A novel hepatitis B virus species discovered in capuchin monkeys sheds new light on the evolution of primate hepadnaviruses

Abstract

The origins of HBV are unclear. The new orthohepadnavirus species from Brazilian capuchin monkeys resembled HBV in elicited infection patterns and could infect human liver cells using the same receptor as HBV. Evolutionary analyses suggested that primate HBV-related viruses might have emerged in African ancestors of New World monkeys millions of years ago. HBV was associated with hominoid primates, including humans and apes, suggesting evolutionary origins of HBV before the formation of modern humans. HBV genotypes found in American natives were divergent from those found in American monkeys, and likely introduced along prehistoric human migration. Our results elucidate the evolutionary origins and dispersal of primate HBV, identify a new orthohepadnavirus reservoir, and enable new perspectives for animal models of hepatitis B.

Evolutionary biology of human hepatitis viruses

“…Nonetheless, the phylogenetic relationships of primate HBV suggest that neither CMHBV, nor WMHBV are direct ancestors of human HBV. 33 Hence, our current knowledge on primate HAV, HBV and HCV diversity does not support a recent origin of human viruses in NHP. Thus, studies investigating hepatitis virus diversity in diverse NHP species and NHP remains are urgently needed.…”

“…32 A distinct HBV species termed capuchin monkey hepatitis B virus (CMHBV) was described in 2018. 33 Endogenous and exogenous viruses distantly related to HBV were detected in reptiles, fish and amphibians. [34][35][36][37] HCV-related viruses were detected in horses in 2012, and evidence for sporadic spill-over infections of the horse-associated viruses into dogs and donkeys was found.…”

“…Interestingly, human HBV can use the Ntcp of great apes and New World monkeys, but 1 specific amino acid exchange in the Ntcp is needed for a cross-species transmission of human HBV to Old World monkeys. 33,171 Similarly, 1 amino acid exchange in the woodchuck Ntcp enables an efficient infection with HBV. 172 However, additional unidentified host-specific co-factors might be essential for viral entry and infection.…”

“…36,203 In addition, evidence for co-speciation exists for the New World monkey hepadnaviruses CMHBV and WMHBV. 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.…”

“…119 However, the relatively large genetic diversity of human viruses compared to viruses from Old World apes may hint at an origin of HBV in the human stem lineage. 33,208 Interestingly, both the WHMBV and the CMHBV surface proteins can use the hNTCP for cell entry, suggesting zoonotic potential of these divergent HBV species from New World monkeys. Nonetheless, the phylogenetic relationships of primate HBV suggest that neither CMHBV, nor WMHBV are direct ancestors of human HBV.…”