A Novel Marsupial Hepatitis A Virus Corroborates Complex Evolutionary Patterns Shaping the Genus Hepatovirus

Abstract

The discovery of highly diverse nonprimate hepatoviruses illuminated the evolutionary origins of hepatitis A virus (HAV) ancestors in mammals other than primates. Marsupials are ancient mammals that diverged from other Eutheria during the Jurassic. Viruses from marsupials may thus provide important insight into virus evolution. To investigate Hepatovirus macroevolutionary patterns, we sampled 112 opossums in northeastern Brazil. A novel marsupial HAV (MHAV) in the Brazilian common opossum (Didelphis aurita) was detected by nested reverse transcription-PCR (RT-PCR). MHAV concentration in the liver was high, at 2.5 × 109 RNA copies/g, and at least 300-fold higher than those in other solid organs, suggesting hepatotropism. Hepatovirus seroprevalence in D. aurita was 26.6% as determined using an enzyme-linked immunosorbent assay (ELISA). Endpoint titers in confirmatory immunofluorescence assays were high, and marsupial antibodies colocalized with anti-HAV control sera, suggesting specificity of serological detection and considerable antigenic relatedness between HAV and MHAV. MHAV showed all genomic hallmarks defining hepatoviruses, including late-domain motifs likely involved in quasi-envelope acquisition, a predicted C-terminal pX extension of VP1, strong avoidance of CpG dinucleotides, and a type 3 internal ribosomal entry site. Translated polyprotein gene sequence distances of at least 23.7% from other hepatoviruses suggested that MHAV represents a novel Hepatovirus species. Conserved predicted cleavage sites suggested similarities in polyprotein processing between HAV and MHAV. MHAV was nested within rodent hepatoviruses in phylogenetic reconstructions, suggesting an ancestral hepatovirus host switch from rodents into marsupials. Cophylogenetic reconciliations of host and hepatovirus phylogenies confirmed that host-independent macroevolutionary patterns shaped the phylogenetic relationships of extant hepatoviruses. Although marsupials are synanthropic and consumed as wild game in Brazil, HAV community protective immunity may limit the zoonotic potential of MHAV.IMPORTANCE Hepatitis A virus (HAV) is a ubiquitous cause of acute hepatitis in humans. Recent findings revealed the evolutionary origins of HAV and the genus Hepatovirus defined by HAV in mammals other than primates in general and in small mammals in particular. The factors shaping the genealogy of extant hepatoviruses are unclear. We sampled marsupials, one of the most ancient mammalian lineages, and identified a novel marsupial HAV (MHAV). The novel MHAV shared specific features with HAV, including hepatotropism, antigenicity, genome structure, and a common ancestor in phylogenetic reconstructions. Coevolutionary analyses revealed that host-independent evolutionary patterns contributed most to the current phylogeny of hepatoviruses and that MHAV was the most drastic example of a cross-order host switch of any hepatovirus observed so far. The divergence of marsupials from other mammals offers unique opportunities to investigate HAV species barrie...

Should I stay or should I go? Pollinator shifts rather than cospeciation dominate the evolutionary history of South African Rediviva bees and their Diascia host plants

“…This led us to hypothesise that the parsimony criteria might be violated for our data set. Hence, we followed the approach of de Oliveira Carneiro et al () and used cost values of −1 for cospeciation and 0 for the other three event types (pollinator shifts, duplications, sorting/loss). This cost scheme maximizes the number of cospeciations and therefore can only be used to compare between the minimum number of pollinator shifts which are needed for a certain maximum number of cospeciations.…”

Evolutionary biology of human hepatitis viruses

“…209,210 Their important role as hosts for zoonotic pathogens has been linked to their species richness, abundance, worldwide distribution, the synanthropic behaviour of some species, the ability of bats to fly, to gregarious populations of some bat species and to unique immunological properties of bats. 209,211,212 Interestingly, highly diversified homologues of HAV, HBV, HCV, and HEV were detected in these 2 mammalian orders 25,28,30,42,43,54,213,214 (Fig. 4), hinting at the importance of small mammals during hepatitis virus evolution.…”

“…23,24 A plethora of HAV-related viruses were recovered from various mammalian species during 2015-2018, including predominantly bats and rodents, but also tree shrews, seals and marsupials. [25][26][27][28][29] HBV-related viruses were detected in bats during 2013-2015 30,31 and in a domestic cat in 2018. 32 A distinct HBV species termed capuchin monkey hepatitis B virus (CMHBV) was described in 2018.…”

“…33 However, cross-species transmission must also have occurred during the evolution of hepatitis viruses. Apart from the zoonotic HEV genotypes, examples of cross-species transmission events include hepatoviruses in marsupials that are of likely rodent origin, 28 horse-associated hepaciviruses in dogs and donkeys, 38,41 gorillas infected with chimpanzee hepadnaviruses, orangutans infected with gibbon hepadnaviruses, 119 and rat hepeviruses in shrews. 204 In addition, the tentative HBV genotype J likely emerged from a recombination event involving human-and gibbon-associated parental strains, hinting at cross-species viral transmission from gibbons to humans (summarised in 80 ).…”

Hepatovirus 3ABC proteases and evolution of mitochondrial antiviral signaling protein (MAVS)

“…Thus, unlike hepatitis B virus (HBV) and hepatitis C virus (HCV) that cause longterm persistant infections and co-evolved with humans and other primate species over millions of years [4][5][6] , HAV likely became established among human populations only when groups living together became large enough to sustain chains of transmission 10-12 thousand years ago. Multiple, distantly related hepatoviruses have recently been discovered among bats, rodents and other small mammals 7,8 . These viruses are hepatotropic, and although distantly related phylogenetically, share antigenic determinants with human HAV.…”