In a world of emerging and devastating viral infections such as Zika, Ebola, and influenza, the importance of understanding how viruses target our immune system, and the need to develop new therapies, has never been greater. Now, a team of scientists at Trinity College Dublin has discovered that a biological molecule important in cell growth (STAT3, or signal transducer and activator of transcription) is also critical in protecting us against infection—so much so that we would be unable to fight the common flu virus without it.
This new discovery could pave the way for the development of novel therapeutics charged with restoring our natural immunity to a whole spectrum of viruses that have evolved roadblocks to the immune response. The findings from this study were published recently in Cellular and Molecular Life Sciences in an article entitled “A Novel Anti-Viral Role for STAT3 in IFN-α Signalling Responses.”
During any viral infection, host cells produce an immune molecule called interferon, which essentially disrupts the battle plans of attacking viruses—preventing them from replicating in our bodies. When cells are stimulated by interferon-α, a cascade of molecules within the cells is activated like a series of dominos, typically leading to clearance of the viral infection.
The interferon signaling pathway initiates the production of several hundred immune molecules that act to destroy viruses and amplify our immune response against them. Yet even with this mechanism in place, many viruses are not cleared by the immune response and can often cause serious illness. With this in mind, the Trinity researchers wondered how viruses suppress the immune response. What they discovered was that cells had evolved numerous methods to inhibit these signaling pathways and thus block responses to interferon.
“We thought that since the interferon signaling pathway enhances the immune response against viruses so effectively, viruses might have evolved means to block it—such a reality would explain why several viruses are so troublesome to defeat,” remarked senior study investigator Nigel Stevenson, Ph.D., assistant professor at Trinity College Dublin.
Over the past few years, Dr. Stevenson and his team have discovered that hepatitis C virus (HCV) and respiratory syncytial virus (RSV), among others, specifically target the interferon signaling pathway, which helps them avoid being naturally cured by our immune systems.
“For decades, we have known that STAT3 is essential for healthy cell growth, but our new revelation identifies it for the first time as an essential antiviral component in the interferon signaling pathway,” Dr. Stevenson explained. “In fact, we found that without STAT3, cells cannot fight the common flu virus or the pox vaccinia virus.”
Scientists had, until now, believed they fully understood how the interferon signaling pathway worked, but by using a series of viral infections and cutting-edge molecular techniques, the Trinity team discovered a new antiviral role for STAT3.
“Of course, a major goal of our ongoing work is to find solutions to the real-world problems faced by the thousands of people who cannot clear certain viruses after they have been infected,” Dr. Stevenson concluded. “This discovery opens the door to new therapeutic options, which, we hope, will be able to help people restore their natural immunity against a host of problematic viruses.”