How to build a giant virus

Mimivirus My final year students will tell you – I’m obsessed with Mimivirus. It’s true – to me these giant viruses are one of the most fascinating areas of microbiology right now, at the convergence of living cells and subcellular infectious agents.

With a particle size comparable to that of small bacteria and a 1.2 Mbp double-strand DNA genome that carries more than 1000 open reading frames, the amoeba-infecting Mimivirus, along with other recently identified members of the Mimiviridae family, are the largest and most complex viruses yet identified. The Mimivirus particle includes an internal membrane that underlies an icosahedral capsid. The assembly mechanism of internal membrane during Mimivirus infection remains unclear, as is the case for other viruses containing internal membranes. By using diverse imaging techniques, this article shows that membrane biogenesis is an elaborate process that occurs at the periphery of viral factories generated at the host cytoplasm. This multistage process, which includes the formation of open membrane sheets, enables efficient and continuous assembly of multiple Mimivirus progeny. The membrane biogenesis process suggested here provides novel insights into the assembly of internal viral membranes in general.

 

Membrane Assembly during the Infection Cycle of the Giant Mimivirus. (2013) PLoS Pathog 9(5): e1003367. doi:10.1371/journal.ppat.1003367
Although extensively studied, the structure, cellular origin and assembly mechanism of internal membranes during viral infection remain unclear. By combining diverse imaging techniques, including the novel Scanning-Transmission Electron Microscopy tomography, we elucidate the structural stages of membrane biogenesis during the assembly of the giant DNA virus Mimivirus. We show that this elaborate multistage process occurs at a well-defined zone localized at the periphery of large viral factories that are generated in the host cytoplasm. Membrane biogenesis is initiated by fusion of multiple vesicles, ~70 nm in diameter, that apparently derive from the host ER network and enable continuous supply of lipid components to the membrane-assembly zone. The resulting multivesicular bodies subsequently rupture to form large open single-layered membrane sheets from which viral membranes are generated. Membrane generation is accompanied by the assembly of icosahedral viral capsids in a process involving the hypothetical major capsid protein L425 that acts as a scaffolding protein. The assembly model proposed here reveals how multiple Mimivirus progeny can be continuously and efficiently generated and underscores the similarity between the infection cycles of Mimivirus and Vaccinia virus. Moreover, the membrane biogenesis process indicated by our findings provides new insights into the pathways that might mediate assembly of internal viral membranes in general.

 

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