Cytomegalovirus can Hijack a Central 'Traffic Controller' for Immune Cells

In a major scientific breakthrough, researchers from Monash University and the Lions Eye Institute have discovered a tissue protein that acts as a central 'traffic controller' for immune cells and can be hijacked by a virus to weaken immune responses. 

Published today in Nature, the study discovered a key mechanism that controls how immune cells coordinate their responses, and how a common virus can sabotage it.

The research reveals that a molecule called CD44 centrally controls the network of support cells that guide immune system function.

Within this network of support cells, stromal cells help immune cells move efficiently and exchange the information needed to fight infections, respond to vaccines, and maintain overall health.

In a landmark finding, the research team discovered that cytomegalovirus (CMV) can hijack this system by producing a protein that blocks CD44 function on stromal cells, derailing immune cell traffic at its source and weakening the body's antiviral response.

Lead researcher Professor Mariapia Degli-Esposti, Head of Experimental and Viral Immunology at Monash Biomedicine Discovery Institute and Head of Experimental Immunology at the Lions Eye Institute, said the findings fundamentally change how scientists understand the signals that shape immune function. 

"Think of the immune system like a busy city with millions of cells patrolling to keep us safe," Professor Degli-Esposti said. 

"CD44 acts as the central traffic controller; it keeps immune cells moving and coordinates their interactions at the right place and time.

"Our study identifies CD44 as a master regulator of immune cell movement and communication and shows that viruses can undermine immunity not only by attacking immune cells directly, but also by targeting the essential tissue infrastructure they rely on.

"This is a completely new way for a virus to target an immune response."

Co-lead researcher Dr Chris Andoniou, a Senior Research Fellow at Monash Biomedicine Discovery Institute and at the Lions Eye Institute, said the findings have wide-ranging implications for human health. 

Because CD44 plays such a central role in regulating immune activity, drugs inspired by the viral protein identified in this study could be developed to precisely dampen harmful inflammation.

By learning from the virus, we may be able to design therapeutic molecules that safely reduce excessive immune activation, which could ultimately help manage and treat autoimmune conditions. 

We are still in the early stages, but this is an exciting development."

Dr. Chris Andoniou, Senior Research Fellow at Monash Biomedicine Discovery Institute and at the Lions Eye Institute

This research was supported by funding from the Australian Research Council and the National Health and Medical Research Council.