Wolfrum Nina, Mühlebach Michael D, Schüle Silke, Kaiser Julia K, Kloke Björn-Philipp, Cichutek Klaus, Schweizer Matthias
Division of Medical Biotechnology, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, Langen, Germany.
Virology. 2007 Aug 1;364(2):330-41. doi: 10.1016/j.virol.2007.03.008. Epub 2007 Apr 5.
Although lentiviruses like HIV-1 are able to infect non-dividing cells, particular resting cells such as non-stimulated primary peripheral blood mononuclear cells (PBMC) are resistant to infection. In contrast to other lentiviruses, SIVsmmPBj can replicate in non-stimulated PBMC. Moreover, SIVsmmPBj-derived, but not HIV-1-derived, replication-incompetent vectors enable gene transfer into G(0)-arrested human cell lines and primary human monocytes. Here, we demonstrate that transduction of G(0)-arrested cell lines by SIVsmmPBj-derived vectors is independent of the viral accessory proteins Vif, Vpx, Vpr, or Nef. In contrast, for the transduction of primary human monocytes, the Vpx protein proved to be essential. However, trans-complementation of HIV-1 vectors with SIVsmmPBj Vpx did not provide the property of gene transfer into monocytes. Taken together, these data indicate that Vpx is essential for the infection of primary monocytes by SIVsmmPBj. Additionally, further genome functions besides the accessory proteins are required for the particular capacity of SIVsmmPBj in transduction or infection events.
尽管像HIV-1这样的慢病毒能够感染非分裂细胞,但某些静息细胞,如未受刺激的原代外周血单核细胞(PBMC)对感染具有抗性。与其他慢病毒不同,SIVsmmPBj能够在未受刺激的PBMC中复制。此外,源自SIVsmmPBj而非HIV-1的复制缺陷型载体能够将基因导入G(0)期停滞的人细胞系和原代人单核细胞。在此,我们证明源自SIVsmmPBj的载体对G(0)期停滞细胞系的转导独立于病毒辅助蛋白Vif、Vpx、Vpr或Nef。相反,对于原代人单核细胞的转导,Vpx蛋白被证明是必不可少的。然而,用SIVsmmPBj Vpx对HIV-1载体进行反式互补并不能赋予其向单核细胞进行基因转移的特性。综上所述,这些数据表明Vpx对于SIVsmmPBj感染原代单核细胞至关重要。此外,除了辅助蛋白之外,SIVsmmPBj在转导或感染事件中的特殊能力还需要其他基因组功能。