生物谷報(bào)道：UCLA科學(xué)家們?cè)?月10日出版的Nature Immunology上報(bào)告說(shuō),，他們鑒別出細(xì)胞抗擊病毒入侵的一種新防御機(jī)制。病毒感染細(xì)胞,、“劫持”宿主的酶和其它的構(gòu)件來(lái)復(fù)制自己,。為了達(dá)到實(shí)現(xiàn)的目的，病毒首先需要通過(guò)與宿主細(xì)胞的膜融合而進(jìn)入細(xì)胞,。但是,，免疫系統(tǒng)也有一套對(duì)付這種侵犯的戰(zhàn)略。           我們的免疫系統(tǒng)中有一種名為防御素（defensin retrocyclin 2, RC2)的蛋白質(zhì),，它會(huì)對(duì)附近出現(xiàn)的病毒做出反應(yīng),，從而阻止病毒與未感染細(xì)胞的融合。現(xiàn)在,，科學(xué)家們?cè)谏钊胝J(rèn)識(shí)防御素如何防止病毒的融合方面邁出重要的一步,。新發(fā)現(xiàn)將導(dǎo)致預(yù)防和治療HIV和流感病毒感染的新方法。           為了認(rèn)識(shí)防御素的抗病毒特性,，Leonid  Chernomordik和同事研究了一種名為RC2的防御素,，他們發(fā)現(xiàn)這種防御能抵御包括流感病毒在內(nèi)的許多病毒。進(jìn)一步的實(shí)驗(yàn)顯示,，RC2似乎是與細(xì)胞膜上的“糖”蛋白質(zhì)結(jié)合在一起,。這個(gè)過(guò)程阻止了細(xì)胞膜與病毒的融合,，從而形成了細(xì)胞膜的一級(jí)防范禁止區(qū)，防止病毒的侵入,。           研究人員將這種發(fā)現(xiàn)拓展到另外一種與糖結(jié)合的免疫分子,，他們希望這種抗病毒戰(zhàn)略有更廣泛的應(yīng)用。

Before a virus can invade a cell, glycoproteins on the viral and cell membranes must spread apart to allow the viral membrane to approach and merge with the cell membrane. Image Courtesy: NICHD. Defensins bind to glycoproteins, preventing them from spreading apart to allow membrane fusion. Image Courtesy: NICHD.

相關(guān)報(bào)道：

·臺(tái)灣研究人員發(fā)現(xiàn)全新蛋白質(zhì)防御素
·RNA沉默：古老的免疫防御機(jī)制對(duì)HIV-1束手無(wú)策

原文來(lái)源：

Leikina E, Delanoe-Ayari H, Melikov K, Cho MS, Chen A, Waring AJ, Wang W, Xie Y, Loo JA, Lehrer RI, Chernomordik LV. Carbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins. Nat Immunol. 2005 Sep 11; [PDF文件下載]

有關(guān)RC1,，2的介紹：

BACKGROUND:  Defensins are cysteine-rich, cationic antimicrobial peptides expressed by leukocytes and epithelial cells of mammals and birds. These peptides, which can be considered endogenous antibiotics, play an important role in innate host defense against pathogens due to their antibacterial, antifungal and antiviral activities. Three defensin subfamilies exist in vertebrates: alpha-defensins, beta-defensins, and theta (circular) minidefensins. All of these have largely beta-sheet structures that are stabilized by three intramolecular cystine disulfide bonds, and derive from a common ancestral gene. Theta defensins are much smaller (18 amino acid residues) than alpha or beta defensins (29-45 residues), and their antiviral properties are considerably more robust than their antibacterial and antifungal effects.

INNOVATION: Retrocyclins 1 and 2 (also called RC-100 and RC100b) are novel circular peptides discovered by UCLA Researchers. Although they are produced synthetically, their structures are based on nucleotide sequences found in the human genome and/or in mRNA expressed by human bone marrow. Since human theta-defensin genes and retrocyclin bone marrow mRNA contain a premature stop codon in their signal sequence, retrocyclin peptides are probably not produced in humans. However, these peptides are found in certain Old World monkeys, and intact theta defensin genes are also present in lesser apes and orangutans (unpublished). Although the ability of theta defensins to kill bacteria is relatively modest, retrocyclin 1 and especially retrocyclin-2 show impressive activity against three different viral pathogens: human immunodeficiency virus (HIV-1), herpes simplex virus-1 and herpes simplex virus-2 (HSV-2). Although such broad specificity is somewhat reminiscent of interferons, retrocyclins operate as entry inhibitors. Retrocyclin-2 showed activity against a wide library of primary HIV-1 isolates of diverse subtypes, including subtypes A, B, C, CRF01, D, G, and recombinant subtypes. Its effectiveness was not dependent on or restricted by co-receptor (R5, X4 or R5X4) usage. The UCLA researchers are using retrocyclins-1 and 2 as platforms to develop analogs with improved pharmacotherapeutic properties.

ADVANTAGES