美国科学家近日研究发现，通过抑制某种酶的活性，能够阻断HIV在体内的传播。这一新颖的方法不仅有助于研发对付这一病毒的药物，更重要的是，由于它针对的不是HIV病毒本身，而是免疫系统中的蛋白，所以它回避了影响传统治疗方案效果的抗性问题。相关论文4月28日在线发表于美国《国家科学院院刊》（PNAS）上。
HIV感染无法治愈，患者需要服用抗逆转录病毒药物以维持身体状况。当前的给药方案攻击病毒的某些部分，但由于这些病毒不断变异，难以避免会出现抗性品系。
在最新的研究中，美国宾夕法尼亚州立大学的Andrew Henderson和美国国立人类基因组研究所的Pamela Schwartzberg发现，当敲除其中的诱导T细胞激酶（ITK）后，免疫细胞变得较不易受HIV的感染。研究人员发现，抑制ITK的活性能够影响HIV生活周期的多个阶段，包括向细胞的进入、病毒基因的表达以及新病毒粒子的产生。
研究人员目前已经为这一新方法申请了专利，他们希望制药公司能够成功开发出实现这一方法的药物。Henderson预测，这应该不会太困难。他说：“有很多种能够标靶这种酶的化合物”，不过，这样的药物在人体中是否足够有效尚不清楚。
Schwartzberg表示，这一新方法并不能够为HIV疫苗的研发提供希望。这应该是一种帮助已经感染了HIV的人的策略，而不是一种预防措施。（科学网 梅进/编译）
生物谷推荐原始出处：
（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.
