More than half of all individuals in the United States are infected with herpes simplex virus type 1 (HSV-1), a virus that lives in the peripheral nervous system and cannot be removed. According to a new study, HSV-1's strategy for infecting the nervous system involves hijacking a cellular protein from the epithelial cells it first infects and then using this protein to infect and reach the nucleus of peripheral nervous system cells.
The findings, according to Northwestern University researchers, could aid in the development of long-needed vaccinations for both HSV-1 and its close relative, HSV-2.
"It reprograms the cell to become a virus factory," Gregory Smith, a Northwestern Medicine immunologist, said.
"The big question is how does it get to the nucleus of a neuron?"
A protein called pUL36, which is encoded by the virus, provides a hint. The protein can lock onto dynein molecules, which are tiny biological motors that click-clack their way along the web of rigid strings that help give a cell its form.
To put it another way, herpes appears to navigate the inside of every cell it infiltrates by hitching a ride on the cell's own rail network, using its own tiny grappling hook.
Observations on many other cells, however, suggested that there had to be more to the story. The rail ride wasn't random or even in a single direction in some tissues. The virus was able to travel to the cell's periphery, which could not be explained only by a dynein ride.
But the herpes virus didn't appear to make anything else that could assist it in navigating the network.
The researchers have now demonstrated that the virus merely steals a tool from the cells it infects. This second molecular device, kinesin, is a motor protein that literally moves along the microtubule strings that support the cell.
It's not uncommon for a virus to use both dynein and kinesin to move about inside a cell. Herpes cleverly grabs one half of this collection from one cell type and uses it in another to migrate more efficiently.
Further research determined how this theft aided the virus's entry into the nucleus of a nerve cell. It was able to take an express straight to DNA central once it entered the neuron's body, avoiding the additional delay of randomly zig-zagging back and forth.
It's the first time a virus has been observed repurposing a protein to aid its infection, a finding that could help us better understand our relationship with this ancient pathogen and, perhaps, find a means to keep it out of our DNA.
Finding a viable cure, if not a vaccine, would provide a great deal of relief and security to individuals all around the world.