浙江省HBV感染人群中HDV感染的调查

ＨＤＶ是亲肝细胞的缺陷性ＲＮＡ病毒 ,必须依赖ＨＢＶ才能复制 ,常与ＨＢＶ引起联合感染或重叠感染 ,在临床上导致肝炎病情加剧 ,并更易发展为肝硬化。我国是ＨＢＶ感染高发区 ,ＨＤＶ感染率在部分地区亦较高 ,因此对于ＨＤＶ的研究工作日益重视。我们在１９９４年１月～２０００年１２月期间进行的ＨＤＶ检测工作中 ,积累了我省ＨＢＶ感染人群中ＨＤＶ感染状况的资料 ,现将结果报道如下。材料和方法一、研究对象１９９４年１月～２０００年１２月在我院同时进行乙肝标志物 (ＨＢｓＡｇ、ＨＢｅＡｇ、ＨＢｃＡｂ、ＨＢｅＡｂ、ＨＢｓＡｂ、…     

短波紫外线与交联淀粉碘联用对血浆中鸭乙型肝炎病毒灭活的研究

采用３Ｈ渗入检测法、免疫电镜、ＥＬＩＳＡ法、雏鸭感染试验等技术,观察短波紫外线（ＵＶＣ）与交联淀粉碘（ＣＳＩ）联用对血浆中鸭乙型肝炎病毒（ＤＨＢＶ）的灭活效果。结果,在７１７０Ｊ／ｍ２ＵＶＣ照射后,再经 ＣＳＩ １００ ｍｇ／ ｍｌ作用 ９０ ｍｉｎ,血浆中 ＤＨＢＶ ＤＮＡ—Ｐ活性下降 ９９．７６％, ＤＨＢＶ颗粒破坏,而 ＤＨＢｓＡｇ为阳性,雏鸭感染比率为 ２／ １３。若 ＣＳＩ作用时间延长至 １２０ ｍｉｎ,血浆中 ＤＨＢｓＡｇ滴度进一步下降但仍呈阳性,雏鸭感染比率却为０／ １０。     

嗜肝DNA病毒感染模型及其在消毒研究中的应用

嗜肝ＤＮＡ病毒 (Ｈｅｐａｄｎａｖｉｒｕｓｅｓ)是一类以肝细胞为靶细胞的嗜肝性ＤＮＡ病毒 ,主要包括乙型肝炎病毒 (ＨｅｐａｔｉｔｉｓＢＶｉｒｕｓ,ＨＢＶ)、地松鼠肝炎病毒(ＧｒｏｕｎｄＳｑｕｉｒｒｅｌＨｅｐａｔｉｔｉｓＶｉｒｕｓ ,ＧＳＨＶ)、土拨鼠肝炎病毒 (ＷｏｏｄｃｈｕｃｋＨｅｐａｔｉｔｉｓＶｉｒｕｓ,ＷＨＶ)和鸭乙型肝炎病毒 (ＤｕｃｋＨｅｐａｔｉｔｉｓＢＶｉｒｕｓ,ＤＨＢＶ)。1 嗜肝ＤＮＡ病毒的感染模型 :1 970年Ｄａｎｅ’ｓ等首先从人血清中分离到ＨＢＶ (当时称Ｄａｎｅ’ｓ颗粒 ) ,在以后的研究中发现 ,ＨＢ…     

人类疱疹病毒6型、EB病毒与霍奇金病关系的研究

新近发现的人类疱疹病毒６型（ＨＨＶ６）在白血病、淋巴瘤中有较高的抗体滴度［１］,与淋巴瘤关系密切。长期以来人们发现ＥＢ病毒（ＥＢＶ）不仅嗜Ｂ淋巴细胞,还发现与Ｔ细胞淋巴瘤和霍奇金病（ＨＤ）有关［２］。为了解ＨＤ中ＨＨＶ６、ＥＢＶ的感染情况、ＨＤ与ＨＨ...     

