Evidence that hematopoietic stem cells in human umbilical cord blood is infectable by dengue virus: proposing a vertical transmission candidate

Abstract

Background Recent studies have shown that dengue virus (DENV) can efficiently infect bone marrow hematopoietic stem cells (HSCs) as well as the placenta of pregnant women. Although mother-to-infant vertical transmission of DENV through the placenta has been well documented, the evidence of cell-associated vertical transmission is still unknown. Whether DENV can infect umbilical cord blood (UCB) cells before reaching the fetus remains to be explored. Here, we proposed that human UCB cells were permissive to the DENV infection and DENV infected CD133+ and CD34+ HSCs are reservoir of the virus that could be reactivated upon re-culturing in suitable cells. Methods Human UCB cells were freshly obtained and subjected to DENV infection. Multicolor flow cytometry (MFCM) was used to demonstrate the phenotypes of the infected HSC populations. Immunofluorescence analysis (IFA) and T-distributed Stochastic Neighbor Embedding (t-SNE) were used to show the association of the DENV antigen, non-structural protein1 (NS1) with HSCs. Key findings UCB cells were highly permissive to DENV infection. DENV altered the phenotype of the infected HSC population, increased the expression of HSCs, and affected the balance of transcription factors (TFs, GATA1/2/3). IFA revealed the association of the DENV antigen, non-structural protein1 (NS1), with CD34 + and CD133 + cells. T-distributed Stochastic Neighbor Embedding (t-SNE) analysis revealed heterogeneity in the distribution of CD133 + NS1 + , and CD34 + NS1 + cells. DENV particles were recovered from CD133 + and CD34 + cells even when virus production in the supernatant was negligible. Significance We predict that infection of CD133+ and CD34+ cells in the UCB serve as reservoirs for the amplification of DENV in UCB prior to the virus reaching the fetus and facilitate vertical transmission.

The Regenerative Power of Stem Cells: Treating Bleomycin-Induced Lung Fibrosis

“… 121 CD44 is an early marker of differentiation for these immature CD34 + cells. 122 Studies have shown that cells with higher CD44 expression levels have better proliferation and differentiation capabilities into AT1 cells. 93 Therefore, the study of HSCs with a general expression of CD34 and CD44 markers could provide insight into the development of lung fibrosis.…”

The Innate Immune Response in DENV- and CHIKV-Infected Placentas and the Consequences for the Fetuses: A Minireview

“…Previous evidence of DENV and CHIKV outbreaks has demonstrated that pregnant women are at high risk of experiencing pregnancy complications during viral infection [ 52 , 75 , 76 , 77 , 78 ]. In addition, there are some reports of the vertical transmission of these microorganisms, raising awareness of the importance of better understanding the role of the placenta in DENV and CHIKV infections [ 79 , 80 , 81 ]. Established in the third week of gestation, the placenta is characterized as a temporary and chimerical organ, formed by maternal and fetal tissue, that plays an essential role in the development and support of pregnancy.…”