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  Location: Home >> Research >> Research Progress
Researchers Discover A New Class of Plant and Animal Viral Proteins That Disrupt Host Cell Division
 
Viruses are ubiquitous pathogens and cause severe infectious diseases in both humans and agricultural crops. As most viruses have simple genomes and encode only a few proteins, they have to usurp host cell resources for propagation. To be successful in this life style, viruses need to manipulate host cell processes using their proteins. Understanding what host processes are disrupted and which viral proteins are involved will greatly facilitate 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), Chinese Academy of Sciences discovered a plant viral protein (namely 17K) that disrupts host cell division to promote its own propagation in the infected tissues.
 
The work is published online in Science Advances on 13 May, 2020. It is the result of a decade long collaboration between the IGDB group led by Dr. WANG Daowen and the laboratory of Dr. ZHAO Yuqi at the School of Medicine of University of Maryland.
 
The 17K protein is conserved in a group of cereal-infecting viruses called barley yellow dwarf viruses (BYDVs). These viruses frequently cause severe epidemics in global wheat, barley, maize and oat crops despite of being studied for more than 60 years. The typical symptoms induced by BYDVs are yellowing and dwarfing of host plants. Therefore 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, to develop, and to reproduce.
 
By testing seven BYDV proteins individually in fission yeast, which is a model system 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 revealed that the 17K protein can disrupt cell division, and thus cell proliferation, on its own as well as in the 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 process in both plants and animals (Fig. 1A).
 
Together, the different datasets generated in the study are consistent with the idea that 17K, by its ability to disrupt cell division, acts as a key factor in the elicitation of host dwarfism by BYDVs. Consequently, 17K may be used as a target for developing novel measures for controlling BYDV diseases in future studies.
 
Notably, the researchers observed that BYDV 17K resembled 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. Remarkably, 17K, Vpr and p17, despite of coming from unrelated plant and animal viruses, share similarity in their secondary structure (Fig. 1B) and a few amino acid residues crucial for cell division disruption. Thus, 17K, Vpr and p17 represent a novel class of cell division regulators conserved between plant and animal viruses. How this phenomenon evolved and its implications 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.
 
Reference
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.
 
Contact:
QI Lei
Institute of Genetics and Developmental Biology (IGDB), Chinese Academy of Sciences
Email: lqi@genetics.ac.cn