Recently, a paper titled “A plant RNA virus activates selective autophagy in a UPR-dependent manner to promote virus infection” was published online by New Phytologist, which revealed that turnip mosaic virus (TuMV) activates and manipulates the unfolded protein response (UPR)-dependent NBR1-ATG8f autophagy to target the VRC to the tonoplast, promoting viral replication and virion accumulation. This work was accomplished by Prof. Li Fangfang and co-workers at IPP-CAAS.
Autophagy is an evolutionarily conserved pathway in eukaryotes that delivers unwanted cytoplasmic materials to the lysosome/vacuole for degradation/recycling. Stimulated autophagy emerges as an integral part of plant immunity against intracellular pathogens. TuMV is a single-stranded positive-sense (+ss) RNA virus belonging to the genus Potyvirus of the family Potyviridae, which represents the largest group of known plant RNA viruses and accounts for more than half of the viral crop damage in the world. Recently, we have shown that TuMV infection perturbs the expression of many key autophagy genes and that Beclin1 (ATG6) restricts TuMV infection through protein-protein interaction-based suppression and autophagy-mediated degradation of NIb. This study was designed to better understand the complex roles of autophagy in TuMV infection. We show that TuMV infection or transient expression of 6K2 alone upregulates the expression of the selective autophagy cargo adaptor gene NBR1 via activation of the IRE1/bZIP60 pathway. We demonstrate that NBR1 interacts selectively with TuMV NIb to promote viral infection. Furthermore, NBR1 physically interacts with ATG8f of both Nicotiana benthamiana and Arabidopsis, and this interaction likewise promotes TuMV replication. Moreover, we discover that in TuMV-infected cells, a large number of viral particles accumulate in the vacuole, and NbATG8f3 interacts with N. benthamiana tonoplast intrinsic protein 1 (NbTIP1), and the interaction complex together with NBR1 colocalizes to the tonoplast-associated VRC. Taken together our data suggest that TuMV takes advantage of NBR1-mediated selective autophagy through a cascade of protein-protein interactions to target the NIb-containing VRC to the tonoplast for viral replication and virion assembly.
A model to summarize how TuMV co-opts NBR1 autophagy to facilitate viral infection (Fig. 1). TuMV genome translation on the rough endoplasmic reticulum (ER) leads to the accumulation of viral proteins including 6K2 and the misfolded or unfolded viral proteins in the ER triggers the IRE/bZIP60 UPR, which further activates the high expression of ATGs. As a selective autophagy cargo receptor, stimulated NBR1 may compete against Beclin1 to interact with NIb, and together the autophagy adaptor ATG8f targets the NIb-containing replication vesicle to the vacuole independent of atuophagic degradation. The tonoplast-associated VRC undergoes robust viral genome translation/replication and virion assembly, leading to the accumulation of numerous viral particles shown as membrane-enclosed linear arrays in the vacuole.
This work was partially supported by the National Natural Science Foundation of China
Fig.1
