Sequences within RNA coding for HIV-1 Gag p17 are efficiently targeted to exosomes
Sequences within RNA coding for HIV-1 Gag p17 are efficiently targeted to exosomes
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DOI：
10.1111/cmi.12046
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发表时间：
2013-03-01
影响因子：
3.4
通讯作者：
Federico, Maurizio
中科院分区：
文献类型：
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作者：
Cabezas, Sandra Columba;Federico, Maurizio
HIV出芽需要与参与外泌体生物发生的细胞因子相互作用。这意味着病毒产物有可能被整合进外泌体。虽然HIV - 1的Gag和Nef蛋白已有相关描述，但到目前为止，对于HIV基因组尚未有确凿的结果。在此，我们报道未剪接的（但不是单剪接或双剪接的）HIV - 1 RNA种类被整合进外泌体。缺失突变分析表明，在Gag p17开放阅读框5′端存在一段序列足以使HIV - 1 RNA整合进外泌体。还发现这些序列在HIV - 1环境之外也与外泌体相关联，这表明向囊泡区室的转移可以在不需要额外的HIV - 1序列的情况下发生。最后，当生产细胞表达病毒基因组包装有缺陷的HIV - 1时，基因组HIV - 1 RNA整合进外泌体的情况显著增加。操纵受感染细胞以促进基因组HIV - 1 RNA选择性整合进外泌体可能具有治疗意义。
HIV budding requires the interaction with cell factors involved in the biogenesis of exosomes. This implies the possibility that viral products undergo exosome incorporation. While this has been already described for both Gag and Nef HIV-1 proteins, no conclusive results on HIV genome have been produced so far. Here, we report that unspliced, but not single or double spliced, HIV-1 RNA species are incorporated in exosomes. Deletion mutant analysis indicated that the presence of a stretch of sequences within the 5 end of the Gag p17 open reading frame is sufficient for HIV-1 RNA exosome incorporation. These sequences were found associating with exosomes also out of the HIV-1 context, thus indicating that the diversion towards the vesicular compartment can occur without need of additional HIV-1 sequences. Finally, the incorporation of genomic HIV-1 RNA in exosomes significantly increased when producer cells express HIV-1 defective for viral genome packaging. Manipulating infected cells to favour the selective incorporation in exosomes of genomic HIV-1 RNA might have therapeutic implications.