用鸭乙型肝炎病毒感染试验评价人乙型肝炎病毒灭活效果的研究

在所试剂量下，煮沸、戊二醛与二氯异氰尿酸钠均可使ＤＨＢＶ与ＨＨＢＶ形态及其ＤＮＡ－Ｐ破坏，使ＤＨＢＶ对雏鸭的感染性灭活；但除用二氯异氰尿酸钠处理外，均不能将其ＤＮＡ与表面抗原完全破坏。结果表明，用ＤＨＢＶ雏鸭感染法进行消毒试验，可间接，但较准确反映出对ＨＨＢＶ的灭活效果。本试验与其他标志物试验相比，较易推广。     

重新评价血清HBV标志物的临床意义

重新评价血清ＨＢＶ标志物的临床意义广东省南海市小塘医院内科（５２８２２２）甘应雄通常用免疫技术测定血清中乙型肝炎病毒（ＨＢＶ）的ＨＢｓＡｇ、ＨＢｅＡｇ、ＨＢｓＡｂ，ＨＢｅＡｂ、ＨＢｃＡｂ标志物来判定是否感染ＨＢＶ和ＨＢＶ感染时病毒复制或非复制阶段、肝...     

丁型肝炎问答

丁型肝炎的传染源与传播途径如何?其实验室诊断研究进展如何?　　丁型肝炎病毒(ＨＤＶ)是一种缺陷病毒。其外壳为ＨＢｓＡｇ,故常发生ＨＢＶ和ＨＤＶ联合感染或重叠感染。如既往未感染过ＨＢＶ,而且同时暴露于ＨＢＶ和ＨＤＶ,则发生联合感染。如既往已感染ＨＢＶ,现为ＨＢｓＡｇ无症状携带者或慢性乙肝患者,再感染ＨＤＶ则发生ＨＤＶ重叠感染。联合感染可表现为重症肝炎。急性和慢性的丁型肝炎病人以及ＨＤＶ携带者是本病的传染源。传染途径主要有两方面:①经血或血制品传播。此为主要传播途径;②日常生活密切接触传播。通过隐性经皮肤或粘…     

抗体消毒法对血浆中鸭乙型肝炎病毒灭活的研究

研究发现，单抗与多抗中和法可使病毒抗原得到封闭，抑制率随剂量的增加而增加。免疫吸附法可清除血浆中的鸭乙型肝炎病毒（ＤＨＢＶ），并有剂量、时间效应关系。每毫升含ＤＨＢＶ血浆中加入５ｍｇ抗体吸附剂，反复处理４次，所测各种ＤＨＢＶ标志物均转为阴性。     

斑点杂交与荧光定量PCR检测血清HBV-DNA的临床意义

ＨＢＶ ＤＮＡ是一种十分重要的ＨＢＶ感染标志 ,是直接反映ＨＢＶ的存在、病毒活动性复制与具有传染性的标志 ,对于确定ＨＢＶ感染的诊断有重要价值[1] 。目前ＨＢＶ感染的基因诊断技术已从定性发展到定量[2 ] 。斑点杂交定性检测不能直接反映病毒负荷量。近年来 ,荧光定量ＰＣＲ逐渐应用于临床检测ＨＢＶ ＤＮＡ。通过对 10 5例慢性乙型肝炎患者用斑点杂交与荧光定量ＰＣＲ两种方法同时进行血清ＨＢＶ ＤＮＡ检测 ,以了解两种方法的一致性 ,探讨两者的临床应用价值及问题。1　材料和方法1.1　研究对象　 2 0 0 1年 3至 7月间中山医科大学…     

