YARAVIRUS BRASILIENSE UPTAKES HOST’S MITOCHONDRIA BY AVOIDING CONTROL POINTS

Ana Karoline da Nóbrega Nunes Alves; Jônatas Santos Abrahão; Sávio Torres de Farias

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Submission

Paper Title

YARAVIRUS BRASILIENSE UPTAKES HOST’S MITOCHONDRIA BY AVOIDING CONTROL POINTS

Authors

Ana Karoline da Nóbrega Nunes Alves
Jônatas Santos Abrahão
Sávio Torres de Farias

Modality

Poster

Subject area

Phylogeny and Evolution

Publishing Date

21/11/2024

Country of Publishing

Brazil | Brasil

Language of Publishing

Inglês

Paper Page

https://www.even3.com.br/anais/xmeeting-2024/829352-yaravirus-brasiliense-uptakes-hosts-mitochondria-by-avoiding-control-points

ISBN

978-65-272-0843-3

Keywords

auxiliary metabolic genes; viral evolution; citric acid cycle; threading

Summary

Viruses are a type of mobile genetic element that encode structural proteins encapsidating their own genomes. Usually, they are seen as having limited metabolic capacities, but there have been several reports of metabolism-related genes in viruses, which give them the potential to actively regulate the host’s metabolism with their own genes by redirecting energy and resources toward viral production, allowing greater viral independence. These reported genes are related to photosynthesis, tricarboxylic acid cycle, glycolysis, and other processes. Here we analyze the Yaravirus brasiliense, an amoeba-infecting 80-nm-sized virus with a 45-kbp dsDNA. Almost all of its 74 genes were previously identified as ORFans, which are coding sequences with few or no homologs in public sequence databases, making it harder to know their origin or function. Considering its unprecedented genetic content, we analyzed Yaravirus genome using structural molecular modeling. We seek to understand its genetic organization, its proteome, and how it interacts with its host. Genomic information is published in the NCBI genome database. The gene sequences were inserted in I-TASSER, a threading-based program. For a deeper understanding of possible ligands, we used COACH. For protein visualization, we used Swiss-Pdb Viewer. Given the structural resemblance between some Yaravirus proteins and proteins related to tricarboxylic acid cycle, glyoxylate cycle, and the mitochondrial respiratory complexes, it is possible that these ORFans also take on these functions. In laboratory conditions, Yaravirus seems to attracts mitochondria to the viral factory, while infecting Acanthamoeba. These proteins could affect the host mitochondria, by manipulation of the mentioned biochemical pathways. The tricarboxylic acid cycle is a series of enzymatic reactions that releases energy through the oxidation of acetyl-CoA. It is linked to the electron transport chain at the respiratory complex II. Yaravirus genome has proteins related to all four respiratory complexes, which could be upregulating the complexes towards energy production. The TCA cycle’s control points are the three exergonic stages (those catalyzed by citrate synthase, isocitrate-dehydrogenase and alpha-ketoglutarate-dehydrogenase); availability of oxaloacetate; and NADH/NAD+ and ATP/ADP ratios. Yaravirus has proteins linked to malate dehydrogenase, citrate synthase, PEP-carboxylase, isocitrate lyase, malate synthase, and fumarase. When oxaloacetate levels are low, malate dehydrogenase and citrate synthase are inactivated. The presence of these TCA cycle-related enzymes could be trying to overcome the control points. As the virus stimulates the cycle to provide energy and substrates for its replication, the control points would eventually reach a limit and be activated. At this point, Yaravirus malate dehydrogenase and citrate synthase could keep the malate to oxaloacetate to citrate reaction going, and, simultaneously, PEP-carboxylase would also maintain oxaloacetate levels. To keep malate available, the glyoxylate cycle would also be functioning, with the presence of an isocitrate lyase (converts isocitrate to glyoxylate and succinate), a succinate dehydrogenase (converts succinate to fumarate) and a malate synthase (converts glyoxylate to malate). Concurrently, a fumarase converts fumarate to malate, which also maintains malate levels. Therefore, we propose that Yaravirus’ proteins are redirecting energy and resources toward viral production, and avoiding Krebs’ cycle control points, therefore “unlocking” the cycle.

Title of the Event: 20º Congresso Brasileiro de Bioinformática: X-Meeting 2024
City of the Event: Salvador
Title of the Proceedings of the event: X-Meeting presentations
Name of the Publisher: Even3
Means of Dissemination: Meio Digital

How to cite

ALVES, Ana Karoline da Nóbrega Nunes; ABRAHÃO, Jônatas Santos; FARIAS, Sávio Torres de. YARAVIRUS BRASILIENSE UPTAKES HOST’S MITOCHONDRIA BY AVOIDING CONTROL POINTS.. In: X-Meeting presentations. Anais...Salvador(BA) Hotel Deville Prime, 2024. Available in: https//www.even3.com.br/anais/xmeeting-2024/829352-YARAVIRUS-BRASILIENSE-UPTAKES-HOSTS-MITOCHONDRIA-BY-AVOIDING-CONTROL-POINTS. Access in: 05/08/2025