Abstract
Autophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication. We therefore asked how measles virus interferes with autophagy receptors during the course of infection. We report that in addition to NDP52/CALCOCO2 and OPTINEURIN/OPTN, another autophagy receptor, namely T6BP/TAXIBP1, also regulates the maturation of autophagosomes by promoting their fusion with lysosomes, independently of any infection. Surprisingly, only two of these receptors, NDP52 and T6BP, impacted measles virus replication, although independently, and possibly through physical interaction with MeV proteins. Thus, our results suggest that a restricted set of autophagosomes is selectively exploited by measles virus to replicate in the course of infection.
Highlights
To maintain their integrity, cells engage various processes including autophagy, a lysosomal-dependent catabolic process, which allows the degradation of deleterious cytoplasmic components [1]
We recently reported that NDP52 and OPTN can both regulate the maturation of autophagosomes, which can contribute to the control of intracellular bacterial growth [15,16]
Since T6BP was recently shown to contribute to the efficient autophagy-mediated clearance of bacteria [17], we started by investigating a potential role for this receptor in autophagosome maturation
Summary
Cells engage various processes including autophagy, a lysosomal-dependent catabolic process, which allows the degradation of deleterious cytoplasmic components [1]. MeV displays a very intricate relationship with autophagy and benefits from this process, only if completed, in order to efficiently produce new infectious particles It remains to be understood how MeV escapes from autophagy degradation, especially in regards to its putative detection by autophagy receptors, whose function is to transfer pathogens to the autophagy machinery for degradation. NDP52, optineurin (OPTN), and T6BP were concomitantly associated with the biogenesis of phagophores [14] Of this role, we recently reported that NDP52 and OPTN can ensure the maturation of autophagosomes by themselves, resulting in the fusion of autophagosomes with lysosomes [15,16]. Since a complete autophagy flux is necessary for efficient MeV replication, we investigated the question of the requirement of autophagy receptors in autophagosome maturation and MeV replication
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