PNNL

The Science

This review paper pays homage to the advancements in omics studies, particularly as they relate to detection and understanding of protein post-translational modifications and how PTMs change during viral infection. Focusing on the discovery and functional elucidation of PTMs—either on host or viral proteins—will not only deepen scientists' understanding of molecular pathology but also pave the way for improvements in therapeutics and diagnostics for infectious diseases.

During infection, viruses hijack cellular machinery and turn host cells into virus factories and PTMs contribute to the activation or dampening of many cellular functions required for productive virus replication. Diverse PTMs play critical roles in the mechanics of the host immune response to infection and targeting the enzymes that add PTM to defensive host proteins could serve as promising anti-viral targets. This highlights the need for more characterization of PTMs to understand virus-host interactions and inspires development of new anti-viral interventions. However, there is a lack of PTM studies in virus infected primary cells and PTM analysis of biofluid samples from infectious disease patients.

The Impact

Removal or addition of PTMs regulate mechanical functions within cells. Better understanding of how and why these modifications happen can help or hinder their impact. In human health, for example, antiviral agents can be designed to target specific enzymes that alter protein PTMs, which are known to be required for virus replication. This prevents the virus from hijacking the cellular functions and, hopefully, stops disease outcomes before they start. To achieve this, though, scientists need to recognize and close knowledge gaps about infection induced PTMs (that could serve as disease progression biomarkers) and overcome technical constraints so that future applications in clinical settings can be realized. 

Summary

Advancements in sample processing and instrument development, such as automation, have allowed researchers to make big discoveries in omics fields. One such discovery—understanding the critical role PTMs play in virus-host interactions—is uniquely complex, but it could also lead to huge impacts in human health. 

Researchers have described about 600 types of PTMs and several are reversible, including phosphorylation, ubiquitination, acetylation, glycosylation, methylation, and redox modifications. In the context of virus-cell interactions, the importance of PTMs has been well-demonstrated--though the science is expanding all the time--and the outcome of PTM regulation can either promote or inhibit viral replication.

Accordingly, investigation of the molecular basis of virus-host interactions has elucidated key steps in how viruses evolve to evade host defensive responses and enhance the intracellular environment to facilitate transmission and spread. Such knowledge is also crucial for developing novel host-directed antiviral strategies.

Contacts

• Tong Zhang, tong.zhang@pnnl.gov, PNNL
• Amy Sims, amy.sims@pnnl.gov, PNNL

Funding

The research described in this paper is part of the Predictive Phenomics Initiative at Pacific Northwest National Laboratory and conducted under the Laboratory Directed Research and Development Program. PNNL is a multiprogram national laboratory operated by Battelle for the Department of Energy under Contract No. DE-AC05-76RL01830.