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Grain Virus Protein Discovery Reveals New Class of Cell Division Disruptors
Viruses are ubiquitous pathogens that cause severe infectious diseases in both humans and agricultural crops. As most viruses have simple genomes and encode only a few proteins, they must usurp host cell resources for propagation. Understanding what host processes are disrupted and which viral proteins are involved greatly facilitates the design of therapeutic measures for controlling viral diseases in humans and crop plants.
Recently, researchers from the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences discovered a plant viral protein named 17K that disrupts host cell division to promote its own propagation in infected tissues. They also linked it structurally to certain animal virus proteins.
The work was published online in Science Advances on May 13. It is the result of a decade-long collaboration between the IGDB group led by Prof. WANG Daowen and the laboratory of Prof. ZHAO Yuqi at the School of Medicine of the University of Maryland.
The 17K protein is conserved in a group of cereal-infecting viruses called barley yellow dwarf viruses (BYDVs). Even though BYDVs have been studied for more than 60 years, they frequently cause severe epidemics in global wheat, barley, maize and oat crops, with yellowing and dwarfing as typical results.
The researchers hypothesized that one or more BYDV proteins may inhibit host cell growth by disrupting cell division, a fundamental process required for plants and animals to grow, develop and reproduce.
By testing seven BYDV proteins individually in fission yeast – a model for cell division studies – 17K was found to be the only BYDV protein capable of inhibiting cell growth.
Through detailed molecular genetic and biochemical analyses, the researchers found that the 17K protein can disrupt cell division, and thus cell proliferation, on its own as well as in barley plants naturally infected by BYDV. They further showed that 17K perturbed the function of Wee1-Cdc25-Cdc2/Cdk1, a molecular switch for the orderly progression of cell division in both plants and animals.
Since the study’s datasets are all consistent with the idea that 17K – by its ability to disrupt cell division – is a key factor in promoting [or eliciting] host dwarfism by BYDVs, 17K may be a future target in BYDV control.
Notably, the researchers observed that BYDV 17K resembles several animal viral proteins, e.g., the Vpr protein of human immunodeficiency virus 1 (HIV-1) and the p17 protein of avian reovirus (ARV), in the inhibition of cell division and growth.
These three viral proteins represent a novel class of cell division regulators conserved between unrelated plant and animal viruses. They share similarities in secondary structure as well as some amino acid residues crucial to disrupting cell division. How they evolved and their implication for comparative studies of plant and animal viral pathogenesis are interesting questions for further research.
Figure 1. Disruption of barley cell division by BYDV 17K and secondary structure similarity among BYDV 17K and two animal viral proteins (HIV-1 Vpr and ARV p17) (Image by IGDB)
(A) A working model on cell division (mitosis) disruption by BYDV-GAV 17K protein in barley plants. Under normal growth conditions, G2/M transition is promoted by regulated phosphorylation and dephosphorylation of CDKA at threonine 14 (T14) and tyrosine 15 (Y15) sites, which involves proper and coordinated actions of Wee1 kinase and Cdc25 phosphatase. In the presence of BYDV infection or transgenically expressed 17K protein, G2/M transition is delayed because of abnormal phosphorylation and dephosphorylation of CDKA at T14 and Y15 sites. This abnormality is caused by direct interruption of Wee1-Cdc25-CDKA by 17K via multiple means, including up-regulated Wee1 accumulation, binding of 17K to CDKA and Cdc25, and possible inhibition of Cdc25's phosphatase activity in vivo. As a result, mitosis and cell proliferation are disrupted, leading to stunted plant growth and dwarfing symptom. (B) Similarities in the secondary structures of BYDV-GAV 17K, HIV-1 Vpr and ARV p17 modeled with the QUART software.
Jin, H., Z. Du, Y. Zhang, J. Antal, Z. Xia, Y. Wang, Y. Gao, X. Zhao, X. Han, Y. Cheng, Q. Shen, K. Zhang, R.E. Elder, Z. Benko, C. Fenyvuesvolgyi, G. Li, D. Rebello, J. Li, S. Bao, R.Y. Zhao*, and D. Wang* (*co-corresponding authors). 2020. A novel class of plant and animal viral proteins that disrupt mitosis by directly interrupting the mitotic entry switch Wee1-Cdc25-Cdk1. Science Advances. Ms#: aba341. In press.
QI Lei
Institute of Genetics and Developmental Biology (IGDB), Chinese Academy of Sciences