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Key role of rodents in the origin and evolution of hepeviruses revealed

Figure 1. Northern three-toed jerboa (Dipus sagitta) is a reservoir of previously unknown hepeviruses.

Hepatitis E diseases cause the death of more than 40,000 people annually. Both ungulates and rats can be reservoirs of this pathogen, which indicates the zoonotic potential of rodent hepeviruses.

To assess this potential, an international team of researchers, including the head of the laboratory of mammalian microevolution of the IPEE RAS, Doctor of Biological Sciences L.A. Lavrenchenko, conducted a large-scale study of small mammals (2565 specimens of 108 species of rodents and shrews) in Africa, Asia and Latin America. 24 new complete genomes were described, all of them had a typical organization for hepeviruses with three partially overlapping open reading frames (ORF1, ORF2 and ORF3), as well as with characteristic functional domains and motifs. Two dwarf fat-tailed jerboas (Pygeretmus pumilio) of the family Dipodidae were coinfected with two different, deeply diverged hepeviruses that differed by more than 20% in amino acid sequences. Rodent hepeviruses were found to be much more diverse than bat and bird hepeviruses, which form monophyletic clades. Rodent hepeviruses are grouped into nine clades that occupy basal positions relative to human (HEV, clades 1-5) and rat (RHEV, clades a-d) hepatitis E viruses.

Figure 2. Phylogenetic tree of hepeviruses. Yellow lines represent the genomes described in this study.

Parsimony analysis and co-phylogenetic correspondence methods showed that rodents were the main source of the “transition” of hepatitis viruses between different orders of mammals.

“Reconstruction of the ancestral state, carried out using Bayesian analysis methods, showed a recent direct origin of the human hepatitis E virus from the hepatitis viruses of artiodactyls (pigs and camels) and an older one – from the hepatitis viruses of rodents,” said L.A. Lavrenchenko, Doctor of Biological Sciences.

The authors of the study showed the potential of using some rodent species as new models for studying the pathogenesis of the hepatitis E virus and developing its preclinical therapy, and substantiated the need for genomic epidemiological surveillance of hepatitis viruses associated with rodents.

The work was published in the journal: Jo W.K., Cassiano M.H.A., de Oliveira-Filho E.F., Brünink S., Yansanjav A., Yihune M., Koshkina A.I., Lukashev A.N., Lavrenchenko L.A., Lebedev V.S., Olayemi A., Bangura U., Salas-Rojas M., Aguilar-Setién Á., Fichet-Calvet E., Drexler J.F., 2024. Ancient evolutionary origins of hepatitis E virus in rodents. Proceedings of the National Academy of Sciences of the United States of America, 121(51): e2413665121.