Learning from a virus: Keeping genes under wraps
By studying how the human cytomegalovirus, or CMV, packages its genetic material during infection, researchers have identified potential inroads for new therapies that could one day prevent birth defects and save transplant patients from virus-caused complications.
July 30, 2013 — An international collaboration of researchers including Felicia Goodrum of the University of Arizona’s immunobiology department has studied how a human herpes virus carried by the majority of the population packages its genetic information during infection.The discoveries improve the chances of developing more targeted therapies in place of existing drugs, which do not always work or come with side effects.Experts estimate that 60 to 90 percent of the world’s population carry the human cytomegalovirus, or CMV, which is one of the eight herpes viruses that infect humans.In healthy individuals, the virus lies dormant and does not cause overt disease. However, it poses a significant risk when contracted by unborn children — whose immune system has not matured yet — and individuals with compromised immune function.CMV is the leading cause of birth defects resulting from any infectious agent. It affects one in 150 births in the US and most commonly results in hearing loss, but can also cause cognitive or physical anomalies and cerebral palsy. Once infected, the virus stays in the body for life and flares up only when the immune system is suppressed, for example in AIDS patients, transplant patients and cancer patients undergoing intensive chemotherapy.For the study, published in the scientific journal Proceedings of the National Academy of Sciences (PNAS), Goodrum teamed up with collaborators in Germany and Israel.The researchers investigated how a fundamental aspect of the human cell regulates the virus: the mechanism by which genetic information is packaged and stored. Understanding how the viral DNA behaves in the human host cells during dormancy and reactivation of the virus provides the basis for the development of drugs that could prevent the virus from “waking up” and causing disease.”The human immune system is very sophisticated, and the way this virus has managed to stealthily integrate into our biology to ensure its own survival is no small feat,” said Goodrum, also a member of the UA’s BIO5 Institute.”CMV is a master of human cell biology. From transcribing DNA into blueprints for proteins to the manufacturing of those proteins, from cell division to cellular metabolism, there is not a process this virus has not tweaked,” Goodrum also said.That mastery, she explained, is the reason the virus is so elusive to vaccine, and there currently is no way to eradicate it. Goodrum noted that with other herpes viruses, like Epstein-Barr or chicken pox, the infection is obvious. But that is not the case with CMV.”From the perspective of a virus, that is the pinnacle of mastery — to infect without ever making its presence known,” Goodrum said.”To develop more effective antiviral strategies, we must understand the biology of the virus infection and how the virus manages to persist for our lifetimes,” she said. “We are trying to understand how our cellular mechanisms are being used by this virus and discover targets for drugs to control it.”Each human cell contains a thread of DNA that is about 6 feet long, stowed away in its nucleus and tightly packaged by proteins called histones. One such package of genetic material is called a chromosome.”You can imagine histones as a spool, and the thread is DNA that wraps around the spool,” Goodrum said. …
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