Abstract
BackgroundTissue resident mesenchymal stem cells (MSCs) are multipotent, self-renewing cells known for their differentiation potential into cells of mesenchymal lineage. The ability of single cell clones isolated from adipose tissue resident MSCs (ASCs) to differentiate into cells of hematopoietic lineage has been previously demonstrated. In the present study, we investigated if the hematopoietic differentiated (HD) cells derived from ASCs could productively be infected with HIV-1.ResultsHD cells were generated by differentiating clonally expanded cultures of adherent subsets of ASCs (CD90+, CD105+, CD45-, and CD34-). Transcriptome analysis revealed that HD cells acquire a number of elements that increase their susceptibility for HIV-1 infection, including HIV-1 receptor/co-receptor and other key cellular cofactors. HIV-1 infected HD cells (HD-HIV) showed elevated p24 protein and gag and tat gene expression, implying a high and productive infection. HD-HIV cells showed decreased CD4, but significant increase in the expression of CCR5, CXCR4, Nef-associated factor HCK, and Vpu-associated factor BTRC. HIV-1 restricting factors like APOBEC3F and TRIM5 also showed up regulation. HIV-1 infection increased apoptosis and cell cycle regulatory genes in HD cells. Although undifferentiated ASCs failed to show productive infection, HIV-1 exposure increased the expression of several hematopoietic lineage associated genes such as c-Kit, MMD2, and IL-10.ConclusionsConsidering the presence of profuse amounts of ASCs in different tissues, these findings suggest the possible role that could be played by HD cells derived from ASCs in HIV-1 infection. The undifferentiated ASCs were non-permissive to HIV-1 infection; however, HIV-1 exposure increased the expression of some hematopoietic lineage related genes. The findings relate the importance of ASCs in HIV-1 research and facilitate the understanding of the disease process and management strategies.
Highlights
Tissue resident mesenchymal stem cells (MSCs) are multipotent, self-renewing cells known for their differentiation potential into cells of mesenchymal lineage
Up-regulation of Human immunodeficiency virus type 1 (HIV-1) susceptibility genes in hematopoietic differentiated (HD) cells HD cells were prepared by differentiating expanded cultures of adipose tissue resident MSCs (ASCs) clones, phenotypically identified as CD90+, CD105+, CD44+, CD4, CD68, CD34, CD45, and CD11b- cells as described previously [25]
The HD cells expressed a number of HIV-1 receptors such CD4 (33.9 ± 3.4 fold), CXCR4 (2.7 ± 0.42 fold), CCR4 (1.64 ± 0.05 fold), and CCR5 (1.93 ± 0.26 fold) compared to undifferentiated ASCs (Figure 1A)
Summary
Tissue resident mesenchymal stem cells (MSCs) are multipotent, self-renewing cells known for their differentiation potential into cells of mesenchymal lineage. We investigated if the hematopoietic differentiated (HD) cells derived from ASCs could productively be infected with HIV-1. Undifferentiated ASCs failed to show productive infection, HIV-1 exposure increased the expression of several hematopoietic lineage associated genes such as c-Kit, MMD2, and IL-10. CXCR4 appears to be the most important for HIV-1 entry into T-lymphocytes (T-tropic), whereas CCR5 is known for viral entry into cells such as monocytes and macrophages (M-tropic) [3]. These receptors promote viral attachment and fusion to cellular membranes, facilitating entry into hematopoietic cells [4]. Even though an early loss of circulating CD34+ HPCs and impaired clonogenic potential and apoptosis of these progenitor cells have been documented in HIV-1 infected individuals [7,8], the evidence of productive infection of HPCs remains controversial [9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
