利用TMV—U1作为载体表达鼠肝炎病毒S糖蛋白片段

为了验证转基因烟草中表达的外壳蛋白（ＣＰ）能够重新包被侵入的烟草花叶病毒（ＴＭＶ）的假设,利用抗原表位标记的方法观察ＣＰ亚单位在病毒５′端的交换。通过ＰＣＲ 方法将来源于鼠肝炎病毒（ＭＨＶ） Ｓ蛋白的两个小肽段（１１ ａ．ａ．和１５ ａ．ａ．）的ＤＮＡ序列分别插入ＴＭＶ－Ｕ１ ＣＰ基因邻近３′端的两个位点,并构建了带有外源序列的ＴＭＶ 侵染克隆Ｖ９ （１１ ａ．ａ．）和Ｅ１５ （１５ ａ．ａ．）。通过体外转录反应,得到Ｖ９ ＲＮＡ 及Ｅ１５ ＲＮＡ。突变病毒ＲＮＡ 侵染烟草（Ｎｉｃｏｔｉａｎａ ｔａｂａｃｕｍ ）后表现不同特性。Ｖ９ 和Ｅ１５ 侵染ＸａｎｔｈｉＮＮ烟草后同野生型ＴＭＶ一样产生枯斑。但是,当它们侵染Ｘａｎｔｈｉｎｎ 烟草时,Ｖ９ 产生同侵染ＸａｎｔｈｉＮＮ 烟草相同的枯斑,而Ｅ１５的特性同ＴＭＶ－Ｕ１几乎完全相同,能对Ｘａｎｔｈｉｎｎ 烟草进行系统侵染并在叶片中聚集大量的带有外源片段的外壳蛋白,而且病毒的结构极其稳定。Ｖ９ 和Ｅ１５ 特性的差异可能是由于外源片段在外壳蛋白中存在位置的不同影响了外壳蛋白的结构所致     

HBIG,无环鸟苷,干扰素联合对慢性乙型肝炎抗病毒效应观察

本文报道血清ＨＢＶ复制标志阳性的慢乙肝５４例,随机分为治疗组及对照组各２７例进行ＨＢＩＧ、无环鸟苷、干扰素联合近、远期抗病毒效应观察。治疗组为无环鸟苷第一周按２５～２０ｍｇ／ｋｇ／ｄ计后改１７～１５ｍｇ／ｋｇ／ｄ×５３天,共６０天;人白细胞干扰素１×１０６Ｕ肌注每周３次×４周,后改１．０×１０６Ｕ肌注每周２次×６周,共１０周;ＨＢＩＧ４００Ｕ肌注隔日１次,共１０周,对照组仅给予一般“保肝”药物。其中治疗组１８例,对照组１９例进行治后半年到２年追踪观察,结果近、远期ＨＢｃＡｇ、ＤＮＡＰ、ＨＢＶ－ＤＮＡ阴转率治疗组均高于对照组,其中治疗组近、远期ＨＢｃＡｇ,ＨＢＶ－ＤＮＡ阴转率均达４０％以上,明显高于对照组（Ｐ＜０．０５～０．０１）,治疗组近、远期各有４例及２例ＨＢｓＡｇ阴转,而对照组则无一例阴转,从近、远期综合抗病毒效应观察,治疗组全阴率分别为３３．３％、４４．４％,而对照组分别为３．７９％及０％,Ｐ＜０．０１,治疗组无明显毒副反应。对比单用无环鸟苷,全阴率３１．８％;无环鸟苷加干扰素两药联合全阴率３７．５％,均有所提高,达到４４．４％,值得进一步研究。     

Monitoring of early events of experimental woodchuck hepatitis infection: Studies of peripheral blood mononuclear cells by cytofluorometry and PCR

Abstract The peripheral blood mononuclear cells (PBMC) of woodchucks experimentally infected by woodchuck hepatitis virus (WHV) were examined simultaneously for the presence of membrane associated WHV antigens by cytofluorometry, and for WHV DNA and RNA sequences by the polymerase chain reaction (PCR). Four woodchucks were inoculated: two with a well-defined infectious inoculum and two with an inoculum obtained from an animal at the late incubation phase, which was positive for WHV DNA by PCR but still devoid of WHV markers. Infection was demonstrated in all four inoculated woodchucks by the appearance at different times of WHV DNA and WHV antigens in both leucocytes and serum. WHV DNA was first detected by PCR either in the serum (two cases) or in leucocytes (two cases). The mean percentage of cells positive for membrane associated WHsAg or WHcAg detected by cytofluorometry were 37%±25 and 17%±15 respectively. After 8 weeks, all inoculated animals were WHsAg positive in serum. These data suggest that PBMC are involved in the early events of hepadnavirus infection. They also show that sera which are positive by PCR for WHV DNA may transmit viral infection even while still seronegative for WHV markers and for WHV DNA by dot blot.     

Interferon antibodies in patients with infectious diseases

Interferons (IFNs) are generally recognized as the most important therapeutic agent in some infectious diseases such as chronic hepatitis B and C. Since the early clinical trials it was documented that the therapeutic use of IFNs could be complicated by the development of antibodies able to neutralize or to bind to the IFN molecule. After several years of research it is now widely accepted that the presence of circulating anti-IFN antibodies may affect the response to IFN. Here we summarize what is currently know on the clinical significance of antibodies to IFN in IFN-treated viral diseases patients.     