乙型肝炎病毒变异与临床的关系

乙型肝炎病毒（ＨＢＶ）是一种高变异病毒,由于它在复制过程中,必须经过ＲＮＡ中间体的逆转录复制,在这一逆转录复制过程中,因ＤＮＡ聚合酶和逆转录酶缺乏校正功能,使病毒基因在复制过程中,可发生一个核苷酸（点突变）和多个核苷酸的变异。发生变异的病毒常引起其生物学特性的改变,尤其是ＨＢＶ编码蛋白如抗原蛋白等发生变异。近年发现ＨＢＶ感染的不同疾病谱和血清学表现的不典型均与病毒变异有关。阅读有关文献,对ＨＢＶ变异所引起的临床、血清学表现、防治等方面的变化,作如下归纳。一、ＨＢＶ变异的原因ＨＢＶ变异可以在慢性持…     

特异光敏效应对血细胞悬液中DHBV的灭活作用

目的　观察设计的靶向光敏剂所产生的特异光化学效应对血细胞悬液中病毒的灭活作用 ,以探索新型的血液病毒灭活技术。方法　以光化学效应为基本原理 ,利用反义核酸技术设计合成与DHBV DNA特异结合的TFO P ,将其作为特异的靶向光敏剂 ,在UVA的协同下将其作用于血细胞悬液中的DHBV。通过电泳转移印迹试验、原代鸭肝细胞感染试验 ,观察TFO P与DHBV DNA的结合效应和在UVA协同下灭活DHBV的效果。结果　所设计的TFO P能与不同株DHBV DNA样本产生不同程度的特异结合 ,在剂量为 0 .1nmol/ml的TFO P和照射强度为 180 0 μW/cm2 的UVA作用下 ,血细胞悬液中DHBV的活性下降 1.9～ 5 .4Log。 结论　TFO P所产生的光化学效应能显著灭活血细胞悬液中的DHBV。     

鸭乙型肝炎病毒耐药株的慢性感染研究

目的:建立鸭乙型肝炎病毒(DHBV)耐药株的慢性感染动物模型。方法:将DHBV野生株及耐药株质粒转染细胞,培养上清接种雏鸭。连续定量检测血清DHBV DNA;印迹杂交检测肝内病毒复制中间体;观察肝组织病理变化。结果:野生株组的病毒滴度和慢性感染率均高于耐药株组;肝组织中检测到DHBV的复制中间体与cccDNA,可见轻度炎症病理改变。结论:DHBV耐药株可形成慢性感染。     

Suramin prevents duck hepatitis B virus infection in vivo.

The effect of suramin on duck hepatitis B virus (DHBV) infection was investigated in vivo. Suramin pretreatment of Pekin ducklings completely prevented DHBV infection. In contrast, suramin given at the time of or after inoculation with DHBV did not inhibit viral infection, replication, or gene expression. These data indicate that suramin effectively blocks the early stages of DHBV infection in vivo.     

Comparative activities of several nucleoside analogs against duck hepatitis B virus in vitro.

Duck hepatitis B virus (DHBV) replication in primary duck hepatocytes was monitored by examining the synthesis of both DHBV DNA and DHBV core antigen. Several nucleoside analogs which were previously shown to inhibit the replication of DNA viruses (i.e., herpesviruses) and retroviruses were examined for their inhibitory effects on the synthesis of DHBV core antigen in primary duck hepatocytes. (S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine, 2',3'-dideoxyadenosine, and 2',3'-dideoxycytidine inhibited DHBV core antigen synthesis at concentrations that were significantly lower than those found to be toxic to the primary hepatocytes. Of all the compounds tested, (S)-HPMPA showed the lowest 50% effective concentration (0.5 micrograms/ml). The selectivity index or ratio of the 50% cytotoxic concentration to the 50% effective concentration of (S)-HPMPA was greater than 300. (S)-HPMPA not only inhibited DHBV core antigen but also DHBV DNA synthesis in DHBV-infected hepatocytes.     

Inhibition of duck hepatitis B virus replication by 2',3'-dideoxy-3'-fluoroguanosine in vitro and in vivo.

