This spring, researchers at the La Jolla Institute for Immunology (LJI) created a particularly exciting new study. They have recently published their complete atomic structure of the Human endogenous retrovirus K (HERV-K) envelope proteins. This exciting discovery is a first for scientists to have solved a human HERV structural protein. It represents the third such retroviral envelope structure found, after the human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) discoveries. The study was published in the journal Science Advances. As LJI President, CEO, and Professor, Erica Ollmann Saphire spearheaded the project.
Co-first authors Jeremy Shek and Chen Sun used cryo-electron microscopy (cryo-EM) to map the structure of HERV-K Env. They looked at the structures of the protein before and after it fuses. This approach further enabled them to fix the protein structure by carefully introducing small substitutions. Their work shows that HERV-K now covers in deep tapestry only 8% of human DNA, frayed ends of viruses long integrated into their hosts. Though mostly quiet under normal conditions, this genomic watermark can be turned on in certain disease conditions.
Saphire emphasized the relevance of their findings, stating, “In many disease states, like autoimmune diseases and cancer, these genes re-awaken and start making pieces of these viruses.” Our research team found something extremely cool! These antibodies showed a distinct HERV expression in neutrophils, which was found in patients with RA and lupus, but not healthy controls.
“Understanding how antibodies recognize these proteins was challenging because there was no structure and precious few good antibodies yet available,” Saphire noted. This newly developed framework opens the door to untangling other diseases associated with viral expressions.
“We can really pick whatever disease we’re interested in and go down that route,” Shek added, indicating the versatility of their findings in addressing diverse medical conditions.