Gene expression differences in lungs of mice during secondary immune responses to respiratory syncytial virus infection

Annemieke Schuurhof, Louis Bont, Jeroen L.A. Pennings, Hennie M. Hodemaekers, Piet W. Wester, Annemarie Buisman, Lia C.G.H. De Rond, Myra N. Widjojoatmodjo, Willem Luytjes, Jan L.L. Kimpen, Riny Janssen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

16 Citaten (Scopus)

Samenvatting

Vaccine-induced immunity has been shown to alter the course of a respiratory syncytial virus (RSV) infection both in murine models and in humans. To elucidate which mechanisms underlie the effect of vaccine-induced immunity on the course of RSV infection, transcription profiles in the lungs of RSV-infected mice were examined by microarray analysis. Three models were used: RSV reinfection as a model for natural immunity, RSV challenge after formalin-inactivated RSV vaccination as a model for vaccine-enhanced disease, and RSV challenge following vaccination with recombinant RSV virus lacking the G gene (ΔG-RSV) as a model for vaccine-induced immunity. Gene transcription profiles, histopathology, and viral loads were analyzed at 1, 2, and 5 days after RSV challenge. On the first 2 days after challenge, all mice displayed an expression pattern in the lung similar of that found in primary infection, showing a strong innate immune response. On day 5 after RSV reinfection or after challenge following ΔG-RSV vaccination, the innate immune response was waning. In contrast, in mice with vaccine-enhanced disease, the innate immune response 5 days after RSV challenge was still present even though viral replication was diminished. In addition, only in this group was Th2 gene expression induced. These findings support a hypothesis that vaccine-enhanced disease is mediated by prolonged innate immune responses and Th2 polarization in the absence of viral replication.

Originele taal-2Engels
Pagina's (van-tot)9584-9594
Aantal pagina's11
TijdschriftJournal of Virology
Volume84
Nummer van het tijdschrift18
DOI's
StatusGepubliceerd - sep. 2010
Extern gepubliceerdJa

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