The antiviral protein viperin interacts with the viral N protein to inhibit proliferation of porcine epidemic diarrhea virus

Abstract

In the early stage of virus infection, the pattern recognition receptor (PRR) signaling pathway of the host cell is activated to induce interferon production, activating interferon-stimulated genes (ISGs) that encode antiviral proteins that exert antiviral effects. Viperin is one of the innate antiviral proteins that exert broad-spectrum antiviral effects by various mechanisms. Porcine epidemic diarrhea virus (PEDV) is a coronavirus that causes huge losses to the pig industry. Research on early antiviral responses in the gastrointestinal tract is essential for developing strategies to prevent the spread of PEDV. In this study, we investigated the mechanisms of viperin in PEDV-infected IPEJ-C2 cells. Increased expression of interferon and viperin and decreased replication of PEDV with a clear reduction in the viral load were observed in PEDV-infected IPEC-J2 cells. Amino acids 1-50 of porcine viperin contain an endoplasmic reticulum signal sequence that allows viperin to be anchored to the endoplasmic reticulum and are necessary for its function in inhibiting PEDV proliferation. The interaction of the viperin S-adenosylmethionine domain with the N protein of PEDV was confirmed via confocal laser scanning microscopy and co-immunoprecipitation. This interaction might interfere with viral replication or assembly to reduce virus proliferation. Our results highlight a potential mechanism whereby viperin is able to inhibit PEDV replication and play an antiviral role in innate immunity.

Interferon Control of Human Coronavirus Infection and Viral Evasion: Mechanistic Insights and Implications for Antiviral Drug and Vaccine Development

“… Restricts viral replication and/or assembly via interactions with N proteins. [230] BST2 Inhibits the release of HCoV-229E and SARS-CoV-2 virion particles. Tethers virions on the cellular surfaces or intracellular membranes.…”

Poly(A)-Binding Protein Cytoplasmic 1 Inhibits Porcine Epidemic Diarrhea Virus Replication by Interacting with Nucleocapsid Protein

“…During virus invasion into host cells, a series of complex interactions occurs between the virus and the host cell, including the regulation and modification of the cell by the virus and antiviral action by the cellular factors. Up to now, several antiviral factors have been explored during PEDV infection, such as bone marrow stromal cell antigen 2, transferrin receptor 1, cholesterol 25-hydroxylase, GTPase-activating protein-binding protein 1, interleukin-11, and IFN-λ [12][13][14][15][16][17][18][19]. The study of host antiviral factors can help to better understand the host-virus interaction.…”

“…Tomatidine inhibits PEDV replication by targeting 3CL protease [14]. Viperin interacts with the viral N protein to inhibit PEDV proliferation [15]. Moreover, cholesterol 25-hydroxylase, GTPase-activating protein-binding protein 1, interleukin-11 and IFN-λ can regulate PEDV infection and replication [16][17][18][19].…”

Mechanisms of host type I interferon response modulation by the nucleocapsid proteins of alpha- and betacoronaviruses

“…Given the antagonizing role of PEDV N protein in the type I IFN response, it is not unexpected that this protein becomes a target of the host innate immune system. One study showed that viperin, an ISG induced by IRF1 and IRF3, interacts with the PEDV N protein and inhibits PEDV proliferation [ 47 ]. IRAV (IFN-regulated antiviral), BST-2 (bone marrow stromal cell antigen-2), and TRIM21 are three additional ISG proteins that have been shown to interact with the PEDV N protein [ 48 – 50 ].…”