How Cytomegalovirus, a Herpes Virus, Sustains Its Lytic Expression Cycle in Infected Cell; Results May Have Broad Implications

Human cytomegalovirus is a leading cause of birth defects and transplant failures. As it's evolved over time, this virus from the herpes family has found a way to bypass the body's defense mechanisms that usually guards against viral infections. Until now, scientists couldn't understand how it manages to do so. A team of scientists led by Leor S. Weinberger, PhD, the William and Ute Bowes Distinguished Professor and Director of the Gladstone-UCSF Center for Cell Circuitry, uncovered the mechanism that allows the virus to replicate. The team’s study, published online on August 27. 2018 in PNAS, could open new therapeutic avenues to treat not only cytomegalovirus, but other viruses as well. The article is titled “Feedback-Mediated Signal Conversion Promotes Viral Fitness." Normally, when a DNA virus enters your cell, that cell blocks the virus's DNA and prevents it from performing any actions. The virus must overcome this barrier to effectively multiply. To get around this obstacle, cytomegalovirus doesn't simply inject its own DNA into a human cell. Instead, it carries its viral DNA into the cell along with proteins called PP71. After entering the cell, the virus releases these PP71 proteins, which enables the viral DNA to replicate and the infection to spread. "The way the virus operates is pretty cool, but it also presents a problem we couldn't solve," said Noam Vardi, PhD, postdoctoral scholar in Dr. Weinberger's laboratory and first author of the new study. "The PP71 proteins are needed for the virus to replicate. But they actually die after a few hours, while it takes days to create new virus.
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