Consequences of viral insertions

A recent study on the 8% of human DNA that is derived from viruses may show a cause of cell mutation and psychiatric disorders such as schizophrenia and mood disorders, according to an article by The University of Texas at Arlington Biology Professor Cédric Feschotte published in the 7 January 2010 issue of Nature magazine.

The study - led by Professor Keizo Tomonaga at Osaka University in Japan - revealed that the genomes of humans and other mammals contain DNA derived from the insertion of bornaviruses, RNA viruses whose replication takes place in the nucleus of cells. It was the first to show sequences derived from a virus other than retroviruses. Researchers have known since 2001 that 8% of human genetic material is derived from retroviruses.

In his article, Feschotte speculates about the role of such viral insertions in causing mutations with evolutionary and medical consequences.

The assimilation of viral sequences into the host genome is a process referred to as endogenisation. This occurs when viral DNA integrates into a chromosome of reproductive cells and is subsequently passed from parent to offspring. Until now, retroviruses were the only viruses known to generate such endogenous copies in vertebrates. But Feschotte said that scientists have found that non-retroviral viruses called bornaviruses have been endogenised repeatedly in mammals throughout evolution.

Bornavirus (BDV) owes its name to the town of Borna, Germany, where a virus epidemic in 1885 wiped out a regiment of cavalry horses. BDV infects a range of birds and mammals, including humans. It is unique because it infects only neurons, establishing a persistent infection in its host's brain, and its entire life cycle takes place in the nucleus of the infected cells.

Feschotte said this intimate association of BDV with the cell nucleus prompted researchers to investigate whether bornaviruses may have left behind a record of past infection in the form of endogenous elements. They searched the 234 known eukaryotic genomes (those genomes that have been fully sequenced) for sequences that are similar to that of BDV.

"The researchers unearthed a plethora of endogenous Borna-like N (EBLN) elements in many diverse mammals," Feschotte said.

The scientists were also able to recover spontaneous BDV insertions in the chromosomes of human cultured cells persistently infected by BVD. Based on these data, Feschotte proposes that BDV insertions could be a source of mutations in the brain cells of infected individuals.

"These data yield a testable hypothesis for the alleged, but still controversial, causative association of BDV infection with schizophrenia and mood disorders," Feschotte said.