Occult Hepatitis B Virus Infection in Chacma Baboons, South Africa

Dickens, Caroline; Kew, Michael C.; Purcell, Robert H.; Kramvis, Anna

doi:10.3201/eid1904.121107

Cited by 11 publications

(8 citation statements)

References 38 publications

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“…Our findings are also consistent with the recent discovery of another Orthohepadnavirus from a New World monkey, the capuchin monkey (CMHBV), and its basal position with woolly monkey HBV (WMHBV) in the phylogenetic tree (7,8). On the other hand, orthohepadnaviruses have not yet been reported in the Old World monkeys and prosimians, except for isolated cases of cross-species transmissions of human HBVs in crab-eating macaques (58) and chacma baboons (59). Specific amino acid differences in the presumed HBV-binding interfaces of NTCPs may explain the supposed absence of HBV-like viruses in Old World monkeys ( Fig.…”

Section: Orthohepadnavirus-receptor Evolutionary Arms Racesupporting

confidence: 91%

Evolution of Hepatitis B Virus Receptor NTCP Reveals Differential Pathogenicities and Species Specificities of Hepadnaviruses in Primates, Rodents, and Bats

Jacquet

Pons

Bernardo

et al. 2019

J Virol

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Human hepatitis B virus (HBV) is a global health problem, affecting more than 250 million people worldwide. HBV-like viruses, named orthohepadnaviruses, also naturally infect nonhuman primates, rodents, and bats, but their pathogenicity and evolutionary history are unclear. Here, we determined the evolutionary history of the HBV receptors NTCP and GPC5 over millions of years of primate, rodent, and bat evolution. We use this as a proxy to understand the pathogenicity of orthohepadnaviruses in mammalian hosts and to determine the implications for species specificity. We found that NTCP, but not GPC5, has evolved under positive selection in primates (27 species), rodents (18 species), and bats (21 species) although at distinct residues. Notably, the positively selected codons map to the HBV-binding sites in primate NTCP, suggesting past genetic "arms races" with pathogenic orthohepadnaviruses. In rodents, the positively selected codons fall outside and within the presumed HBV-binding sites, which may contribute to the restricted circulation of rodent orthohepadnaviruses. In contrast, the presumed HBV-binding motifs in bat NTCP are conserved, and none of the positively selected codons map to this region. This suggests that orthohepadnaviruses may bind to different surfaces in bat NTCP. Alternatively, the patterns may reflect adaptive changes associated with metabolism rather than pathogens. Overall, our findings further point to NTCP as a naturally occurring genetic barrier for cross-species transmissions in primates, which may contribute to the narrow host range of HBV. In contrast, this constraint seems less important in bats, which may correspond to greater orthohepadnavirus circulation and diversity. IMPORTANCE Chronic infection with hepatitis B virus (HBV) is a major cause of liver disease and cancer in humans. Mammalian HBV-like viruses are also found in nonhuman primates, rodents, and bats. As for most viruses, HBV requires a successful interaction with a host receptor for replication. Cellular receptors are thus key determinants of host susceptibility as well as specificity. One hallmark of pathogenic virus-host relationships is the reciprocal evolution of host receptor and viral envelope proteins, as a result of their antagonistic interaction over time. The dynamics of these so-called "evolutionary arms races" can leave signatures of adaptive selection, which in turn reveal the evolutionary history of the virus-host interaction as well as viral pathogenicity and the genetic determinants of species specificity. Here, we show how HBV-like viruses have shaped the evolutionary history of their mammalian host receptor, as a result of their ancient pathogenicity, and decipher the genetic determinants of cross-species transmissions.W ith approximately 257 million cases of chronic infections, human hepatitis B virus (HBV) infection is one of the most common viral infections and the leading cause of liver diseases worldwide. HBV is a member of the family Hepadnaviridae, which are ancient pathogens that naturally inf...

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Section: Orthohepadnavirus-receptor Evolutionary Arms Racesupporting

confidence: 91%

Evolution of Hepatitis B Virus Receptor NTCP Reveals Differential Pathogenicities and Species Specificities of Hepadnaviruses in Primates, Rodents, and Bats

Jacquet

Pons

Bernardo

et al. 2019

J Virol

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“…Earlier mutagenesis studies of NTCP from the crab-eating monkey (Macaca fascicularis) have shown that this small region is key to restricting human HBV infection (Yan et al 2012). Intriguingly, some wild-caught baboons in South Africa display occult infection with a virus related to human HBV genotype A2 (Dickens et al 2013). Low-level infection with HBV resembling the human genotype D virus has also been reported in macaques from Mauritius (Dupinay et al 2013).…”

Section: Ntcp Determines the Species Specificity Of Hbv And Hdv At Thmentioning

confidence: 96%

The Hepatitis B Virus Receptor

2015

Annu. Rev. Cell Dev. Biol.

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Hepatitis B virus (HBV) infection affects 240 million people worldwide. A liver-specific bile acid transporter named the sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV and its satellite, the hepatitis D virus (HDV). NTCP likely acts as a major determinant for the liver tropism and species specificity of HBV and HDV at the entry level. NTCP-mediated HBV entry interferes with bile acid transport in cell cultures and has been linked with alterations in bile acid and cholesterol metabolism in vivo. The human liver carcinoma cell line HepG2, complemented with NTCP, now provides a valuable platform for studying the basic biology of the viruses and developing treatments for HBV infection. This review summarizes critical findings regarding NTCP's role as a viral receptor for HBV and HDV and discusses important questions that remain unanswered.

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“…An HBV variant was identified in Woolly monkeys (endangered species) and could lead to acute, but not persistent, experimental infection in Spider monkeys . Among Old World monkeys, there is evidence of occult human HBV infection of subgenotype A2 in baboons with detection of the HBV DNA genome at low titers in serum, but not the HBV surface antigen (HBsAg) . However, HBV could be transmitted to naïve baboons and HBV DNA could be detected for at least 6 months.…”

mentioning

confidence: 99%