Retrovirus Biology

我们对HIV-1 Rev反应元件进行了详细的结构-功能研究 以及HERV-K人内源性病毒RNA中的类似元件。的结果 这些研究对于特异性的起源具有重要的意义， 这些RNA元件与病毒编码的调节蛋白。这些相互作用对于 病毒复制，因为它们使剪接和未剪接的病毒 来自细胞核的RNA。最近发现细胞蛋白Serinc 5以某种方式 干扰HIV-1颗粒在含Serinc 5的细胞中组装的能力， 成功进入新的宿主细胞HIV-1 Nef蛋白抵消Serinc 5的作用。 我们发现Serinc 5也能阻断许多其他逆转录病毒的进入， 白血病病毒（MLV，其是γ逆转录病毒属的成员）和马传染性病毒（HCV）， 贫血病毒（像HIV-1，一种慢病毒）编码“辅助蛋白”， 关于Serinc 5 Serinc 5的作用机制尚不清楚。我们系统地调查了 逆转录病毒对Serinc 5的敏感性;这些研究的目的是试图 识别可能是Serinc 5操作目标的共同特征。我们发现 逆转录病毒在Serinc 5敏感性方面差异很大，但我们还没有发现 这些差异背后的模式。我们还与亚历克斯·康普顿博士（艾滋病毒 DRP）在另一种抗病毒蛋白的作用的研究中，即，干扰素诱导的 跨膜蛋白3（IFITM 3）。有趣的是，相同的MLV辅助蛋白抵消了 Serinc 5和IFITM 3的作用。我们还分析了小鼠的抗病毒作用 Apobec 3（mA 3），其对HIV-1和MLV具有显著不同的作用。协同 约翰·布里格斯博士和其他人，我们发现成熟的HIV-1和MLV颗粒的结构是 这些结构上的差异似乎是导致 他们对mA 3反应的差异。我们正在从几个方面探索这种可能性， 包括测试mA 3和已充分表征的人类之间嵌合体的影响 APOBEC3G。_我们还在研究MuERV-L的性质，MuERV-L是一个逆转录转座子家族。 在非常早期的小鼠胚胎发育中表达。这个表达式的功能意义是 未知

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.