The virtosome—a novel cytosolic informative entity and intercellular messenger

Abstract

Studies on a range of prokaryote and eukaryote cells and tissues have shown that a newly synthesized DNA/RNA-lipoprotein complex is released in a regulated manner. This complex, termed a virtosome, is a novel cytosolic component of eukaryote cells. The released virtosomes can readily enter other cells where they can modify the biology of the recipient cells. Such modifications include immunological changes and transformation from normal to cancer cells. The virtosomes form a normal component of the circulating nucleic acids in plasma and serum currently used for clinical diagnostic purposes. Given the transformative powers of virtosomes released from tumour cells, the presence of such a complex in human plasma could readily offer the basis of an alternative mechanism for the initiation of metastases.

A historical and evolutionary perspective on the biological significance of circulating DNA and extracellular vesicles

“…In 1982, Adams and Gahan determined that all the elements of the nucleoprotein complex are synthesized together in the cells, with the exception of the RNA, which is transcribed in the cytoplasm just before the complex exits the cells [101]. These nucleoprotein complexes, later named virtosomes [15], share striking similarities with Bell's I-somes. Both consist of DNA released into the cytoplasm, forming complexes with proteins, RNA and RNA transcription machinery that transcribe RNA in the cytoplasm before the complexes exit the cells.…”

“…These factors collectively contribute to the difficulty to reach a consensus on structural definitions. Except for EVs, CirDNA can be part of protein complexes or attach themselves to binding proteins or phospholipids on outer cell surfaces for absorption or release purposes [15,167,[180][181][182]. CirDNA can also be in the form of mitochondrial DNA and nucleosomes as a result of apoptotic processes [182,183].…”

“…The DNA content has been demonstrated to hybridize with nuclear DNA, and thus bears great similarity to cellular DNA. The type of RNA present has not yet been determined, but it has similar effects on recipient cells than that of siRNA or miRNA [15]. Liposomes, containing apolipoprotein A-I, have many times been used as an artificial vehicle to deliver small interfering RNAs to target animal cells.…”

“…Although apoptosis and necrosis are considered to be the main processes for producing cirDNA, numerous studies have demonstrated that cirDNA can also be derived from active cellular release mechanisms [7][8][9][10][11][12]. Further examination showed that actively released DNA is often associated with RNA and a lipid-protein complex, can translocate to neighboring or remote parts of the body, enter target cells, and alter their biology [12][13][14][15][16][17][18]. In the following years, it became clear that the active release and uptake of nucleic acids are a characteristic shared by all organisms and cell types [19].…”

Generation of blood circulating DNA: the sources, peculiarities of circulation and structure

“…[50]. В настоящее время достоверно известно, что эндогенные нуклеиновые кислоты могут циркулировать в крови в составе апоптотических телец, микровезикул, нуклеосом, экзосом, нуклеопротеиновых комплексов с белками крови и, возможно, в свободном виде [5,11,[51][52][53] (таблица).…”