Open AccessThe Self-Interaction of a Nodavirus Replicase Is Enhanced by Mitochondrial Membrane Lipids
Author(s) -
Yang Qiu,
Zhaowei Wang,
Yongxiang Liu,
Yajuan Han,
Mingyao Meng,
Nan Qi,
Jie Yang,
Hongjie Xia,
Xiaofeng Li,
ChengFeng Qin,
Yuanyang Hu,
Xi Zhou
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0089628
Subject(s) - rna , rna dependent rna polymerase , biology , viral replication , intracellular , inner mitochondrial membrane , microbiology and biotechnology , membrane , biochemistry , phospholipid , virology , virus , gene
RNA replication of positive-strand (+)RNA viruses requires the protein-protein interactions among viral replicases and the association of viral replicases with intracellular membranes. Protein A from Wuhan nodavirus (WhNV), which closely associate with mitochondrial membranes, is the sole replicase required for viral RNA replication. Here, we studied the direct effects of mitochondrial membrane lipids (MMLs) on WhNV protein A activity in vitro . Our investigations revealed the self-interaction of WhNV protein A is accomplished via two different patterns (i.e., homotypic and heterotypic self-interactions via different interfaces). MMLs stimulated the protein A self-interaction, and this stimulation exhibited selectivity for specific phospholipids. Moreover, we found that specific phospholipids differently favor the two self-interaction patterns. Furthermore, manipulating specific phospholipid metabolism affected protein A self-interaction and the activity of protein A to replicate RNA in cells. Taken together, our findings reveal the direct effects of membrane lipids on a nodaviral RNA replicase.