Respiratory syncytial virus replication is prolonged by a concomitant allergic response

Abstract

SummaryEpidemiological studies show an association between early exposure to respiratory syncytial virus (RSV) and the development or exacerbation of asthma. This idea is supported by studies in mice that demonstrate worsened airway hyper-reactivity (AHR) when RSV-infected animals are exposed to allergen. The effect of allergen on RSV disease, however, has not been reported. Cotton rats (Sigmodon hispidus) that have been used as a model to study RSV pathogenesis were sensitized to extracts of Aspergillus fumigatus (Af ), a common household mould. The allergic response to Af included eosinophilia, formation of granulomas and induction of Th2 type cytokines. RSV infection prior to allergen challenge resulted in exacerbation of the inflammatory response as well as increased airway responsiveness to methacholine. The exacerbated response was indeed dependent on virus replication. Virus replication in turn was influenced by the allergic response, with persistence in the noses for 2 days longer in animals challenged with allergen. This diminished clearance corresponded to decreased induction of mRNA for IFN-g, a Th1-type cytokine that is characteristic of viral infection. Treatment of RSV-infected Af-challenged animals with recombinant IFN-g reduced the allergic inflammatory response as well as the relative levels of Th1 and Th2 cytokine mRNA. However, this treatment did not reduce airway reactivity, showing that these pathologic and physiologic measures of exacerbated disease are independent. We speculate that the reciprocal effect of the allergic response on viral immunity may benefit the host by limiting exacerbation of physiologic responses that are IFN-g-dependent.

Viral Disruption of Olfactory Progenitors Is Exacerbated in Allergic Mice

“…However, there have been contradictory reports on the effects of allergy on the interferon gamma response (IFNγ). Although IFNγ responses were suppressed in a rat allergy model induced by Aspergillus fumigatus [25,26], no changes in IFNγ levels were observed in a mouse allergy model induced by CRA [25,26]. This discrepancy might be due to a difference in the antigens used to induce allergy or viruses and host species.…”

Defective innate immune responses to respiratory syncytial virus infection in ovalbumin-sensitized mice

“…Hassantoufighi et al 16 had also shown prolonged viral clearance in Aspergillus-sensitized cotton rats after low-dosage RSV infection (10 4.5 pfu/animal), 16 which was speculated to be related to inhibited IFN-g expression. Although our study showed decreased IFN-g in both the OVA þ RSV and OVA þ hMPV groups, no difference was observed in the viral titer between the OVA þ hMPV and hMPV groups.…”

“…15 However, Peebles and colleagues concluded differently; they showed that deteriorated AHR of allergic mice during viral infection was not associated with a type 2 cytokine response. 16 Currently, most of our knowledge regarding the mechanism of viral asthma exacerbation is derived from the study of rhinovirus infection. Reports showed several proinflammatory mediators, including IL-1b, IL-6, IL-8, RANTES, and eotaxin, to be related with rhinovirus-induced asthma exacerbation.…”

Effect of Th1/Th2 Cytokine Pretreatment on RSV-Induced Gene Expression in Airway Epithelial Cells

“…There is convincing evidence that the induction of antiviral proteins, including IFIT1 and Mx1, prior to RSV infection may suppress virus replication early on [46,47,48]. RSV replication is prolonged by a concomitant allergic response in cotton rats [49]. Therefore, in contrast to the Th1-predisposed hosts, it is possible to assume that the Th2-predisposed hosts prior to RSV infection could result in delayed RSV clearance, persistently leading to an increased inflammatory response by promoting viral replication and resulting in more severe illness.…”