Abstract
Human Metapneumovirus (HMPV) is a leading respiratory pathogen that causes lower respiratory tract infections worldwide. Acute HMPV infection induces an exacerbated inflammatory neutrophilic response leading to bronchiolitis and pneumonia. However, the mechanism by which the virus regulates neutrophil infiltration into the airways still remains unexplored. In this work, we used an experimental mouse model of HMPV infection to demonstrate that the attachment (G) protein of HMPV contributes to the recruitment of neutrophils into the airways and modulate the production of neutrophil chemoattractants and Type I IFN responses, specifically IFN-α. These findings provide the first evidence that the HMPV G protein contributes to the in vivo neutrophilic response to HMPV infection and furthers our understanding on virus induced inflammatory responses in the airways.
Highlights
Human metapneumovirus (HMPV) is a single negative-stranded RNA, enveloped virus classified in the Paramyxoviridae family
In order to determine the effect of the HMPV G protein in the IFN response in vivo, BALB/c mice were infected with rHMPV, rHMPV-∆G or mock infected
We observed that mice infected with rHMPV-∆G induced a 1.3-fold increase in the production of IFN-α as compared to full-length rHMPV infected mice
Summary
Human metapneumovirus (HMPV) is a single negative-stranded RNA, enveloped virus classified in the Paramyxoviridae family. HMPV was first identified in 2001 from nasopharyngeal aspirates of hospitalized infants [2], and has soon emerged to be a leading respiratory pathogen worldwide infecting infants, elders, and immunocompromized individuals [3]. HMPV is responsible for 5 to 15% of pediatric hospitalizations for respiratory tract infections [4,5,6,7]. It is second only to Respiratory Syncytial virus (RSV) infection in infants admitted with lower respiratory tract viral infections causing mortality and morbidity [4,8,9,10]. In elderly adults aged ≥65 years old, HMPV accounts for about 4.1% hospitalizations with respiratory tract infections, impacting more severely those subjects with underlying conditions, such as cardiovascular diseases, organ transplantation, or other hematologic malignancies [11,12,13,14]. One hallmark of HMPV infection is that it is characterized by aggravated inflammatory responses leading to bronchiolitis and pneumonia [8]
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