HIV-1 inhibits haematopoiesis via microRNA secreted by virus-infected CD4+ T cells.

Introduction: HIV-1-infected patients develop haematological disorders such as cytopenias. One possible explanation is the inhibition of haematopoiesis at the level of differentiation of CD34+ haematopoietic progenitor stem cells. Based on our previous studies, we hypothesised that there may be viral encoded, or host cellular factors which participate in the process of inhibition of haematopoiesis.

Materials And Methods: Virus-depleted media from infected CD4+ T cells was prepared by filtration and added to CD34+ cell differentiation semisolid medium. We have also used the virus-depleted media to isolate host/viral factors including miRNA. Isolated miRNAs were screened for their haematopoietic inhibitory function using the miRNA mining approach.

Results: Addition of virus-depleted media caused a 40% inhibition of differentiation of CD34+ cells into myeloid and erythroid colony formation. Real-time RT-PCR showed miR-15a and miR-24 from both pIndie-C1 and pNL4.3 HIV-1-infected cells showed a significant differential expression when compared to control media.

Conclusion: In this study, we have identified two miRNAs, miR-15a and miR-24 secreted from purified HIV-1-infected CD4+ T cells that inhibited CD34+ haematopoietic progenitor stem cell differentiation into myeloid and erythroid colonies in vitro.