Regulation of HIV-1 Gag expression by SR proteins

艾滋病毒感染会导致艾滋病，是一种世界性的流行病。2010年，新增感染者270万人，艾滋病相关死亡180万人，艾滋病毒携带者3400万人。目前，已批准的抗逆转录病毒药物针对艾滋病毒生命周期的四个阶段，2010年有700多万人接受抗逆转录病毒治疗。然而，艾滋病毒耐药株是一个重大问题，仍然非常需要新的药物靶点。开发新的抗病毒药物的一个有希望的方法是靶向细胞蛋白质。这项提议将研究一系列称为SR蛋白的细胞蛋白如何调节HIV结构蛋白GAG的表达，GAG是制造病毒粒子所必需的。我们将确定12个人类SR蛋白中哪些调节Gag的表达，并从机制上描述它们是如何做到这一点的。这将确定哪些SR蛋白可以作为抗逆转录病毒药物的靶点，以抑制HIV Gag的表达。

HIV infection causes AIDS and is a worldwide pandemic. In 2010, there were 2.7 million new infections, 1.8 million AIDS-related deaths, and 34 million people living with HIV. Currently, there are approved antiretroviral drugs targeting four stages of the HIV life cycle and in 2010 there were over 7 million people receiving antiretroviral therapy. However, drug resistant strains of HIV are a significant problem and there is still a great need for novel drug targets. One promising approach to develop new antiviral drugs is to target cellular proteins. This proposal will investigate how a family of cellular proteins, called SR proteins, regulate expression of the HIV structural protein Gag, which is necessary to make virions. We will identify which of the 12 human SR proteins regulate Gag expression and mechanistically characterise how they do so. This will identify which SR proteins could be targeted by antiretroviral drugs to inhibit HIV Gag expression.