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New Insight into a Leading Cause of Birth Defects

Researchers reveal preferential repair of the viral genome within a cell infected with Human Cytomegalovirus.

--by Alexia Severson A geneticist looking through a microscope

The Gist

Researchers reveal new insights into the behavior of Human Cytomegalovirus (HCMV), a leading cause of birth defects in the United States, in a new study published in the open-access journal PLOS Pathogens.

HCMV, also known as CMV, is a common virus that remains dormant in healthy individuals, but is cause for concern among pregnant women with weakened immune systems. According to the Mayo Clinic, CMV spreads through bodily fluids, such as blood, saliva, urine, semen, and breast milk.

While there is currently no cure for CMV, researchers in this study discovered that the virus co-opts cells’ ability to repair themselves, providing a new understanding of the ways infections defeat cells’ defenses and offering hope for future treatment of the virus.

About 40,000, or one percent, of babies born in the United States are infected with HCMV each year. And though it is rare, about 4,000 babies infected with HCMV are born with conditions such as loss of vision and hearing, cerebral palsy, mental retardation, and microcephaly, or small head size. Others may develop problems such as progressive hearing loss during childhood.

The Expert Take

When HCMV infects a cell, it sets up centers inside the nucleus to replicate itself, and the proteins that repair cellular damage, including one known as the “guardian of the genome,” become trapped in these centers.

If researchers can figure out how the virus interacts with these cellular proteins to keep them from repairing the cellular DNA, they could target those specific viral proteins and preserve the DNA, said Lee Fortunato, the study’s senior corresponding author and an associate professor of biological sciences at the University of Idaho.

In this study, Fortunato hypothesized that the virus was using the cell’s repair mechanisms for itself, leaving the cells unable to fix themselves or to stop the spread of the virus. To test this, the researchers exposed infected cells to ultraviolet (UV) irradiation, damaging the cellular and viral DNA. A day after being exposed to UV rays, researchers found that the viral DNA had been repaired and was back to normal. However, the cellular DNA was still damaged, which could still lead to an infected fetus.

“This is a double-stranded DNA virus,” Fortunato said. “By separating out the viral DNA versus the cellular DNA we could determine what was happening specifically to the viral DNA and what was happening specifically to the cellular DNA. What we’ve shown is that the viral genome actually is repaired and that the host genome is not.”

Fortunato said researchers need to get a better grasp on which components of the virus are causing this this inability to repair the host genome and that further research is required.  

“It really is a big health problem in terms of being one of the major causes of birth defects,” she said. “We should be paying more attention to this virus and what it does to cells and be aware that it really does damage them very specifically.”

Source and Method

Researchers used an agarose gel assay to help understand what happened as the cells’ repair machinery tried to operate. In these assays, damaged DNA runs as a long smear when passing through the gel due to the presence of small fragments. As repair occurs, these small fragments come back together to form larger strands of DNA that stay near the top of the gel.

Unlike typical studies that examine total DNA, both cellular and viral, in an infected cell together, Fortunato’s test tracked viral and cellular DNA repair separately in each sample.

The Takeaway

Currently, maternal CMV infections can be circumvented with immune boosting drugs that help decrease the risk of the baby being born with symptoms of CMV infection, according to the American Pregnancy Association, but there are no treatments for prenatal or postnatal infection.

The research by Fortunato and her colleagues could lead to future antiviral therapies. In the meantime, CMV is preventable. The American Pregnancy Association recommends using safe hygiene practices, such as good hand washing and wearing gloves when changing diapers and interacting with children.

Other Research

Various studies have been done on HCMV in recent years. One of the most recent studies published online in PLOS ONE and sited online in Science Daily in November 2012, revealed for the first time that primitive human stem cells are resistant to HCMV. Researchers concluded that this research may allow them to find effective treatments and ways of preventing the virus’ devastating consequences.

In a study published in 2012 in the journal of the American Association for the Advancement of Science, researchers discovered a surprisingly complex protein-coding capacity of human cytomegalovirus, providing a better understanding of how the virus manipulates human cells during infection. While the genome of HCMV was first sequenced more than 20 years ago, researchers investigated the proteome, or the complete set of expressed proteins, of this common pathogen.

Another study, published in the Journal of Clinical Virology in 2009, evaluated the impact of prenatal CMV infection screening and counseling among pregnant women informed about CMV infection. Researchers in this study concluded that if clear information is given on CMV infection during pregnancy, the rate of seroconversion is lower following counseling than before counseling.

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Tags: Latest Studies & Research , Treatments

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