细胞新“铠甲”可防AIDS病毒感染

New Cellular 'Armor' Developed to Prevent Infection by AIDS Virus
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ScienceDaily (July 31, 2010) — Research by the Consejo Superior de Investigaciones Científicas (CSIC) and led by Mr Félix Goñi, director of the Biophysics Unit at the CSIC-University of the Basque Country Mixed Centre, has led to the development of a novel method of attack against the AIDS virus. The method involves creating a prevention system, i.e. an 'armour' in the cells that are likely to be infected and thus impede the virus from accessing them and starting to act on their immunological system.
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The study, which appears in the journal Chemistry & Biology, published by Cell Press, lays down the bases of possible future pharmaceutical drugs that will enable combating the AIDS virus at its initial phase. Participating in the research, apart from Mr Goñi, was a team from the National Biotechnology Centre (CSIC-Universidad Autónoma de Madrid) and another from the Institute of Applied Chemistry of Cataloniaa (CSIC, Barcelona).

4 Y1 t4 J! c  s- U  O- G4 d& NThe research is based on the regulation of the fluidity of the cell membranes and seeks to avoid the phenomenon known as the fusion of membranes, a consequence of contact between the cell membranes and the membrane of the virus itself.

The membrane is the "coating" of the cell cytoplasm and which protects it from the outside, and which has a structure similar to that of the membranes of the AIDS virus. When both membranes come into contact, and due to the fact that the cell membrane is very "fragile," an orifice is created and fusion occurs -- and a route is opened for the AIDS virus to enter, connect to a specific "receptor" of the cell and commence its viral activity.

* z  A2 Z8 D: {; A) t/ L( ?What the researchers are seeking with this study is to strengthen the membrane structure, making it more rigid, in order to avoid this fusion of membranes and, thus, the inoculation of the cell by the AIDS virus.
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+ F: J2 @, t/ A/ Q1 v4 S/ S2 [Practically all treatment for the AIDS virus currently being applied is based on halting the progress of the virus once it is inside the host cell. There is but one treatment, commercially known as Enfurvitide, which attempts to stop the virus actually entering the cell. The research published in Chemistry & Biology comes to the same conclusion, but by a totally different and novel route.
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"For the cell membranes and the virus to come together and this orifice be opened to allow the entrance of the virus, the membranes have to have a certain degree of fluidity, of mobility. We discovered a procedure to make the cell membranes more rigid. This could well give rise to a new pharmaceutical drug which makes the membranes more rigid and impede the entrance of the AIDS virus. Instead of the membrane being flexible, a kind of armour is established which makes the cell impenetrable," explained Félix Goñi.
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. J' y7 L  ^6 C" w' FThe research started three years ago and has employed various techniques in the field of chemistry and molecular biology.
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At the Institute of Applied Chemistry of Catalonia (CSIC, Barcelona), Ms Gemma Fabriàs has synthesised the GT11 molecule by means of organic chemistry synthesis techniques. Mr Santos Mañes, from the National Biotechnology Centre, studied the viral infection of the cells, and from the Biophysics Unit at the CSIC-University of the Basque Country work has been undertaken at molecular level to demonstrate that there are changes in the rigidity of the membranes when the GT11 molecule is incorporated into them, and that when the membranes are more rigid the virus cannot fuse with the cell membrane and, thus, from penetrating the cell. A highly important role was also placed by Mr José Luis Nieva, from the Biophysics Unit, in studying this fusion of the membranes induced by the AIDS virus.

" ?, y8 l5 M- Z. oThis scientific discovery by this consortium represents, in the opinion of Mr Goñi, "a completely new means for attacking the virus, and which makes this original."

