Multipotent mesenchymal stromal cells are fully permissive for human cytomegalovirus infection

Abstract

Congenital human cytomegalovirus (HCMV) infection is a leading infectious cause of birth defects. Previous studies have reported birth defects with multiple organ maldevelopment in congenital HCMV-infected neonates. Multipotent mesenchymal stromal cells (MSCs) are a group of stem/progenitor cells that are multi-potent and can self-renew, and they play a vital role in multi-organ formation. Whether MSCs are susceptible to HCMV infection is unclear. In this study, MSCs were isolated from Wharton's jelly of the human umbilical cord and identified by their plastic adherence, surface marker pattern, and differentiation capacity. Then, the MSCs were infected with the HCMV Towne strain, and infection status was assessed via determination of viral entry, replication initiation, viral protein expression, and infectious virion release using western blotting, immunofluorescence assays, and plaque forming assays. The results indicate that the isolated MSCs were fully permissive for HCMV infection and provide a preliminary basis for understanding the pathogenesis of HCMV infection in non-nervous system diseases, including multi-organ malformation during fetal development.

Isolation, Characterization, Differentiation and Immunomodulatory Capacity of Mesenchymal Stromal/Stem Cells from Human Perirenal Adipose Tissue

“…The susceptibility and permissibility of prASCs to HCMV was not known before our experiments, but is consistent with reported productive infection of MSC derived from bone marrow [20], umbilical cord Wharton’s jelly [49], placenta [50] and MSC from subcutaneous adipose tissue [51] The perivascular niche was described as a relevant MSC origin across the human organs [1]. In addition perivascular stromal cells host HCMV and are a likely long term reservoir [52].…”

Review of the potential of mesenchymal stem cells for the treatment of infectious diseases

“…Qiao et al [ 204 ]and Soland et al [ 205 ] reported that human MSCs were fully permissive to human cytomegalovirus infection, and the highest infection rate was observed in lung perivascular MSCs, suggesting that MSCs in different organs might act as a viral reservoir in humans. Further, Meisel et al [ 206 ] found that MSCs infected with CMV lose their immunosuppressive and antimicrobial properties, and Sundin et al [ 207 ] found that parvovirus B19 persisted in BM-MSCs even after several years of infection.…”

Multipotent Stromal Cells and Viral Interaction: Current Implications for Therapy

“…MSC surface receptor expression and viral tropism may partially explain MSC susceptibility to viral infection. MSCs are highly permissive to infection by many genera of Herpesviruses, including Herpes Simplex-1 (HSV-1), Varicella Zoster virus (VZV) and Cytomegalovirus (CMV) [ 27 ]. HSV-1 can infect MSCs through the heparan sulfate receptor [ 28 ].…”