Deltaviruses spread through a viral Trojan Horse.

Abstract

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.