Learning new infectivity tricks from old endogenous retroviruses

Endogenous retroviruses are abundantly embedded within their host genome and provide a unique snapshot of multiple past viral infections. Over time, these ancient retroviral “relics” contribute important regulatory and protein-coding functions to the host. However, due to their repetitive nature and degenerate sequences, endogenous retroviruses are challenging to study. In this talk, I will present our efforts to uncover new mechanisms of viral infectivity by studying endogenous retroviruses. We have shown that a group of endogenous retroviruses in Drosophila is able to infect neighboring cells, yet lacks the classic infective envelope glycoprotein (Env). Instead, encoded in their genome is a highly conserved small open reading frame (sORF) that bears uncanny resemblance to fusion-associated small transmembrane (FAST) proteins. FAST proteins are extraordinary in the sense they mediate cell-cell, not virus-cell, fusion, and thus may functionally replace the envelope as an entirely new virulence trait in retroviruses. By studying the function and phylogeny of endogenous retroviral sORFs, this research provides insights into the evolutionary processes that drive innovation and diversification of viral infectivity strategies.