Navigation Links
A viral cloaking device

PASADENA, Calif.--Viruses achieve their definition of success when they can thrive without killing their host. Now, biologists Pamela Bjorkman and Zhiru Yang of the California Institute of Technology have uncovered how one such virus, prevalent in humans, evolved over time to hide from the immune system.

The human immune system and the viruses hosted by our bodies are in a continual dance for survival--viruses ever seek new ways to evade detection, and our immune system devises new methods to hunt them down. Human Cytomegalovirus (HCMV), says Bjorkman, Caltech's Delbrck Professor of Biology and a Howard Hughes Medical Institute (HHMI) Investigator, "is the definition of a successful virus--it thrives but it doesn't affect the host."

HCMV is carried by eight in 10 people. Although it generally harms only those who are immunocompromised, it has also been linked with brain tumors like the one for which Ted Kennedy recently had surgery. 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 Caltech biology postdoc and HHMI associate Zhiru Yang. She and Bjorkman published their findings on HCMV survival mechanisms in the July 15 edition of Proceedings of the National Academy of Sciences. They describe the underpinnings of a viral cloaking device, partly made of stolen goods from healthy cells, that helps HCMV to move undetected through the body.

For 20 years, Bjorkman's lab has been dedicated to understanding class 1 major histocompatibility complex (MHC) proteins and the immune response, most recently related to AIDS research. MHC proteins carry peptides, small pieces that are chopped up from the cell's internal proteins, to the cell's surface. If a cell has been infected, MHC presents viral peptides to signal T cells to kill it. So some viruses evolved to evade T cells by keeping MHC from reaching the cell surface. In turn, the immune system recruited other hunters to search for cells that don't show MHC proteins.

Sometime along its treacherous evolutionary path, HCMV stole a class 1 MHC molecule from its host and modified it for supreme stealth. "This is a decoy," Bjorkman says. She and Yang analyzed the structure of the mimic, called UL18, to compare how similar it is to the real thing. They found that despite a mere 23 percent match in genetic sequences, UL18 looks almost exactly the same as a true class 1 MHC.

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 found that UL18 happens to bind 1,000 times tighter to these 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," Yang notes. "Only a small number of UL18 molecules are required to have the same inhibitory effect as a large number of MHC class I molecules."

"What I find astounding is that the virus stole this gene and kept it almost identical but improved upon its binding," Bjorkman says.

UL18 didn't stop there. "It also binds peptides--that's unique to this MHC mimic. We don't know why," Bjorkman adds. The peptide is obscured from killer cells by yet another shield, Yang says. In a trait it shares with HIV proteins, HCMV's UL18 covers itself with carbohydrates, which are unrecognizable to the immune system. A real class 1 MHC molecule has one site for adding carbohydrates; the fake has 13, Bjorkman notes. The only place where it's not covered is where it binds to the inhibitory receptor.

All its efforts have made UL18 virtually undetectable. "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.


Contact: Elisabeth Nadin
California Institute of Technology

Related biology news :

1. Clearance of hepatitis C viral infection after liver transplantation
2. Feline virus, antiviral drug studied to understand drug resistance
3. Drug aimed at 2 bioterror agents blocks live viral infection, Weill Cornell team reports
4. Tumor-targeting viral therapy slows neuroblastoma, malignant peripheral nerve sheath tumors
5. Scientists discover DNA knot keeps viral genes tightly corked inside shell
6. Control switches found for immune cells that fight cancer, viral infection
7. Device helps patients survive, regain function til transplant
8. Researchers developing device to predict proper light exposure for human health
9. IGERT fellows to design biodevices using flexible electronics
10. MIT aids creation of neural prosthetic devices
11. Atmospheric measuring device for understanding smog formation
Post Your Comments:
(Date:11/9/2015)... , Nov. 9, 2015  Synaptics Inc. (NASDAQ: ... today announced broader entry into the automotive market with ... match the pace of consumer electronics human interface innovation. ... are ideal for the automotive industry and will be ... Europe , Japan ...
(Date:10/29/2015)... , Oct. 29, 2015  The J. Craig Venter ... titled, "DNA Synthesis and Biosecurity: Lessons Learned and Options ... of Health and Human Services guidance for synthetic biology ... --> --> ... has the potential to pose unique biosecurity threats. It ...
(Date:10/29/2015)... , October 29, 2015 ... authentication company focused on the growing mobile commerce ... announces that StackCommerce, a leading marketplace to discover ... the Wocket® smart wallet on StackSocial for this ... ("NXT-ID" or the "Company"), a biometric authentication company ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... - ProMetic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) ("ProMetic" ... , President and Chief Executive Officer of ProMetic, will be ... th Annual Healthcare Conference to be held at the ... st , at 8.50am (ET) and ProMetic,s management team ... presentation will be available live via a webcast accessible at ...
(Date:11/24/2015)... Nev. , Nov. 24, 2015  PDL BioPharma, Inc. ... P. McLaughlin , the company,s president and chief executive officer, ... Healthcare Conference next week in New York City ... occur on Tuesday, December 1, 2015 at 9:30 a.m. EST. ... Please connect to the website at least 15 minutes prior ...
(Date:11/24/2015)... Nov. 24, 2015 According to two new studies, ... This is something that many doctors, scientists, and public health ... remains: with fewer PSA tests being done, will there be ... Dr. David Samadi, "Despite the efforts made in ... the second leading cancer cause of death in men, killing ...
(Date:11/23/2015)... 2015 China Cord Blood Corporation (NYSE: ... of cord blood collection, laboratory testing, hematopoietic stem cell ... preliminary unaudited financial results for the second quarter and ... 2015. --> --> ... for the second quarter of fiscal 2016 increased by ...
Breaking Biology Technology: