When investors hedge a bet, they divide their money between risky investments that can bring big returns and reliable investments that help ensure that not everything is lost in the event of a market crash. Researchers at the Gladstone Institute have found that herpesvirus cytomegalovirus uses a similar approach to infecting the human body. The study is published in the journal Proceedings of the National Academy of Sciences.
Cytomegalovirus is a common virus of the same family as herpes simplex, chickenpox, and mononucleosis. More than half of all people become infected with cytomegalovirus throughout their lives. When infection occurs, the virus often goes into a dormant state, providing a person with a lifetime infection. However, in some cases, the virus emerges from a dormant state; for example, in children, and in transplant recipients. This not only leads to serious health problems but can also result in death. Indeed, cytomegalovirus is the main cause of birth defects in children and the main cause of transplant failure after transplantation.
In a new study, scientists describe in detail how cytomegalovirus goes into a dormant state: by changing the levels of certain proteins in its viral particles. This gives some of them a greater ability to cause disease, while others give a tendency to a latent state. This is the viral version of the “safe bet” that allows the virus to persist throughout the patient’s life.
Cytomegalovirus is a devastating disease that causes serious birth defects. We now have a new understanding of how the virus establishes latency, which, in our opinion, will help pave the way for new methods of treatment.
Lor Weinberger, first author of the study and director of the Center for Cellular Scheme at Gladstone Institutes
Under a microscope, scientists noticed that some cytomegalovirus particles have a very high level of pp71 protein, while others do not. Protein pp71 is involved in the replication of viral DNA, and also helps the virus evade the immune response of the human body. However, the researchers wondered why some particles contain much more protein than others.
Some particles had 40 times more protein. Other viral proteins changed the concentration only twice between the individual particles of cytomegalovirus. Scientists then discovered that particles with more pp71 protein were more contagious and reproduce more of their DNA than particles with less pp71.
When pp71 protein was present at higher levels, the virus had an advantage and could undergo faster replication. But the discovery posed an interesting question: if high protein levels provide an evolutionary advantage for the virus by enhancing replication, why does the virus still create some particles with a relatively small amount of pp71?
Scientists have suggested that particles with a low pp71 level should also have an evolutionary advantage under various conditions. And, indeed, the researchers found that a low level of pp71 was needed by the virus to establish latency.
A better understanding of how viruses establish latency can help researchers develop more effective treatments that eliminate not only the entire active virus in someone else’s body but also its hidden copies.