/ g; I, u" R" i8 q. M! r, Y"There is medication, and which is working very well, to avoid the propagation of the virus once it is inside the cell. But to impede this inoculation in the first place, only one product (Enfurvitide) exists, but this drug is based on a completely distinct principle. The idea of modifying the rigidity of the membranes is completely new and also demonstrating that, by equipping these membranes with greater rigidity, the AIDS virus cannot penetrate," stated Mr Goñi. This same strategy may well serve for other viruses with membrane, such as, for example, the flu virus.
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/ k: ^3 [9 a9 k1 Z# Ghttp://www.sciencedaily.com/releases/2010/07/100730191616.htm
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细胞新“铠甲”可防AIDS病毒感染

《每日科学》2010年7月31日报道 ——由生物物理学科室主任 Félix Goñi 率队进行的 CSIC的 一项研究已开发出一种抗击AIDS病毒的新方法（CSIC为西班牙国家科学研究理事会，生物物理学科室则附属于CSIC — 西班牙巴斯克地区大联 合中心）。该方法创建一种预防系统，比如说，让可能受感染的细胞披上“铠甲”来阻止病毒进入细胞，从而让病毒无法对细胞的免疫系统产生影响。

本研究刊登于细胞出版社出版的《化学与生物学》（Chemistry & Biology）杂志， 为感染初期即可狙击AIDS病毒的可能的未来药物奠定了基础。除 Goñi外, 参与该研究的还有一支来自国家生物技术中心（CSIC-马德里自治大学）与另外一支来自加泰罗尼亚应用化学研究院（CSIC，巴塞罗那）的研究小组。

8 N! e6 \/ y+ R+ w; P3 O" T基于细胞膜流动性的调节，本研究寻求避免众所熟知的细胞膜融合现象，因为这种融合是由细胞膜与病毒膜彼此接触的结果。
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细胞膜是细胞质的“外衣”，保护细胞质使之与外界隔离。当双方的膜开始接触时，因为细胞膜非常“娇嫩”，于是出现小孔进而开始融合　——　于是ＡＩＤＳ病毒开始登堂入室、与细胞的特定“感受器”结合而开始病毒感染活动。
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　在本研究中，研究者所寻求的是加强细胞膜的结构，使之更加坚固从而避免膜间融合，从而避免了ＡＩＤＳ病毒对细胞的接触感染。
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9 T8 N4 Z- O/ `: I. u: _% Z, C% V　　目前临床所用针对ＡＩＤＳ病毒的疗法实际上都着手于病毒侵入宿主细胞后阻止其感染进程。只有一种商业上称之为恩夫韦肽（enfurvitide）的治疗旨在抑制膜间融合，使病毒无法进入细胞。而发表于《化学与生物学》杂志的本研究得出同一结论，只是采用了迥然不同的、新颖独创的途径来实现同一目的而已。

) ?$ ]1 T9 g( }0 S* z  T4 t　　Félix Goñi 解释说：“如果细胞膜与病毒膜必须接触从而打开小孔让病毒进入细胞的话，膜必须具有一定程度的流动性与机动性。我们发现了提高细胞膜强度的方法。这一方法能够催生使细胞膜更加坚固的新的药品，从而阻止ＡＩＤＳ病毒进入细胞。为了让细胞膜不受影响，我们的药物给细胞披上的某种铠甲，使得细胞牢不可破无法穿越。”
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3 W; E: F$ n/ K　　本研究始于3年之前，采用了化学与分子生物学领域的多种技术。
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6 _( P+ l  p* s" A+ E* W0 F　在加泰罗尼亚应用化学研究院（CSIC，巴塞罗那）， Gemma Fabriàs通过有机化学合成技术合成了ＧＴ１１分子；来自生物技术中心的Santos Mañes研究了细胞的病毒感染过程； 以及来自附属于CSIC-马德里自治大学的生物物理学科室的研究小组在分子水平上证明了GT11分子与细胞膜结合时膜的硬度出现了变化，而膜硬度增加时病毒无法与细胞融合因而无法穿透细胞；来自生物物理学科室的 José Luis Nieva也在研究由AIDS病毒诱导的膜间融合的研究中起了非常重要的作用。

按照Mr Goñi的说法，联合研究小组的这一科学发现代表了“一种全新的攻击艾滋病毒的方法，一种原创性方法。”

6 l( m  u1 Q, ^" s, c  U  HGoñi. 说：“能发挥良好作用的药物是存在的，这些药物能够在艾滋病毒进入细胞后避免其进一步繁殖。但要在第一步就阻止这个接触感染过程的话，只有一种产品（恩夫韦肽）亮相，只是药理全然不同。改变细胞膜的硬度的想法是个全新的金点子，这个点子向我们显示：让细胞膜拥有更高的硬度，AIDS病毒就无法穿越！” 这一策略可能对其它诸如流感病毒等有膜病毒也有效。
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