HIJACKING OF AN AUTOPHAGY-LIKE PROCESS IS ESSENTIAL FOR THE LIFE CYCLE OF A LARGE DNA VIRUS INFECTING OCEANIC ALGAL BLOOMS

Daniella Schatz ¹ Adva Shemi ¹ Shilo Rosenwasser ¹ Helena Sabanay ² Sharon Wolf ² Shifra Ben-Dor ³ Assaf Vardi ¹

¹Department of Plant Sciences, Weizmann Institute of Science, Rehovot
²Department of Chemical Research Support, Weizmann Institute of Science, Rehovot
³Department of Biological Services, Weizmann Institute of Science, Rehovot

Marine photosynthetic microorganisms (phytoplankton) are the basis of marine food webs and are responsible for nearly 50% of the global primary production. Viruses infecting phytoplankton are major evolutionary and biogeochemical drivers in the marine environment. Emiliania huxleyi is a globally important coccolithophore, forming massive blooms in the North Atlantic Ocean that are routinely infected and terminated by large double-stranded DNA coccolithoviruses. The cellular mechanisms that govern the replication cycle of these giant viruses are largely unknown. Here we show that hallmarks of autophagy, such as double membrane vesicles and acidification of distinct vacuoles, are induced during the lytic phase of E. huxleyi viral infection, concomitant with upregulation of a suite of autophagy related genes (ATG genes). We found profound induction and lipidation of the Atg8 protein, an essential component in autophagosome formation, exclusively during lytic infection. Pre-treatment of the cells with an inhibitor of autophagy prior to viral infection causes major reduction in extracellular viral particles, without affecting viral DNA replication within the cell. The host-encoded membrane-bound protein Atg8 was detected within purified virions, demonstrating the pivotal role of the autophagy-like process in viral assembly and egress from the cells. We provide compelling evidence that autophagy, which is classically considered as a defense mechanism, is hijacked by the virus and is essential for its propagation and for facilitating a high burst size. This fundamental cellular mechanism will have major impact on the fate of the viral infected blooms, and therefore on the cycling of nutrients within the marine ecosystem.