# Let them eat virus: exploring how TBK1 (TANK binding kinase 1) enhances autophagic flux to promote autophagic degradation of coxsackievirus B

## TL;DR

This study shows that TBK1 helps control Coxsackievirus B by promoting autophagy to prevent viral spread, suggesting it could be a new target for antiviral treatments.

## Contribution

The study reveals a novel role of TBK1 in suppressing viral egress via autophagy, independent of its role in interferon signaling.

## Key findings

- TBK1 promotes autophagic flux to limit Coxsackievirus B egress from cells.
- Genetic inhibition of TBK1 increases viral infection and extracellular vesicle release in vitro and in mice.
- Amlexanox treatment enhances CVB-induced pancreatitis and infectious EV levels in mice.

## Abstract

Coxsackievirus B (CVB) is a common human enterovirus that can cause an array of systemic inflammatory diseases. We and others have demonstrated that macroautophagy/autophagy is activated during CVB infection leading to viral engulfment within autophagosomes. Interestingly, rather than this mechanism leading to bulk degradation of intracellular virus (also referred to as xenophagy), autophagosome-lysosomal fusion appears to be circumvented, leading to extracellular release of CVB via ejected autophagosomes. In our present study, we have found that TBK1 (TANK binding kinase 1) plays a role in limiting CVB infection by promoting autophagic flux to limit autophagy-based viral egress. This aspect of viral defense also appears to be independent of TBK1’s well-characterized involvement in interferon signaling. Indeed, genetic inhibition of TBK1 significantly enhances CVB infection in vitro and dramatically increases the amount of vesicle-bound virus being released from the cell. Furthermore, inhibition of TBK1 via amlexanox treatment markedly increases serum levels of infectious extracellular vesicles (EV) and severity of pancreatitis in CVB-infected mice. In all, the identification of TBK1’s involvement in the suppression of CVB egress pegs it as a promising therapeutic target for the development of novel antiviral strategies against not only CVB but potentially other viruses that exploit autophagy to promote viral spread.