American scientists have found that human cytomegalovirus (HCMV) uses a cloaking device, partly made of stolen goods from healthy cells, to avoid being detected and killed by the immune system.
Although HCMV is carried by eight in 10 people and generally does not affect the host, it has been linked to brain tumours.
AdvertisementBiologists Pamela Bjorkman and Zhiru Yang of the California Institute of Technology say that understanding how HCMV survives may help in the development of a vaccine, as well as in the fight against other viruses with similar evasive tactics.
"We are interested in mechanisms taken by viruses to escape our immune system," says Zhiru Yang.
Writing about their findings in the Proceedings of the National Academy of Sciences, the researchers have revealed that whenever a cell is infected, class 1 major histocompatibility complex (MHC) proteins presents viral peptides to signal T cells to kill it.
According to them, some viruses evolved to evade T cells by keeping MHC from reaching the cell surface, and the immune system in turn recruited other hunters to search for cells that don't show MHC proteins.
The researchers say that sometimes along its treacherous evolutionary path, HCMV stole a class 1 MHC molecule from its host and modified it for supreme stealth.
Bjorkman and Yang analysed the structure of the mimic, called UL18, to compare how similar it is to the real thing, and found that despite a mere 23 percent match in genetic sequences, UL18 looked almost exactly the same as a true class 1 MHC.
They say that the same immune cells that search for missing MHC proteins are designed to bind to them when they find them, thereby inhibiting an immune response.
Yang and Bjorkman have discovered that UL18 binds1,000 times tighter to such inhibitory receptors than real MHC molecules do.
"This is exactly what the virus wants--to avoid being recognized by T cells, but to engage inhibitory receptors to turn off immune cells. Only a small number of UL18 molecules are required to have the same inhibitory effect as a large number of MHC class I molecules," Yang says.
"What I find astounding is that the virus stole this gene and kept it almost identical but improved upon its binding," Bjorkman adds.
Bjorkman further states: "It (UL18) also binds peptides--that's unique to this MHC mimic. We don't know why," Bjorkman adds.
Yang says that in a trait it shares with HIV proteins, HCMV's UL18 covers itself with carbohydrates, which are unrecognisable to the immune system.
"It's a good example of a viral protein that evolved from its host ancestor to block unwanted interactions," Yang says.
"The more we understand that, the more effectively we can fight viruses that hide out," Bjorkman adds.