Discovery and analysis of the first endogenous lentivirus

Abstract

The lentiviruses are associated with a wide range of chronic diseases in mammals. These include immunodeficiencies (such as HIV/AIDS in humans), malignancies, and lymphatic and neurological disorders in primates, felids, and a variety of wild and domesticated ungulates. Evolutionary analyses of the genomic sequences of modern-day lentiviruses have suggested a relatively recent date for their emergence, but the failure to identify any endogenous, vertically transmitted examples has meant that their longer term evolutionary history and origin remain unknown. Here we report the discovery and characterization of retroviral sequences belonging to a new lentiviral subgroup from the European rabbit (Oryctolagus cuniculus). These viruses, the first endogenous examples described, are >7 million years old and thus provide the first evidence for an ancient origin of the lentiviruses. Despite being ancient, this subgroup contains many of the features found in present-day lentiviruses, such as the presence of tat and rev genes, thus also indicating an ancient origin for the complex regulation of lentivirus gene expression. Although the virus we describe is defective, reconstruction of an infectious progenitor could provide novel insights into lentivirus biology and host interactions.