Effect of Mutations in the Small Envelope Protein of Hepatitis B Virus on Assembly and Secretion of Hepatitis Delta Virus

Jenna, Sarah; Sureau, Camille

doi:10.1006/viro.1998.9391

Cited by 36 publications

(54 citation statements)

References 29 publications

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“…These experiments confirmed the previous data of Jenna and Sureau (14) and demonstrated and that codon 196 is critical for HDV packaging. But, importantly, the data demonstrated that the key clinically relevant mutants currently being selected during antiviral therapy have a differential HDV packaging profile.…”

Section: Figsupporting

confidence: 91%

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Failure of the Lamivudine-Resistant rtM204I Hepatitis B Virus Mutants To Efficiently Support Hepatitis Delta Virus Secretion

Vietheer

Netter

Sozzi

et al. 2005

J Virol

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Hepatitis delta virus (HDV) is encapsidated by the envelope proteins of hepatitis B virus (HBV).The hepatitis delta virus (HDV) can cause severe chronic and acute hepatitis in humans (11). HDV coexists with hepatitis B virus (HBV) as it is dependent on the HBV envelope proteins for virus assembly. Inside the HBV envelope, the HDV virion contains a 1.7-kb circular RNA genome complexed with two HDV-encoded proteins, the large (214-aminoacid) and small (195-amino-acid) forms of hepatitis delta antigen (HDAg-L and HDAg-S, respectively) (22, 28). HDAg-L is crucial for virus assembly and interaction with the HBV envelope proteins (6). The other viral protein, HDAg-S, is essential for viral RNA replication (17).The HBV genome is approximately 3.2 kb and contains a number of overlapping reading frames. The HBV envelope consists of three surface proteins, small (hepatitis B surface antigen; HBsAg), middle, and large. All three HBV envelope proteins are encoded by a single open reading frame. The mRNA transcripts have different in-phase translational start codons and share a common stop codon, resulting in proteins with identical C-terminal ends and different N-terminal sequences. The HBsAg protein can form subviral particles that are secreted in excess in comparison to the HBV virion. The presence of HBsAg alone is sufficient for HDV assembly, although as with HBV, the large hepatitis B surface protein is required for infectivity. The envelope genes overlap the gene encoding the polymerase, and mutations may result in concomitant changes in both reading frames (21).The nucleoside analogue lamivudine (LMV) has been used for the treatment of hepatitis B infection (12,19,20). Lau and coworkers (18) demonstrated that although LMV is a potent inhibitor of HBV DNA replication, it did not inhibit HDV RNA replication or improve disease activity. Nevertheless, LMV is being used to treat hepatitis B infection in patients that are coinfected with HDV (4, 20, 29, 30). The major problem with LMV treatment has been the selection of HBV-resistant strains. In a study of long-term LMV treatment, HBV resistance was detected in 67% of patients after 4 years and 69% of patients after 5 years (19,20). Resistance to LMV is associated with a mutation in the reverse transcriptase (rt) region of the polymerase gene at the M204V/I codon (rtM204V/I), with or without an accompanying rtL180M mutation (according to the nomenclature by Stuyver and coworkers [24]) ( Table 1). The rtL180M change does not result in an amino acid change within the envelope protein. The concomitant HBsAg mutations selected by the antiviral agents are located towards the C-terminal region of the envelope protein. The mutation at the rtM204V codon results in a change in the envelope gene at the sI195M codon, and the rtM204I mutation results in changes to the sW196L/S/Stop codon. In addition to these changes, the rtV173L mutation occurs in 9 to 22% of patients with LMV resistance (8,9). This mutation results in a change in the envelope gene at the sE164D codon. Recently, Tor...

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Section: Figsupporting

confidence: 91%

“…3B). The previously described sW196F mutation (14) was used as a control, and its presence resulted in reduced HDV secretion by a factor of 5, as measured by densitometry, compared to that of wild-type HBsAg (Table 1).…”

mentioning

confidence: 99%

Failure of the Lamivudine-Resistant rtM204I Hepatitis B Virus Mutants To Efficiently Support Hepatitis Delta Virus Secretion

Vietheer

Netter

Sozzi

et al. 2005

J Virol

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“…The cytoplasmic orientation of the CYLs of the S protein, provides a reasonable condition for these sites to interact with pre-mature HDV virions in the cytosol (Figure 1) [22] . The importance of S-HBsAg residues 24 to 28 and 56 to 80 for HDV secretion has been shown in previous studies [23,24] . Also, a C-terminal truncation of HBsAg by 50 amino acids inhibits HDV envelopment and secretion [25] .…”

