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-␣/␤) 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-␣ in the airways. RSV-infected BALB/c mice treated intranasally with either poly-ICLC, a potent inducer of IFN-␣, or directly with recombinant IFN-␣ 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-␣ than hMPV. Similarly, when the ability to directly induce IFN-␣ production was assessed, RSV was clearly a weaker inducer of IFN-␣ than hMPV, as shown by both kinetics and the absolute amount of IFN-␣ secreted into the bronchoalveolar lavage. To further investigate the putative inhibitory effect of these viruses on IFN-␣ 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-␣ 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-␣ in the lung during infection by members of the Pneumovirinae family.

A comlex of polyriboinosinic-polyribocytidylic acid (poly I-poly C) with poly-L-lysine and carboxymethylcellulose has been prepared. This complex is five to 10 times as resistant to hydrolysis by primate serum as the parent poly I-poly C. It has a thermal denaturation temperature about 40 C higher than that of poly I-poly C. The complex induces significant levels of serum interferon in monkeys and chimpanzees under conditions in which poly I-poly C itself induces no interferon.