Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats

Abstract

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.

Intranasal Administration of Antibody-Bound Respiratory Syncytial Virus Particles Efficiently Primes Virus-Specific Immune Responses in Mice

“…It has been shown in both laboratory animals Significance was calculated using a two-way ANOVA. *, P Ͻ 0.05; **, P Ͻ 0.01; ***, P Ͻ 0.001. and humans, that systemic antibodies do not completely prevent early viral replication steps and innate immune responses (34,35,40). This may be explained by inadequate serum titers and/or insufficient access of antibodies to the airway lumen.…”

“…Abortive replication in vivo can be monitored by comparing lung viral loads using the PFU assay and by the PCR detection technique and has been observed in animals treated prophylactically by virus neutralizing antibodies instilled systemically. Abortive replication still induces inflammatory immune responses via cytoplasmic recognition of genomic viral RNA and replication intermediates (35). Also, viral antigen expression might still occur.…”

The role of cytokines and chemokines in severe respiratory syncytial virus infection and subsequent asthma

“…RSV can induce high levels of type I IFNs immediately upon infection, but this burst was shortlived with a sharp decline in type I IFNs production as the infection progressed, while influenza virus can induce durative high levels of type I IFNs [35]. Pletneva et al [37] also reported that type I IFNs were activated by RSV infection in the lung relatively early and transitorily during infection. Previous study has suggested that RSV activated interferon regulatory factor 3 (IRF-3), which is a key inducers of IFN-b, efficiently early in infection but that continued activation was observed only in cells infected by the NS1/NS2 gene deletion mutants [38].…”

Systematic analysis of viral genes responsible for differential virulence between American and Australian West Nile virus strains

“…1 of each virus and analysing the accumulation of Mx1 mRNA by qRT-PCR. Mx1 is an IFN-stimulated gene that is commonly used to measure IFN signalling in response to infections (Hoenen et al, 2014;Holzinger et al, 2007;Pletneva et al, 2008). Mx1 expression values were normalized to the levels of viral RNA in order to account for variations in viral replication efficiency between the viruses.…”