Hijacking of an autophagy‐like process is critical for the life cycle of a DNA virus infecting oceanic algal blooms

Abstract

Marine photosynthetic microorganisms are the basis of marine food webs and are responsible for nearly 50% of the global primary production. Emiliania huxleyi forms massive oceanic blooms that are routinely terminated by large double-stranded DNA coccolithoviruses. The cellular mechanisms that govern the replication cycle of these giant viruses are largely unknown.We used diverse techniques, including fluorescence microscopy, transmission electron microscopy, cryoelectron tomography, immunolabeling and biochemical methodologies to investigate the role of autophagy in host–virus interactions.Hallmarks of autophagy are induced during the lytic phase of E. huxleyi viral infection, concomitant with up-regulation of autophagy-related genes (ATG genes). Pretreatment of the infected cells with an autophagy inhibitor causes a major reduction in the production of extracellular viral particles, without reducing viral DNA replication within the cell. The host-encoded Atg8 protein was detected within purified virions, demonstrating the pivotal role of the autophagy-like process in viral assembly and egress.We show that autophagy, which is classically considered as a defense mechanism, is essential for viral propagation and for facilitating a high burst size. This cellular mechanism may have a major impact on the fate of the viral-infected blooms, and therefore on the cycling of nutrients within the marine ecosystem.

Elucidating the composition and conservation of the autophagy pathway in photosynthetic eukaryotes

“…2A and ref. 74 ). Differential expression of ATG genes was also detected in expressed sequence tag (EST) libraries derived from different E. huxleyi strains, which differ in their viral susceptibility.…”

Targeted and untargeted lipidomics of Emiliania huxleyi viral infection and life cycle phases highlights molecular biomarkers of infection, susceptibility, and ploidy

“…At the cellular level, as a large dsDNA virus with high metabolic demand for the building blocks of DNA, lipids and protein synthesis, EhV triggers a rapid remodeling of the host metabolism Schatz et al, 2014). In particular, recent studies have highlighted the crucial role of membrane lipids in the progression and regulation of EhV infection (Vardi et al, 2009(Vardi et al, , 2012Rosenwasser et al, 2014).…”

“…Evidence from genome and microscopic investigation suggests that EhV86 utilizes an animal-like, membrane-dependent infection strategy. EhV entry, by membrane fusion or endocytosis and the acquisition of host membrane lipids via budding (Mackinder et al, 2009;Schatz et al, 2014), seem to be localized to membrane lipid raft regions (Rose et al, 2014). Furthermore, the EhV genome contains a cluster of genes composing a nearly complete sphingolipid biosynthetic pathway analogous to the host pathway (Wilson et al, 2005;Monier et al, 2009).…”

Viral serine palmitoyltransferase induces metabolic switch in sphingolipid biosynthesis and is required for infection of a marine alga

“…The EhV virion comprises at least two internal lipid bilayers (37,38), which are composed largely of virus-specific GSLs (vGSLs) (8,34,35). Genome analysis of EhV has revealed a set of putative SL biosynthetic genes that have not been described in any other viral genome (17,18,39).…”