Reactivated Virus May Contribute to ALS

by Margaret Wahl on Mon, 2011-03-07 13:02

Normally dormant viral DNA  could be causing damage in brains affected by amyotrophic lateral sclerosis

Article Highlights:
  • Autopsy samples have shown a viral protein called HERV-K reverse transcriptase is much more prevalent in ALS brain samples than in brain samples from people who died from other causes.
  • HERV-K is a "human endogenous retrovirus," a type of virus that often inserts itself into the human genome but is usually dormant.
  • There is evidence that the HERV-K virus is abnormally activated in the ALS patients studied.
  • If the HERV-K virus is activated and is producing one or more proteins, blocking its activity or its proteins could be beneficial in ALS.

New research suggests that the DNA of a normally dormant virus may be playing a role in causing amyotrophic lateral sclerosis (ALS).

If the findings are confirmed, they could ultimately have implications for treatment of the disease.

About the HERV-K virus

Renée Douville at Johns Hopkins University in Baltimore, and colleagues, published the findings in the January 2011 issue of Annals of Neurology. Avindra Nath at Hopkins coordinated the study team, which included Jeffrey Rothstein, director of the MDA/ALS Center at Hopkins and an MDA research grantee studying ALS. The study was funded by the National Institutes of Health (NIH).

The investigators examined brain tissue from 28 people who died of ALS and compared it to brain tissue from 12 people who died from other chronic systemic illnesses; 12 who died with Parkinson disease; and 10 who died from accidents or other causes without any pre-existing systemic illness.

They found that the brains of those who died of ALS had significantly higher levels of a viral protein called HERV-K reverse transcriptase than did samples from any of the other groups, and that the protein was located in specific areas of the brain known to be affected in ALS. Also, the viral protein was found in the same areas as another protein, TDP43, overproduction of which has been implicated in ALS pathology.

The viral protein is produced by the virus HERV-K (human endogenous retrovirus K), and is used by the virus to help it replicate.

Normally, viruses like HERV-K lie dormant in the human genome and don't replicate. However, it appears that HERV-K may have become activated in people with ALS. (Much of the human genome is made up of pieces of viral genomes. It’s likely the HERV-K genome inserted itself into the human genome many generations ago.)

The unusual activity of HERV-K suggests that this virus could be part of the problem in sporadic ALS, the most common form of the disease and one for which the cause is unknown. Sporadic ALS accounts for 90 percent to 95 percent of cases of cases, with familial (inherited) ALS accounting for the other 5 percent to 10 percent.

Previous studies have found reverse transcriptase in ALS patients' serum, but they have not been tied to production by a specific set of viral genetic instructions, as has this protein. (See Origin of Viral Protein in ALS Serum Samples Remains Elusive.)

Meaning for people with ALS

The findings open new possibilities for therapeutic targets in ALS, such as silencing the viral genetic instructions or proteins made from these instructions.

Further studies are needed to clarify the role of  HERV-K reverse transcriptase (and perhaps other viral proteins) in the nervous system, and whether blocking them would be helpful.

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