Adenovirus replication and host innate response in primary human airway epithelial cells

Abstract

Background: Adenovirus infections are very common in children and sometimes fatal. Immune responses and hypercytokinemia are related to disease severity in patients with adenovirus infection. Understanding of viral replication and immune responses could help elucidate the immunopathogenesis of severe adenovirus infections. Methods: Polarized human airway epithelial cells (hAECs) were set up to mimic human airway, and we conducted high (1 the multiplicity of infection, MOI) and low dosage (0.5 MOI) of wild-type adenovirus serotype 3 infection in hAECs from both apical (AP) and basolateral (BL) compartments, compared the viral replication kinetics and measured 25 cytokine and 9 chemokine levels by multiplex immunoassay to evaluate the host immune response. Results: Virus titer was the highest in the apical compartment in low dose apical infection. BL infection showed a relative steady viral titer in different doses and infection sites. Responses of several cytokines such as IL-1RA, IL-21 and all of the chemokines were found after adenovirus infection. Besides, the responses detected in the BL compartment were generally higher than those in the apical compartment, especially IL-1RA, IL-21, GM-CSF, GRO-α, SDF-1α and IL-8. Conclusion: During the infections of hAECs by adenovirus, higher viral replication was found in the apical compartment but cytokine and chemokine responses were higher in the basolateral compartment. This indicated viral entrance and replication occurred more in the apical part and major innate response took place in the basolateral part, which may make adenovirus infect human airway efficiently and cause different degree of severity. Keywords: Adenovirus, Human airway epithelial cells, Cytokine, Chemokine