Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats.
Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis in young children. In general, RSV is considered to be a poor inducer of type I (alpha/beta) interferons (IFNs). Measurement of active type I IFN production during infection in vivo is demanding, as multiple IFN subtypes with overlapping activities are produced. In contrast, Mx gene expression, which is tightly regulated by type I IFN expression, is easily determined. This study therefore measured Mx expression as a reliable surrogate marker of type I IFN activity during RSV infection in vivo in a cotton rat model. It was shown that expression of Mx genes was dramatically augmented in the lungs of infected animals in a dose- and virus strain-dependent manner. The expression of Mx genes in the lungs was paralleled by their induction in the nose and spleen, although in spleen no simultaneous virus gene expression was detected. Reinfection of RSV-immune animals leads to abortive virus replication in the lungs. Thus, type I IFN and Mx gene expression was triggered in reinfected animals, even though virus could not be isolated from their lungs. Furthermore, it was demonstrated that immunity to RSV wanes with time. Virus replication and Mx gene expression became more prominent with increasing intervals between primary infection and reinfection. These results highlight the role of type I IFN in modulation of the immune response to RSV.
Pletneva
Lioubov M
LM
Virion Systems Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, USA.
Haller
Otto
O
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany.
Porter
David D
DD
Virion Systems Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, USA.
Prince
Gregory A
GA
Virion Systems Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, USA.
Blanco
Jorge C G
JCG
Virion Systems Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, USA.
D000818:Animals; D019204:GTP-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D007370:Interferon Type I / Q000096:biosynthesis*; D008168:Lung / Q000503:physiopathology / Q000821:virology; D064547:Myxovirus Resistance Proteins; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics; D012008:Recurrence; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000503:physiopathology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016205:Sigmodontinae; D014779:Virus Replication
D007370:Interferon Type I; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D019204:GTP-Binding Proteins