Résumé
Hepatitis D-like satellite viruses, known as deltaviruses, have been recently discovered in a wide range of animals. These viruses are thought to expropriate glycoproteins from helper viruses to form infectious particles. Here, we challenge this paradigm and demonstrate that deltaviruses are packaged within helper virus particles, using them as viral Trojan Horses for cell entry. By leveraging orthogonal electron and optical super-resolution microscopy, we visualize deltaviruses enclosed within virions from rhabdo-, herpes-, and arenavirus families. We show that this conserved hitchhiking mechanism ensures concomitant deltavirus-helper virus spread, thereby promoting the dissemination of deltaviruses, broadening their host range, and expanding their tropism. Our findings reveal a previously unrecognized mode of viral transmission, providing a framework to investigate overlooked deltavirus infections outside of the human liver.
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•Deltaviruses hitchhike within helper virus virions, using them as viral Trojan Horses•The Trojan Horse model is mandatory for productive herpesvirus-deltavirus associations•This mode of propagation favors deltavirus infectivity•Trojan Horse model warrants screening for extra-hepatic deltavirus infections in humans
McKellar et al. have discovered that some satellite viruses act as the ultimate hitchhikers. They physically become a virus inside a virus, hiding within helper virus particles by hitching a ride as a Trojan Horse and sneaking into new animal species and organs they could not reach alone, including the human brain.