title: Efficiency in Complexity: Composition and Dynamic Nature of Mimivirus Replication Factories.
abstract: The recent discovery of multiple giant double-stranded DNA (dsDNA) viruses blurred the consensual distinction between viruses and cells due to their size, as well as to their structural and genetic complexity. A dramatic feature revealed by these viruses as well as by many positive-strand RNA viruses is their ability to rapidly form elaborate intracellular organelles, termed "viral factories," where viral progeny are continuously generated. Here we report the first isolation of viral factories at progressive postinfection time points. The isolated factories were subjected to mass spectrometry-based proteomics, bioinformatics, and imaging analyses. These analyses revealed that numerous viral proteins are present in the factories but not in mature virions, thus implying that multiple and diverse proteins are required to promote the efficiency of viral factories as "production lines" of viral progeny. Moreover, our results highlight the dynamic and highly complex nature of viral factories, provide new and general insights into viral infection, and substantiate the intriguing notion that viral factories may represent the living state of viruses.IMPORTANCELarge dsDNA viruses such as vaccinia virus and the giant mimivirus, as well as many positive-strand RNA viruses, generate elaborate cytoplasmic organelles in which the multiple and diverse transactions required for viral replication and assembly occur. These organelles, which were termed "viral factories," are attracting much interest due to the increasing realization that the rapid and continuous production of viral progeny is a direct outcome of the elaborate structure and composition of the factories, which act as efficient production lines. To get new insights into the nature and function of viral factories, we devised a method that allows, for the first time, the isolation of these organelles. Analyses of the isolated factories generated at different times postinfection by mass spectrometry-based proteomics provide new perceptions of their role and reveal the highly dynamic nature of these organelles.
authors: Department of Structural Biology, The Weizmann Institute of Science, Rehovot, Israel yael.fridmann-sirkis@weizmann.ac.il avi.minsky@weizmann.ac.il.
authors: Yael
authors: Y
authors: Fridmann-Sirkis
authors: Department of Structural Biology, The Weizmann Institute of Science, Rehovot, Israel.
authors: Elad
authors: E
authors: Milrot
authors: Department of Structural Biology, The Weizmann Institute of Science, Rehovot, Israel.
authors: Yael
authors: Y
authors: Mutsafi
authors: Bioinformatics Unit, The Weizmann Institute of Science, Rehovot, Israel.
authors: Shifra
authors: S
authors: Ben-Dor
authors: Proteomics Unit, The Weizmann Institute of Science, Rehovot, Israel.
authors: Yishai
authors: Y
authors: Levin
authors: Proteomics Unit, The Weizmann Institute of Science, Rehovot, Israel.
authors: Alon
authors: A
authors: Savidor
authors: Department of Chemical Research Support, The Weizmann Institute of Science, Rehovot, Israel.
authors: Elena
authors: E
authors: Kartvelishvily
authors: Department of Structural Biology, The Weizmann Institute of Science, Rehovot, Israel yael.fridmann-sirkis@weizmann.ac.il avi.minsky@weizmann.ac.il.
authors: Abraham
authors: A
authors: Minsky