Abstract：
The chimeric protein TRIM5α-HRH is a promising antiviral factor for HIV-1 gene therapy. This protein is able to protect cells from HIV-1 by blocking the virus in the cytoplasm. We are developing protocol of HIV-1 gene therapy, which involves the delivery of the TRIM5α-HRH gene into CD4^(+) T-lymphocytes by lentiviral vectors (LVs). However, LVs containing TRIM5α-HRH have a low infectious titer, which prevents effective T cell modification. Here, we found that the expression of TRIM5α-HRH during pseudoviral particle production in HEK293 T cells, as well as the presence of the Eflα promoter in our construction are responsible for titer reduction. These results allow us to determine the directions for further optimization of LV with the TRIM5α-HRH gene to improve its infectious titer.
摘要：
嵌合蛋白TRIM5α-HRH是HIV-1基因治疗的一种有前途的抗病毒因子。这种蛋白质能够通过阻断细胞质中的病毒来保护细胞免受HIV-1的侵害。我们正在开发HIV-1基因治疗方案,涉及通过慢病毒载体（LV）将TRIM5α-HRH基因传递到CD4^（）T淋巴细胞中。然而,含有TRIM5α-HRH的LV具有低感染滴度，这阻止了有效的T细胞修饰。这里,我们发现TRIM5α-HRH在HEK293T细胞产生假病毒颗粒过程中的表达，以及在我们的构建中Eflα启动子的存在是滴度降低的原因。这些结果使我们能够确定进一步优化具有TRIM5α-HRH基因的LV以提高其感染滴度的方向。
