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

Abstract

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.