HIV-1慢性感染Jurkat细胞系的建立及其特性研究

目的　建立艾滋病病毒Ⅰ型( HIV21) 慢性感染J urkat 细胞系,研究其生物学特性。方法　参照文献方法改良,建立HIV21 ⅢB慢性感染J urkat 细胞系。其细胞系特性采用以下方法检测:光学显微镜观察细胞形态;流式细胞仪检测HIV21 ⅢB感染细胞的阳性率;噻唑蓝(MTT) 法检测抗病毒药物对慢性感染细胞的毒性作用;酶联免疫吸附试验( EL ISA) 检测药物对慢性感染细胞中病毒复制的影响;合胞体形成方法检测药物对HIV21 ⅢB慢性感染细胞与正常细胞融合的阻断作用。结果　成功建立了HIV21 慢性感染J urkat 细胞系(J urkat/ HIV21 ⅢB ) ,感染细胞阳性率> 90 %。检测影响病毒复制各周期的抗病毒药物对J urkat/ HIV21 ⅢB细胞的作用,发现J urkat/ HIV21 ⅢB细胞具有 HIV21 慢性感染细胞的生物学特征。结论　成功建立J urkat/ HIV21 ⅢB 细胞系,为抗HIV21 药物的研发和病毒感染机制研究提供了新的工具。

云南省HIV-1分子流行病学研究进展

云南省是中国HIV-1感染最早和最为严重的地区之一,流行的HIV-1病毒亚型种类复杂多样。已有证据表明国内其它地区的HIV-1亚型很可能主要来源于云南省。本文对云南省的HIV-1亚型的流行情况进行综述,希望能为预防控制云南省乃至全国HIV-1的流行以及合理设计HIV-1疫苗提供基础信息。

半乳糖神经酰胺脂质体对HIV-1感染性的影响

目的研究体外空白及包封抗HIV药物和PFA的GalCer脂质体对HIV-1复制的影响。方法通过HIV p24抗原测定、合胞体抑制实验、融合阻断实验和对HIV感染细胞的保护作用实验等，观察了空白GalCer脂质体、AZT-GalCer脂质体和PFA-GalCer脂质体对HIV-1复制的影响。结果空白GalCer脂质体预处理细胞，能促进HIV-1感染CD4＋细胞；空白GalCer脂质体预处理HIV-1，则抑制了病毒吸附和结合宿主细胞；GalCer脂质体还具有阻断HIV-1感染细胞与正常CD4＋细胞间的融合作用；GalCer脂质体包封AZT或PFA不能显著提高药物体外抗HIV-1活性。结论空白GalCer脂质体预处理细胞，能促进HIV-1感染性；预处理HIV-1，则抑制了病毒的感染。

非核苷类逆转录酶抑制剂在抗HIV-1中的作用

非核苷类RT抑制剂是一大类化学结构各异的化合物,它们结合于RT上一个非底物结合的变构部位,使RT失去活性。从天然化合物中寻找新的非核苷类RT抑制剂是一条治疗HIV-1感染的极有希望的途径。

Anti-HIV-1 property of trichosanthin correlates with its ribosome inactivating activity

Trichosanthin (TCS) is a type I ribosome inactivating (RI) protein possessing anti-tumor and antiviral activity, including human immunodeficiency virus (HIV). The mechanism of these actions is not entirely clear, but is generally attributed to its RI property. In order to study the relationship between the anti-HIV-1 activity of TCS and its RI activity, three TCS mutants with different RI activities were constructed by using site-directed mutagenesis. The anti-HIV-1 activities of the three mutants were tested in vitro. Results showed that two TCS mutants, namely TCSM((120-123)), TCSE160A/E189A, with the greatest decrease in RI activity, lost almost all of the anti-HIV activity and cytopathic effect. Another mutant TCSR122G, which exhibited a 160-fold decrease in RI activity, retained some anti-HIV activity. The results from this study suggested that RI activity of TCS may have significant contribution to its anti-HIV-1 property. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Independency of anti-HIV-1 activity from ribosome-inactivating activity of trichosanthin

Trichosanthin (TCS) is a type I ribosome-inactivating (RI) protein possessing multiple biological and pharmacological activities. Its major action is inhibition of human immunodeficiency virus (HIV) replication but the mechanism is still elusive. All evidences showed that this action is related to its RI activity. Previous studies found that TCS mutants with reduced RI activity simultaneously lost some anti-HIV activity. In this study, an exception was demonstrated by two TCS mutants retaining almost all RI activity but were devoid of anti-HIV-1 activity. Five mutants were constructed by using site-directed mutagenesis with either deletion or addition of amino acids to the C-terminal sequence. Results showed that the RI activity of mutants with C-terminal deletion mutants (TCSC2, TCSC4, and TCSC14) decreased by 1.2-3.3-fold with parallel downshifting of its anti-HIV-1 activity (1.4-4.8-fold). Another two mutants, TCSC19aa and TCSKDEL having 19 amino acid extension and a KDEL signal sequence added to the C-terminal sequence, retained all RI activity but subsequently lost most of the anti-HIV-1 activity. These findings suggested that ribosome inactivation alone might not be adequate to explain the anti-HIV action of TCS. (C) 2003 Elsevier Science (USA). All rights reserved.

