Sequences within RNA coding for HIV-1 Gag p17 are efficiently targeted to exosomes

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.