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

Thanunchai, Maytawan; Kanrai, Pumaree; Wiboon-ut, Suwimon; Puthavathana, Pilaipan; Hongeng, Suradej; Thitithanyanont, Arunee

doi:10.1371/journal.pone.0081805

Cited by 26 publications

(31 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recently, two publications have shown that MSCs reduced influenza virus-induced ALI in mice infected with HPAI H5N1 and H9N2 without affecting the virus replication [9,12]. We and others have shown previously that influenza virus infected MSCs and that infected MSCs produced inflammatory cytokines [13][14][15]. Of the in vivo studies that examined the therapeutic efficacy of MSCs in influenza virus-induced ALI, none examined the infection of administered MSCs with influenza virus.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model

2018

View full text Add to dashboard Cite

Background: Mesenchymal stem (stromal) cells (MSCs) mediate their immunoregulatory and tissue repair functions by secreting paracrine factors, including extracellular vesicles (EVs). In several animal models of human diseases, MSC-EVs mimic the beneficial effects of MSCs. Influenza viruses cause annual outbreaks of acute respiratory illness resulting in significant mortality and morbidity. Influenza viruses constantly evolve, thus generating drug-resistant strains and rendering current vaccines less effective against the newly generated strains. Therefore, new therapies that can control virus replication and the inflammatory response of the host are needed. The objective of this study was to examine if MSC-EV treatment can attenuate influenza virus-induced acute lung injury in a preclinical model. Methods: We isolated EVs from swine bone marrow-derived MSCs. Morphology of MSC-EVs was determined by electron microscopy and expression of mesenchymal markers was examined by flow cytometry. Next, we examined the anti-influenza activity of MSC-EVs in vitro in lung epithelial cells and anti-viral and immunomodulatory properties in vivo in a pig model of influenza virus.

show abstract

Section: Discussionmentioning

confidence: 99%

“…However, MSC therapy in mice models of influenza show inconsistent results [9][10][11][12]. Also, we and others have shown that influenza virus infects MSCs and that infection may alter the immunoregulatory and differentiation properties of MSCs [13][14][15].…”

mentioning

confidence: 97%

Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model

2018

View full text Add to dashboard Cite

show abstract

“…This can occur rapidly following exposure of uninfected MSCs [23] and virus-infected MSCs may thus not be functionally effective at stopping virus replication and lung inflammation. [24][25][26][27]. BM-MSCs express influenza virus alpha-2,3 and alpha-2,6 sialic acid receptors on their cell surfaces and can support replication of both avian H1N1 and H9N5 influenza strains.…”

Section: Effects Of Respiratory Viruses On Msc Actionsmentioning

confidence: 99%

Current status of cell-based therapies for respiratory virus infections: applicability to COVID-19

et al. 2020

View full text Add to dashboard Cite

Severe respiratory consequences of the COVID-19 pandemic have prompted urgent need for novel therapies. Cell-based approaches, primarily using mesenchymal stem (stromal) cells (MSCs), have demonstrated safety and possible efficacy in patients with the acute respiratory distress syndrome (ARDS), although not as yet well studied in respiratory virusinduced ARDS. Limited pre-clinical data suggest that systemic MSC administration can significantly reduce respiratory virus (Influenza strains H5N1 and H9N2)-induced lung injury, however, there are no available data in models of coronavirus respiratory infection.There are a rapidly increasing number of clinical investigations of cell-based therapy approaches for COVID-19. These utilize a range of different cell sources, doses, dosing strategies, and targeted patient populations. To provide a rationale strategy to maximize potential therapeutic use, it is critically important to understand the relevant pre-clinical studies and postulated mechanisms of MSC actions in respiratory virus-induced lung injuries. These are presented along with consideration of current clinical investigations.

show abstract

“…The present study demonstrated that hNPCs support H5N1 influenza virus replication in vitro. Although infections with the avian H5N1 virus of stem/progenitor cells from blood and bone marrow [40,41], or human neuronal and astrocytic cell lines [26], have been reported, the present study appears the first to describe the interaction of H5N1 virus with human NPCs. Infection of the H5N1 virus in human brain cells has been shown previously to bring about upregulation of mRNA levels of pro-and anti-inflammatory cytokines [26].…”

Section: Discussionmentioning

confidence: 74%

Tropism and Induction of Cytokines in Human Embryonic-Stem Cells-Derived Neural Progenitors upon Inoculation with Highly- Pathogenic Avian H5N1 Influenza Virus

et al. 2015

View full text Add to dashboard Cite

Central nervous system (CNS) dysfunction caused by neurovirulent influenza viruses is a dreaded complication of infection, and may play a role in some neurodegenerative conditions, such as Parkinson-like diseases and encephalitis lethargica. Although CNS infection by highly pathogenic H5N1 virus has been demonstrated, it is unknown whether H5N1 infects neural progenitor cells, nor whether such infection plays a role in the neuroinflammation and neurodegeneration. To pursue this question, we infected human neural progenitor cells (hNPCs) differentiated from human embryonic stem cells in vitro with H5N1 virus, and studied the resulting cytopathology, cytokine expression, and genes involved in the differentiation. Human embryonic stem cells (BG01) were maintained and differentiated into the neural progenitors, and then infected by H5N1 virus (A/Chicken/Thailand/CUK2/04) at a multiplicity of infection of 1. At 6, 24, 48, and 72 hours post-infection (hpi), cytopathic effects were observed. Then cells were characterized by immunofluorescence and electron microscopy, supernatants quantified for virus titers, and sampled cells studied for candidate genes.The hNPCs were susceptible to H5N1 virus infection as determined by morphological observation and immunofluorescence. The infection was characterized by a significant up-regulation of TNF-α gene expression, while expressions of IFN-α2, IFN-β1, IFN-γ and IL-6 remained unchanged compared to mock-infected controls. Moreover, H5N1 infection did not appear to alter expression of neuronal and astrocytic markers of hNPCs, such as β-III tubulin and GFAP, respectively. The results indicate that hNPCs support H5N1 virus infection and may play a role in the neuroinflammation during acute viral encephalitis.

show abstract

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

Cited by 26 publications

References 51 publications

Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model

Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model

Current status of cell-based therapies for respiratory virus infections: applicability to COVID-19

Tropism and Induction of Cytokines in Human Embryonic-Stem Cells-Derived Neural Progenitors upon Inoculation with Highly- Pathogenic Avian H5N1 Influenza Virus

Contact Info

Product

Resources

About