Xanthohumol, a novel anti-HIV-1 agent purified from Hops Humulus lupulus

Xanthohumol, prenylchacone flavonoid, is a natural product with multi-biofunctions purified from Hops Humulus lupulus. Its anti-HIV-1 activity was tested in the present study. Results showed that xanthohumol inhibited HIV-1 induced cytopathic effects, the production of viral p24 antigen and reverse transcriptase in C8166 lymphocytes at non-cytotoxic concentration. The EC50 values were 0.82, 1.28 and 0.50 mug/ml, respectively. The therapeutic index (TI) was about 10.8. Xanthohumol also inhibited HIV-1 replication in PBMC with EC50 value of 20.74 mug/ml. The activity of recombinant HIV-1 reverse transcriptase and the HIV-1 entry were not inhibited by xanthohumol. The results from this study suggested that xanthohumol is effective against HIV-1 and might serve as an interesting lead compound. It may represent a novel chemotherapeutic agent for HIV-1 infection. However, the mechanism of its anti-HIV-1 effect needs to be further clarified. (C) 2004 Elsevier B.V. All rights reserved.

Zinc coupling potentiates anti-HIV-1 activity of baicalin

Baicalin (BA) has been shown with anti-HIV-1 activity. Zinc is a nutrient element. The anti-HIV-1 activity of zinc complex of baicalin (BA-Zn) in vitro was studied and compared with the anti-HIV-1 activities between BA and BA-Zn in the present study. Our results suggested that BA-Zn has lower cytotoxicity and higher anti-HIV-1 activity compared with those of BA in vitro. The CC(50)s of BA-Zn and BA were 221.52 and 101.73 muM, respectively. The cytotoxicity of BA-Zn was about 1.2-fold lower than that of BA. The BA and BA-Zn inhibited HIV-1 induced syncytium formation, HIV-1 p24 antigen and HIV-1 RT production. The EC(50)s of BA-Zn on inhibiting HIV-1 induced syncytium formation (29.08 muM) and RT production (31.17 muM) were lower than those of BA (43.27 and 47.34 muM, respectively). BA-Zn was more effective than BA in inhibiting the activities of recombinant RT and HIV-1 entry into host cells. Zinc coupling enhanced the anti-HTV-1 activity of baicalin. (C) 2004 Elsevier Inc. All rights reserved.

The anti-HIV-1 effect of scutellarin

Scutellarin was purified from the plant Erigeron breuiscapus (Vant.) Hand.-Mazz. The activity against 3 strains of human immunodeficiency virus (HIV) was determined in vitro in this study. These were laboratory-derived virus (HIV-I-IIIB), drug-resistant virus (HIV-I-74V), and low-passage clinical isolated virus (HIV-1(KM018)). From syncytia inhibition study, the EC50 of scutellarin against HIV-I-IIB direct infection in C8166 cells was 26 mu M with a therapeutic index of 36. When the mode of infection changed from acute infection to cell-to-cell infection, this compound became even more potent and the EC50 reduced to 15 mu M. This suggested that cell fusion might be affected by this compound. By comparing the inhibitory effects on p24 antigen, scutellarin was also found to be active against HIV-1(74V) (EC50 253 mu M) and HIV-1(KM018) (EC50 136 mu M) infection with significant difference in potency. The mechanism of its action was also explored in this study. At a concentration of 433 mu M, scutellarin inhibited 48% of the cell free recombinant HIV-1 RT activity. It also caused 82% inhibition of HIV-1 particle attachment and 45% inhibition of fusion at the concentrations of 54 mu M. In summary, scutellarin was found to inhibit several strains of HIV-1 replication with different potencies. It appeared to inhibit HIV-1 RT activity, HIV-1 particle attachment and cell fusion. These are essential activities for viral transmission and replication. (c) 2005 Elsevier Inc. All rights reserved.

Halichondria sulfonic acid, a new HIV-1 inhibitory guanidino-sulflonic acid, and halistanol sulfate isolated from the marine sponge Halichondria rugosa Ridley & Dendy

A new sulfur-containing guanidino derivative, halichondria sulfonic acid (1) showing anti-HIV-1 activity, and halistanol trisulfate (2) with anti-tumor activity have been isolated from the marine sponge Halichondria rugosa Ridley & Dendy collected in the

Anti-HIV-1 activities of extracts from the medicinal plant Rhus chinensis

Rhus chinensis, a species used in folk medicine by Chinese native people, the anti-HIV-1 activities of the petroleum ether, ethyl acetate, butanol and aqueous extract of Rhus chinensis, named as RC-1, RC-2, RC-3 and RC-4, respectively, was evaluated. The

Triterpenoids from Schisandra lancifolia with anti-HIV-1 activity

A new trinorcycloartane triterpenoid, lancifodilactone H (1), and a new A ring-secocycloartane triterpenoid, lancifoic acid A (2), together with a known compound, nigranoic acid (3), were isolated from the leaves and stems of Schisandra lancifolia. Their

A beta-galactose-specific lectin isolated from the marine worm Chaetopterus variopedatus possesses anti-HIV-1 activity

A 30 kDa beta-galactose-specific lectin named CVL was isolated from the polychaete marine worm Chaetopterus variopedatus (Annelida) and its anti-HIV-1 activity in vitro was determined. Results showed that CVL inhibited cytopathic effect induced by HIV-1 a

An inhibitor of c-Jun N-terminal kinases (CEP-11004) counteracts the anti-HIV-1 action of trichosanthin

Trichosanthin (TCS) is a type I ribosome-inactivating protein possessing multiple biological and pharmacological activities. One of its major actions is inhibition of human immunodeficiency virus (HIV) replication. The mechanism is still not clear. It is