Abstract
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.
Highlights
The highly pathogenic avian influenza A virus of the H5N1 subtype was originally endemic to poultry, but crossed the avianhuman species barrier
We demonstrated that highly pathogenic avian influenza (HPAI) H5N1 virus could productively infect and replicate in CD34+ hematopoietic stem cells (HSCs) and mesenchymal stromal cells (MSCs)
We demonstrated that CD34+ HSCs and MSCs expressed receptors of both avian (SAa2,3-Gal) and human (SAa2,6-Gal) influenza viruses (Figure 1)
Summary
The highly pathogenic avian influenza A virus of the H5N1 subtype was originally endemic to poultry, but crossed the avianhuman species barrier. It has emerged as a highly fatal infectious disease in the human population with a 60% mortality observed in more than ten countries, as reported to the World Health Organization since 2003 [1,2]. The virus can spread from the lungs to other organs [5] and can pass to the fetus [4,5], causing systemic disease which leads to an unusually high mortality rate. Hematologic abnormalities were commonly observed in severe cases, including lymphoid depletion, leucopenia, thrombocytopenia and pancytopenia, which are likely related to bone marrow (BM) suppression, and/or virus-associated hemophagocytosis. If the virus-mediated BM suppression is a possible factor contributing to the observed substantial cell loss, hematologic abnormalities, and hyperinflammatory cytokine production, it is intriguing to determine whether the observed suppression is a result of direct invasion of virus
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