PEBP regulates balance between apoptosis and autophagy, enabling coexistence of arbovirus and insect vector

Abstract

Apoptosis and autophagy are two most prominent forms of programmed cell deaths (PCD) that have been implicated in antiviral immunity in vertebrate and plant hosts. Arboviruses are able to coexist with its arthropod vectors by coordinating the PCD immunity, but the regulatory mechanism involved is largely unknown. We found that the coat protein (CP) of an insect-borne plant virus TYLCV directly interacted with a phosphatidylethanolamine-binding protein (PEBP) of its insect vector whitefly to negatively influence the MAPK signaling cascade. As a result, the apoptosis was activated in whitefly which increased viral loading. Simultaneously, the PEBP4-CP interaction liberated ATG8, the hallmark of autophagy initiation, and eliminates arbovirus. Furthermore, apoptosis-promoted virus loading was compromised by agonist-induced autophagy, but autophagy-associated suppression on virus loading was unaffected by apoptosis agonist or inhibitor, suggesting that virus loading was predominantly determined by autophagy rather than by apoptosis. Our results demonstrated that maintaining a mild immune response by coordinating apoptosis and autophagy processes presumably could facilitate coexistence of the arbovirus and its insect vector. Taken together, immune homeostasis shaped by two types of PCD may facilitate the arbovirus preservation within the insect vector.Graphical abstractHighlightsInteraction between whitefly PEBP4 and TYLCV CP suppresses phosphorylation of MAPK cascade, activating apoptosisTYLCV CP liberates PEBP4-bound ATG8, resulting in lipidation of ATG8 and initiation of autophagy.PEBP4 balances apoptosis and autophagy in viruliferous whitefly to optimize virus loading without obvious fitness cost.

Factors Determining Transmission of Persistent Viruses by Bemisia tabaci and Emergence of New Virus–Vector Relationships

“…Activated synthesis of antimicrobial peptides inhibits TYLCV accumulation in B. tabaci [ 61 ]. Interestingly, infection with TYLCV simultaneously induces autophagy and apoptosis in B. tabaci midguts [ 52 , 59 , 62 , 63 ], albeit both pathways are found to be independent of each other. Genes regulating the autophagy–lysosome pathway such as autophagy related genes, cathepsins, and acid phosphatase are upregulated in the midguts following acquisition of TYLCV [ 59 , 62 ].…”

“…Activation of autophagy-pathway-related genes inhibits TYLCV accumulation in B. tabaci [ 62 ], whereas induced apoptosis in whiteflies causes higher accumulation of the virus in the midgut, possibly by helping virions escape from degradation [ 63 ]. Phosphatidyl ethanolamine binding protein (PEBP) of the whitefly was recently reported as a regulatory protein coordinating the autophagy and apoptosis pathways to limit virus load from attaining levels that would affect host fitness [ 52 ]. The autophagy pathway of the whitefly is triggered with an accumulation of TYLCV up to a threshold level until the virus can replicate within the whitefly host [ 57 , 62 ].…”