HIV-1 and HIV-2 are two etiological agents of Acquired Immune Deficiency Syndrome (AIDS). Several differences exist between these two retroviruses in terms of geographical distribution, replication, transmission and progression to AIDS. The molecular reasons explaining these features are largely unknown. One reason could rely on host factors able to differently counteract HIV replication. Among these factors, cellular microRNAs (miRNAs) have recently emerged as playing crucial roles. One aspect of the complex interplay between HIV and host miRNAs is the ability of HIV-1 to modulate host miRNAs and thereby to create favorable conditions for its replication. Here, we sought to compare the miRNA modulations elicited by HIV-1 and HIV-2 using an unbiased experimental strategy based on miRNA arrays. Surprisingly, we observed that these two unrelated HIVs similarly modulated the host miRNA repertoire, when utilizing CD4 and CXCR4 for entry. However, these modulations were different from the changes triggered by HIV-1 using CD4 and CCR5. In accordance with the mode of action of miRNAs, our observations were confirmed at the mRNA level. We concluded that co-receptor utilization (CXCR4 or CCR5), as opposed to genomic organization and phylogeny, is a key event determining the modulations of the host miRNA repertoire.
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