J Virol：科学家发现逆转录病毒的结构并不相同

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图片来源：medicalxpress.com

近日在一项最新研究中，来自明尼苏达大学的研究人员通过研究发现，大多数类型的逆转录病毒或许并没有相同的病毒结构，相关研究刊登于国际杂志the Journal of Virology上。

文章中，研究者分析了包括HIV和HLTV-1在内的7种类型的逆转录病毒，HLTV-1是一种引发T细胞白血病的逆转录病毒，同时研究者还检测了感染鸟、小鼠、黑猩猩和鱼类的逆转录病毒如何引发癌症或免疫缺陷综合征。Louis Mansky博士说道，每一种逆转录病毒都具有不同的结构特性，而且每一种病毒都会以不同方式来组装病毒颗粒。此前很多研究者猜测所有逆转录病毒都和HIV一样，但实际上并非如此。研究者指出，当研究逆转录病毒以及开发新型抗病毒疗法或疫苗时，并不能以一刀切的方法来研究。

研究小组观察了逆转录病毒Gag蛋白的行为，该蛋白可以驱动逆转录病毒颗粒形成，一旦病毒进入到细胞中，病毒的逆转录酶就会将病毒RNA转化成DNA，随后合成Gag蛋白。阐明Gag蛋白同其它蛋白相互作用的机制及其结构形成的过程或可帮助科学家们理解病毒的工作机制，同时也将帮助鉴别出新型方法来第一时间靶向作用病毒，抑制病毒感染细胞。

研究者Jessica Martin说道，在逆转录病毒中我们发现了明显的差异，我们进行了一项平行对比研究来评估了逆转录病毒Gag蛋白以及病毒颗粒形成的过程。此外研究者意外发现，角膜白斑真皮肉瘤病毒（WDCV）并不容易产生病毒颗粒，该疾病会影响1%-30%的角膜白斑患者，而本文研究结果或可帮助更好地理解该病的发病机制。

研究者希望本文研究可以帮助阐明多种逆转录病毒的重要差异，这对于后期开发治疗人类病毒性疾病的新型疗法或将提供较大帮助。同时也将帮助研究者深入研究HIV病毒的发病机理。最后研究者Mansky说道，本文的研究结果或将帮助开发新型的抗病毒疗法，同时我们也将通过后期更为深入的研究来阐明如何阻断这些病毒引发人类致死性的疾病，比如癌症或AIDS等。

来源：生物谷

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Distinct particle morphologies revealed through comparative parallel analyses of retrovirus-like particles

Jessica L. Martina,c, Sheng Caoa,b, Jose O. Maldonadoa,b, Wei Zhanga,b,d# and Louis M. Mansky

ABSTRACT
The Gag protein is the main retroviral structural protein, and its expression alone is usually sufficient for production of virus-like particles (VLPs). In this study, we sought to investigate – in parallel comparative analyses – Gag cellular distribution, VLP size, and basic morphological features using Gag expression constructs (Gag or Gag-YFP) created from all representative retroviral genera: alpharetrovirus, betaretrovirus, deltaretrovirus, epsilonretrovirus, gammaretrovirus, lentivirus, and spumaretrovirus. We analyzed Gag cellular distribution by confocal microscopy, VLP budding by thin-section transmission electron microscopy (TEM), and general morphological features of the VLPs by cryogenic transmission electron microscopy (cryo-TEM). Punctate Gag was observed near the plasma membrane for all Gag constructs tested except for the representative beta- and epsilonretrovirus Gag proteins. This is the first report of epsilonretrovirus Gag localizing to the nucleus of HeLa cells. While VLPs were not produced by the representative beta- and epsilonretrovirus Gag proteins, the other Gag proteins produced VLPs as confirmed by TEM, and morphological differences were observed by cryo-TEM. In particular, we observed deltaretrovirus-like particles with flat regions of electron density that did not follow viral membrane curvature, lentivirus-like particles with a narrow range and consistent electron density, suggesting a tightly packed Gag lattice, and spumaretrovirus-like particles with large envelope protein spikes and no visible electron density associated with a Gag lattice. Taken together, these parallel comparative analyses demonstrate for the first time the distinct morphological features that exist among retrovirus-like particles. Investigation of these differences will provide greater insights into the retroviral assembly pathway.

Importance
Comparative analysis among retroviruses has been critically important in enhancing our understanding of retroviral replication and pathogenesis – including that of important human pathogens such as human T-cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1). Here in this study, parallel comparative analyses have been used to study Gag expression and virus-like particle morphology among representative retroviruses in the known retroviral genera. Distinct differences were observed, which enhances current knowledge of the retroviral assembly pathway.

http://jvi.asm.org/content/early/2016/06/23/JVI.00666-16

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非常不错，学习了