Metabolic arsenal of giant viruses: Host hijack or self-use?

Abstract

Viruses generally are defined as lacking the fundamental properties of living organisms in that they do not harbor an energy metabolism system or protein synthesis machinery. However, the discovery of giant viruses of amoeba has fundamentally challenged this view because of their exceptional genome properties, particle sizes and encoding of the enzyme machinery for some steps of protein synthesis. Although giant viruses are not able to replicate autonomously and still require a host for their multiplication, numerous metabolic genes involved in energy production have been recently detected in giant virus genomes from many environments. These findings have further blurred the boundaries that separate viruses and living organisms. Herein, we summarize information concerning genes and proteins involved in cellular metabolic pathways and their orthologues that have, surprisingly, been discovered in giant viruses. The remarkable diversity of metabolic genes described in giant viruses include genes encoding enzymes involved in glycolysis, gluconeogenesis, tricarboxylic acid cycle, photosynthesis, and β-oxidation. These viral genes are thought to have been acquired from diverse biological sources through lateral gene transfer early in the evolution of Nucleo-Cytoplasmic Large DNA Viruses, or in some cases more recently. It was assumed that viruses are capable of hijacking host metabolic networks. But the giant virus auxiliary metabolic genes also may represent another form of host metabolism manipulation, by expanding the catalytic capabilities of the host cells especially in harsh environments, providing the infected host cells with a selective evolutionary advantage compared to non-infected cells and hence favoring the viral replication. However, the mechanism of these genes' functionality remains unclear to date.

Keywords: energy production; giant viruses; infectious disease; microbiology; primary metabolism.

Figure 1.. Schematic representation of the metabolic enzymes and pathways detected in NCLDVs.

Schematic of the TCA cycle (dark blue) feeding into the Urea cycle (black); Carbon transfer (red); Gluconeogenesis (scarlet); Glycolysis (marine); Photosynthesis (green); Amino acid metabolism (blue); Fermentation (purple); and lipid β-oxidation (orange). Also shown in the Legend are the identified cellular enzymes and putative substrates which have been identified as being encoded in specific NCLDV genomes, here represented by Mimiviridae, Phycodnaviridae, and Pandoraviridae.

Figure 2.. Transmission electron microscopy images of Mimivirus (A), Pandoravirus massiliensis (B) and Tupanvirus (C).

(A) Mimivirus particle is composed of an external layer of dense fibers surrounding an icosahedral capsid and an internal membrane sac enveloping the virus genomic material. (B) Pandoravirus massiliensis virion is ovoid-shaped with an ostiole-like apex, measuring 1.0 μm in length and 0.5 μm in diameter. (C) Tupanvirus exhibits an icosahedral capsid similar to those of Mimivirus measuring ~450 nm. However, Tupanvirus virion harbors a large cylindrical tail (550 nm extension;~450 nm diameter, including fibrils) attached to the base of the capsid. Electron micrographs were acquired on a Tecnai G2 transmission electron microscope (Scale bar, 200 nm).