Lupus Genetic Polymorphism Could Confer Antiviral Defense

A certain widespread genetic polymorphism associated with lupus could actually provide defense against viruses.

This is the discovery published in a new article from The American Journal of Human Genetics.

Lupus is an autoimmune disease of uncertain cause, characterized by widespread inflammation that leads to swollen joints and lymph nodes, tiredness, and a characteristic red butterfly rash across the face.

Prior research has linked polymorphisms at the human chromosomal site 11p15 to the disease. One such polymorphism at the IRF7 gene leads to increased DNA binding of IFN Regulatory Factor 7, inducing a cascade of molecular responses that ultimately results in interferon-α production and inflammation.

A team of scientists led by researchers from Cincinnati Children's Hospital Medical Center used CRISPR technology to introduce this variant into mouse Irf7. After inducing a lupus response, they detected increased production of anti-dsDNA autoantibodies in the mice engineered to have the lupus risk variant.

Furthermore, the researchers created pulmonary infections in the mice using VSV (vesicular stomatitis virus) and saw decreased titers of that virus after day one in the lungs of the genetically engineered mice compared to the lungs of the control mice.

Taken together, the researchers concluded that the IRF7 variant increases the risk of autoimmunity, while also enhancing antiviral defense. They believe that latter part may explain why this particular variant has been conserved over time in humans.

The researchers stress that they did not identify any specific selective pressure that would lead to the genetic variant's prevalence in ancient human populations.

Image: George Henry Fox