Dynamic genome evolution and complex virocell metabolism of globally-distributed giant viruses

Abstract

The discovery of eukaryotic giant viruses has transformed our understanding of the limits of viral complexity, but the extent of their encoded metabolic diversity remains unclear. Here we generate 501 metagenome-assembled genomes of Nucleo-Cytoplasmic Large DNA Viruses (NCLDV) from environments around the globe, and analyze their encoded functional capacity. We report a remarkable diversity of metabolic genes in widespread giant viruses, including many involved in nutrient uptake, light harvesting, and nitrogen metabolism. Surprisingly, numerous NCLDV encode the components of glycolysis and the TCA cycle, suggesting that they can re-program fundamental aspects of their host’s central carbon metabolism. Our phylogenetic analysis of NCLDV metabolic genes and their cellular homologs reveals distinct clustering of viral sequences into divergent clades, indicating that these genes are virus-specific and were acquired in the distant past. Overall our findings reveal that giant viruses encode complex metabolic capabilities with evolutionary histories largely independent of cellular life, strongly implicating them as important drivers of global biogeochemical cycles.

Tricarboxylic acid cycle and proton gradient inPandoravirus massiliensis: Is it still a virus?

“…genes, encoding enzymes that are known to be essential in the metabolism of endogenous regulatory molecules and exogenous drugs, but not their ancillary enzymatic redox partners, which could be recruited from host (12). Recently, a deep analysis of 501 environmental metagenome-assembled genomes of NCLDV revealed a diversity of metabolic genes involved in nutrient uptake, light harvesting, nitrogen metabolism, glycolysis and the TCA cycle (41). Moreover, tupanviruses possess a gene encoding citrate synthase, the first enzyme in the TCA cycle, for which no homologs were found in any other known virus.…”

“…The phylogenetic origin of the TCA cycle may be the reverse TCA cycle, an endergonic anabolic pathway [37] that is used by some bacteria to produce carbon compounds [37][38][39][40][41][42][43].…”

Giant viruses encode novel types of actins possibly related to the origin of eukaryotic actin: the viractins

“…Table 1 summarizes genomic statistics for the NCLDV isolate genome and MAGs containing a viractin. MAGs were affiliated to Hokovirus (n=1) and Yasminevirus (n=1) within Klosneuvirinae, as well as to two lineages related to Mimiviridae dubbed MVGL55 (n=15) and MM15 (n=1) that were recently characterized from large metagenomic surveys 10,11 . These clades correspond to the newly revealed diversity of Mimiviridae relatives that have been recently included into the Imitervirales 5 order.…”

Investigating the Concept and Origin of Viruses

“…For instance, despite overwhelming scientific evidence supporting a natural zoonotic transmission of SARS-CoV-2 from animals to humans [ 6 ], many still suspect that the virus was purposefully engineered in laboratories. Similarly, viruses are generalized as noxious pathogens in common discussions and this focus greatly underestimates the many beneficial roles they play in the biosphere [ 7 , 8 ] and as mutualistic symbionts of many hosts (reviewed in [ 9 , 10 ]). In this article, we revisit fundamental questions about the nature, origins, and evolution of viruses during a time when public interest in virus biology is at its peak.…”

“…In some viral infections, large cell-like ‘ virion factories ’ are clearly visible [ 19 ]. This remarkable transformation is due to the virus-mediated manipulation and alteration of host metabolism and defenses [ 7 ]. The intracellular stage therefore involves substantial viral activity and is often the target of antiviral drugs to combat virus infection (e.g., antivirals that target HIV polymerase).…”