Researchers from the University of Toronto and Affinium Pharmaceuticals Inc. have found evidence that herpesviruses invoke several strategies that help it control components of the nucleus of the host cell that they are infecting. The study, published in the open-access journal PLoS Pathogens, has led to new information about the possible functions of over 100 previously uncharacterized viral proteins.

The researchers studied the three most common human herpesviruses – herpes simplex virus (type 1), Epstein-Barr virus, and cytomegalovirus. This ability of this class of virus to manipulate its host cell environment has resulted in a complex life cycle. Herpesviruses often present no symptoms, but they can lead to life-threatening diseases. By examining each viral protein individually in human cells, researchers were able to gather a more complete understanding of how the viruses change their host cells.

The three herpesviruses provided the investigators with more than 230 individual proteins to analyze. Their focus was on 93 identified viral proteins located in the cell nucleus that were known to change important cellular components responsible for the regulation of gene expression, cell growth and death, and antiviral responses.

Promyelocytic leukemia (PML) bodies are important nuclear structures on which cells depend to control cellular reproduction and survival, repair to damaged DNA, and the halting of virus replication. The researchers found that 24 of the nuclear viral proteins interrupted or reorganized PML bodies. Though several of these proteins did not have known functions, these findings suggest that herpesviruses use them as part of a multi-strategy approach for controlling a key regulator of necessary cellular processes, and thus enabling viral infection.

More research is required to determine the mechanisms in which identified viral proteins function in the context of viral infection, but ” Our study has given the first information on the potential function of 120 previously unstudied viral proteins and shows that each virus has multiple mechanisms to disrupt PML bodies that were not previously recognized,” conclude the authors.

Genome-Wide Screen of Three Herpesviruses for Protein Subcellular Localization and Alteration of PML Nuclear Bodies
Salsman J, Zimmerman N, Chen T, Domagala M, Frappier L
PLoS Pathogens (2008). 4(7):e1000100.
doi:10.1371/journal.ppat.1000100
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Written by: Peter M Crosta