Tropism of Avian Influenza A (H5N1) Virus to Mesenchymal Stem Cells and CD34+ Hematopoietic Stem Cells

• Published in: PloS one Vol. 8; no. 12; p. e81805
• Main Authors: Thanunchai, Maytawan, Kanrai, Pumaree, Wiboon-ut, Suwimon, Puthavathana, Pilaipan, Hongeng, Suradej, Thitithanyanont, Arunee
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.12.2013; Public Library of Science (PLoS)
• Subjects: Antigens; Antigens, CD34; Apoptosis; Avian flu; Bone marrow; CD34 antigen; Cell death; Cord blood; Cytokines; Dendritic cells; Female; Fetal Blood - metabolism; Fetal Blood - virology; Hematopoietic stem cells; Hematopoietic Stem Cells - metabolism; Hematopoietic Stem Cells - pathology; Hematopoietic Stem Cells - virology; Hospitals; Humans; Immunomodulation; Infections; Influenza; Influenza A; Influenza A Virus, H5N1 Subtype - physiology; Influenza, Human - metabolism; Influenza, Human - pathology; Influenza, Human - therapy; Lymphopenia; Male; Medicine; Mesenchymal stem cells; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Mesenchymal Stromal Cells - virology; Mesenchyme; Monocytes; Mortality; Pancytopenia; Pathogenesis; Respiratory distress syndrome; Stem cells; Stromal cells; Thrombocytopenia; Transplants & implants; Tropism; Umbilical cord; Viral infections; Viral Tropism - physiology; Viruses; Thailand; Bangkok Thailand
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081805

The presence of abnormal hematologic findings such as lymphopenia, thrombocytopenia, and pancytopenia were diagnosed in severe cases of avian influenza A H5N1. Whether direct viral dissemination to bone marrow (BM) cells causes this phenomenon remains elusive. We explore the susceptibility of the two stem cell types; hematopoietic stem cells (HSCs) and mesenchymal stromal cells (MSCs) isolated from human BM cells or cord blood, to infection with avian H5N1 viruses. For the first time, we demonstrated that the H5N1 virus could productively infect and induce cell death in both human stem cell types. In contrast, these activities were not observed upon human influenza virus infection. We also determined whether infection affects the immunomodulatory function of MSCs. We noted a consequent dysregulation of MSC-mediated immune modulation as observed by high cytokine and chemokine production in H5N1 infected MSCs and monocytes cocultures. These findings provide a better understanding of H5N1 pathogenesis in terms of broad tissue tropism and systemic spread.