Activity and regulation of alpha interferon in respiratory syncytial virus and human metapneumovirus experimental infections.
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause a similar spectrum of respiratory infections in humans. Classified within the Paramyxoviridae family, Pneumovirinae subfamily, RSV and hMPV present a significant degree of divergence in genome constellation, organization, and protein sequences. RSV has been reported to be a poor inducer of alpha/beta interferons (IFN-alpha/beta) and partially resistant to its antiviral activity. The nature of the innate immune response to hMPV is currently unknown. Herein, an experimental mouse model was used to investigate the interplay between RSV and hMPV infections and IFN-alpha in the airways. RSV-infected BALB/c mice treated intranasally with either poly-ICLC, a potent inducer of IFN-alpha, or directly with recombinant IFN-alpha showed significantly reduced lung viral titers, inflammation, and clinical disease than untreated controls. However, RSV was significantly less sensitive to the antiviral activity of IFN-alpha than hMPV. Similarly, when the ability to directly induce IFN-alpha production was assessed, RSV was clearly a weaker inducer of IFN-alpha than hMPV, as shown by both kinetics and the absolute amount of IFN-alpha secreted into the bronchoalveolar lavage. To further investigate the putative inhibitory effect of these viruses on IFN-alpha production, mice were infected for 48 h prior to treatment with poly-ICLC or a specific Toll-like receptor 9 ligand, CpG oligodeoxynucleotides. Strikingly, both poly-ICLC- and CpG-mediated IFN-alpha production was abrogated by either RSV or MPV infection. These results suggest that a complex interplay between virus-specific and host-mediated responses regulates IFN-alpha in the lung during infection by members of the Pneumovirinae family.
Guerrero-Plata
Antonieta
A
Department of Pediatrics, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0369, USA.
Baron
Samuel
S
Poast
Joyce S
JS
Adegboyega
Patrick A
PA
Casola
Antonella
A
Garofalo
Roberto P
RP
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002266:Carboxymethylcellulose Sodium / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D016898:Interferon-alpha / Q000096:biosynthesis / Q000627:therapeutic use*; D016899:Interferon-beta / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism; D029121:Metapneumovirus; D051379:Mice; D008807:Mice, Inbred BALB C; D018184:Paramyxoviridae Infections / Q000188:drug therapy* / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D011107:Polylysine / Q000031:analogs & derivatives / Q000494:pharmacology; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D011107:Polylysine; D016899:Interferon-beta; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C