A bioactive phlebovirus-like envelope protein in a hookworm endogenous virus

Endogenous viral elements (EVEs), accounting for 15% of our genome, serve as a genetic reservoir from which new genes can emerge. Nematode EVEs are particularly diverse and informative of virus evolution. We identify Atlas virus—an intact retrovirus-like EVE in the human hookworm Ancylostoma ceylanicum, with an envelope protein genetically related to G(N)-G(C) glycoproteins from the family Phenuiviridae. A cryo-EM structure of Atlas G(C) reveals a class II viral membrane fusion protein fold not previously seen in retroviruses. Atlas G(C) has the structural hallmarks of an active fusogen. Atlas G(C) trimers insert into membranes with endosomal lipid compositions and low pH. When expressed on the plasma membrane, Atlas G(C) has cell-cell fusion activity. With its preserved biological activities, Atlas G(C) has the potential to acquire a cellular function. Our work reveals structural plasticity in reverse-transcribing RNA viruses.