A lot of microRNAs (miRNAs) derived from viral genomes have been identified. Many of them play various important roles in virus replication and virus-host interaction. Cellular miRNAs have been shown to participate in the regulation of HIV-1 viral replication, while the role of viral-encoded miRNAs in this process is largely unknown. In this report, through a strategy combining computational prediction and deep sequencing, we identified a novel HIV-1-encoded miRNA, miR-H3. MiR-H3 locates in the mRNA region encoding the active center of reverse transcriptase (RT) and exhibits high sequence conservation among different subtypes of HIV-1 viruses. Overexpression of miR-H3 increases viral production and the mutations in miR-H3 sequence significantly impair the viral replication of wildtype HIV-1 viruses, suggesting that it is a replication-enhancing miRNA. MiR-H3 upregulates HIV-1 RNA transcription and protein expression. A serial deletion assay suggests that miR-H3 targets HIV-1 5′ LTR and upregulates the promoter activity. It interacts with the TATA box in HIV-1 5′ LTR and sequence-specifically activates the viral transcription. In addition, chemically-synthesized small RNAs targeting HIV-1 TATA box activate HIV-1 production from resting CD4⁺ T cells isolated from HIV-1-infected patients on suppressive highly active antiretroviral therapy (HAART). We have identified a novel HIV-1-encoded miRNA which specifically enhances viral production and provide a specific method to activate HIV-1 latency.

Uridine insertion and deletion RNA editing generates functional mitochondrial mRNAs in Trypanosoma brucei. The mRNAs are differentially edited in bloodstream form (BF) and procyclic form (PF) life cycle stages, and this correlates with the differential utilization of glycolysis and oxidative phosphorylation between the stages. The mechanism that controls this differential editing is unknown. Editing is catalyzed by multiprotein ∼20S editosomes that contain endonuclease, 3′-terminal uridylyltransferase, exonuclease, and ligase activities. These editosomes also contain KREPB5 and KREPA3 proteins, which have no functional catalytic motifs, but they are essential for parasite viability, editing, and editosome integrity in BF cells. We show here that repression of KREPB5 or KREPA3 is also lethal in PF, but the effects on editosome structure differ from those in BF. In addition, we found that point mutations in KREPB5 or KREPA3 differentially affect cell growth, editosome integrity, and RNA editing between BF and PF stages. These results indicate that the functions of KREPB5 and KREPA3 editosome proteins are adjusted between the life cycle stages. This implies that these proteins are involved in the processes that control differential editing and that the 20S editosomes differ between the life cycle stages.

Acinetobacter pittii 44551 was recovered from a patient with gout combined with tuberculosis and was found to harbor the carbapenemase genes bla_NDM-1 and bla_OXA-58 on two different plasmids pNDM-44551 and pOXA58-44551, respectively. pNDM-44551 displayed high self-transferability across multiple bacterial species, while pOXA58-44551 was likely co-transferable with pNDM-44551 into A. baumannii receipts. pNDM-44551 was a close variant of the previously characterized pNDM-BJ01, and the bla_NDM-1 gene cluster was arranged sequentially as orfA, ISAba14, aphA6, ISAba125, bla_NDM-1, ble_MBL, ΔtrpF, dsbC, tnpR, and zeta. pOXA58-44551 was a repAci9-containing plasmid, and bla_OXA-58 was embedded in a 372F-ISAba3-like-bla_OXA-58-ISAba3 structure. The mobile genetic platforms of bla_NDM-1 and bla_OXA-58 herein showed some differences from their previously characterized variants. The production of NDM-1 in strain 44551 contributed the majority to its high resistance to carbapenems, while the bla_OXA-58 stayed silent most likely due to the lack of an upstream promoter to drive its transcription. Increased surveillance of Acinetobacter co-harboring bla_NDM-1 (active) and bla_OXA-58 (either active or silent) is urgently needed.