生物谷报道：一项针对病毒复制的最新研究，证实了科学家此前的认识，即多种类型的病毒有着共同的繁殖特性，而这些病毒中的一些是导致重大人类疾病(比如艾滋病、非典以及丙肝)的罪魁祸首。这一成果有望加深科学家对病毒普遍弱点的理解，并促进新的光谱抗病毒药物的研制。相关论文8月14日在线发表于《PLoS生物学》上。
领导该项研究的是美国威斯康星-麦迪逊大学霍华德休斯医学研究所(Howard Hughes Medical Institute)的Paul Ahlquist。他和同事在论文中详细描述了一种名为“兽棚病毒”(flock house virus，简称FHV)的典型RNA病毒，是如何利用细胞内的蛋白膜结构来建造安全的“繁殖基地”的。
利用强大的电子显微技术，Ahlquist小组得到了首张FHV病毒复制复合体(replication complex)的三维图像。与其它病毒类似，FHV也需要在宿主细胞内制造新的遗传物质，并且继续维持感染链(chain of infection)。
研究人员发现，FHV挤入了宿主细胞线粒体的内外膜之间，并促使其制造了数万个气球状的囊或者小球。在它们的内部，一层蛋白外壳保护FHV成功逃脱了宿主的监测和防御机制，安全地复制出新的病毒基因组副本。Ahlquist表示，“病毒显然已经拥有一种极佳的策略，它令宿主细胞为自身RNA合成创造出了新的迷你细胞器。其整个复制和装配过程都与细胞内的其他生理过程，尤其是防御响应完全隔绝。”
此外，Ahlquist和同事还注意到，这些形成的囊或小球都具有狭窄的“颈”伸入线粒体膜外的细胞质，这是FHV病毒复制所需物质进入和新的病毒基因组放出的通道。
Ahlquist表示，病毒利用宿主细胞的蛋白外壳来复制遗传基因，很可能就是不同种类的病毒的共同特性之一。而这种共性可以扩展到绝大多数的RNA病毒和逆转录病毒上，这表明它们或许具有共同的进化祖先。(科学网任霄鹏/编译)
原始出处:
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.
