122例肝病患者肝内HDV,HBV感染的研究

本文对１２２例各型肝病患者用ＡＢＣ法同时检测肝内ＨＤＶ及ＨＢＶ抗原。结果显示，ＨＢｓＡｇ和／或ＨＢｃＡｇ检出率为２７．８７％（３４例），其中ＨＢｃＡｇ为１３．２２％（１６例），ＨＢｓＡｇ为１８．１８％（２２例），两者无显著性差异（Ｐ＞０．０５）．ＨＤＡｇ检出率为４．９２％（６例），这６例丁型肝炎血中均检出ＨＢｓＡｇ和抗一ＨＢｃ，为慢性肝炎．在重肝、肝硬化和肝癌患者的肝内未检出ＨＤＡｇ．说明我国肝炎病毒感染仍以ＨＢＶ为主，ＨＤＶ感染率明显低于欧美，ＨＤＶ感染与ＨＢＶ感染关系密切，ＨＢＶ感染合并ＨＤＶ感染时易使病程慢性化。     

The small delta antigen of hepatitis delta virus is an acetylated protein and acetylation of lysine 72 may influence its cellular localization and viral RNA synthesis

Hepatitis delta virus (HDV) is a single-stranded RNA virus that encodes two viral nucleocapsid proteins named small and large form hepatitis delta antigen (S-HDAg and L-HDAg). The S-HDAg is essential for viral RNA replication while the L-HDAg is required for viral assembly. In this study, we demonstrated that HDAg are acetylated proteins. Metabolic labeling with [(3)H]acetate revealed that both forms of HDAg could be acetylated in vivo. The histone acetyltransferase (HAT) domain of cellular acetyltransferase p300 could acetylate the full-length and the N-terminal 88 amino acids of S-HDAg in vitro. By mass spectrometric analysis of the modified protein, Lys-72 of S-HDAg was identified as one of the acetylation sites. Substitution of Lys-72 to Arg caused the mutant S-HDAg to redistribute from the nucleus to the cytoplasm. The mutant reduced viral RNA accumulation and resulted in the earlier appearance of L-HDAg. These results demonstrated that HDAg is an acetylated protein and mutation of HDAg at Lys-72 modulates HDAg subcellular localization and may participate in viral RNA nucleocytoplasmic shuttling and replication.     

儿童乙型肝炎病人血清中HDAg与抗HD的检测及分析

我们检测了 2 61例乙型肝炎儿童血清中 HDAg和抗 HD,结果发现有 2 8例重叠有 HDV感染 ,感染率为 1 0 .7% ,明显高于文献报道。     

Variable In Vivo Hepatitis D Virus (HDV) RNA Editing Rates According to the HDV Genotype

Human hepatitis delta virus (HDV) is a small defective RNA satellite virus that requires hepatitis B virus (HBV) envelope proteins to form its own virions. The HDV genome possesses a single coding open reading frame (ORF), located on a replicative intermediate, the antigenome, encoding the small (s) and the large (L) isoforms of the delta antigen (s-HDAg and L-HDAg). The latter is produced following an editing process, changing the amber/stop codon on the s-HDAg-ORF into a tryptophan codon, allowing L-HDAg synthesis by the addition of 19 (or 20) C-terminal amino acids. The two delta proteins play different roles in the viral cell cycle: s-HDAg activates genome replication, while L-HDAg blocks replication and favors virion morphogenesis and propagation. L-HDAg has also been involved in HDV pathogenicity. Understanding the kinetics of viral editing rates in vivo is key to unravel the biology of the virus and understand its spread and natural history. We developed and validated a new assay based on next-generation sequencing and aimed at quantifying HDV RNA editing in plasma. We analyzed plasma samples from 219 patients infected with different HDV genotypes and showed that HDV editing capacity strongly depends on the genotype of the strain.     

慢性乙型肝炎患者重叠感染HDV的研究

目的了解慢性乙型肝炎患者重叠感染丁型肝炎病毒（ＨＤＶ）的状况，并探讨慢性乙型肝炎患者重叠感染ＨＤＶ的临床特征。方法采用ＥＬＩＳＡ法对３８２例慢性乙型肝炎患者进行了血清丁型肝炎病毒抗原（ＨＤＡｇ）检测，并对所检出的乙肝病毒（ＨＢＶ）和ＨＤＶ重叠感染患者及其对照组进行了疗效比较。结果在慢性乙型肝炎不同临床类型的患者之间，血清ＨＤＡｇ阳性率的差异有显著意义Ｐ＜００１，慢性乙型肝炎重度组患者血清ＨＤＡｇ阳性率为最高。ＨＢＶ、ＨＤＶ重叠感染患者与单一ＨＢＶ感染患者的治疗结果之间也存在显著差异，各项指标之间均Ｐ＜００１。结论在慢性乙型肝炎患者中，病情越重，重叠感染ＨＤＶ的比率越高，重叠感染ＨＤＶ与乙型肝炎的慢性化及病情加重有关。     

血清抗—HD—IgM方法的建立及初步应用

本文采用国产试剂建立抗-HD-IgM的EIA检测方法,开采用不同血清稀释度进行研究。结果表明最适宜血清稀释度为10~(-2),按10~(-2)作血清稀释,对45份HDV/HBV感染的患者血清进行抗-HD-IgM检测,阳性23例(51.11％),17份单纯HBV感染者及9份正常人标本均为阴性,表明本方法具有较好的特异性和敏感性。45例HDV/HBV感染者中,血清HDAg(+)32例(71.11％),抗-HD(+)18例(40％)。     

A Rapid Point-of-Care Test for the Serodiagnosis of Hepatitis Delta Virus Infection

Hepatitis Delta virus (HDV) is a satellite of the Hepatitis B virus (HBV) and causes severe liver disease. The estimated prevalence of 15–20 million infected people worldwide may be underestimated as international diagnostic guidelines are not routinely followed. Possible reasons for this include the limited awareness among healthcare providers, the requirement for costly equipment and specialized training, and a lack of access to reliable tests in regions with poor medical infrastructure. In this study, we developed an HDV rapid test for the detection of antibodies against the hepatitis delta antigen (anti-HDV) in serum and plasma. The test is based on a novel recombinant large hepatitis delta antigen that can detect anti-HDV in a concentration-dependent manner with pan-genotypic activity across all known HDV genotypes. We evaluated the performance of this test on a cohort of 474 patient samples and found that it has a sensitivity of 94.6% (314/332) and a specificity of 100% (142/142) when compared to a diagnostic gold-standard ELISA. It also works robustly for a broad range of anti-HDV titers. We anticipate this novel HDV rapid test to be an important tool for epidemiological studies and clinical diagnostics, especially in regions that currently lack access to reliable HDV testing.