New Discovery Could Revolutionize Treatment for Common Birth Defect Cause

Scientists have uncovered a hidden mechanism employed by cytomegalovirus (CMV), a widespread herpes virus. This finding provides fresh insight into preventing birth defects and vascular diseases, opening doors to novel antiviral drug development and possibly helping combat other herpes viruses.

CMV’s Clever Entry Strategy

Researchers from the University of Pittsburgh School of Medicine and the La Jolla Institute for Immunology have made a breakthrough. They’ve identified a unique way CMV, a herpes virus infecting most adults worldwide, infiltrates blood vessel cells. It uses an alternative “key” to evade the body’s immune defenses.

CMV employs a protein called gH to enter cells, similar to other herpes viruses. Unlike its herpes relatives, CMV exchanges gL with a partner, UL116, and recruits UL141. This gH-UL116-UL141 complex, dubbed GATE by the study authors, provides a backdoor into blood vessel lining cells, preventing immune detection.

“If we don’t know what weapons the enemy is using, it is hard to protect against it. We found a missing puzzle piece that represents one possible reason why immunization efforts against CMV have been unsuccessful.”

—Jeremy Kamil, Ph.D., Senior Author, Associate Professor of Microbiology and Molecular Genetics at Pitt

Implications and Potential Therapies

Congenital CMV infection affects around one in 200 babies in the United States. Of those infected, about 20% suffer birth defects like hearing loss, and may face long-term health problems. Globally, congenital CMV is the leading infectious cause of birth defects (CDC, 2024).

The GATE complex may be a new target for CMV vaccines and other herpes viruses. Previous efforts at producing a CMV vaccine failed before the identification of GATE, according to the researchers. Targeting GATE could improve the prospects of combating CMV infections, potentially clearing this persistent infection from our bodies.

Next Steps

The collaborative study included researchers such as Michael Norris, Lauren Henderson, Mohammed Siddiquey, Jieyun Yin, Kwangsun Yoo, Simon Brunel, Michael Mor, and Erica Ollmann Saphire. This work received support from the National Institutes of Health and ARPA-H.

The research team aims to develop antiviral drugs and vaccines that can block CMV’s entry. These could address the diseases the virus causes in both developing babies and individuals with weakened immune systems.