Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Parvovirus B19 and Human Parvovirus 4 Encode a Homologous “X Protein” in a Reading Frame Overlapping the VP1 Capsid Gene: A VP1/X Overlap in Parvovirus B19 and PARV4

Version 1 : Received: 5 April 2020 / Approved: 6 April 2020 / Online: 6 April 2020 (14:20:35 CEST)
Version 2 : Received: 14 September 2023 / Approved: 15 September 2023 / Online: 15 September 2023 (11:31:52 CEST)

A peer-reviewed article of this Preprint also exists.

Karlin, D.G. Parvovirus B19 and Human Parvovirus 4 Encode Similar Proteins in a Reading Frame Overlapping the VP1 Capsid Gene. Viruses 2024, 16, 191. Karlin, D.G. Parvovirus B19 and Human Parvovirus 4 Encode Similar Proteins in a Reading Frame Overlapping the VP1 Capsid Gene. Viruses 2024, 16, 191.

Abstract

Viruses frequently contain overlapping genes, which encode functionally unrelated proteins from the same DNA or RNA region but in different reading frames. Yet overlapping genes are often overlooked during genome annotation, in particular in DNA viruses. Here we looked for the presence of overlapping genes likely to encode a functional protein in human parvovirus B19 (genus erythroparvovirus), using an experimentally validated software, Synplot2. Synplot2 detected an open reading frame, X, conserved in all erythroparvoviruses, which overlaps the VP1 capsid gene, and is under highly significant selection pressure. In a related virus, human parvovirus (genus tetraparvovirus), Synplot2 also detected an open reading frame under highly significant selection pressure, ARF1, which overlaps the VP1 gene. X and ARF1 have exactly the same location (both overlap the region of VP1 encoding the phospholipase A2 domain), and encode proteins with similar predicted properties, such as a transmembrane region, strongly suggesting that they are homologous. These findings provide compelling evidence that the X protein must be expressed and functional. It is probably translated either from a polycistronic mRNA by a non-canonical mechanism, or from an unmapped monocistronic mRNA. Finally, we also discovered proteins predicted to be expressed from a frame overlapping VP1 in other species related to parvovirus B19: porcine parvovirus 2 (Z protein) and bovine parvovirus 3 (X-like protein).

Keywords

Overlapping genes; overlapping coding sequences; overlapping reading frames; 9 kDa protein; erythroparvovirus; tetraparvovirus; Y region; Y coding sequence; PLA2

Subject

Biology and Life Sciences, Virology

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