An Endogenous Retrovirus from Human Hookworm Encodes an Ancient Phlebovirus-Like Class II Envelope Fusion Protein

• Main Authors: Monique Merchant, Carlos P. Mata, Yorgo Modis
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: Proceedings
• Subjects: transposable element; retrotransposon; endogenous retrovirus (ERV); envelope protein; membrane fusion; horizontal gene transfer (HGT)
• Online Access: https://www.mdpi.com/2504-3900/50/1/33
• ISSN: 2504-3900

Within the parasitic nematode <i>Ancylostoma ceylanicum</i>, a ~20 million-year-old Bel/Pao LTR retrotransposon encodes an ancient viral class II envelope fusion protein termed Atlas Gc. Typically, retroviruses and related degenerate retrotransposons encode a hemagglutinin-like class I envelope fusion protein. A subset of Bel/Pao LTR retrotransposons within the phylum <i>Nematoda</i> have acquired a phlebovirus-like envelope gene and utilized the encoded fusion machinery to escape the genome as intact exogenous retroviruses. This includes <i>C. elegans</i> retroelement 7 virus which was recently reclassified as a member of the genus <i>Semotivirus</i>. A 3.76 Å cryoEM reconstruction confirms Atlas Gc as a closely related phleboviral homologue and class II fusion protein in a novel case of gene exaptation. Preliminary biophysical and biochemical characterization indicate Atlas Gc functions under specific physiological conditions targeting late-endosomal membranes, much like modern viral class II envelope fusion proteins. Phylogenetic analyses support the reclassification of the Atlas endogenous retrovirus and five other <i>A. ceylanicum</i> ERVs as novel semotiviruses of <i>Belpaoviridae</i> of the new viral order of reverse-transcribing viruses <i>Ortervirales</i>.