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  • Foot-and-mouth disease virus induces PERK-mediated autophagy to suppress the antiviral interferon response.

Foot-and-mouth disease virus induces PERK-mediated autophagy to suppress the antiviral interferon response.

Journal of cell science (2020-06-03)
Huildore Bommanna Ranjitha, Veena Ammanathan, Neha Guleria, Madhusudan Hosamani, B Parameshwaraiah Sreenivasa, Valiya Valappil Dhanesh, Rashmi Santhoshkumar, B K Chandrasekhar Sagar, Bishnu Prasad Mishra, Raj Kumar Singh, Aniket Sanyal, Ravi Manjithaya, Suresh H Basagoudanavar
ABSTRACT

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 the unfolded protein response (UPR), in turn inducing autophagy to restore cellular homeostasis. We observed that inhibition of BiP (also known as HSPA5 and GRP78), 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 the PKR-like ER kinase (PERK; also known as EIF2AK3)-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 [the lipidated form of LC3B (also known as MAP1LC3B)]. 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 the UPR and autophagy by pharmacological and genetic approaches resulted in reduced numbers of viral progeny, by enhancing the antiviral interferon response. Taken together, this study underscores the prospect of exploring PERK-mediated autophagy as an antiviral target.

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Anti-Rabbit IgG - Atto 633 antibody produced in goat, 1 mg/mL IgG
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Kanamycin sulfate from Streptomyces kanamyceticus, powder, BioReagent, suitable for cell culture, suitable for plant cell culture