Retrovirus Biology

我们已经对HIV-1REV反应元件和HERV-K人内源性病毒RNA中的类似元件进行了详细的结构-功能研究。这些研究的结果对于这些RNA元件与病毒编码的调节蛋白相互作用的特异性的起源具有重要的意义。这些相互作用对病毒复制至关重要，因为它们使从细胞核输出剪接和非剪接的病毒RNA成为可能。最近发现，细胞蛋白Serinc5以某种方式干扰了在含有Serinc5的细胞中组装的HIV-1颗粒成功进入新宿主细胞的能力。HIV-1Nef蛋白可以抵消Serinc5的作用。我们已经发现，Serinc5还可以阻止许多其他逆转录病毒的进入；小鼠白血病病毒(MLV，属于伽马逆转录病毒属)和马传染性贫血病毒(如HIV-1，一种慢病毒)都会编码“辅助蛋白”，以对抗Serinc5的影响。Serinc5的作用机制尚不清楚。我们系统地调查了逆转录病毒对Serinc5的敏感性；这些研究的目的是试图确定一个可能成为Serinc5行动目标的共同特征。我们发现逆转录病毒对Serinc5的敏感性有很大的不同，但我们还没有发现这些差异背后的模式。我们还与Alex Compton博士(HIV DRP)合作研究了另一种抗病毒蛋白，即干扰素诱导的跨膜蛋白3(IFITM3)的作用。有趣的是，相同的MLV辅助蛋白可以抵消Serinc5和IFITM3的影响。我们还分析了小鼠APOBEC3(MA3)的抗病毒作用，它对HIV-1和MLV具有明显不同的作用。在与John Briggs博士和其他人的合作中，我们发现成熟的HIV-1和MLV颗粒的结构明显不同；似乎这些结构差异可能是它们对MA3反应的差异的原因。我们正在通过几种方式探索这种可能性，包括测试MA3和特征良好的人类APOBEC3G之间的嵌合体的影响。_我们还在研究反转录病毒L的性质，这是一个在小鼠胚胎发育非常早期表达的反转录转座子家族。这个表达的功能意义尚不清楚。

We have performed detailed structure-function studies of the HIV-1 Rev Response Element and of an analogous element in the RNA of the HERV-K human endogenous virus. The results of these studies have important implications for the origin of specificity in the interactions of these RNA elements with virus-coded regulatory proteins. These interactions are critical for virus replication, as they make it possible for the export of both spliced and unspliced viral RNAs from the nucleus. It has recently been found that the cellular protein Serinc5 somehow interferes with the ability of HIV-1 particles assembled in Serinc5-containing cells to successfully enter new host cells. The HIV-1 Nef protein counteracts the effects of Serinc5. We have found that Serinc5 also blocks the entry of many other retroviruses; both murine leukemia viruses (MLVs, which are members of the gammaretrovirus genus) and equine infectious anemia virus (like HIV-1, a lentivirus) encode "accessory proteins" that counter the effects of Serinc5. The mechanism of Serinc5 action is not understood. We have systematically surveyed retroviruses for their sensitivity to Serinc5; the purpose of these studies is to try to identify a common feature that might be the target for Serinc5 action. We found that retroviruses differ widely with respect to Serinc5 sensitivity, but we have not yet discerned a pattern underlying these differences. We have also collaborated with Dr. Alex Compton (HIV DRP) in a study of the effects of another antiviral protein, i.e., interferon-induced transmembrane protein 3 (IFITM3). Interestingly, the same MLV accessory protein counteracts the effects of both Serinc5 and IFITM3. We are also analyzing the antiviral action of mouse Apobec3 (mA3), which has strikingly different effects on HIV-1 and MLVs. In collaboration with Dr. John Briggs and others, we found that the structures of mature HIV-1 and MLV particles are remarkably different; it seems possible that these structural differences are responsible for the differences in their response to mA3. We are exploring this possibility in several ways, including testing the effects of chimeras between mA3 and the well-characterized human APOBEC3G. ______We are also studying the properties of MuERV-L, a family of retrotransposons expressed in very early mouse embryogenesis. The functional significance of this expression is unknown.