Usutu virus growth in human cell lines: induction of and sensitivity to type I and III interferons.

The mechanisms of Usutu virus (USUV) pathogenesis are largely unknown. The aim of this study was to evaluate the sensitivity of USUV to interferon (IFN) and the capacity of USUV to stimulate IFN production. Initial experiments were conducted to characterize the susceptibility of human cell lines to USUV infection and to evaluate the single-growth cycle replication curve of USUV. Results indicate that USUV is able to infect a variety of human cell lines, completing the replication cycle in Hep-2 and Vero cells within 48 h. Pre-treatment of cells with types I and III IFNs significantly inhibited the replication of USUV. However, the inhibitory effects of IFNs were considerably less if IFN was added after viral infection had been initiated. Also, USUV weakly induced types I and III IFNs.

Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients.

BACKGROUND: Increased synthesis of neopterin and degradation of tryptophan to kynurenine, measured as kynurenine/tryptophan ratio (kyn/trp ratio), are considered in vitro markers of interferon beta-1a (IFNß-1a) activity. The aim of the study was to investigate the dynamic profile of neopterin and kyn/trp ratio in patients with relapsing remitting multiple sclerosis (RRMS) treated with two different doses of IFNß-1a over a period of 24 months. METHODS: RRMS patients (n = 101) received open-label IFNß-1a 22 mcg (low dose, LD) or 44 mcg (high dose, HD) subcutaneously (sc), three times weekly for 24 months. Serum measurements of neopterin, kyn/trp ratio and neutralizing antibodies (NAbs) were obtained before treatment (i.e., at baseline) and 48 hours post-injection every 3 months thereafter. Clinical assessments were performed at baseline and every 6 months. Changes in biomarkers over time were compared between LD- and HD-group as well as between patients with/without relapses and with/without NAbs using Analysis of Variance and Mann-Whitney tests. RESULTS: Neopterin (p < 0.001) and kyn/trp ratio (p = 0.0013) values increased over time vs baseline in both treatment groups. Neopterin values were higher (p = 0.046) in the HD-compared to the LD-group at every time point with the exclusion of months 21 and 24 of therapy. Conversely, there were no differences between the two doses groups in the kyn/trp ratio with the exclusion of month 6 of therapy (p < 0.05). Neopterin levels were significantly reduced in NAb-positive patients starting from month 9 of therapy (p < 0.05); the same result was observed for kyn/trp ratio but only at month 9 (p = 0.02). Clinical status did not significantly affect neopterin production and tryptophan degradation. CONCLUSIONS: Although differences in serum markers concentration were found following IFNß administration the clinical relevance of these findings needs to be confirmed with more detailed studies.

Pandemic 2009 H1N1 influenza virus is resistant to the antiviral activity of several interferon alpha subtypes.

Interferons (IFNs) are critically important in the control of influenza A virus infections. To better understand the pathogenic characteristics of the pandemic 2009 H1N1 influenza virus (pH1N1) from an innate immunity viewpoint, we investigated whether in vitro pH1N1 is sensitive to the antiviral activity of IFN beta, leukocyte IFN alpha, and several IFN alpha subtypes in a human lung adenocarcinoma epithelial cell line under single-growth cycle conditions. The results showed that 50% inhibitory concentration values against pH1N1 for various type I IFN preparations were higher than those against the IFN-sensitive encephalomyocarditis virus. Leukocyte IFN alpha and IFN alpha 5, 7, 8, 10, 14, 17, and 21 subtypes also appeared to be less active against pH1N1 than the Puerto Rico/8/34 H1N1 human influenza strain A. Taken together, the results provide new insights into the contributions of the various IFN alpha subtypes toward the regulation of innate immunity against pH1N1.