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Background Upper respiratory tract infections (URTIs) are important triggers for asthma exacerbations. We hypothesized that inhalation of the anti‐viral cytokine, interferon (IFN)‐β, during URTI, could prevent these exacerbations. Objective To evaluate the efficacy of on‐demand inhaled IFN‐β1a (AZD9412) to prevent severe asthma exacerbations following symptomatic URTI. Methods This was a randomized, double‐blind, placebo‐controlled trial in which patients with severe asthma (GINA 4‐5; n = 121) reporting URTI symptoms were randomized to 14 days of once‐daily nebulized AZD9412 or placebo. The primary endpoint was severe exacerbations during treatment. Secondary endpoints included 6‐item asthma control questionnaire (ACQ‐6) and lung function. Exploratory biomarkers included IFN‐response markers in serum and sputum, blood leucocyte counts and serum inflammatory cytokines. Results Following a pre‐planned interim analysis, the trial was terminated early due to an unexpectedly low exacerbation rate. Asthma worsenings were generally mild and tended to peak at randomization, possibly contributing to the lack of benefit of AZD9412 on other asthma endpoints. Numerically, AZD9412 did not reduce severe exacerbation rate, ACQ‐6, asthma symptom scores or reliever medication use. AZD9412 improved lung function (morning peak expiratory flow; mPEF) by 19.7 L/min. Exploratory post hoc analyses indicated a greater mPEF improvement by AZD9412 in patients with high blood eosinophils (>0.3 × 109/L) at screening and low serum interleukin‐18 relative change at pre‐treatment baseline. Pharmacodynamic effect of AZD9412 was confirmed using IFN‐response markers. Conclusions & Clinical Relevance Colds did not have the impact on asthma patients that was expected and, due to the low exacerbation rate, the trial was stopped early. On‐demand AZD9412 treatment did not numerically reduce the number of exacerbations, but did attenuate URTI‐induced worsening of mPEF. Severe asthma patients with high blood eosinophils or low serum interleukin‐18 response are potential subgroups for further investigation of inhaled IFN‐β1a.

Viruses alter host cell processes to optimize their replication cycle. Human adenoviruses (Ad) encode proteins that promote viral macromolecular synthesis and counteract innate and adaptive responses to infection. The focus of this review is on how Ad evades innate cellular responses to infection, including an interferon (IFN) response and a DNA damage response (DDR). Ad blocks the IFN response by inhibiting cytoplasmic signaling pathways and the activation of IFN-stimulated genes (ISGs), as well as the functions of ISG products, such as PML. Ad also inhibits DDR sensors, for instance, the Mre11-Rad50-Nbs1 complex, and DDR effectors like DNA ligase IV. These innate cellular responses impact many different viruses, and studies on Ad have provided broad insight into these areas.

Objective Saffold virus (SAFV) classified in the species Theilovirus of the genus Cardiovirus is a novel human cardiovirus. The pathogenicity of SAFV in humans still remains unclear. Viruses in the genus Cardiovirus produce Leader protein, which is a small non-structural protein. Evidence that Leader protein of murine cardioviruses is a key factor in their biological activities has been provided. Therefore, the studies on the function of SAFV-L are likely to be important in order to clarify the pathogenicity of SAFV. Methods We investigated the interferon (IFN) response in the early stage of SAFV infection by reverse transcription polymerase chain reaction and the growth kinetics of the chimera virus, SAFL/DA. Results The study showed that SAFV-L suppresses the type I IFN response, and that the responsible region of anti-IFN activity of SAFV-L is a zincbinding motif. Furthermore, the anti-apoptotic activity of SAFV-L was suggested from the growth kinetics analysis of SAFL/DA. Conclusions The present study suggested that SAFV-L might be a multifunctional protein; for example, the suppression of IFN induction, antiapoptotic effect and/or productive virus growth. (Clin. Exp. Neuroimmunol. doi: 10.1111/cen3.12109, March 2014)

In order to elucidate the mechanisms of breast-feeding-induced resistance to respiratory syncytial virus (RSV) infection, groups of breast-fed and bottle-fed infants with this infection were tested at the onset of illness and then again 1 and 2 weeks later for the presence of interferon (IFN) as well as of virus-specific lymphocyte transformation (LTF) activity. Alpha-IFN was detected in nine out of ten breast-fed infants, while it was found in only 11 out of 21 bottle-fed subjects. The rate of the detection of IFN was significantly higher in the former group (P less than .05). Mean levels of IFN activity were also higher in breast-fed infants than in bottle-fed subjects during the course of the illness. It was noted, however, that previous breast feeding elicited little enhancing effect on the IFN response of infants with RSV infection. Combining the two feeding groups, suppressed LTF activity to RSV seemed to be related to a positive IFN response, although the association was not statistically significant. These observations suggest that breast feeding has unique mechanisms for modulating the immune response of infants with RSV infection.