Cassava brown streak virus Ham1 protein hydrolyses mutagenic nucleotides and is a necrosis determinant
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Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Molecular plant pathology
Abstract
Cassava brown streak disease (CBSD) is a leading cause of cassava
losses in East and Central Africa, and is currently having a
severe impact on food security. The disease is caused by two viruses
within the Potyviridae family: Cassava brown streak virus
(CBSV) and Ugandan cassava brown streak virus (UCBSV), which
both encode atypical Ham1 proteins with highly conserved
inosine triphosphate (ITP) pyrophosphohydrolase (ITPase) domains.
ITPase proteins are widely encoded by plant, animal,
and archaea. They selectively hydrolyse mutagenic nucleotide
triphosphates to prevent their incorporation into nucleic acid
and thereby function to reduce mutation rates. It has previously
been hypothesized that U/CBSVs encode Ham1 proteins
with ITPase activity to reduce viral mutation rates during infection.
In this study, we investigate the potential roles of U/
CBSV Ham1 proteins. We show that both CBSV and UCBSV Ham1
proteins have ITPase activities through in vitro enzyme assays.
Deep-sequencing experiments found no evidence of the U/CBSV
Ham1 proteins providing mutagenic protection during infections
of Nicotiana hosts. Manipulations of the CBSV_Tanza infectious
clone were performed, including a Ham1 deletion, ITPase
point mutations, and UCBSV Ham1 chimera. Unlike severely necrotic
wild-type CBSV_Tanza infections, infections of Nicotiana
benthamiana with the manipulated CBSV infectious clones do
not develop necrosis, indicating that that the CBSV Ham1 is a
necrosis determinant. We propose that the presence of U/CBSV
Ham1 proteins with highly conserved ITPase motifs indicates
that they serve highly selectable functions during infections of
cassava and may represent a euphorbia host adaptation that
could be targeted in antiviral strategies.
Description
Keywords
Cassava, Cassava brown streak disease, Cassava brown streak virus, Food security, Ugandan cassava brown streak virus, Virus
Citation
Tomlinson, K. R., Pablo‐Rodriguez, J. L., Bunawan, H., Nanyiti, S., Green, P., Miller, J., ... & Foster, G. D. (2019). Cassava brown streak virus Ham1 protein hydrolyses mutagenic nucleotides and is a necrosis determinant. Molecular plant pathology, 20(8), 1080-1092. DOI : 10.1111/mpp.12813