title: Respiratory syncytial virus strain A2 is resistant to the antiviral effects of type I interferons and human MxA.
abstract: Respiratory syncytial virus (RSV) belongs to Paramyxoviridae family of enveloped negative-strand RNA viruses and causes severe bronchiolitis and pneumonia in children younger than 2 years of age. As members of Paramyxoviridae family, RSV and parainfluenza type 3 (PIV3) have similar modes of infection and replication. A variety of negative-strand RNA virus infections, including that of PIV3, are inhibited by human MxA protein, a type I interferon (IFN)-inducible GTPase. We tested whether the MxA protein, induced either by type I human IFNs or by stable transfection of human MxA gene in human (U-87) or simian (Vero) cells, confers resistance to these cells against infection by RSV strain A2. RSV infection was resistant to antiviral effects induced by 0-10,000 U/ml type I IFNs (IFN-alpha or -beta) in both human lung epithelial, A549, and fibroblast, MRC-5 cells. RSV virus yield was reduced only by 10- to 20-fold, and viral protein synthesis was not significantly affected under conditions of IFN treatment where PIV3 yield was reduced by 1000- to 10,000-fold. Human or simian cell lines constitutively expressing MxA were protected against infection by PIV3 but not by RSV. Our results indicate that RSV A2 is resistant to the antiviral effects of MxA, even though RSV and PIV3 have similar replication strategies. In IFN-treated coinfected cultures, IFN-resistant RSV A2 did not prevent the IFN-mediated inhibition of PIV3 multiplication. Hence the resistance of RSV A2 to type I IFNs does not appear to be due to soluble factors released into the medium or a disruption in the cellular antiviral machinery brought about by RSV A2 infection.
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, HFM-445, Bethesda, Maryland 20892, USA. atreyap@cber.fda.gov
authors.forename: P L
authors.initials: PL
authors.lastname: Atreya
authors.forename: S
authors.initials: S
authors.lastname: Kulkarni
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics* / Q000494:pharmacology; D016899:Interferon-beta / Q000235:genetics* / Q000494:pharmacology; D064547:Myxovirus Resistance Proteins; D011506:Proteins / Q000235:genetics*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D016899:Interferon-beta; D019204:GTP-Binding Proteins