Viral inosine triphosphatase: A mysterious enzyme with typical activity, but an atypical function

Abstract

Plant viruses typically have highly condensed genomes, yet the plant‐pathogenic viruses Cassava brown streak virus, Ugandan cassava brown streak virus, and Euphorbia ringspot virus are unusual in encoding an enzyme not yet found in any other virus, the “house‐cleaning” enzyme inosine triphosphatase. Inosine triphosphatases (ITPases) are highly conserved enzymes that occur in all kingdoms of life and perform a house‐cleaning function by hydrolysing the noncanonical nucleotide inosine triphosphate to inosine monophosphate. The ITPases encoded by cassava brown streak virus and Ugandan cassava brown streak virus have been characterized biochemically and are shown to have typical ITPase activity. However, their biological role in virus infection has yet to be elucidated. Here we review what is known of viral‐encoded ITPases and speculate on potential roles in infection with the aim of generating a greater understanding of cassava brown streak viruses, a group of the world's most devastating viruses.

Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases

“…To conciliate our result in cassava with that broadly accepted idea, we hypothesise that some plants accumulate unexpectedly high concentration of ITP/XTP in certain subcellular compartments, whereas in those locations where they have damaging consequences, such as in the nucleus, ITP/XTP are kept at much lower concentration. The recent suggestion that euphorbiaceous HAM1-like proteins might harbour a nuclear localization signal [51] fits pretty well with this assumption. Therefore, it is possible that viruses infecting plants from the Euphorbiacea family (e.g.…”

Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases

“…To conciliate our result in cassava with that broadly accepted idea, we hypothesise that some plants accumulate unexpectedly high concentration of ITP/XTP in certain subcellular compartments, whereas in those locations where they have damaging consequences, such as in the nucleus, ITP/XTP are kept at much lower concentration. The recent suggestion that euphorbiaceous HAM1-like proteins might harbour a nuclear localization signal (James et al, 2021) fits pretty well with this assumption. Therefore, it is possible that viruses infecting plants from the Euphorbiacea family (e.g.…”

An inosine triphosphate pyrophosphatase safeguards plant nucleic acids from aberrant purine nucleotides

“…As it has been recently reported that plant viruses infecting Euphorbiaceae and especially Manihot esculenta (commonly known as Cassava) possess a homologue of ITPA (James et al, 2021; Leiva et al, 2022), we were curious whether ITP and IDP concentrations change during infection with such a virus. We chose to investigate this question in N. benthamiana because Arabidopsis is not a known host of viruses encoding ITPA.…”

“…So far, there have been several sporadic reports about the existence of ITPA in plants (Lin et al, 2001;James et al, 2021), but this enzyme and corresponding mutant plants…”