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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.
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This content will become publicly available on March 18, 2026
Evolution of ubiquitin, cytoskeleton, and vesicular trafficking machinery in giant viruses
ABSTRACT Members of the phylumNucleocytoviricota, which include “giant viruses” known for their large physical dimensions and genome lengths, are a diverse group of dsDNA viruses that infect a wide range of eukaryotic hosts. The genomes of nucleocytoviruses frequently encode eukaryotic signature proteins (ESPs) such as RNA- and DNA-processing proteins, vesicular trafficking factors, cytoskeletal components, and proteins involved in ubiquitin signaling. Despite the prevalence of these genes in many nucleocytoviruses, the timing and number of gene acquisitions remains unclear. While the presence of DNA- and RNA-processing proteins in nucleocytoviruses likely reflects ancient gene transfers, the origins and evolutionary history of other proteins are largely unknown. In this study, we examined the distribution and evolutionary history of a subset of viral-encoded ESPs (vESPs) that are widespread in nucleocytoviruses. Our results demonstrate that most vESPs involved in vesicular trafficking were acquired multiple times independently by nucleocytoviruses at different time points after the emergence of the eukaryotic supergroups, while viral proteins associated with cytoskeletal and ubiquitin system proteins exhibited a more complex evolutionary pattern exhibited by both shallow and deep branching viral clades. This pattern reveals a dynamic interplay between the co-evoluton of eukaryotes and their viruses, suggesting that the viral acquisition of many genes involved in cellular processes has occurred both through ancient and more recent horizontal gene transfers. The timing and frequency of these gene acquisitions may provide insight into their role and functional significance during viral infection.IMPORTANCEThis research is pertinent for understanding the evolution of nucleocytoviruses and their interactions with eukaryotic hosts. By investigating the distribution and evolutionary history of viral-encoded eukaryotic signature proteins, the study reveals gene transfer patterns, highlighting how viruses acquire genes that allow them to manipulate host cellular processes. Identifying the timing and frequency of gene acquisitions related to essential cellular functions provides insights into their roles during viral infections. This work expands our understanding of viral diversity and adaptability, contributing valuable knowledge to virology and evolutionary biology, while offering new perspectives on the relationship between viruses and their hosts.
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- Award ID(s):
- 2141862
- PAR ID:
- 10659160
- Editor(s):
- Parent, Kristin N
- Publisher / Repository:
- American Society for Microbiology
- Date Published:
- Journal Name:
- Journal of Virology
- Volume:
- 99
- Issue:
- 3
- ISSN:
- 0022-538X
- Subject(s) / Keyword(s):
- Viruses, Giant Viruses, Evolution, Genomics
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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