Herpes virus mutant points to new vaccine strategy

Northwestern Now: Summaries

Axons, like those pictured above, are the so-called highways of the nervous system, which the herpes virus traffics to establish lifelong infection in a host. Photo by Laura Ruhge.
A Northwestern Medicine study published in PLOS Pathogens describes a newly-designed mutant herpes virus called R2 that provides a strategy for the development of novel herpes virus vaccines.
Herpes simplex viruses, known for causing cold sores and genital herpes, are two members of the alpha herpes virus family, which also includes the varicella-zoster virus, the cause of chickenpox. These viruses share a unique property: the ability to routinely and robustly infect the nervous system, establishing lifelong infection.
When a herpes virus initially enters a skin, or epithelial, cell, it begins shedding its outer layers, releasing viral proteins to perform their functions, but a small subset of viral proteins remains bound to the DNA-filled capsid, a protein shell that holds the DNA that will turn the cell into a herpes virus factory.
One of the proteins that escorts the DNA-filled capsid is the focus of the current study. Collaborators at Tufts University found that this protein, called protein UL37, has three distinct regions conserved in alpha herpes viruses, and the scientists discovered that mutating the second region, termed R2, exhibited an exciting trait.
Lead author Alexsia Richards, PhD, a former postdoctoral fellow in the laboratory of senior author Gregory Smith, PhD, professor of Microbiology-Immunology, explained that although the R2 mutant successfully infected epithelial cells, the virus failed to infect neurons.
These photos show a fluorescent herpes virus spreading in the tissues of a mouse. The virus is found in the mouse eye after infection of the cornea (top left) and proficiently invades the nervous system (top right). When mice are infected with the R2 mutant, the virus spreads in the mouse eye (bottom left) but is not detected in the nervous system ( …

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