美國(guó)科學(xué)家近日研究發(fā)現(xiàn)，通過(guò)抑制某種酶的活性,，能夠阻斷HIV在體內(nèi)的傳播,。這一新穎的方法不僅有助于研發(fā)對(duì)付這一病毒的藥物，更重要的是,，由于它針對(duì)的不是HIV病毒本身,，而是免疫系統(tǒng)中的蛋白，所以它回避了影響傳統(tǒng)治療方案效果的抗性問(wèn)題,。相關(guān)論文4月28日在線發(fā)表于美國(guó)《國(guó)家科學(xué)院院刊》（PNAS）上。
HIV感染無(wú)法治愈,，患者需要服用抗逆轉(zhuǎn)錄病毒藥物以維持身體狀況,。當(dāng)前的給藥方案攻擊病毒的某些部分,，但由于這些病毒不斷變異，難以避免會(huì)出現(xiàn)抗性品系,。
在最新的研究中,，美國(guó)賓夕法尼亞州立大學(xué)的Andrew Henderson和美國(guó)國(guó)立人類基因組研究所的Pamela Schwartzberg發(fā)現(xiàn)，當(dāng)敲除其中的誘導(dǎo)T細(xì)胞激酶（ITK）后,，免疫細(xì)胞變得較不易受HIV的感染,。研究人員發(fā)現(xiàn)，抑制ITK的活性能夠影響HIV生活周期的多個(gè)階段,，包括向細(xì)胞的進(jìn)入,、病毒基因的表達(dá)以及新病毒粒子的產(chǎn)生。
研究人員目前已經(jīng)為這一新方法申請(qǐng)了專利,，他們希望制藥公司能夠成功開發(fā)出實(shí)現(xiàn)這一方法的藥物,。Henderson預(yù)測(cè)，這應(yīng)該不會(huì)太困難,。他說(shuō)：“有很多種能夠標(biāo)靶這種酶的化合物”,，不過(guò)，這樣的藥物在人體中是否足夠有效尚不清楚,。
Schwartzberg表示,，這一新方法并不能夠?yàn)镠IV疫苗的研發(fā)提供希望。這應(yīng)該是一種幫助已經(jīng)感染了HIV的人的策略,，而不是一種預(yù)防措施,。（科學(xué)網(wǎng) 梅進(jìn)/編譯）
生物谷推薦原始出處：
（PNAS），doi：10.1073/pnas.0709659105,，Julie A. Readinger,，Pamela L. Schwartzberg
Selective targeting of ITK blocks multiple steps of HIV replication
Julie A. Readinger*, Gillian M. Schiralli,, Jian-Kang Jiang,¶, Craig J. Thomas,¶, Avery August, Andrew J. Henderson,,||, and Pamela L. Schwartzberg*,||
*Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; Center for Molecular Immunology and Infectious Diseases, Integrated Biosciences Graduate Program, Department of Veterinary Sciences, Pennsylvania State University, University Park, PA 16802; Chemical Biology Core Facility, National Institute of Diabetes, Digestive and Kidney Disorders, National Institutes of Health, Bethesda, MD 20892; ¶NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; and Center for HIV/AIDS Care and Research, Department of Medicine, Boston University School of Medicine, Boston, MA 02118
Edited by Stephen P. Goff, Columbia University College of Physicians and Surgeons, New York, NY, and approved March 19, 2008 (received for review October 10, 2007)
Abstract
Treatment for HIV has relied on the use of antiretroviral agents that can be subject to the development of resistant viruses. The study of inhibitors directed against cellular proteins required for HIV replication is therefore of growing interest. Inducible T cell kinase (ITK) is a Tec family tyrosine kinase that regulates T cell receptor (TCR)-induced activation of PLC-1, Ca2+ mobilization and transcription factor activation, and actin rearrangement downstream of both TCR and chemokine receptors. Because productive infection of T cells with HIV requires T cell activation, chemokine receptors and actin reorganization, we asked whether ITK affects HIV infection using ITK-specific siRNA, a kinase-inactive ITK mutant or an ITK inhibitor. We demonstrate that loss of ITK function resulted in marked reductions in intracellular p24 levels upon HIV infection. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. Inhibition of ITK did not affect expression of the HIV coreceptors CD4 or CXCR4 but partially blocked HIV viral entry, an effect that correlated with decreased actin polarization to gp120. Additionally, ITK was required for efficient HIV transcription, and overexpression of ITK increased both viral transcription and virus-like particle formation. Our data suggest that inhibition of ITK blocks HIV infection by affecting multiple steps of HIV replication.
