Reovirus triggers cell type-specific proinflammatory responses dependent on the autocrine action of IFN-beta

Resident cells of the respiratory and gastrointestinal tracts, including ep ithelial and fibroblast cells, are the initial sites of entry for many vira l pathogens. We investigated the role that these cells play in the inflamma tory process in response to infection with reovirus 1/L. In A549 human bron chial or HT-29 human colonic epithelial cells, interferon (IFN)-beta, regul ated on activation T cell expressed and secreted (RANTES), IFN-gamma -induc ible protein (IP)-10, and interleukin-8 were upregulated regardless of whet her cells were infected with replication-competent or replication-deficient reovirus 1/L. However, in CCD-34Lu human lung fibroblast cells, IFN-beta, IP-10, and RANTES were expressed only after infection with replication-comp etent reovirus 1/L. Expression of interleukin-8 in CCD-34Lu fibroblast cell s was viral replication independent. This differential expression of IFN-be ta, RANTES, and IP-10 was shown to be due to the lack of induction of IFN r egulatory factor-1 and -2 in CCD-34Lu fibroblast cells treated with replica tion-deficient reovirus 1/L. We have shown that cytokine and/or chemokine e xpression may not be dependent on viral replication. Therefore, treatment o f viral infections with inhibitors of replication may not effectively allev iate inflammatory mediators because most viral infections result in the gen eration of replication-competent and replication-deficient virions in vivo.