Section: Shirvani-dastgerdi E Et Al Hbv-hdv Interactionssupporting

confidence: 59%

Molecular interactions between hepatitis B virus and delta virus

Shirvani-Dastgerdi¹

2015

WJV

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HBV HBsAgs. While HBsAg is the only protein required by HDV, the exact interaction sites between the S protein and pre-mature HDV are not well defined yet. In fact, these sites are distributed along the S protein with some hot spots for the envelopment process. Moreover, in most clinically studied samples, HDV infection is associated with a dramatically reduced HBV viral load, temporarily or permanently, while HBsAg resources are available for HDV packaging. Thus, beyond interacting with HBV envelope proteins, controlling mechanisms exist by which HDV inhibits HBV-DNA replication while allowing a selective transcription of HBV proteins. Here we discuss the molecular interaction sites between HBsAg and the HDV-RNP complex and address the proposed indirect mechanisms, which are employed by HBV and HDV to facilitate or inhibit each other's viral replication. Understanding molecular interactions between HBV and HDV may help to design novel therapeutic strategies for delta hepatitis. Core tip: Hepatitis D virus (HDV) causes accelerated liver disease in form of fulminant or chronic hepatitis in patients with hepatitis B virus (HBV) infection. HBV supports HDV replication by sharing its surface proteins. Even without overt HBV-DNA replication, transcription of HBV surface proteins (HBsAgs) remains stable in HDV infected cells, which is essential for assembly of HDV virions containing HBsAg proteins. HDV replication is oftentimes associated with a suppression of HBV-DNA levels, and several mechanisms have been suggested how HBV or HDV may influence each other's replication. Understanding molecular interactions between HBV and HDV may help to design novel therapeutic strategies. Molecular interactions between hepatitis B virus and delta virus AbstractAs a deficient virus due to the lack of envelope proteins, hepatitis D virus (HDV) causes chronic or fulminant "delta hepatitis" only in people with simultaneous hepatitis B virus (HBV) infection. HBV encodes three types of surface proteins known as small (S), medium (M) and large (L) envelope proteins. All three types of HBV surface antigens (HBsAgs) are present on HDV virions. The envelopment process of HDV occurs through interactions between the HDV ribonucleoprotein (RNP) complex and 36 EDITORIALSubmit a

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“…In some cases of HDV infection, quantitative HBsAg concentrations decreased during lamivudine treatment (2). It has been shown that HBVenvelope protein plays an important role in HDV particle assembly (18), suggesting that reduction of HBsAg by lamivudine therapy could help reduce HDV-induced hepatic injury. However, HBsAgconcentration was not decreased by lamivudine administration in the present case.…”

Section: Discussionmentioning

confidence: 99%

Chronic Hepatitis B with Flare Due to Co-infection of Hepatitis Delta Virus during Lamivudine Therapy

et al. 2003

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In 1997, a 27-year-old homosexual mancontracted acute hepatitis B that developed into chronic hepatitis. Because of repeated flares, administration of lamivudine was started in March 2002. Hepatitis B virus (HBV) DNA immediately decreased, but the serum level of alanine aminotransferase gradually increased. Drug-induced hepatitis due to lamivudine was excluded. It was suspected that the progression of liver damagewas caused by hepatitis delta virus (HDV), because the patient was positive for both anti-HDV antibody and HDVRNA.Coinfection of HDVshould be considered a possibility if liver injury is not improved by lamivudine therapy. (Internal Medicine 42: 581-586, 2003)

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Effect of Mutations in the Small Envelope Protein of Hepatitis B Virus on Assembly and Secretion of Hepatitis Delta Virus

Cited by 36 publications

References 29 publications

Failure of the Lamivudine-Resistant rtM204I Hepatitis B Virus Mutants To Efficiently Support Hepatitis Delta Virus Secretion

Failure of the Lamivudine-Resistant rtM204I Hepatitis B Virus Mutants To Efficiently Support Hepatitis Delta Virus Secretion

Molecular interactions between hepatitis B virus and delta virus

Chronic Hepatitis B with Flare Due to Co-infection of Hepatitis Delta Virus during Lamivudine Therapy

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