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.

Virus-like transposons cross the species barrier and drive the evolution of genetic incompatibilities

“…Analogous to endogenous retroelements that gained env genes, Mavericks captured a novel fusogen, MFUS-1, which is likely instrumental for HGT in nematodes [67,68]. However, we could not detect transcription of the fusogen or any other Maverick gene.…”

“…Thanks to their unique biology, which shares features of both transposons and viruses, Mavericks are responsible for the widespread transfer of genes across extremely divergent species. Analogous to endogenous retroelements that gained env genes, Mavericks captured a novel fusogen, MFUS-1, which is likely instrumental for HGT in nematodes [67,68]. However, we could not detect transcription of the fusogen or any other Maverick gene.…”

Virus-like transposons cross the species barrier and drive the evolution of genetic incompatibilities

“…Because of their unique biology, which shares features of both transposons and viruses, Mavericks are responsible for the widespread transfer of genes across extremely divergent species. Analogous to endogenous retroelements that gained env genes, Mavericks captured a novel fusogen, mfus-1 , which is likely instrumental for HGT in nematodes ( 70 , 71 ). However, we could not detect transcription of the fusogen or any other Maverick gene.…”

Discovery of archaeal fusexins homologous to eukaryotic HAP2/GCS1 gamete fusion proteins

“…Viral capture of fusexin genes from early eukaryotic cells and further evolution within the virosphere led to extant viral (class II) fusexins (3). Common to all models, viral fusexin genes were captured by different eukaryotic lineages (4), leading to phlebovirus-like integrated fusogens and EFF-1 somatic fusogens 48 , 67 . Solid lines represent evolutionary trajectories of Archaea (red), viruses (blue), Eukarya (black), and eukaryogenesis (red to black gradient).…”

“…These putative events are at odds with the distribution of fusexins in extant viruses. All currently known viral fusexins belong to RNA viruses that are confined to a few multicellular hosts: vertebrates, arthropods, and flowering plants 47 , 48 . This distribution favors a scenario where viral fusexins, like many other eukaryotic viral proteins, have eukaryotic cellular origins 49 .…”