Open AccessFoot-and-mouth disease virus induces PERK mediated autophagy to suppress antiviral interferon response
Author(s) -
Huildore Bommanna Ranjitha,
Veena Ammanathan,
Neha Guleria,
M. Hosamani,
B.P. Sreenivasa,
V.V. Dhanesh,
Rashmi Santhoshkumar,
B K Chandrasekhar Sagar,
Bishnu Prasad Mishra,
Raj Kumar Singh,
Aniket Sanyal,
Ravi Manjithaya,
Suresh H. Basagoudanavar
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.240622
Subject(s) - autophagy , unfolded protein response , biology , protein kinase r , interferon , foot and mouth disease virus , eif 2 kinase , endoplasmic reticulum , viral replication , virology , virus , microbiology and biotechnology , gene knockdown , protein kinase a , kinase , apoptosis , genetics , cyclin dependent kinase 2 , mitogen activated protein kinase kinase
Foot-and-mouth disease virus (FMDV) is a picornavirus that causes contagious acute infection in cloven-hoofed animals. FMDV replication associated viral protein expression induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR), in turn inducing autophagy to restore cellular homeostasis. We observed that inhibition of BiP, a master regulator of ER stress and UPR, decreased FMDV infection confirming their involvement. Further, we show that the FMDV infection induces UPR mainly through PKR-like ER kinase (PERK)-mediated pathway. Knockdown of PERK and chemical inhibition of PERK activation resulted in decreased expression of FMDV proteins along with the reduction of autophagy marker protein LC3B-II. There are conflicting reports on the role of autophagy in FMDV multiplication. Our study systematically demonstrates that during FMDV infection, PERK mediated UPR stimulated an increased level of endogenous LC3B-II and turnover of SQSTM1, thus confirming the activation of functional autophagy. Modulation of UPR and autophagy by pharmacological and genetic approaches resulted in reduced viral progeny, by enhancing antiviral interferon response. Taken together, this study underscores the prospect of exploring the PERK mediated autophagy as an antiviral target.