title: Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection.
abstract: BACKGROUND
  Tissue 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.
  
  
  RESULTS
  HD 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.
  
  
  CONCLUSIONS
  Considering 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.
authors.affiliation: Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, New Orleans, Louisiana, USA.
authors.forename: Timo Z
authors.initials: TZ
authors.lastname: Nazari-Shafti
authors.forename: Eva
authors.initials: E
authors.lastname: Freisinger
authors.forename: Upal
authors.initials: U
authors.lastname: Roy
authors.forename: Christine T
authors.initials: CT
authors.lastname: Bulot
authors.forename: Christiane
authors.initials: C
authors.lastname: Senst
authors.forename: Charles L
authors.initials: CL
authors.lastname: Dupin
authors.forename: Abigail E
authors.initials: AE
authors.lastname: Chaffin
authors.forename: Sudesh K
authors.initials: SK
authors.lastname: Srivastava
authors.forename: Debasis
authors.initials: D
authors.lastname: Mondal
authors.forename: Eckhard U
authors.initials: EU
authors.lastname: Alt
authors.forename: Reza
authors.initials: R
authors.lastname: Izadpanah
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D018816:Genes, cdc; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D054398:Receptors, CCR4 / Q000096:biosynthesis / Q000235:genetics; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C515354:CCR4 protein, human; D015704:CD4 Antigens; D016655:HIV Core Protein p24; D054398:Receptors, CCR4; D019713:Receptors, CCR5