Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus

Abstract

<jats:p>Hepatitis delta virus (HDV) is a human hepatitis-causing RNA virus, unrelated to any other taxonomic group of RNA viruses. Its occurrence as a satellite virus of hepatitis B virus (HBV) is a singular case in animal virology for which no consensus evolutionary explanation exists. Here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species <jats:italic>Proechimys semispinosus</jats:italic>. The rodent deltavirus is highly distinct, showing a common ancestor with a recently described deltavirus in snakes. Reverse genetics based on a tandem minus-strand complementary DNA genome copy under the control of a cytomegalovirus (CMV) promoter confirms autonomous genome replication in transfected cells, with initiation of replication from the upstream genome copy. In contrast to HDV, a large delta antigen is not expressed and the farnesylation motif critical for HBV interaction is absent from a genome region that might correspond to a hypothetical rodent large delta antigen. Correspondingly, there is no evidence for coinfection with an HBV-related hepadnavirus based on virus detection and serology in any deltavirus-positive animal. No other coinfecting viruses were detected by RNA sequencing studies of 120 wild-caught animals that could serve as a potential helper virus. The presence of virus in blood and pronounced detection in reproductively active males suggest horizontal transmission linked to competitive behavior. Our study establishes a nonhuman, mammalian deltavirus that occurs as a horizontally transmitted infection, is potentially cleared by immune response, is not focused in the liver, and possibly does not require helper virus coinfection.</jats:p>

Identification of novel avian and mammalian deltaviruses provides new insights into deltavirus evolution

“…The discoveries of non-HDV deltaviruses have also provided insights into the relationships between deltaviruses and their helper viruses. Recently identified non-HDV deltaviruses apparently did not co-infect with hepadnaviruses, suggesting the presence of other helper viruses (16)(17)(18)(19). This is also supported by the lack of large isoform of DAg protein expression, which is mediated by RNA-editing and is necessary for HDV to interact with the hepadnaviral envelope protein as described above, in rodent deltavirus (19).…”

“…Since HDV has been the sole member of the genus Deltaviurs (2), its evolutionary origin had been enigmatic. However, recent studies discovered several deltaviruses from vertebrates and invertebrate species (16)(17)(18)(19), which drastically changed our understanding of the evolution of deltaviruses. These non-HDV deltaviruses are distantly related to HDV, but apparently share the same origin because they have similar genome structures: their genomes are circular RNA approximately 1.7 kb, encode DAglike proteins, possess ribozymes sequences, and show high self-complementarities (16)(17)(18)(19).…”

“…These findings would be clues to understanding the origin and evolution of deltaviruses. Indeed, previous studies proposed several interesting hypotheses: for example, a recent study proposed a hypothesis that mammalian deltaviruses have been co-diverged with mammalian species (19). Thus far, however, only a handful of deltaviruses were found, but they are genetically highly diverse (16)(17)(18)(19).…”

“…Indeed, previous studies proposed several interesting hypotheses: for example, a recent study proposed a hypothesis that mammalian deltaviruses have been co-diverged with mammalian species (19). Thus far, however, only a handful of deltaviruses were found, but they are genetically highly diverse (16)(17)(18)(19). Therefore, to assess the hypothesis as well as for a deeper understanding of the evolution of deltaviruses, the phylogenetic gaps between the deltaviruses are needed to be filled by exploring novel deltaviruses.…”

Petabase-scale sequence alignment catalyses viral discovery

“…Prior to 2018, HDV was the sole known member of its genus; ten members have since been characterised [21][22][23][24][25]. We identified an additional six deltaviruses ( Figure 3a) and assembled complete circular genomes for five (Extended Figure 6).…”