A Possible Mechanism by Which Viruses Can Establish Chronic Infections; Some Viruses Drive Production of Cytokine That Inhibits Function of CD8+ T-Cells

How do viruses that cause chronic infections, such as those caused by HIV or hepatitis c virus, manage to outsmart their hosts' immune systems? The answer to that question has long eluded scientists, but new research from McGill University has uncovered a molecular mechanism that may be a key piece of the puzzle. The discovery could provide new targets for treating a wide range of diseases. Fighting off infections depends largely on our bodies' capacity to quickly recognize infected cells and destroy them, a job carried out by a class of immune cells known as CD8+ T-cells. These soldiers get some of their orders from chemical mediators known as cytokines that make them more or less responsive to outside threats. In most cases, CD8+ T-cells quickly recognize and destroy infected cells to prevent the infection from spreading. "When it comes to viruses that lead to chronic infection, immune cells receive the wrong set of marching orders, which makes them less responsive," says Martin Richer, PhD, an Assistant Professor at McGill's Department of Microbiology & Immunology and senior author of the study, published online on January 23, 2018 Immunity. The article is titled “Interleukin-10 Directly Inhibits CD8+ T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity.” The research, conducted in Dr. Richer's lab by graduate student Logan Smith, revealed that certain viruses persist by driving the production of a cytokine (IL-10, image shown here) that leads to modification of glycoproteins on the surface of the CD8+ T-cells, making the cells less functional. That maneuver buys time for the pathogen to outpace the immune response and establish a chronic infection. Importantly, this pathway can be targeted to restore some functionality to the T-cells and enhance the capacity to control infection.
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