Ancient Virus Could Play A Role In Motor Neuron Disease

Looking for viral genes in the brain. Courtesy of Nath lab, NINDS.

Way back in time, ancient viruses are believed to have infected the reproductive cells of our ancestors, leaving behind fossils of their genomes that we still see in our DNA today. In fact, as much as 8% of our DNA is made up of the remnants of these infections, known as endogenous retroviruses. Usually they lie dormant, but they can be awoken, reigniting the production of viral elements.

Controversially, such reactivation of these sleepy sequences has now been linked with a progressive disease of the nervous system, called Lou Gehrig’s disease. We’re way off from confirming that these viral genes play a causative role in this condition, but if this turns out to be the case, then it may be that some patients can be helped with drugs that we already use to treat infections with similar viruses.

This finding followed a series of observations regarding the condition, also called amyotrophic lateral sclerosis (ALS) or motor neuron disease, which slowly destroys the nerves involved in movements. While roughly 10% of ALS patients also have a relative afflicted with the disease, indicating heritability, some have no family history, hence the name sporadic ALS.

Interestingly, some patients with AIDS – caused by the retrovirus HIV – show symptoms reminiscent of ALS, but they can often be reversed using antiviral drugs. Tenuous to some, but another hint of a possible connection came from blood samples of ALS patients, which in some cases showed the presence of a retroviral protein, reverse transcriptase, that is used to turn their RNA genome into DNA.

Following these viral breadcrumbs, researchers at the National Institutes of Health decided to examine brain tissue to look for viral signatures. As described in Science Translational Medicine, this revealed that one particular endogenous retrovirus, called HERV-K, was activated in the samples from deceased patients with sporadic ALS, but not healthy controls. By activation, the scientists are referring to the genes being made into blueprints for proteins, which are called transcripts.

The team then dug a little deeper and found evidence for one particular HERV-K protein across the cortex region of the brain, and also in certain neuronal populations of the spinal cord. This retroviral protein, called Env, normally pokes out of the viral membrane like a lollipop and is used to gain entry to target cells.

Next, they grew human neurons in dishes and demonstrated that activated HERV-K, or more specifically the Env protein produced by the virus, caused them to degenerate. Taking this one step further, they added the gene for Env into mice so that the protein was produced throughout their nervous system. These animals went on to develop ALS-like symptoms, such as problems with locomotion and balance that worsened with age. And when they performed autopsies, the team found that the only nerves to experience degeneration were those that control movement – motor neurons.

These are an interesting set of results, for sure, but in no way can they be used to say that an endogenous retrovirus is a cause of sporadic ALS; the researchers themselves are even cautionary and want others to replicate their findings. But it should be noted that these ancient viruses have been implicated in a number of other diseases, ranging from schizophrenia to cancer, although no studies have definitively proven a causative role. Still, the team thinks that they should pursue the possibility of using antiretroviral drugs as a form of treatment for those with sporadic ALS, and there’s already a wide range available, for example those used to treat HIV. 

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