Diversification of mammalian deltaviruses by host shifting

Abstract Hepatitis deltavirus (HDV) is an obligate hyper-parasite that increases the severity of hepatitis B virus (HBV) in humans. The origins of HDV and the mechanisms through which it and related animal deltaviruses diversify are unknown. We report the epidemiology and evolutionary history of new mammal-infecting deltaviruses. Despite geographic under-representation in over 348 terabases of globally-distributed RNA sequence data from mammals, deltaviruses originated exclusively from the Americas, infecting bats, rodents and a cervid. Phylogenetic analyses revealed multiple host shifts among mammalian orders. Consistent absence of HBV-like viruses in two deltavirus-infected bat species indicated acquisitions of novel helper viruses during the divergence of animal and human-infecting deltaviruses. Our analyses support an American zoonotic origin of HDV and show that deltaviruses can diversify by host shifting despite dependence on unrelated viruses.