生物谷報道：一項針對病毒復(fù)制的最新研究,，證實了科學家此前的認識，即多種類型的病毒有著共同的繁殖特性,，而這些病毒中的一些是導(dǎo)致重大人類疾病(比如艾滋病,、非典以及丙肝)的罪魁禍首。這一成果有望加深科學家對病毒普遍弱點的理解,，并促進新的光譜抗病毒藥物的研制,。相關(guān)論文8月14日在線發(fā)表于《PLoS生物學》上。
領(lǐng)導(dǎo)該項研究的是美國威斯康星-麥迪遜大學霍華德休斯醫(yī)學研究所(Howard Hughes Medical Institute)的Paul Ahlquist,。他和同事在論文中詳細描述了一種名為“獸棚病毒”(flock house virus,，簡稱FHV)的典型RNA病毒，是如何利用細胞內(nèi)的蛋白膜結(jié)構(gòu)來建造安全的“繁殖基地”的,。
利用強大的電子顯微技術(shù),，Ahlquist小組得到了首張FHV病毒復(fù)制復(fù)合體(replication complex)的三維圖像。與其它病毒類似,，F(xiàn)HV也需要在宿主細胞內(nèi)制造新的遺傳物質(zhì),，并且繼續(xù)維持感染鏈(chain of infection)。
研究人員發(fā)現(xiàn),，F(xiàn)HV擠入了宿主細胞線粒體的內(nèi)外膜之間,，并促使其制造了數(shù)萬個氣球狀的囊或者小球。在它們的內(nèi)部,，一層蛋白外殼保護FHV成功逃脫了宿主的監(jiān)測和防御機制,，安全地復(fù)制出新的病毒基因組副本。Ahlquist表示,，“病毒顯然已經(jīng)擁有一種極佳的策略,，它令宿主細胞為自身RNA合成創(chuàng)造出了新的迷你細胞器。其整個復(fù)制和裝配過程都與細胞內(nèi)的其他生理過程,，尤其是防御響應(yīng)完全隔絕,。”
此外，Ahlquist和同事還注意到，這些形成的囊或小球都具有狹窄的“頸”伸入線粒體膜外的細胞質(zhì),，這是FHV病毒復(fù)制所需物質(zhì)進入和新的病毒基因組放出的通道,。
Ahlquist表示，病毒利用宿主細胞的蛋白外殼來復(fù)制遺傳基因,，很可能就是不同種類的病毒的共同特性之一,。而這種共性可以擴展到絕大多數(shù)的RNA病毒和逆轉(zhuǎn)錄病毒上,，這表明它們或許具有共同的進化祖先,。(科學網(wǎng)任霄鵬/編譯)
原始出處:
PLoS Biology
Received: March 30, 2007; Accepted: June 15, 2007; Published: August 14, 2007
Three-Dimensional Analysis of a Viral RNA Replication Complex Reveals a Virus-Induced Mini-Organelle
Benjamin G. Kopek1, Guy Perkins2,3, David J. Miller4,5, Mark H. Ellisman2,3, Paul Ahlquist1,6*
1 Institute for Molecular Virology, University of Wisconsin–Madison, Madison, Wisconsin, United States of America, 2 National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, California, United States of America, 3 Department of Neurosciences, University of California San Diego, La Jolla, California, United States of America, 4 Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America, 5 Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America, 6 Howard Hughes Medical Institute, University of Wisconsin–Madison, Madison, Wisconsin, United States of America
Positive-strand RNA viruses are the largest genetic class of viruses and include many serious human pathogens. All positive-strand RNA viruses replicate their genomes in association with intracellular membrane rearrangements such as single- or double-membrane vesicles. However, the exact sites of RNA synthesis and crucial topological relationships between relevant membranes, vesicle interiors, surrounding lumens, and cytoplasm generally are poorly defined. We applied electron microscope tomography and complementary approaches to flock house virus (FHV)–infected Drosophila cells to provide the first 3-D analysis of such replication complexes. The sole FHV RNA replication factor, protein A, and FHV-specific 5-bromouridine 5'-triphosphate incorporation localized between inner and outer mitochondrial membranes inside 50-nm vesicles (spherules), which thus are FHV-induced compartments for viral RNA synthesis. All such FHV spherules were outer mitochondrial membrane invaginations with interiors connected to the cytoplasm by a necked channel of 10-nm diameter, which is sufficient for ribonucleotide import and product RNA export. Tomographic, biochemical, and other results imply that FHV spherules contain, on average, three RNA replication intermediates and an interior shell of 100 membrane-spanning, self-interacting protein As. The results identify spherules as the site of protein A and nascent RNA accumulation and define spherule topology, dimensions, and stoichiometry to reveal the nature and many details of the organization and function of the FHV RNA replication complex. The resulting insights appear relevant to many other positive-strand RNA viruses and support recently proposed structural and likely evolutionary parallels with retrovirus and double-stranded RNA virus virions.
