AsianScientist (Jul 10, 2014) – Scientists have determined the structure of a protein that the cytomegalovirus uses to evade the immune system, an important first step towards producing better vaccines and drugs to fight viral disease. This research has been published in the Journal of Biological Chemistry.
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 Center of Excellence at Monash and Melbourne Universities have determined the basic structure of one of the two known families of these deceptive proteins known as immunoevasins.
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 asymptomatically. However, 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.
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. However, 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. Understanding the basic structure of these proteins could help scientists develop ways to treat cytomegalovirus infection.
“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,” said Professor Jamie Rossjohn, Chief Investigator of the Imaging Center of Excellence.
The article can be found at: Berry et al. (2014) The Structure of the Cytomegalovirus-Encoded m04 Glycoprotein, a Prototypical Member of the m02 Family of Immunoevasins.
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Source: Monash University; Photo: Yale Rosen/Flickr/CC.
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