The work was reported in the October 16 issue of the journal Cell Host & Microbe.
The study described the suppression of this immune response in mice infected with lymphocytic choriomeningitis virus, pointing to potential new avenues for the development of drug treatments for immunosuppressive diseases in humans.
"It's the first demonstration that a virus causes suppression of the interferon response in vivo," says the paper's senior author Michael Oldstone, a Scripps Research professor and a pioneer in immune system studies. "This model explains how a secondary infection can be caused by a normal virus infection and this provides the guide for what to do and where to look in human diseases, which are of course more difficult."
Mammals have two main ways to fight off infections. Adaptive immune responses are those that involve the production of antibodies and T lymphocytes that attack specific infections. In contrast, innate immune responses are genetically encoded and are generally the same regardless of infection type. One key component of the innate immune system is interferon, which plays a range of roles including direct antiviral effects, activating innate natural killer cells and adaptive T lymphocytes, which destroy a wide range of infectious invaders.
To better understand this system, the Scripps Research team, spearheaded by Elina Zuniga, formerly a postdoctoral fellow in the Oldstone lab who is now assistant professor at the University of California, San Diego, worked with mice infected with lymphocytic choriomeningitis virus, a model Oldstone describes as a Rosetta Stone for understanding viral pathogenesis and immune system recognition of foreign substances like microbes and viruses. The researchers found that the virus suppressed the mouse immune system by interacting with immune cells known as plamacytoid dendritic cells, which are key producers of one of two critical groups of interferons, known as type I.
When plasmacytoid dendritic cells come in contact with viruses and other foreign invaders, they bind with them via membrane proteins known as toll-like receptors. Under normal conditions, this binding triggers massive production of type I interferon that then triggers other immune responses.
But the lymphocytic choriomeningits virus, and presumably other immunosupressor viruses like measles and HIV, disable this system. This then compromises other reactions, most critically activation of the natural killers that would otherwise destroy the virus-infected cells, as well as other invaders.
The researchers showed that once in this infected condition, a secondary opportunistic agent, in this case the herpes virus murine cytomegalovirus, which the mice could have otherwise fought off, grew unchecked. Remarkably, opportunistic infections with herpes viruses are frequently observed in patients infected with HIV and the mechanism described in this study could well be one of the underlying causes.
One critical aspect of the group's findings is that while the initial lymphotcytic choriomeningitis virus effectively blocked interferon production, it did not kill the dendritic cells, instead allowing them to function as long-term hosts. This allows such viruses to persist, causing persistent immunosuppression.
"I think the implications are that many of the diseases we don't know the causes for, be they behavioral, mental, cardiovascular, or endocrine, may well be caused by viruses that persist without destroying the differentiated cells they infect, alter their functions, and by this means alter homeostasis and cause disease," says Oldstone. "Examples would be viruses that persistently infect neurons and cause problems in learning and behavior, viruses that infect oligodendrocytes and cause demyelination, and viruses that infect endocrine cells and alter their production of hormones. There may be some differences, but most certainly there are a lot of commonalities."
Oldstone says that knowing such basic details about how a virus can suppress the mouse immune system could well aid the development of new treatments for the many immunosuppressive conditions such as HIV and measles that plague humans. "I think that our study opens up an avenue for people who work in those human diseases to translate our findings," says Oldstone.
For now, Oldstone's group is focused on identifying the signals and molecules involved in the lymphocytic choriomeningitis virus's crippling of the dendritic cells' interferon production.
Keith McKeown | EurekAlert!
‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie
Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
24.10.2016 | Earth Sciences
24.10.2016 | Life Sciences
24.10.2016 | Physics and Astronomy