# Hijacking a cellular highway: non-lipidated LC3 proteins and PCNT (pericentrin) drive influenza a virus uncoating

## TL;DR

This paper shows that non-lipidated LC3 proteins and PCNT help influenza A virus uncoat in host cells, revealing a new role for these proteins outside of autophagy.

## Contribution

The study identifies a novel, autophagy-independent role for non-lipidated LC3s and PCNT in viral uncoating.

## Key findings

- Non-lipidated LC3s and PCNT form a dynein adaptor complex that facilitates influenza A virus uncoating at late endosomes.
- The function of LC3s in this process does not require Atg8ylation or the core autophagy machinery.
- PCNT's role in viral uncoating is independent of its centrosomal localization.

## Abstract

MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) proteins have long been thought to carry out their cellular and organismal functions, including macroautophagy/autophagy, exclusively in their lipidated form, also referred to as Atg8ylation. They are anchored mainly to the phosphatidylethanolamine present in membranes through the action of two ubiquitin-like conjugation systems. Our recent work, however, uncovered a role of non-lipidated LC3s during influenza A virus (IAV) infection. We revealed that LC3s, together with the centrosomal scaffold protein PCNT (pericentrin), form a dynein adaptor complex that facilitates IAV uncoating at late endosomes (LEs). We also showed that co-opting the LC3s-PCNT complex is an alternative strategy to aggresome processing machinery (APM) hijacking via HDAC6, allowing IAV to exploit the force generated by dynein-dependent motors for virion uncoating and genome delivery in the host cytoplasm. Notably, the function of LC3s in IAV uncoating does not require their Atg8ylation or the core autophagy machinery, and PCNT’s role is independent from its centrosomal localization. These findings redefine LC3s as multifunctional adaptor proteins and reveal how viruses can co-opt centrosome assembly machinery components for host invasion.

Abbreviation: AKAP9/AKAP450- A-kinase anchoring protein 9; APM- aggresome processing machinery; IAV- influenza A virus; LC3s-I- non-lipidated LC3s; Les- late endosomes; MAP1LC3/LC3s-microtubule associated protein 1 light chain 3 proteins; MT-microtubule; NEU- neuraminidase; PCNT-pericentrin; TNPO1-transportin 1; vRNP-viral ribonucleoprotein