Advancing the health and well-being of animals and people

Outwitting a virus

BainesCan herpes viruses across species be disabled with a single knockout punch?

What comes to mind when you think of a herpes virus? For most non-scientists, probably a cold sore, or maybe the relatively benign STD that afflicts humans. Together, these well-known human viruses are otherwise known as Herpes simplex virus (HSV) 1 and 2. In fact, HSV is just one of a great multitude of viruses that belong to the herpes family, all sharing a common viral structure and replication mechanism.

And their effects can be quite devastating. In horses and dogs, herpes can cause abortion, neurological disorders, and juvenile deaths. In cats, the virus causes nearly 50% of all upper respiratory infections. In humans, herpes viruses are second only to influenza and the common cold in causing viral disease. The Epstein-Barr virus, one of eight herpes viruses that affect humans, is associated with infectious mononucleosis and two forms of cancer. Herpes viruses are also responsible for chicken pox and shingles. “This is a highly successful group of viruses,” said Joel Baines, James Law Professor of Virology in the Department of Microbiology & Immunology. “Every animal species has at least one herpes virus associated with it, and some of these are actually quite deadly.”

Baines speaks from battle line experience. His lab is investigating the process through which HSV assembles itself in the host cell nucleus, transforming that cell into a virus-producing factory that will ultimately release between 100 and 1000 infectious units. Specifically, Baines studies terminase, an enzyme that docks at a portal in the protein shell, or capsid, that surrounds the virus. After it has strategically positioned itself at the portal, this enzyme proceeds to pump 150 base pairs of DNA per second inside the capsid. “This is one of the most powerful molecular motors known in nature,” said Baines. “The force that is required per unit of mass rivals that of an internal combustion engine.” According to Baines, another outstanding feature of this wily virus is its ability to induce stress in a cell, then use the cell’s stress response to replicate itself all the more efficiently.

Baines’ work is particularly promising because terminase is the most genetically conserved feature to be found across the entire family of herpes viruses. By understanding the structure of terminase in greater detail, Baines hopes to identify the most highly conserved pockets within that structure. This could potentially lead to the coup de grace - synthesis of a drug that would bind specifically to these common structures, thereby disabling the DNA packaging process across all herpes viruses. Baines says that, with luck, such a drug could potentially be in clinical trails as early as 2015. His work is funded by the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the NIH.