Role of chemokine receptor 5 during respiratory syncytial virus infection

Lower respiratory tract disease caused by respiratory syncytial virus (RSV) is characterized by profound airway mucosa inflammation, both in infants with naturally acquired infection and in experimentally inoculated animal models. Chemokines are central regulatory molecules in inflammatory, immune and infectious processes of the lung. Previously we have shown that the depletion of MIP-1α/CCL3 reduces lung inflammation and chemokine expression in RSV-infected lung tissue. In this study, we demonstrate that depletion of CCR5 as a receptor for MIP-1α results in upregulation of chemokines and cytokines in RSV-infected lung tissue but had no influence on viral clearance or histopathology compared with the wild type animals. Genetically altered mice with additional deletion of the MIP-1α/CCL3 gene demonstrated an upregulation in the chemokine mRNA expression paralleled by comparable cytokine expression following RSV infection, compared with wild type mice. There was no difference in lung inflammation or viral clearance. Pathology scores were only reduced in mice depleted for MIP-1α/CCL3. These results provide some evidence that the pattern of chemokine expressed in lung tissue determines the severity of lung inflammation during RSV infection.