非逆转录RNA病毒的DNA形式

逆转录病毒由于编码逆转录酶,在感染的宿主细胞中很容易检测到病毒DNA,同时病毒DNA也能整合到宿主基因组中。但令人惊奇的是在淋巴细胞性脉络丛脑膜炎病毒(LCMV)、丙型肝炎病毒(HCV)和丁型肝炎病毒(HDV)等非逆转录RNA病毒感染的宿主细胞中也能检测到病毒DNA,这种DNA形式甚至还存在于宿主细胞的基因组中。本文就这方面的有关研究情况作了综述。

EBLN2基因对肝癌细胞增殖的抑制作用及其机制

目的探讨人类内源性非逆转录博纳病毒样核蛋白序列2(EBLN2)基因对肝癌细胞增殖的抑制作用及其机制。方法采用实时定量RT-PCR技术和蛋白印迹技术检测EBLN2基因在肝癌细胞系(Hep G2、SK-hep-1、Huh7、Hep3B、MHCC-97H、PLC/PRF/5、Focus、SMMC7721、YY-8103、LO2)和人肝癌组织样本中的表达;选取EBLN2表达水平较低的肝癌细胞株Focus和YY-8103进行外转质粒过表达,Pcmv-EBLN2重组质粒转入肝癌细胞株Focus和YY-8103,24 h观察EBLN2基因过表达对肝癌细胞株细胞增殖、平板克隆形成能力及软琼脂克隆形成能力、细胞周期的影响。结果定量和半定量PCR实验结果表明EBLN2基因在59%的肝癌样本中表达下调,且在10株肝癌细胞系(Hep G2、SK-hep-1、Huh7、Hep3B、MHCC-97H、PLC/PRF/5、Focus、SMMC7721、YY-8103、LO2)中表达水平与正常肝组织相比明显下调,依次下调48%、73%、72%、79%、84%、72%、87%、74%、82%、80%,P均<0.05;PcmvEBLN2质粒转染肝癌细胞株YY-8103和Focus 24 h后,肝癌细胞株YY-8103和Focus的细胞增殖率分别为72.2%、85.0%,平板克隆形成率分别为52.6%、25.6%,软琼脂克隆形成率分别为40.9%、37.5%,与空白对照相比,P均<0.05;肝癌细胞株YY-8103和Focus从G1期进入S期受到抑制。结论 EBLN2基因在肝癌组织中表达下调,其可能通过调节细胞周期抑制肝癌细胞增殖。

传毒媒介基因组中内源性病毒元件多样性及功能的研究进展

在病毒与宿主的长期相互作用中,部分病毒基因序列可以被整合到宿主基因组中,形成内源性病毒元件(endogenous viral element,EVE)。随着近年来基因组学和宏病毒组学的发展,研究人员发现除逆转录病毒外,非逆转录RNA病毒同样可以被整合到传毒媒介等真核生物基因组中,形成内源性非逆转录RNA病毒元件(non-retroviral EVE,nrEVE),但关于其具体功能的研究较少。鉴于传毒媒介传播的动物病毒和植物病毒对人、动物及植物造成严重危害,该文聚焦近年来国内外关于传毒媒介基因组中的EVE,特别是nrEVE的研究,总结了EVE的定义及发现,蚊子、蚜虫、蓟马、飞虱和蜱虫等重要传毒媒介中EVE的多样性及功能,并对该领域的后续研究重点进行展望,以期为揭示RNA病毒与宿主的长期协同进化关系及发展新的抗虫策略提供理论基础。

Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

N-1-alkyl-5-halogeno-6-alkylamino uracils,which are novel 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio) thymine (HEPT) analogues,were synthesized as the selective and potent non-nucleoside human immunodeficiency virus(HIV)-1 reverse transcriptase inhibitors.Some of the compounds showed potent inhibitory activity against HIV-1 reverse transcriptase.For instance,compounds 1d,1m and 1n exhibited potent anti-HTV-1 activity with the IC_(50) values of 13.3,11.7 and 3.15μM,respectively, which are comparable to that of nevirapine(IC_(50) 8.38μM).

Route improvement of 3-substituted-4-(2-methylcyclohexyloxy)-6-phenethylpyridinone

trans-3-Isopropyl-4-（2-methylcyclohexyloxy）-6-phenethylpyridin-2（1H）-one, as reverse transcriptase （NNRTIs）, exhibited significant potent activity not only against wild-type HIV-1 strains but also on mutant strains. For furthering study this compound, the original synthetic route should be shorten to improve the total yield. In this report, we designed an efficient synthetic strategy to obtain the target compound with higher yield.

Synthesis and biological evaluation of novel 1-aryl-5-iodo-6-benzyluracils as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

We have synthesized the novel compounds 1a-1i,which are a series of hybrid analogues to 6-benzyl-1-（benzyloxymethyl）- 5-iodouracil,a compound showing strong activity against HIV-1.We also evaluated the activity of these compounds as the inhibitors of HIV-1 reverse transcriptase（HIV-1 RT）,and they have demonstrated moderate activity.

Synthesis and biological evaluation of novel 2-arylalkylthio-5-iodo-6-benzyl S-DABOs as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

A series of novel dihydro-alkylthio-benzyl-oxopyrimidines （S-DABOs） 7a-f have been designed and synthesized with an efficient method. Biological evaluation of their HIV-1 reverse transcriptase inhibitory activities was performed using Nevirapine （NVP） as a reference compound. Among the series, compound 7d shows the highest reverse transcriptase inhibitory activity, which is better than Nevirapine.

Pyridin-2(1H)-ones as HIV-1 NNRTIs:a combinatorial optimization strategy

With rapid spread of HIV(human immunodeficiency virus) on a global scale and increasingly severe drug-resistance of it,it is urgently necessary to develop novel effective anti-HIV drugs.Non-nucleoside reverse transcriptase inhibitor(NNRTIs)is one of the most significant antiretroviral drugs for fighting against HIV infection due to their various structures,unique mode of action,good efficacy and low toxicity.Pyridinone derivatives,a type of NNRTIs,have been reported to achieve remarkable development in the past few decades.In this review,we summarized current drug design and medicinal chemistry efforts toward the development of next-generation pyridinones as HIV-1 NNRTIs.