Background:  Micro-RNA are 20- to 22-nt small RNA that regulate gene expression by post-transcriptional suppression. They therefore play a major role in controlling host response and viral replication in several viral infections. Their presence and role during HIV infection, especially of viral encoded micro-RNA, has remained a controversial issue.

Methods:  In the present study, we applied our powerful integrated bioinformatics-biological platform for micro-RNA profiling and detection together with Dicer- and Drosha-suppressed cellular systems to the study of host and viral encoded micro-RNA during HIV infection.

Results:  Comparing infected and non-infected cells we have revealed differential expression of several host micro-RNA, as well as the increased expression of some predicted HIV encoded micro-RNA, notably that present within the TAR region. Suppression of this micro-RNA leads to suppressed viral replication, and may also contribute to the latency phase of HIV infection. Several of the up-regulated host micro-RNA have more than 1 binding site on the 3' UTR of micro-RNA that influence viral replication and immune activation, notably those belonging to the Interferon family and to a number of cytokines. Dicer- and Drosha-suppressed cell systems show increased HIV viral replication.

Conclusions:  HIV infection is associated with differential expression of several host micro-RNA, notably those related to viral control and cell activation. Some of the host and of the viral encoded micro-RNA, particularly the 1 located in the TAR region, may have a direct effect on viral replication and latency. Micro-RNA may be a key to the persistence of HIV infection in the HIV reservoirs, control of micro-RNA expression or its modulation offers a novel approach for ART.