Cotton leaf curl Multan virus βC1 Protein Induces Autophagy by Disrupting the Interaction of Autophagy-Related Protein 3 with Glyceraldehyde-3-Phosphate Dehydrogenases[OPEN]

Abstract

Autophagy plays an important role in plant-pathogen interactions. Several pathogens including viruses induce autophagy in plants, but the underpinning mechanism remains largely unclear. Furthermore, in virusplant interactions, viral factor(s) that induce autophagy have yet to be identified. Here, we report that the βC1 protein of Cotton leaf curl Multan betasatellite (CLCuMuB) interacts with cytosolic glyceraldehyde-3phosphate dehydrogenase (GAPC), a negative autophagic regulator, to induce autophagy in Nicotiana benthamiana. CLCuMuB βC1 bound to GAPCs and disrupted the interaction between GAPCs and autophagyrelated protein 3 (ATG3). A mutant βC1 protein (βC1 3A) in which I45, Y48, and I53 were all substituted with alanine (A), had a dramatically reduced binding capacity with GAPCs, failed to disrupt the GAPCs-ATG3 interactions and failed to induce autophagy. Furthermore, mutant virus carrying βC1 3A showed increased symptoms and viral DNA accumulation associated with decreased autophagy in plants. These results suggest that CLCuMuB βC1 activates autophagy by disrupting GAPCs-ATG3 interactions.

Friend or Enemy: A Dual Role of Autophagy in Plant Virus Infection

“…Silencing of ATG5 or ATG7 caused more severe symptoms and increased viral DNA accumulation (Haxim et al, 2017), indicating that autophagy may be a general antiviral mechanism against diverse geminiviruses. Recently, a study clarified the mechanism of CLCuMV-encoded βC1 inducing autophagy (Ismayil et al, 2020). Cytosolic glyceraldehyde-3phosphate dehydrogenase (GAPC), is a negative autophagy regulator that interacts with ATG3 to inhibit autophagy in N. benthamiana (Han et al, 2015).…”

“…Cytosolic glyceraldehyde-3phosphate dehydrogenase (GAPC), is a negative autophagy regulator that interacts with ATG3 to inhibit autophagy in N. benthamiana (Han et al, 2015). Wherever, βC1 interacts with GAPC by disrupting GAPCs-ATG3 interactions to activate autophagy pathway (Ismayil et al, 2020). Turnip mosaic virus (TuMV) of the potyvirus group also induces autophagy in plants.…”

A plant RNA virus activates selective autophagy in a UPR‐dependent manner to promote virus infection

“…In most cases, autophagy acts as one of the most ancient cell‐autonomous defence mechanisms to restrict virus infection. Such an antiviral role of autophagy has been demonstrated in several plant species against both DNA and RNA viruses including cotton leaf curl Multan betasatellite virus (CLCuMuB), cauliflower mosaic virus (CaMV), turnip mosaic virus (TuMV) and cucumber mosaic virus (CMV) (Nakahara et al ., 2012; Hafrén et al ., 2017, 2018; Haxim et al ., 2017; Li et al ., 2018; Li et al ., 2020; Ismayil et al ., 2020a). Conversely, at least some RNA viruses seem to have evolved the ability to take advantage of the autophagy machinery to directly or indirectly facilitate their infection (Derrien et al ., 2012; Cheng & Wang, 2017; Fu et al ., 2018; Hafrén et al ., 2018; Yang et al ., 2018).…”

Transcriptomic and functional analyses reveal an antiviral role of autophagy during pepper mild mottle virus infection

“…For example, Neighbor of BRCA1 gene 1 (NBR1)-mediated selective autophagy pathway can inhibit cauliflower mosaic virus (CaMV) infection via binding to viral capsid protein and virus particles [ 23 ]. Autophagy can target the virulence factor βC1 of cotton leaf curl Multan virus (CLCuMuV) for degradation [ 24 ], and CLCuMuV βC1 protein induces autophagy by disrupting the interaction of autophagy-related gene 3 (ATG3) with glyceraldehyde-3-phosphate dehydrogenases [ 25 ].…”