A new Northwestern Medicine study has uncovered the way herpes viruses use ubiquitin, a regulatory protein found in most cells, a finding that may explain their ability to routinely enter the nervous system and their prevalence in human hosts. Gregory Smith, PhD, associate professor of Microbiology-Immunology , and Nicholas Huffmaster, a graduate student in the Driskill Graduate Program in Life Sciences , documented how herpes viruses repurpose ubiquitin to switch between two invasive states in a paper recently published in the Proceedings of the National Academy of Sciences.
Cells use ubiquitin to modify other proteins, and herpes viruses tap into this system to orchestrate a well-timed alteration of their properties. By removing the ubiquitin modifier, the virus calibrates to the first invasive state, which allows it to access nerve endings while replicating within the skin tissue. The second invasive state is triggered by the addition of the ubiquitin modifier.
It is in this state that the virus acquires the ability to travel within nerve fibers further into the nervous system. Unlike other viruses, the switch between invasive states allows the herpes virus to overcome successive barriers that normally protect the peripheral nervous system from infection.
With over half the U. The virus outsmarts the immune system by interfering with the process that normally allows immune cells to recognize and destroy foreign invaders. How exactly the herpes simplex 1 virus pulls off its nifty scheme has long been elusive to scientists. Now new research from The Rockefeller University sheds light on the phenomenon.
A team of structural biologists in Jue Chen's Laboratory of Membrane Biology and Biophysics have captured atomic images of the virus in action, revealing how it inserts itself into another protein to cause a traffic jam in an important immune system pathway.
The findings were published in Nature on January Our findings provide a mechanistic explanation for how it's able to escape detection by immune cells. When a virus enters the body, it gets chewed up inside cells, and little pieces end up stuck to the outside of the cell.
One piece of the machinery involved in getting bits of virus to the cell's surface is a protein called TAP. It's a transporter that acts as a bridge to move the virus pieces across the membrane of the endoplasmic reticulum, a structure within the cell that packages the virus bits.
From here they move to the cell's surface, alerting immune cells to the virus's presence. One, it precludes the regular protein from binding. Two, it makes the transporter stuck in this conformation. It has been notoriously difficult to investigate the structure of proteins embedded in cellular membranes, such as TAP, because the samples are not stable and disintegrate easily.
The team studied the herpesvirus in animals, and also in human and animal cells in culture under high-resolution microscopy.
In one experiment, scientists mutated the virus with a slower form of the protein dyed red, and raced it against a healthy virus dyed green. They observed that the healthy virus outran the mutated version down nerves to the neuron body to insert DNA and establish infection. It is striking to watch," Smith says. He says that understanding how the viruses move within people, especially from the skin to the nervous system, can help better prevent the virus from spreading.
Additionally, Smith says, "By learning how the virus infects our nervous system, we can mimic this process to treat unrelated neurologic diseases. Even now, laboratories are working on how to use herpesviruses to deliver genes into the nervous system and kill cancer cells.
Smith's team will next work to better understand how the protein functions. He notes that many researchers use viruses to learn how neurons are connected to the brain. Materials provided by Northwestern University. Note: Content may be edited for style and length. Science News.
Story Source: Materials provided by Northwestern University.
0コメント