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. 2023 Sep 5;47(5):fuad053.
doi: 10.1093/femsre/fuad053.

Virologs, viral mimicry, and virocell metabolism: the expanding scale of cellular functions encoded in the complex genomes of giant viruses

Mohammad Moniruzzaman  1 , Maria Paula Erazo Garcia  2 , Roxanna Farzad  2 , Anh D Ha  2 , Abdeali Jivaji  2 , Sangita Karki  2 , Uri Sheyn  2 , Joshua Stanton  2 , Benjamin Minch  1 , Danae Stephens  1 , Dustin C Hancks  3 , Rodrigo A L Rodrigues  4 , Jonatas S Abrahao  4 , Assaf Vardi  5 , Frank O Aylward  2   6
Affiliations

Virologs, viral mimicry, and virocell metabolism: the expanding scale of cellular functions encoded in the complex genomes of giant viruses

Mohammad Moniruzzaman et al. FEMS Microbiol Rev. .

Abstract

The phylum Nucleocytoviricota includes the largest and most complex viruses known. These "giant viruses" have a long evolutionary history that dates back to the early diversification of eukaryotes, and over time they have evolved elaborate strategies for manipulating the physiology of their hosts during infection. One of the most captivating of these mechanisms involves the use of genes acquired from the host-referred to here as viral homologs or "virologs"-as a means of promoting viral propagation. The best-known examples of these are involved in mimicry, in which viral machinery "imitates" immunomodulatory elements in the vertebrate defense system. But recent findings have highlighted a vast and rapidly expanding array of other virologs that include many genes not typically found in viruses, such as those involved in translation, central carbon metabolism, cytoskeletal structure, nutrient transport, vesicular trafficking, and light harvesting. Unraveling the roles of virologs during infection as well as the evolutionary pathways through which complex functional repertoires are acquired by viruses are important frontiers at the forefront of giant virus research.

Keywords: auxiliary metabolic genes; giant viruses; mimicry; nucleocytoviricota; viral diversity; viral evolution.

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Conflict of interest statement

None declared.

Figures

Figure 1.
Figure 1.
Phylogeny of the Nucleocytovoricota, adapted from Aylward et al. (2021). Collapsed branches depict families or family-level lineages. Families accepted by the ICTV are in bold italic, and commonly used family names that have not yet been officially accepted are in bold. Notable viruses mentioned in the text are listed in bold. Aav, Aureococcus anophagefferens virus; ChoanoV1, Choanoflagellate virus; CpV, Chrysochromulina parva virus; HaV, Heterosigma akashiwo virus; IC, Internode Certainty; PgV, Phaeocystis globosa virus; TetV, Tetraselmis virus.
Figure 2.
Figure 2.
Illustration of possible roles of virologs in diverse processes within virocells. Panel (A): overview of a eukaryotic cell featuring key organelles and a virus factory. Each area highlighted using rectangles of different colors is shown in detail in panels (B)–(G). The top halves of panels (B)–(G) represent processes in infected cells carried out in part by virus-encoded virologs, while the bottom halves represent processes as they occur in healthy cells. Virus-encoded proteins and related processes or organelles are shown in shades of purple. Panel (B): virus infection of a cell and subsequent injection of viral DNA initiate reprogramming of the healthy cell metabolism into a virocell. Viral-encoded potassium channels cause depolarization of the host membrane and thereby facilitate viral entry. In the virocell, viral-encoded transporters help import nutrients, facilitating the infection process. Panel (C): virologs involved in central carbon metabolism (glycolysis and TCA cycle—purple letters and arrows) potentially augment cellular energy metabolism, leading to increased production of ATP. Panel (D): ROS cause damage to cellular components. During viral replication, viral-encoded SODs potentially prevent damage to viral proteins and nucleic acids within the virocell. Panel (E): While histones in a regular cell contribute to the structural organization of cellular DNA, within a virocell, viral-encoded histones can help package and organize viral DNA within the capsid. Panel (F): many GVs encode tRNAs in their genomes, which can potentially augment the cellular tRNA pool to sustain viral protein production. Panel (G): although the functions of viral-encoded actin and myosin genes have yet to be characterized, they could potentially assist in the localization and structure of the virus factory. Viral myosin might help transport molecular cargoes related to virus replication and assembly processes along the actin filaments. Abbreviations: Nuc—nucleus, ER—endoplasmic reticulum, VF—virus factory, Mt—mitochondria, GA—Golgi apparatus, Act—actin filaments, GV—giant virus, TP—transporters, ROS—reactive oxygen species, SOD—superoxide dismutase, H2O—water, His—histone, RB—ribosome, Pep—peptide chain, tRNA—transfer RNA, My—myosin, and CG—molecular cargo.
Figure 3.
Figure 3.
Phylogenetic trees of select virologs mentioned in the text. Some virologs have deep placement indicative of ancient gene exchange (DNA primase and mRNA capping enzyme), while others have been acquired more recently (K+ transporter and myosin). Moreover, some virologs appear to have been acquired by viruses multiple times independently (rhodopsin, synaptobrevin, Bax1 apoptosis inhibitor and K+ transporter).
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