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New Compound May Assist in the Fight Against Cytomegalovirus

JAN 23, 2017 | KRISTI ROSA
Advancements are being made when it comes to a lifelong virus that has infected about 50% of individuals in the United States. The virus in question? Cytomegalovirus (CMV). Most of the time, a healthy individual’s immune system is able to keep the virus at bay, but those who are immunocompromised are not as lucky. For them, the virus can cause severe complications. Recently, researchers at Penn State College of Medicine have developed a compound that may be able to stop the virus from copying itself, and thus, may help prevent these individuals from experiencing effects from the disease.

There are medications available for those with weakened immune systems or babies who are presenting with symptoms of congenital CMV infection, but these current treatments can have a number of harmful side effects. The fact that a number of new mutations in the virus are becoming resistant to the medication is also another reason that new therapies are needed.

A Retro94-based compound discovered by the Penn State researchers might work to provide a new therapy as a recent press release from Penn State boasts that the compound can successfully keep the virus from copying itself. This means that immunocompromised individuals who have active CMV infection can be “treated with antiviral medication or even protected from the virus reactivating in the body before it occurs.”

Though about half of the individuals in the United States are infected with CMV, it can infect almost the entire adult population in developing countries. In addition to those who are immunocompromised (such as those living with HIV, those on chemotherapy, or those with transplants, among others), infants born with the virus can experience a number of serious health issues: loss of hearing, vision problems, microcephaly, and even intellectual impairment.

When CMV infects a human cell, a compartment is created where proteins are then “assembled into infectious viral particles.” Therefore, one of the big questions that the researchers wanted to answer was: how does this assembly compartment form? According to the press release, the researchers noted that in cells that are infected with the virus, there is a higher “level” of a protein called Syntaxin 5. Keeping this in mind, the researchers postulated that in order to create the compartment, the virus must take this protein from the host cell.

Using a technique called miRNA knockdown, the researchers were able to reduce the amount of Syntaxin 5 protein in infected cells. The results? “The compartments formed irregular shapes and produced fewer new virus particles,” according to the press release. By understanding the role that this protein plays in the infection, they found that “STX5 is important for normal cVac morphology and the proper localization of viral protein.”

The study authors noted that past research has shown that Retro94 has also been known to hinder this process. Therefore, working in a collaborative effort with Dhimant Desai, PhD, and Shantu Amin, PhD, in the department of pharmacology, the researchers created a “Retro94-based compound” and sought to test how it might influence infected cells.

In the press release, lead researcher Nicholas J. Buchkovich, assistant professor of microbiology and immunology at Penn State said, “We knew of a compound that modulates Syntaxin 5. We tested to see if that would inhibit the formation of the assembly compartment and, in turn, inhibit the actual production of the virus. That is, in fact, what we found.”

Due to the fact that the Retro94-based compound worked to inhibit the formation of the assembly compartments without negatively impacting the host cells, the researchers feel that Retro94 should be a focus of further research. They believe that it can potentially be used in a future therapy to combat CMV. In fact, Dr. Buchkovich already aims to test the Retro94-based compound in an animal model.
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