A Short N-Proximal Region in the Large Envelope Protein Harbors a Determinant That Contributes to the Species Specificity of Human Hepatitis B Virus

Chouteau, Philippe; Seyec, Jacques Le; Cannie, Isabelle; Nassal, Michael; Guguen‐Guillouzo, Christiane; Gripon, Philippe

doi:10.1128/jvi.75.23.11565-11572.2001

Cited by 63 publications

(53 citation statements)

References 40 publications

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“…Chimeric proteins containing WMHBV and HBV sequences have been used to examine the infectivity of hepadnaviral particles on human hepatocytes. In those studies, HBV residues 1 to 30 of the L protein restored infectivity of human hepatocytes for hepadnaviral particles containing a chimeric WMHBV envelope (7). In contrast, our findings with the HDV system suggest that HBV residues 1 to 40 are insufficient to provide the WMHBV envelope with the capacity to infect human hepatocytes at an efficiency equivalent to that of HBV-HDV.…”

Section: Discussioncontrasting

confidence: 55%

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Analysis of Host Range Phenotypes of Primate Hepadnaviruses by In Vitro Infections of Hepatitis D Virus Pseudotypes

Barrera

Guerra

Lee

et al. 2004

J Virol

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Hepatitis B virus (HBV) and woolly monkey hepatitis B virus (WMHBV) have natural host ranges that are limited to closely related species. The barrier for infection of primates seems to be at the adsorption and/or entry steps of the viral replication cycle, since a human hepatoma cell line is permissive for HBV and WMHBV replication following transfection of cloned DNA. We hypothesized that the HBV and WMHBV envelope proteins contain the principal viral determinants of host range. As previously shown by using the hepatitis D virus (HDV) system, recombinant HBV-HDV particles were infectious in chimpanzee as well as human hepatocytes. We extended the HDV system to include HDV particles pseudotyped with the WMHBV envelope. In agreement with the natural host ranges of HBV and WMHBV, in vitro infections demonstrated that HBV-HDV and WM-HDV particles preferentially infected human and spider monkey cells, respectively. Previous studies have implicated the pre-S1 region of the large (L) envelope protein in receptor binding and host range; therefore, recombinant HDV particles were pseudotyped with the hepadnaviral envelopes containing chimeric L proteins with the first 40 amino acids from the pre-S1 domain exchanged between HBV and WMHBV. Surprisingly, addition of the human amino terminus to the WMHBV L protein increased infectivity on spider monkey hepatocytes but did not increase infectivity for human hepatocytes. Based upon these data, we discuss the possibility that the L protein may be comprised of two domains that affect infectivity and that sequences downstream of residue 40 may influence host range and receptor binding or entry.Many virus-receptor interactions contribute to viral host range and therefore constitute an interspecies barrier, as is the most apparent circumstance for hepatitis B virus (HBV). Hepadnaviruses, like HBV, characteristically display very narrow host ranges that extend only to closely related species. The discovery and characterization of a nonhuman primate hepadnavirus from woolly monkeys confirmed the restrictions on the transmissibility of the virus between species, as chimpanzees were not susceptible to an efficient infection with woolly monkey hepatitis B virus (WMHBV) (18). However, analyses of the host range of WMHBV indicated that the host range extends to the close relative of the woolly monkey, the black-handed spider monkey; both primates are within the Atelidae family and the Atelinae subfamily. Transfection of the cloned genomes for both HBV and WMHBV into the human liver cell line Huh7 demonstrated assembly of infectious particles following unimpeded replication of both viruses (17), suggesting that the barrier for interspecies transmission is at the initial steps of infection, which include virus adsorption and uptake.The viral glycoproteins contained in the HBV envelope are encoded by a single open reading frame and are translated from different in-frame start codons to a common stop codon to generate the small (S), middle (M), and large (L) proteins. All three proteins conta...

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Section: Discussioncontrasting

confidence: 55%

“…The evolutionary gap between HBV and WMHBV spans host species that represent Old World primates and New World primates. The pre-S1 domain is believed to dictate the species specificity observed by primate hepadnaviruses and has been implicated in receptor binding and host range (7).…”

mentioning

confidence: 99%

Analysis of Host Range Phenotypes of Primate Hepadnaviruses by In Vitro Infections of Hepatitis D Virus Pseudotypes

Barrera

Guerra

Lee

et al. 2004

J Virol

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“…Cells were prepared by perfusion of histologically normal liver fragments using a collagenase solution (Jigorel et al, 2005). They were primary cultured on plastic dishes in Williams' E medium as already reported (Chouteau et al, 2001;Jigorel et al, 2005;Le Vee et al, 2008). All of the experimental procedures complied with French laws and regulations and were approved by the National Ethics Committee.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Drug Transporter Expression in Human Hepatocytes Exposed to the Proinflammatory Cytokines Tumor Necrosis Factor-α or Interleukin-6

