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Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection.

Nazari-Shafti TZ, Freisinger E, Roy U, Bulot CT, Senst C, Dupin CL, Chaffin AE, Srivastava SK, Mondal D, Alt EU, Izadpanah R - Retrovirology (2011)

Bottom Line: HD-HIV cells showed decreased CD4, but significant increase in the expression of CCR5, CXCR4, Nef-associated factor HCK, and Vpu-associated factor BTRC.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.The findings relate the importance of ASCs in HIV-1 research and facilitate the understanding of the disease process and management strategies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, New Orleans, Louisiana, USA.

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.

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Gene expression analysis of HD cells following hematopoietic differentiation. Compared to ASCs, the expression level of HIV receptor genes (CD4, CXCR4, CCR4, and CCR5) were up regulated in HD cells as result of differentiation (A). Expression of several genes involved in innate and adaptive immune reactions (B), and cell cycle regulators (C) were altered in HD cells. A fold change was applied to select genes (P < 0.05). All values are normalized to ASCs (X axis).
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Figure 1: Gene expression analysis of HD cells following hematopoietic differentiation. Compared to ASCs, the expression level of HIV receptor genes (CD4, CXCR4, CCR4, and CCR5) were up regulated in HD cells as result of differentiation (A). Expression of several genes involved in innate and adaptive immune reactions (B), and cell cycle regulators (C) were altered in HD cells. A fold change was applied to select genes (P < 0.05). All values are normalized to ASCs (X axis).

Mentions: HD cells were prepared by differentiating expanded cultures of ASC clones, phenotypically identified as CD90+, CD105+, CD44+, CD4-, CD68-, CD34-, CD45-, and CD11b- cells as described previously [25]. For the initial assessment of HD cells, we performed a transcriptomic analysis after 8 days of differentiation. 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). HD cells also expressed a series of genes involved in innate and adaptive immune reactions and key cellular cofactors for HIV-1 infection such as IL-8, SERPINA1, CCL8, CD69 and interleukins 2, 10, and 16 (Figure 1B). The expression of lymphoid associated gene BCL11B was markedly up regulated. Further, the expression of a number of cell cycle regulators, such as BAX, CDKN1A, FOS, GADD45A, NFATC1, CEBPB, STAT1, and STAT3, decreased while the expression of NFκB1A slightly increased as a result of differentiation (Figure 1C).


Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection.

Nazari-Shafti TZ, Freisinger E, Roy U, Bulot CT, Senst C, Dupin CL, Chaffin AE, Srivastava SK, Mondal D, Alt EU, Izadpanah R - Retrovirology (2011)

Gene expression analysis of HD cells following hematopoietic differentiation. Compared to ASCs, the expression level of HIV receptor genes (CD4, CXCR4, CCR4, and CCR5) were up regulated in HD cells as result of differentiation (A). Expression of several genes involved in innate and adaptive immune reactions (B), and cell cycle regulators (C) were altered in HD cells. A fold change was applied to select genes (P < 0.05). All values are normalized to ASCs (X axis).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3025950&req=5

Figure 1: Gene expression analysis of HD cells following hematopoietic differentiation. Compared to ASCs, the expression level of HIV receptor genes (CD4, CXCR4, CCR4, and CCR5) were up regulated in HD cells as result of differentiation (A). Expression of several genes involved in innate and adaptive immune reactions (B), and cell cycle regulators (C) were altered in HD cells. A fold change was applied to select genes (P < 0.05). All values are normalized to ASCs (X axis).
Mentions: HD cells were prepared by differentiating expanded cultures of ASC clones, phenotypically identified as CD90+, CD105+, CD44+, CD4-, CD68-, CD34-, CD45-, and CD11b- cells as described previously [25]. For the initial assessment of HD cells, we performed a transcriptomic analysis after 8 days of differentiation. 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). HD cells also expressed a series of genes involved in innate and adaptive immune reactions and key cellular cofactors for HIV-1 infection such as IL-8, SERPINA1, CCL8, CD69 and interleukins 2, 10, and 16 (Figure 1B). The expression of lymphoid associated gene BCL11B was markedly up regulated. Further, the expression of a number of cell cycle regulators, such as BAX, CDKN1A, FOS, GADD45A, NFATC1, CEBPB, STAT1, and STAT3, decreased while the expression of NFκB1A slightly increased as a result of differentiation (Figure 1C).

Bottom Line: HD-HIV cells showed decreased CD4, but significant increase in the expression of CCR5, CXCR4, Nef-associated factor HCK, and Vpu-associated factor BTRC.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.The findings relate the importance of ASCs in HIV-1 research and facilitate the understanding of the disease process and management strategies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, New Orleans, Louisiana, USA.

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.

Show MeSH
Related in: MedlinePlus