Respiratory Syncytial Virus Infection in Human Bone Marrow Stromal Cells

Abstract

Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children. The pathophysiology of this infection in the respiratory system has been studied extensively, but little is known about its consequences in other systems. We studied whether RSV infects human bone marrow stromal cells (BMSCs) in vitro and in vivo, and investigated whether and how this infection affects BMSC structure and hematopoietic support function. Primary human BMSCs were infected in vitro with recombinant RSV expressing green fluorescent protein. In addition, RNA from naive BMSCs was amplified by PCR, and the products were sequenced to confirm homology with the RSV genome. The BMSC cytoskeleton was visualized by immunostaining for actin. Finally, we analyzed infected BMSCs for the expression of multiple cytokines and chemokines, evaluated their hematopoietic support capacity, and measured their chemotactic activity for both lymphoid and myeloid cells. We found that BMSCs support RSV replication in vitro with efficiency that varies among cell lines derived from different donors; furthermore, RNA sequences homologous to the RSV genome were found in naive primary human BMSCs. RSV infection disrupted cytoskeletal actin microfilaments, altered cytokine/chemokine expression patterns, decreased the ability of BMSCs to support B cell maturation, and modulated local chemotaxis. Our data indicate that RSV infects human BMSCs in vitro, and this infection has important structural and functional consequences that might affect hematopoietic and immune functions. Furthermore, we have amplified viral RNA from naive primary BMSCs, suggesting that in vivo these cells provide RSV with an extrapulmonary target.

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

“…We will review the evidence that supports a causal relationship between infection with infant RSV and RV and asthma, asking the following questions (Table 1): (1) Does (77,116,118) Precedent allergen sensitization (77) Male sex (77) Genetic polymorphisms (17) White race (77) Seasonality of birth (118,120) Genetic polymorphisms commonly in immune response genes (1, 9) Host genetic and viral genetic determinants of disease risk and severity 1 Host: Several genes are associated with both RSV infection and asthma, suggesting a genetic susceptibility to both (1, 9, 10).…”

“…Altering the host immune response could be another potential early-life intervention preventing morbidity from early-life infection as well as recurrent wheezing and virally induced asthma exacerbations. Finally, because RV is most strongly associated with asthma exacerbations in children, continued efforts to advance our understanding of the altered immune response to viruses across the entire age continuum in patients with asthma and in atopic patients will aide in secondary prevention strategies and will likely provide insights into infant host susceptibility (118). n Author disclosures are available with the text of this article at www.atsjournals.org.…”

Sustained Protein Kinase D Activation Mediates Respiratory Syncytial Virus-Induced Airway Barrier Disruption

“…Polarized human airway epithelial cells were infected apically with RSV derived from RSV strain A2 (a kind gift from Edward E. Walsh, University of Rochester, Rochester, NY). In some experiments, we used rgRSV (RSV derived from RSV A2 expressing the green fluorescent protein gene), a kind gift from Mark Peeples (Nationwide Children's Hospital Research Institute, Columbus, OH) and Peter Collins (National Institutes of Health, Bethesda, MD), as described previously (16,17). UV-inactivated RSV (UV-RSV) was used as a negative control.…”

RSV-Related Thrombocytopenia Associated with Transient Cytogenetic Abnormalities in a Recipient of Umbilical Cord Blood Transplantation

“…Recent data suggest that RSV might infect bone marrow stromal cells [6] which might provide the right milieu for such transient cytogenetic changes to occur. Alternatively, thrombocytopenia and cytogenetic abnormalities might have occurred independently.…”