'How rabies virus blocks out immune response decoded'

Researchers have found a way to prevent rabies virus from shutting down the body's immune defence against it, an advance that may lead to the development of more effective anti-rabies vaccines.

The researchers, including those from the University of Melbourne in Australia, said many viruses, including the one that caused rabies, which kills more than 60,000 people globally each year, targeted the human protein STAT1 and related proteins to shut down the host's immune defences.

It was unknown until now exactly how the rabies virus' P-protein -- its main protein binding with the host immune system -- took hold of STAT1, they said.

This was due to a lack of direct structural data on how STAT1 bound with viral proteins, the researchers added.

As part of the study, published in the journal Cell Reports, the researchers produced the key proteins on the viral and host sides in a test tube, and kept them stable to interrogate their interaction directly.

When the researchers brought the two proteins together, using a chemical analysis technique called nuclear magnetic resonance spectroscopy, they could find the precise regions where the viral protein stuck and held onto STAT1 -- preventing it from cells that activated the host's immune response.

"We were able to find new regions and new sites for mutations and so could target these in a virus, completely preventing it from being able to grab hold of STAT1," said study co-author Paul Gooley from the University of Melbourne.

The researchers said this was the first direct structural analysis of a full-sized STAT1 binding to a viral protein.

Since many viruses, including the one causing measles, targeted STAT-1, the researchers said by disabling this binding they could strongly weaken even a highly pathogenic virus.

Gooley said the state-of-the-art technological tools and methods used in the study may also be applied more broadly to counter other viruses that target STAT proteins.

With a global drive underway to find better strategies against rabies, the researchers said methods used in several places across the world such as culling dogs have not worked to control the disease, and while mass vaccination is effective, they said, catching and injecting animals is problematic.

"The development of a new safe and highly effective rabies vaccine that can be given orally or as 'baits' would be a major step forward," said study co-author Greg Moseley from Monash University in Australia.