A newly discovered defense mechanism stands to transform treatment for deadly mosquito-borne viruses. In a new study, researchers from the University of Pittsburgh Center for Vaccine Research provide the first-ever description of the process whereby the eastern equine encephalitis virus (EEEV) hijacks cellular systems and evades the immune system. Besides illuminating a new drug target for a virus that kills half of the people it infects, the discovery could also improve treatment for the West Nile virus, dengue, severe acute respiratory syndrome (SARS), and rhinovirus.
Although the biological quirks of viruses tend to make conventional drugs futile, the body’s own army of immune cells eventually clears minor infections on their own. However, some intruders have evolved mechanisms that allow them to circumvent these defenses and continue to drive pathogenicity. The current study, which is published in the journal Nature, sought to determine how this feat is performed by EEEV — a rare but deadly inflammation of the brain.
According to William Klimstra, associate professor and senior author of the new study, the investigation has yielded promising results. "Anytime you understand how a virus causes a disease, you can find ways to interrupt that process," he said. "And this discovery is particularly exciting because it is the first time that anyone has shown a virus using this particular strategy to evade its host's immune system and exacerbate disease progression."
EEEV and Immune Suppression
To understand Klimstra and his colleague’s discovery, it is important to have a handle on what a virus does. A virus is an infectious agent that consists of particles called virions — tiny spheres containing genetic material. These particles live brief and boring lives that revolve around one thing: the continuation of their genome. To do this, the particles must invade an organic body, hijack its cells, and reduce host nuclei to cellular “virus factories” that spit out copies of the virion until they literally burst.
What the current study shows is that EEEV particles carry genetic instructions that can interact with so-called microRNA produced by the host. This allows the infection to restrict its replication in cells associated with the immune system. As a result, viral business goes largely undetected by the body’s defenses. "Viruses are constantly evolving and changing," Klimstra explained. "However, the genetic sequence that allows EEEV to bind to our microRNA has persisted. We find it in samples from the 1950s, which indicates tremendous evolutionary selection pressure to maintain this mechanism.”
The team found that, in mutant EEEV strains engineered to botch this crucial RNA binding process, the sophisticated stealth mechanism did not kick in. Instead, the host body was able to mount an appropriate immune response, ultimately subduing the infection. According to the researchers, such mutant strains could hold the key to treating and preventing the infection.
Towards Better Preventative Care
According to the Centers for Disease Control and Prevention (CDC), EEEV is one of several medically important members of the Alphavirus genus. While severe infections are characterized by sudden headaches and seizures, most patients will not exhibit any symptoms until it is too late. In the United States, it is estimated that one-third of patients die during the virus’ foray into the nervous system. The vast majority of survivors are left with significant brain damage.
Speaking to Medical News Today, Klimstra expressed confidence that the new study will guide future efforts to develop effective preventative measures against the deadly disease. “Ultimately, these results suggest that the mutant virus could be used as an EEEV vaccine and that microRNA blockers could have potential for use as a therapeutic treatment for EEEV-infected patients who currently can be treated only with supportive care.”
Source: Trobaugh D, Gardner C, Sun C, Klimstra W et al. “RNA viruses can hijack vertebrate microRNAs to suppress innate immunity.” Nature. 2013.