Anti-Hepatitis A Virus Antibody Response Elicited in Mice by Different Forms of a Synthetic VP1 Peptide

Peptide VP1 (11-25) of the capsid of hepatitis A virus was synthesized by the Fmoc-polyamide solid phase method, and administered to mice in different forms: (1) free, (2) encapsulated in multilamellar liposomes, (3) coupled to keyhole limpet hemocyanin (KHL), and (4) incorporated into a tetrameric branched lysine core. The highest anti-VP1 peptide responses were generated by synthetic peptides entrapped into liposomes and coupled to KLH. No anti-HAV response was generated with the free peptide, while all the other forms induced both anti-HAV and HAV-neutralizing antibodies. Maximum neutralization indices were observed in ascites from mice treated with liposome-entrapped and KLH peptides.     

Molecular structure of the Japanese hepatitis C viral genome

The amino acid sequence of the polyprotein deduced from the nucleotide sequence of the Japanese hepatitis C virus genome (N. Kato et. al. (1990) Proc. Natl. Acad. Sci. USA 87, 9524–9528)indicated that this virus is a member of a new class of positive-stranded RNA viruses. Several domains of this polyprotein also showed weak homology with those of flaviviruses and pestiviruses including the chymotrypsin-like serine proteinase. NTPase and RNA-dependent RNA polymerase     

急性病毒性肝炎的发病率慢性肝炎患病率和肝病死亡率的研究

1984～1987年,在黑龙江、河北、河南、湖南、上海五个省市城乡10.08855人口中进行急性肝炎发病率、慢性肝炎患病率、与病毒性肝炎有关的肝病死亡率的研究。急性肝炎标化发病率为152.19/10万,主要发生在20～50岁组人群;因无甲肝暴发流行,除上海外各点季节发病率分布均衡。慢性肝炎标化患病率为158.25/10万(诊断标准为6个月前有明确急性肝炎病史,现有明显的临床症状或体征,肝功能异常,故实际慢肝患病率要高于此数字);与病毒性肝炎有关的肝病死亡(包括肝癌)标化率为22.65/10万,其中肝病为 13.14/10万。男性死亡率显著高于女性。     

病毒唑及其与干扰素联合对慢性乙型肝炎抗病毒效应观察

本文报道了病毒唑及其与干扰素联合对23例慢乙肝近、远期抗病毒效应观察结果,并与12例未经抗病毒治疗的慢乙肝作对照(Ⅲ组),其中病毒唑与干扰素联合组(I组)12例,病毒唑组(Ⅱ组)11例。近期HBeAg、DNAP及HBV·DNA阴转率,I组分别为(41.6％、55.5％及28.s％,Ⅱ组45.4％、100％及33.3％,Ⅲ组8.3％、16.6％及8.3％。远期HBeAg及DNAP阴转率在I组分别为70％、83.7％。Ⅱ组60％、100％,Ⅲ组8.3％,50％。综合抗病毒效应,近期有效率在I、Ⅱ、Ⅲ组分别为50％、72.7％及16.6％。远期则分别为70％、55.5％及8.3％。无一例出现毒副反应。均完成疗程。上述结果提示病毒唑及其与干扰素联合对慢乙肝均有一定抗病毒效应,联合应用并不优于单一用药,但毒副反应也未见加重,而且病毒唑药源较方便,使用较安全,值得进一步研究。     

慢性乙型肝炎患者血清IL-17A、GP73水平与肝功能指标及病情严重程度的关系分析

摘要 目的：探讨慢性乙型肝炎(CHB)患者血清白细胞介素-17A (IL-17A)、高尔基体蛋白73(GP73)水平与肝功能指标及病情严重程度的关系。方法：选取2018年10月至2019年10月于青海大学附属医院就诊的CHB患者93例作为研究对象（CHB组）,另选取同时期于我院体检的健康志愿者33例作为对照组。比较不同病情严重程度、不同乙型肝炎e抗原（HbeAg）表达的CHB患者IL-17A、GP73水平及肝功能相关指标[丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）、白蛋白、总胆红素（TBiL）]的差异,并分析IL-17A、GP73水平与患者病情严重程度及肝功能相关指标的相关性。结果：CHB组中轻度、中度、重度患者血清IL-17A、GP73、ALT、AST及TBiL水平均高于对照组,白蛋白水平低于对照组（P<0.05）,并且随着CHB患者病情严重程度的加重其血清中IL-17A、GP73、ALT、AST及TBiL水平逐渐升高,白蛋白水平逐渐降低（P<0.05）。CHB组HbeAg阴性患者血清中的IL-17A、GP73、ALT及AST水平均明显高于HbeAg阳性患者（P<0.05）,而白蛋白和TBiL水平无明显差异（P>0.05）。CHB患者血清IL-17A、GP73均与ALT、AST及TBiL呈正相关,与白蛋白呈负相关,与患者病情严重程度呈正相关（P<0.05）。结论：CHB患者血清中IL-17A、GP73水平明显升高,且与患者病情严重程度及肝功能相关指标呈明显相关性,临床中可联合检测用于患者病情评估及预后监测。