Nobelist Leads Effort Revealing Beneficial Function of Endogenous Retroviruses in Immune Response

Retroviruses are best known for causing contagious scourges such as AIDS, or more sporadically, cancer. But researchers at the University of Texas (UT) Southwestern Medical Center and Karolinska Institutet in Stockholm, Sweden, have found that endogenous retroviruses (ERV) also play a critical role in the body’s immune defense against common bacterial and viral pathogens. “Most scientists have become used to the view that retroviruses are generally harmful,” said Nobel Laureate Dr. Bruce Beutler, Professor and Director of UT Southwestern’s Center for the Genetics of Host Defense. “We have found that ERV fulfill at least one beneficial function critical to producing protective antibodies.” Retroviruses are able to insert into the genomic DNA of cells they infect, including germ cells. In this way, and by a process called retrotransposition, they have become a major part of the genome of each person. About 45 percent of a person’s DNA is of retroviral origin, and some of the better preserved copies are termed “endogenous retroviruses” (ERV). Writing in the journal Science in an article published online on December 19, 2014, the researchers found that when B cells are activated by large polymeric antigens such as polysaccharides of bacteria, they rapidly produce protective antibodies in what is termed the Type II T-independent antibody response. This response, central to the body’s defense against common bacterial and viral pathogens, is dependent on ERV. Within activated B cells, the ERV are driven to express RNA copies of themselves, which in turn are copied into DNA by an enzyme called reverse transcriptase. The RNA copies of ERV are detected by a protein called RIG-I, and the DNA copies are detected by another protein called cGAS.
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