Year: 2026
Type: preprint
Abstract: 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.
Authors: Felix Lehmann, Andres Moreira-Soto, Maria Angélica Mares-Guia, Alejandro Alfaro-Alarcón, Camila Vieira Molina, Ianei Oliveira Carneiro, Breno Frederico de Carvalho Domingu Souza, Aroldo José Borges Carneiro, Gabriela Hernández-Mora, Dieter Glebe, Angélica Cristine de Almeida Campos, Carlos Roberto Franke, Edison Luiz Durigon, Ana Maria Bispo de Filippis, Jan Felix Drexler
Institutions: Humboldt-Universität zu Berlin, Charité – Universitätsmedizin Berlin, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Universidad Nacional, Institut Pasteur de São Paulo, Universidade Federal da Bahia, Complexo Hospitalar Universitário Professor Edgard Santos, Ministério da Saúde, Ministerio de Agricultura y Ganadería de Costa Rica, Justus-Liebig-Universität Gießen
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7208781247