Saito Hideki, Takeuchi Hiroaki, Masuda Takao, Noda Takeshi, Yamaoka Shoji
Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Department of Immunotherapeutics, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
PLoS One. 2017 Sep 5;12(9):e0182434. doi: 10.1371/journal.pone.0182434. eCollection 2017.
Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA) core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA. Studies with an HIV-1-murine leukemia virus (MLV) chimeric virus carrying the MLV-derived Gag revealed that Gag is a determinant of this inhibition. Intriguingly, mutational studies have revealed that the blockade by N-terminally-truncated POM121C is closely linked to its binding to importin-β/karyopherin subunit beta 1 (KPNB1). These results indicate that N-terminally-truncated POM121C inhibits HIV-1 infection after completion of reverse transcription and before integration, and suggest an important role for KPNB1 in HIV-1 replication.
最近的研究已经确定了宿主细胞因子，这些因子调节HIV-1感染的早期阶段，包括病毒cDNA合成以及HIV-1衣壳（CA）核心朝向核膜的定向，但目前尚不清楚病毒DNA如何通过核孔导入并被引导至宿主染色体DNA。在此，我们证明核孔复合体的一个组分——N端截短的POM121C可阻断HIV-1感染。这种截短的蛋白主要定位于细胞质中，不与CA结合，不影响病毒cDNA合成，减少2-LTR的形成并降低整合的前病毒DNA的量。对携带源自鼠白血病病毒（MLV）的Gag的HIV-1-MLV嵌合病毒的研究表明，Gag是这种抑制作用的决定因素。有趣的是，突变研究表明，N端截短的POM121C的阻断作用与其与输入蛋白-β/核转运蛋白亚基β1（KPNB1）的结合密切相关。这些结果表明，N端截短的POM121C在逆转录完成后和整合前抑制HIV-1感染，并提示KPNB1在HIV-1复制中起重要作用。
