Scientists can’t prove it yet, but they suspect the missing immune system component, a group of molecules known as the Major Histocompatibility Complex (MHC) Class Ia, has a previously unrecognized backup that is similar enough to step in and fill the void left by its absence. If so, that backup may become a new focus for efforts to design antiviral vaccines.
"This surprising finding contradicts a long-held belief about control of viral infection: that the immune system must have MHC Class I molecules to recognize and destroy virus-infected cells," says senior author Skip Virgin, M.D., Ph.D., professor of pathology and immunology and of molecular microbiology. "It also suggests that we may need to take a more extensive look at what immune system elements play a role in controlling chronic viral infections."
The study will be published in the May issue of Public Library of Science Pathogens.
In chronic herpes virus infections, the body brings the invader under control, reducing its replication and spread, but is unable to completely eliminate it, resulting in lifelong infection.
The mice in the study were injected with murine gamma herpes virus 68, a herpes virus that infects mice and is closely related to the human gamma herpes viruses Epstein-Barr virus (EBV, the cause of mononucleosis) and Kaposi’s sarcoma-associated herpes virus (KSHV, the cause of a form of cancer known as Kaposi’s sarcoma). Other herpes viruses that infect humans include the alpha herpes viruses herpes simplex virus 1 and 2, which cause cold sores and genital herpes, and varicella zoster virus, which causes chickenpox. Infection with gamma herpes viruses such as EBV and KSHV increases the risk of some cancers, especially in persons with weakened immune systems.
Immune system cells known as CD8 or cytotoxic T cells are responsible for recognizing virus-infected cells and killing them or sounding alarms that summon other defensive measures. To enable this recognition process, other cells regularly chop up viral proteins found in their interiors and display them on their surfaces. MHC Class I molecules act as a kind of stage for this inspection process, binding to the protein parts as they are sent to the surface and allowing CD8 T cells to recognize the presence of a foreign invader. When the CD8 T cells recognize a viral protein part, they either destroy the cell displaying the part or emit inflammatory hormones known as cytokines that trigger other immune defense measures.
Because the genetically modified mice used in their experiment lacked the genes that contain instructions for making MHC Class I molecules, Virgin and his colleagues expected to see little response from CD8 T cells when they injected the mice with herpes virus. Initially, that was exactly what they found.
"This was a study of chronic infection, though, and when we looked at the mice seven weeks later, we were surprised to find the mice making a very robust and effective CD8 T cell response," he says. "This suggests there’s an alternate way of generating CD8 T cells."
The researchers believe a closely related stand-in for MHC Class I makes it possible for mouse CD8 T cells to recognize and fight the virus.
"It would be reasonable for there to be backup plans, particularly given that some viruses have evasion strategies that they use to block the classical antigen recognition processes that rely on MHC Class I," Virgin says.
Follow-up studies now underway have produced preliminary evidence that these backup plans may be active even when normal MHC Class I is engaged in the fight against chronic infection. Additional studies will look at whether the backup system can enable an active immune response to other chronic infectious agents.
Some current efforts to develop antiviral vaccines focus exclusively on portions of viral proteins likely to be picked up and presented by MHC Class I molecules. If these backup mechanisms are important to control of herpes and other chronic diseases, they may pick up and display other parts of viral proteins for CD8 T cells to recognize. If so, vaccine developers may need to revise their approach in order to create vaccines that trigger the most potent antiviral immune responses.
"The ultimate relevance of these backup systems to human disease isn’t known yet, but it’s worth noting that we never would have even known to look for them if it weren’t for our ability to study genetically altered mice," he says.
Michael Purdy | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy