February 07, 2012
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Major Key to Viral Latency DiscoveredViral latency or dormancy has long puzzled medical researchers. It's the process by which an active infection ceases because viral production has ceased. This may sound like a step in the right direction, but in the case of dormant viruses like herpes, the virus has not been eliminated. It has beaten a strategic retreat and is hiding, no longer susceptible to drugs or a patient's immune system. Eventually, the virus reactivates, causing another full-blown infection. This "on again, off again" cycle can continue for a patient'sentire life. Until now, researchers have made little headway in understanding how a virus becomes latent or maintains latency. It's been akin to magic. The team at Duke's department of molecular genetics and microbiology has changed all this. Working with herpes simplex 1 virus (HSV-1), the cold sore virus, the team has found that its latency is maintained by a specific piece of RNA manufactured by the virus, even in its latent stage. Scientists had previously observed that latent HSV-1 produces only one gene product, called "latency associated transcript RNA" (LAT RNA). This product had no known function. The head of the team, Dr. Jennifer Lin Umbach, explains that LAT RNA "is processed into smaller parts called microRNAs, and those microRNAs are actually used to target the genes that are required for active replication." In other words, dormant HSV-1 produces just enough LAT RNA to act as a damper on the genetic switch that causes viral replication. Eventually, some unknown factor interferes with this mechanism and viral reproduction (and disease symptoms) temporarily resume(s). If this mechanism could be blocked, the virus would remain susceptible to attack Dr.Umbach said that her team is already experimenting with a drug that blocks latency by binding to the microRNAs and inhibiting their function. This causes the virus to reactivate, hopefully allowing a drug like acyclovirTM, coupled with a healthy immune system, to eliminate the virus from the body, ending the infection for good. This strategy appears to be working, at least in the test tube. But as Dr. Umbach cautions "There are animal trials underway and we are looking into clinical trials for humans. But it will be a while before we can get there." Up to 80% of Americans are infected with the cold sore virus. Some infected people show no symptoms at all, but many will suffer outbreaks of cold sores around the lips and mouth. While this is inconvenient and may be painful, it can't compare with the problems experienced by sufferers of genital herpes (HSV-2) and shingles (Varicella Zoster), which are also caused by herpes viruses. Now there is at least a clue as to how the causative agents of those diseases maintain latency, and an approach on how to deal with it. In fact, the Duke group plans to target the shingles virus next. July 18, 2008
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