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bioRxiv · 10.64898/2026.09.02.747548

Infection of neotropical non-human primates with bat deltaviruses

Lehmann, F.·Moreira-Soto, A.·Mares-Guia, M. A.·Alfaro-Alarcon, A.·Molina, C. V.·Carneiro, I. O.·Souza, B. F. d. C. D.·Carneiro, A. J. B.·Hernandez-Mora, G.·Glebe, D.·Campos, A. C. d. A.·Franke, C. R.·Durigon, E. L.·Bispo de Filippis, A. M.·Drexler, J. F.
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Abstract

Background & Aims: The origin of hepatitis D virus (HDV) and related deltaviruses remains elusive. Contrarily, hepatitis B virus, HDV's helper virus, and related hepadnaviruses display long-term association with primates. Current data suggest cross-order host shifts as a common mechanism in deltavirus ecology, but corroborative evidence is lacking. Here, we aimed to elucidate the genealogy of primate deltaviruses. Methods: We screened 961 non-human primate (NHP) liver specimens obtained in Brazil between 2017-2023 for deltaviruses and hepadnaviruses. Complete deltaviral genomes were obtained via overlapping nested RT-PCR, cloned, expressed in vitro and analyzed via immunoblot and immunofluorescence analysis. Anti-deltaviral antibodies in NHP and vampire bats were detected via immunofluorescence analysis. Results: We detected deltaviruses in two NHP. Complete deltaviral genomes exhibited common features including high self-complementarity, genomic and antigenomic ribozymes, and a delta antigen open reading frame. NHP deltaviruses were phylogenetically related to viruses found in common vampire bats. The NHP deltaviruses replicated in vitro without the expression of a large delta antigen. We did not detect anti-deltaviral antibodies in NHP sera (0/249), in contrast to sera from common vampire bats (7/112; 6.2%, 95% CI: 1.8-10.7), indicating viral circulation in bats. Ancestral state reconstruction suggested a bat origin of NHP deltaviruses. Targeted screening excluded a coinfecting hepadnavirus in the deltavirus-positive animals but led to the discovery of a hepadnavirus, corroborating a non-recent introduction of hepadnaviruses into the primate stem-lineage. Conclusions: Our data are consistent with deltaviral cross-order host shifts and suggestive of the susceptibility of primates to reservoir-bound deltaviruses, lending credibility to a zoonotic origin of HDV.

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Lehmann, F., Moreira-Soto, A., Mares-Guia, M. A., Alfaro-Alarcon, A., Molina, C. V., Carneiro, I. O., Souza, B. F. d. C. D., Carneiro, A. J. B., Hernandez-Mora, G., Glebe, D., Campos, A. C. d. A., Franke, C. R., Durigon, E. L., Bispo de Filippis, A. M., Drexler, J. F.. 2026-09-03. Infection of neotropical non-human primates with bat deltaviruses. https://doi.org/10.64898/2026.09.02.747548

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