How viruses hoodwink the immune system

The human immune system is a startlingly complex and effective faculty. Given the countless pathogens to which we're exposed on a daily basis, it's remarkable that so few cause us even a twinge or a sniffle.

Yet some viruses are able to bypass this finely tuned system and cause chronic infections, and it's been the work of Dr Gabrielle Belz, Dr Adele Mount and colleagues at the Walter and Eliza Hall Institute to find out how.

“Chronic infections are one of the greatest health challenges for the Western world, but currently we have very few ways of dealing with them,” Dr Belz said in a statement. “They require ongoing medical care and support due to an inability to treat infection effectively.

“We are trying to understand how chronic infections sneak past the usually highly effective immune armoury and covertly establish disease. If we can stop these infections establishing then we can eliminate, or substantially reduce, that societal burden.”

In research published in the Journal of Immunology, they have revealed a cunning mechanism employed by viruses that interferes with the function of dendritic cells, which are antigen presenting cells that prime killer T cells to hunt down and eradicate the virus-infected cells.

They found a gene, K3, which is present in the gamma herpesvirus-68 in mice, which is a model for the human gamma herpesvirus 4, or Epstein-Barr virus. This gene is able to disable the key immune function of dendritic cells, preventing the immune system from recognising the viral infection.

“This gene quickly helps the virus to hide from the immune system by subverting normal antigen presentation to T cells, which have the critical task of destroying virally-infected cells,” Dr Belz said.

“The virus carries out a top-secret operation. It shuts down the normal mechanisms that allow the immune system to recognise an infection and then boards the antigen-presenting cells which ferry the virus through the blood and tissues, allowing it to spread throughout the body and establish system infection.”

The research could have implications on how we go about combating chronic infections.

“Our research shows that viral evasion of the immune system in chronic infections happens incredibly early,” Dr Belz said.

“Dendritic cells are compromised long before they have the chance to interact with T cells for the next phase of the immune response, so the T cells are never really activated properly. If we want to make an effective vaccine, we need to look at these early escape points used by the virus as the first target for trying to generate a more efficient immune response that will contain the virus and prevent it establishing a systemic infection.”

The paper was published in the Journal of Immunology.