美国犹他大学医学院Wesley I. Sundquist和美国弗吉尼亚大学Owen Pornillos研究组合作取得最新进展。他们体外重组和可视化了HIV-1衣壳依赖性复制和整合。这一研究成果于2020年10月9日发表在国际顶尖学术期刊《科学》上。

他们在无细胞系统中重建并成像了HIV-1复制的早期阶段。从渗透病毒粒子释放的HIV-1核心，支持有效的衣壳依赖型内源性逆转录，以产生双链DNA基因组，有时从破裂的衣壳壁中循环出来。将两个病毒DNA末端协同整合到目标质粒中，然后进行依赖于细胞提取物的反应。这个重构系统揭示了衣壳在模板复制中的作用。

研究人员表示，在病毒生命周期的前半段，HIV-1逆转录其RNA基因组并将双链DNA拷贝整合到宿主细胞染色体中。 尽管在表征和抑制这些过程方面取得了进展，但是原位机械和结构研究仍然具有挑战性。这是因为这些操作是由细胞深处的各个病毒预整合复合物执行的。

附：英文原文

Title: Reconstitution and visualization of HIV-1 capsid-dependent replication and integration in vitro

Author: Devin E. Christensen, Barbie K. Ganser-Pornillos, Jarrod S. Johnson, Owen Pornillos, Wesley I. Sundquist

Issue&Volume: 2020/10/09

Abstract: During the first half of the viral life cycle, HIV-1 reverse transcribes its RNA genome and integrates the double-stranded DNA copy into a host cell chromosome. Despite progress in characterizing and inhibiting these processes, in situ mechanistic and structural studies remain challenging. This is because these operations are executed by individual viral preintegration complexes deep within cells. We therefore reconstituted and imaged the early stages of HIV-1 replication in a cell-free system. HIV-1 cores released from permeabilized virions supported efficient, capsid-dependent endogenous reverse transcription to produce double-stranded DNA genomes, which sometimes looped out from ruptured capsid walls. Concerted integration of both viral DNA ends into a target plasmid then proceeded in a cell extract–dependent reaction. This reconstituted system uncovers the role of the capsid in templating replication.

DOI: 10.1126/science.abc8420

Source: https://science.sciencemag.org/content/370/6513/eabc8420