Evolutionary Origins of Enteric Hepatitis Viruses

Abstract

The enterically transmitted hepatitis A (HAV) and hepatitis E viruses (HEV) are the leading causes of acute viral hepatitis in humans. Despite the discovery of HAV and HEV 40-50 years ago, their evolutionary origins remain unclear. Recent discoveries of numerous nonprimate hepatoviruses and hepeviruses allow revisiting the evolutionary history of these viruses. In this review, we provide detailed phylogenomic analyses of primate and nonprimate hepatoviruses and hepeviruses. We identify conserved and divergent genomic properties and corroborate historical interspecies transmissions by phylogenetic comparisons and recombination analyses. We discuss the likely non-recent origins of human HAV and HEV precursors carried by mammals other than primates, and detail current zoonotic HEV infections. The novel nonprimate hepatoviruses and hepeviruses offer exciting new possibilities for future research focusing on host range and the unique biological properties of HAV and HEV.

Evolutionary biology of human hepatitis viruses

“…42 For hepeviruses, there is evidence for recombination involving different host orders, similar to hepatoviruses. 29 Importantly, the camelid-associated HEV genotypes 7 and 8 show…”

“…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.…”

“…This includes the apparent absence of a C-terminal VP1 capsid protein extension termed pX in some HAV-related bat viruses 25 and the lack of short amino acid motifs termed late domain motifs in several divergent hepeviruses from diverse mammals and birds. 29 In contrast, HBV-related viruses (henceforth, hepadnaviruses) are enveloped viruses, yet fish were recently found to host a non-enveloped Hepadnaviridae sister family, termed Nackednaviridae. 36 The discovery of nackednaviruses suggested that envelopment emerged de novo in hepadnaviruses capable of infecting mammals and ultimately humans.…”

“…On the other hand, ancestral animal hepatitis viruses may exploit unknown strategies for envelopment that differ from those found in human viruses. 29 Recombination events occurred during hepatitis virus evolution Recombination events among viruses can occur when 1 cell is co-infected with 2 different viruses that interact during replication. For all human hepatitis viruses, recombination has been exhaustively described.…”

“…For hepatoviruses there is evidence for recombination in the coding sequence of very distantly related viruses associated with different host orders, which hints at a broad host range. 29 In addition, variations in the 5 0 -genome ends of animal hepatoviruses harbouring the internal ribosome entry site (IRES) hint at ancient recombination events involving different viral families. 25 For hepadnaviruses, the mosaic genome structure of extinct and extant HBV genotypes suggests that recombination has been a major micro-evolutionary feature of HBV evolution.…”