Some viruses can hide in our bodies for decades and make 'fake' human proteins that trick our immune cells into believing nothing is wrong. Now researchers at the Imaging Centre of Excellence at Monash and Melbourne Universities have determined the basic structure of one of the two known families of these deceptive proteins.
Using synchrotron light on a common virus that lives in people happily and for the most part harmlessly, they have worked out the structure of the fake proteins. The research, published online by the Journal of Biological Chemistry, is an important first step towards producing better vaccines and drugs to fight viral disease.
The research team focused on the structure of m04 immunoevasin from mouse cytomegalovirus, a member of the m02 protein family. Cytomegaloviruses belong to the herpes virus family, which can cause glandular fever, chicken pox and cold sores. About half the population become infected with the virus, develop flu-like illness and then carry the virus for life. But the virus can be dangerous to pregnant women and people whose immune system becomes suppressed.
Monash University's Dr Richard Berry, a senior author of the paper, said the discovery was important for understanding how this family of viruses can hide from our immune systems.
"Our work highlights how these viruses mimic the immune system in order to evade it," Dr Berry said.
Immune T-cells patrol our bodies checking on the health of cells. One of the things they look for is a complex of proteins on the surface of cells. This major histocompatibility complex (MHC) presents a snapshot of what's inside the cell. If bits of viral protein are detected by the T cells, they flag the infected cell for destruction.
Viruses fight back by disrupting the production of the MHC protein complex, thus reducing the numbers on the outer membrane.
But then, the next stage of what could be described as an evolutionary arms race kicks in. If there are too few MHC proteins on the outer membrane of a cell, then a different type of immune cell, termed the natural killer cell, will kill the cell just to be safe.
Cytomegaloviruses have responded to this by making large families of fake cellular proteins that interfere with natural killer cell recognition. It is the basic structure of one of these families the researchers have revealed for the first time.
Professor Jamie Rossjohn, the other senior author and a Chief Investigator of the Imaging Centre, leads the research group.
"It's been a race against our international competitors which we won with the help of the Australian Synchrotron. We were only able to produce very small protein crystals from which to solve the structures -- too small to allow us to gain meaningful data with anything other than synchrotron X-rays," Professor Rossjohn said.
- R. Berry, J. P. Vivian, F. A. Deuss, G. R. Balaji, P. M. Saunders, J. Lin, D. R. Littler, A. G. Brooks, J. Rossjohn. The Structure of the Cytomegalovirus-Encoded m04 Glycoprotein, a Prototypical Member of the m02 Family of Immunoevasins. Journal of Biological Chemistry, 2014; DOI: 10.1074/jbc.M114.584128
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