The antiviral activity of 2',3'-dideoxy-3'-fluoroguanosine (FdG) or its triphosphate was evaluated in the duck hepatitis B virus (DHBV) system in vitro and in vivo. In primary DHBV-infected hepatocytes FdG results in a dose-dependent inhibition of viral replication with a nearly complete inhibition at a concentration of 1 microM. Also in vivo, FdG treatment of DHBV-infected ducklings reduces DHBV DNA replication by more than 90%. These data demonstrate that FdG is a strong inhibitor of DHBV replication in vitro and in vivo.     

Entecavir therapy combined with DNA vaccination for persistent duck hepatitis B virus infection

This study was designed to test the efficacy of antiviral treatment with entecavir (ETV) in combination with DNA vaccines expressing duck hepatitis B virus (DHBV) antigens as a therapy for persistent DHBV infection in ducks. Ducks were inoculated with 10(9) DHBV genomes at 7 days of age, leading to widespread infection of the liver and viremia within 7 days, and were then treated orally with either ETV (0.1 mg/kg of body weight/day) or distilled water from 21 days posthatch for 244 days. Treatment with ETV caused a 4-log drop in serum DHBV DNA levels within 80 days and a slower 2- to 3-log drop in serum DHBV surface antigen (DHBsAg) levels within 120 days. Following withdrawal of ETV, levels of serum DHBV DNA and DHBsAg rebounded to match those in the water-treated animals within 40 days. Sequential liver biopsy samples collected throughout the study showed that ETV treatment reduced DHBV DNA replicative intermediates 70-fold in the liver, while the level of the stable, template form, covalently closed circular DNA decreased only 4-fold. ETV treatment reduced both the intensity of antigen staining and the percentage of antigen-positive hepatocytes in the liver, but the intensity of antigen staining in bile duct cells appeared not to be effected. Intramuscular administration of five doses of a DNA vaccine expressing the DHBV presurface, surface, precore, and core antigens, both alone and concurrently with ETV treatment, on days 50, 64, 78, 127, and 141 did not result in any significant effect on viral markers.     

In vitro antiviral activity of penciclovir, a novel purine nucleoside, against duck hepatitis B virus.

The in vitro antihepadnavirus activities of the purine nucleoside analogs ganciclovir (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine) and penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; BRL 39123] were compared in primary duck hepatocyte cultures congenitally infected with the duck hepatitis B virus (DHBV). Both compounds inhibited DHBV DNA replication to a comparable extent during continuous short-term treatment of the cultures. However penciclovir was more active both during longer-term continuous treatment (50% inhibitory concentrations: penciclovir, 0.7 +/- 0.1 microM; ganciclovir, 4.0 +/- 0.2 microM) and in washout experiments (50% inhibitory concentrations: penciclovir, 3.0 +/- 0.4 microM; ganciclovir, 46 +/- 1.5 microM) designed to compare the persistence of inhibitory activity after removal of the extracellular compound. The effects on viral protein synthesis were similar to the effects on viral DNA replication. These data suggest that penciclovir or its oral form, famciclovir, may have clinical utility in the treatment of chronic hepatitis B virus infection.     

Antiviral activities of penciclovir and famciclovir on duck hepatitis B virus in vitro and in vivo

Chronic hepatitis B virus (HBV) infection is a major health problem worldwide. Antiviral strategies available at present, including interferon-alpha, have only limited efficacy, leading us to analyse the antiviral effects of penciclovir and famciclovir in the duck hepatitis B virus (DHBV) model of HBV infection in vitro and in vivo. In DHBV-infected duck hepatocytes, penciclovir effectively inhibited viral replication, with a concentration giving half-maximal inhibition of 0.25 microM. Furthermore, in vivo, penciclovir and its orally administered prodrug famciclovir strongly inhibited DHBV replication. These data demonstrate that penciclovir and famciclovir both have strong antiviral activities, and suggest that these agents might be useful for treating HBV infection in humans.