Two mechanisms by which expressed intragenomic miRNAs can affect viral replication. (A) An integrated HIV-1 genome is transcribed into viral mRNAs containing the embedded primary miRNA. This viral mRNA with an embedded primary miRNA may be recognized and cleaved in the nucleus by Drosha (in yellow). If Drosha-mediated cleavage is overly efficient, few uncleaved viral RNA would be left available to export into the cytoplasm for translation and/or packaging. This would then result in attenuated or incompetent viral replication like the NL4-3 miR211 virus. (B) For most chimeric NL4-3 miRNA viruses, Drosha processing of the embedded primary miRNA is relatively inefficient. Thus two pools of RNAs (unprocessed viral RNA and processed pre-miRNAs) are exported from the nucleus into the cytoplasm. In the case of the NL4-3 miR326 virus, the primary miR326 is further processed by Dicer into mature miR326 which associates with RISC and silences complementary viral target sequence leading to the attenuation of viral replication.