Infection cycles of large DNA viruses: Emerging themes and underlying questions

Abstract

The discovery of giant DNA viruses and the recent realization that such viruses are diverse and abundant blurred the distinction between viruses and cells. These findings elicited lively debates on the nature and origin of viruses as well as on their potential roles in the evolution of cells. The following essay is, however, concerned with new insights into fundamental structural and physical aspects of viral replication that were derived from studies conducted on large DNA viruses. Specifically, the entirely cytoplasmic replication cycles of Mimivirus and Vaccinia are discussed in light of the highly limited trafficking of large macromolecules in the crowded cytoplasm of cells. The extensive spatiotemporal order revealed by cytoplasmic viral factories is described and contended to play an important role in promoting the efficiency of these 'nuclear-like' organelles. Generation of single-layered internal membrane sheets in Mimivirus and Vaccinia, which proceeds through a novel membrane biogenesis mechanism that enables continuous supply of lipids, is highlighted as an intriguing case study of self-assembly. Mimivirus genome encapsidation was shown to occur through a portal different from the 'stargate' portal that is used for genome release. Such a 'division of labor' is proposed to enhance the efficacy of translocation processes of very large viral genomes. Finally, open questions concerning the infection cycles of giant viruses to which future studies are likely to provide novel and exciting answers are discussed.

Efficiency in Complexity: Composition and Dynamic Nature of Mimivirus Replication Factories

“…The comparison also demonstrated that the number of proteins present in the factory is larger than the number detected in mature virions. This finding supports the conjecture that VFs should be considered "production lines" of viruses (10,18) in which numerous proteins are required for virus production but not for the onset of the infection process.…”

“…The exquisite spatial order that characterizes mimivirus VFs (10) further supports the hypothesis that these organelles can be considered "mini-nuclei" (11) that eventually might have evolved to eukaryotic nuclei (13,(15)(16)(17). This conjecture is intriguing in light of the realization that eukaryotic nuclei are highly ordered, as are VFs (18), and that this order plays a central role in their function (19,20). It was further suggested that VFs should be considered the actual living stage of viruses, whereas mature virions might be viewed as mere seeds that mediate intercellular transfer of genetic material (21,22).…”

“…is consistent with previous observations according to which extensive assembly processes of viral components such as membranes and capsid generation take place at these p.i. stages (1,18). It was previously demonstrated by diverse imaging techniques that membranes are present in mature mimivirus virions (36) as well as in VFs (10,37).…”

“…Notably, the mimivirus infection cycle occurs entirely within the host cytoplasm (12,26), in contrast to other double-stranded DNA (dsDNA) viruses, with the exception of vaccinia virus (8,27) and pithovirus (23). Thus, host nuclei that generally provide optimal platforms for replication of dsDNA viruses (18) do not function as such with these viruses. In and of itself, this observation underscores the stringent requirements imposed upon cytoplasmic VFs that enable them to act as efficient sites for autonomous generation of viral progeny.…”

Isolation and characterization of a virus infecting the freshwater algae Chrysochromulina parva

“…At the other end of the viral life cycle, it was not clear from this study how the virus enters cells. While some algal viruses such as the chloroviruses inject only their genome into their hosts leaving empty capsids on the cell surface (Yamada et al, 2006), other algal viruses such as Emiliania huxleyi virus 86 (Mackinder et al, 2009) as well as many other NCLDV like Mimivirus enter their hosts as intact particles via phagocytosis (Mutsafi et al, 2014). Although many cells were observed at various stages of infection including apparently uninfected cells ( Fig.…”