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

Merchant, Monique; Mata, Carlos P; Liu, Yangci; Zhai, Haoming; Protasio, Anna V; Modis, Yorgo · Sci Adv · 2022

basic_science · Level V

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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 <i>Ancylostoma ceylanicum</i>, with an envelope protein genetically related to G<sub>N</sub>-G<sub>C</sub> glycoproteins from the family Phenuiviridae. A cryo-EM structure of Atlas G<sub>C</sub> reveals a class II viral membrane fusion protein fold not previously seen in retroviruses. Atlas G<sub>C</sub> has the structural hallmarks of an active fusogen. Atlas G<sub>C</sub> trimers insert into membranes with endosomal lipid compositions and low pH. When expressed on the plasma membrane, Atlas G<sub>C</sub> has cell-cell fusion activity. With its preserved biological activities, Atlas G<sub>C</sub> has the potential to acquire a cellular function. Our work reveals structural plasticity in reverse-transcribing RNA viruses.

Medical subject headings