Vée

Lecureur²,

Stieger

et al. 2009

Drug Metabolism and Disposition

223

162

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ABSTRACT:Tumor necrosis factor (TNF)-␣ and interleukin (IL)-6 are proinflammatory cytokines known to alter expression of drug transporters in rodent liver. However, their effects toward human hepatic transporters remain poorly characterized. Therefore, this study was designed to analyze the effects of these cytokines on drug transporter expression in primary human hepatocytes. Exposure to 100 ng/ml TNF-␣ or 10 ng/ml IL-6 for 48 h was found to down-regulate mRNA levels of major sinusoidal influx transporters, including sodium-taurocholate cotransporting polypeptide (NTCP), organic anion-transporting polypeptide (OATP) 1B1, OATP1B3, OATP2B1, organic cation transporter (OCT) 1, and organic anion transporter 2. TNF-␣ and IL-6 concomitantly reduced NTCP and OATP1B1 protein expression and NTCP, OATP, and OCT1 transport activities. IL-6, but not TNF-␣, was also found to decrease mRNA expression of the canalicular transporters multidrug resistance 1 gene, multidrug resistance gene-associated protein (MRP) 2, and breast cancer resistance protein (BCRP); it concomitantly decreased MRP2 and BCRP protein expression. TNF-␣, unlike IL-6, markedly reduced bile salt export pump mRNA levels and increased BCRP protein expression. Expression of the sinusoidal MRP3 efflux pump was found to be up-regulated at protein level by both TNF-␣ and IL-6. Taken together, these data show that TNF-␣ and IL-6 similarly altered expression of sinusoidal drug transporters and rather differentially that of canalicular efflux transporters. Such pronounced changes in hepatic transporter expression are likely to contribute to both cholestasis and alterations of pharmacokinetics caused by inflammation in humans.

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“…Woolly monkey HBV (WMHBV) is the only hepadnavirus of a nonhuman primate with an established infectious clone and has been studied in some detail (10)(11)(12)(13)(14)(15)(16)(17)(18). It was originally isolated from a woolly monkey (Lagothrix lagotricha) with fulminant hepatitis.…”

mentioning

confidence: 99%

Sodium Taurocholate Cotransporting Polypeptide Mediates Woolly Monkey Hepatitis B Virus Infection of Tupaia Hepatocytes

Zhong

Yan

Wang

et al. 2013

J Virol

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dPrimary Tupaia hepatocytes (PTHs) are susceptible to woolly monkey hepatitis B virus (WMHBV) infection, but the identity of the cellular receptor(s) mediating WMHBV infection of PTHs remains unclear. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as a functional receptor for human hepatitis B virus (HBV) infection of primary human and Tupaia hepatocytes. In this study, a synthetic pre-S1 peptide from WMHBV was found to bind specifically to cells expressing Tupaia NTCP (tsNTCP) and it efficiently blocked WMHBV entry into PTHs; silencing of tsNTCP in PTHs significantly inhibited WMHBV infection. Ectopic expression of tsNTCP rendered HepG2 cells susceptible to WMHBV infection. These data demonstrate that tsNTCP is a functional receptor for WMHBV infection of PTHs. The result also indicates that NTCP's orthologs likely act as a common cellular receptor for all known primate hepadnaviruses. Human hepatitis B virus (HBV) is a leading cause of liver diseases ranging from acute hepatitis to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. With approximately 240 million cases of chronic infection worldwide, HBV is responsible for about 600,000 deaths annually (1). Despite its enormous medical and social relevance, progress in HBV research has been impeded by the lack of understanding of HBV entry by which the virus specifically infects human liver cells. Recently we found that sodium taurocholate cotransporting polypeptide (NTCP; also known as SLC10A1 [solute carrier family 10 member 1]), a hepatic sodium/bile acid symporter presumed to span the cellular membrane up to 10 times with small extracellular loops (2-5), is a functional receptor for human HBV and hepatitis D virus (HDV) infections of human and Tupaia hepatocytes (6). The pre-S1 domain of the HBV large envelope protein (L protein) is the key determinant of interaction with the cellular receptor NTCP (6). Furthermore, the critical receptor-binding motif in the pre-S1 domain of human HBV (7-10) is conserved among all hepadnaviruses from humans and nonhuman primates, including chimpanzees, gorillas, orangutans, gibbons, and woolly monkeys (Fig. 1A). Therefore, it is tempting to speculate that NTCP may play an important role in the entry of all known primate hepadnaviruses into host cells.Woolly monkey HBV (WMHBV) is the only hepadnavirus of a nonhuman primate with an established infectious clone and has been studied in some detail (10-18). It was originally isolated from a woolly monkey (Lagothrix lagotricha) with fulminant hepatitis. It has the same genetic organization as and shares 78% sequence identity with human HBV (12). Both the woolly monkey and a closely related New World monkey, the spider monkey (Ateles geoffroyi), are susceptible to WMHBV infection, while chimpanzees are minimally susceptible (11,12). In cell cultures, WMHBV or WMHBV envelope pseudotyped HDV could consistently infect spider monkey and, with much lower efficiency, chimpanzee and human hepatocytes (10,14,15). Similar to HBV, WMHBV infects hepat...

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A Short N-Proximal Region in the Large Envelope Protein Harbors a Determinant That Contributes to the Species Specificity of Human Hepatitis B Virus

Cited by 63 publications

References 40 publications

Analysis of Host Range Phenotypes of Primate Hepadnaviruses by In Vitro Infections of Hepatitis D Virus Pseudotypes

Analysis of Host Range Phenotypes of Primate Hepadnaviruses by In Vitro Infections of Hepatitis D Virus Pseudotypes

Regulation of Drug Transporter Expression in Human Hepatocytes Exposed to the Proinflammatory Cytokines Tumor Necrosis Factor-α or Interleukin-6

Sodium Taurocholate Cotransporting Polypeptide Mediates Woolly Monkey Hepatitis B Virus Infection of Tupaia Hepatocytes

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