDV replication by regulating late-endosome synthesis and innate immune response

Wen-Jun Tian; Xiu-Zhong Zhang; Jing Wang; Jian-Feng Liu; Fu-Huang Li; Xiao-Jia Wang

doi:10.1016/j.virs.2024.05.006

June 2024

Citation: Wen-Jun Tian, Xiu-Zhong Zhang, Jing Wang, Jian-Feng Liu, Fu-Huang Li, Xiao-Jia Wang. Calmodulin-like 5 promotes PEDV replication by regulating late-endosome synthesis and innate immune response .VIROLOGICA SINICA, 2024, 39(3) : 501-512. http://dx.doi.org/10.1016/j.virs.2024.05.006

Calmodulin-like 5 promotes PEDV replication by regulating late-endosome synthesis and innate immune response

Wen-Jun Tian ^a ,
Xiu-Zhong Zhang ^a ,
Jing Wang ^a ,
Jian-Feng Liu ^{b
,,} ,
Fu-Huang Li ^{c
,,} ,
Xiao-Jia Wang ^{a
,,}

a. National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
b. College of Animal Science and Technology, China Agricultural University, Beijing 100193, China;
c. Beijing General Station of Animal Husbandry Service (South Section), Beijing, 102218, China

Corresponding author: Jian-Feng Liu, liujf@cau.edu.cn
Fu-Huang Li, lfh5118@126.com
Xiao-Jia Wang, wangxj@cau.edu.cn
Received Date: 06 December 2023
Accepted Date: 15 May 2024
Available online: 23 May 2024

Abstract

The infection caused by porcine epidemic diarrhea virus (PEDV) is associated with high mortality in piglets worldwide. Host factors involved in the efficient replication of PEDV, however, remain largely unknown. Our recent proteomic study in the virus-host interaction network revealed a significant increase in the accumulation of CALML5 (EF-hand protein calmodulin-like 5) following PEDV infection. A further study unveiled a biphasic increase of CALML5 in 2 and 12 h after viral infection. Similar trends were observed in the intestines of piglets in the early and late stages of the PEDV challenge. Moreover, CALML5 depletion reduced PEDV mRNA and protein levels, leading to a one-order-of-magnitude decrease in virus titer. At the early stage of PEDV infection, CALML5 affected the endosomal trafficking pathway by regulating the expression of endosomal sorting complex related cellular proteins. CALML5 depletion also suppressed IFN-β and IL-6 production in the PEDV-infected cells, thereby indicating its involvement in negatively regulating the innate immune response. Our study reveals the biological function of CALML5 in the virology field and offers new insights into the PEDV-host cell interaction.
- Porcine epidemic diarrhea virus(PEDV)
- , EF-hand protein calmodulin-like 5(CALML5)
- , Late endosomes
- , Innate immune response

Electronic Supplementary Material

10.1016j.virs.2024.05.006-ESM.docx
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