A role for airway remodeling during respiratory syncytial virus infection

BACKGROUND: Severe respiratory syncytial virus infection (RSV) during infancy has been shown to be a major risk factor for the development of subsequent wheeze. However, the reasons for this link remain unclear. The objective of this research was to determine the consequences of early exposure to RSV and allergen in the development of subsequent airway hyperreactivity (AHR) using a developmental time point in the mouse that parallels that of the human neonate. METHODS: Weanling mice were sensitized and challenged with ovalbumin (Ova) and/or infected with RSV. Eight days after the last allergen challenge, various pathophysiological endpoints were examined. RESULTS: AHR in response to methacholine was enhanced only in weanling mice exposed to Ova and subsequently infected with RSV. The increase in AHR appeared to be unrelated to pulmonary RSV titer. Total bronchoalveolar lavage cellularity in these mice increased approximately two-fold relative to Ova alone and was attributable to increases in eosinophil and lymphocyte numbers. Enhanced pulmonary pathologies including persistent mucus production and subepithelial fibrosis were observed. Interestingly, these data correlated with transient increases in TNF-α, IFN-γ, IL-5, and IL-2. CONCLUSION: The observed changes in pulmonary structure may provide an explanation for epidemiological data suggesting that early exposure to allergens and RSV have long-term physiological consequences. Furthermore, the data presented here highlight the importance of preventative strategies against RSV infection of atopic individuals during neonatal development

Isolation and characterization of Nylanderia fulva virus 1, a positive-sense, single-stranded RNA virus infecting the tawny crazy ant, Nylanderia fulva.

We report the discovery of Nylanderia fulva virus 1 (NfV-1), the first virus identified and characterized from the ant, Nylanderia fulva. The NfV-1 genome (GenBank accession KX024775) is 10,881 nucleotides in length, encoding one large open reading frame (ORF). Helicase, protease, RNA-dependent RNA polymerase, and jelly-roll capsid protein domains were recognized within the polyprotein. Phylogenetic analysis placed NfV-1 in an unclassified clade of viruses. Electron microscopic examination of negatively stained samples revealed particles with icosahedral symmetry with a diameter of 28.7±1.1nm. The virus was detected by RT-PCR in larval, pupal, worker and queen developmental stages. However, the replicative strand of NfV-1 was only detected in larvae. Vertical transmission did not appear to occur, but horizontal transmission was facile. The inter-colonial field prevalence of NfV-1 was 52±35% with some local infections reaching 100%. NfV-1 was not detected in limited samples of other Nylanderia species or closely related ant species.JSL was supported by the National Science Foundation under Grant DEB-0743542. AEF is supported by the Wellcome Trust (Grant no. [106207]) and the European Research Council (ERC) under the European Union׳s Horizon 2020 research and innovation programme (Grant agreement no. [646891]).This is the final version of the article. It first appeared from Elsevier at https://doi.org/10.1016/j.virol.2016.06.014

Immunomodulation with IL-4Rα antisense oligonucleotide prevents respiratory syncytial virus-mediated pulmonary disease

Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Severe RSV infections in infants cause bronchiolitis, wheeze, and/or cough and significantly increase the risk for developing asthma. RSV pathogenesis is thought to be due to a Th2-type immune response initiated in response to RSV infection, specifically in the infant. Using a neonatal mouse system as an appropriate model for human infants, we sought to determine whether local inhibition of IL-4Rα expression during primary RSV infection in the neonate would prevent Th2-skewed responses to secondary RSV infection and improve longterm pulmonary function. To reduce IL-4Rα expression, antisense oligonucleotides (ASOs) specific for IL-4Rα were administered intranasally to neonatal mice at the time of primary infection. Mice were initially infected with RSV at 1 wk of age and were reinfected at 6 wk of age. Administration of IL-4Rα ASOs during primary RSV infection in neonatal mice abolished the pulmonary dysfunction normally observed following reinfection in the adult. This ablation of pulmonary dysfunction correlated with a persistent rebalancing of the Th cell compartment with decreased Th2 responses (i.e., reduced goblet cell hyperplasia, Th2 cells, and cytokine secretion) and increased Th1 responses (i.e., elevated Th1 cell numbers and type I Abs and cytokines). Our data support our hypothesis that a reduction in the Th2 immune response during primary infection in neonates prevents Th2-mediated pulmonary pathology initially and upon reinfection and further suggest that vaccine strategies incorporating IL-4Rα ASOs may be of significant benefit to infants. Copyright © 2010 by The American Association of Immunologists, Inc

Pathogenic Role of Epstein–Barr Virus in Lung Cancers

Human oncogenic viruses account for at least 12% of total cancer cases worldwide. Epstein–Barr virus (EBV) is the first identified human oncogenic virus and it alone causes ~200,000 cancer cases and ~1.8% of total cancer-related death annually. Over the past 40 years, increasing lines of evidence have supported a causal link between EBV infection and a subgroup of lung cancers (LCs). In this article, we review the current understanding of the EBV-LC association and the etiological role of EBV in lung carcinogenesis. We also discuss the clinical impact of the knowledge gained from previous research, challenges, and future directions in this field. Given the high clinical relevance of EBV-LC association, there is an urgent need for further investigation on this topic

A role for airway remodeling during respiratory syncytial virus infection

Abstract Background Severe respiratory syncytial virus infection (RSV) during infancy has been shown to be a major risk factor for the development of subsequent wheeze. However, the reasons for this link remain unclear. The objective of this research was to determine the consequences of early exposure to RSV and allergen in the development of subsequent airway hyperreactivity (AHR) using a developmental time point in the mouse that parallels that of the human neonate. Methods Weanling mice were sensitized and challenged with ovalbumin (Ova) and/or infected with RSV. Eight days after the last allergen challenge, various pathophysiological endpoints were examined. Results AHR in response to methacholine was enhanced only in weanling mice exposed to Ova and subsequently infected with RSV. The increase in AHR appeared to be unrelated to pulmonary RSV titer. Total bronchoalveolar lavage cellularity in these mice increased approximately two-fold relative to Ova alone and was attributable to increases in eosinophil and lymphocyte numbers. Enhanced pulmonary pathologies including persistent mucus production and subepithelial fibrosis were observed. Interestingly, these data correlated with transient increases in TNF-α, IFN-γ, IL-5, and IL-2. Conclusion The observed changes in pulmonary structure may provide an explanation for epidemiological data suggesting that early exposure to allergens and RSV have long-term physiological consequences. Furthermore, the data presented here highlight the importance of preventative strategies against RSV infection of atopic individuals during neonatal development.</p

\u3ci\u3eEupatorium capillifolium\u3c/i\u3e Essential Oil: Chemical Composition, Antifungal Activity, and Insecticidal Activity

Natural plant extracts often contain compounds that are useful in pest management applications. The essential oil of Eupatorium capillifolium (dog-fennel) was investigated for antifungal and insecticidal activities. Essential oil obtained by hydrodistillation of aerial parts was analyzed by gas chromatography (GC) and gas chromatography–mass spectrometry (GC/MS). The major components were determined to be thymol methyl ether (=methyl thymol) (36.3%), 2,5-dimethoxy-p-cymene (20.8%) and myrcene (15.7%). Antifungal activity of the essential oil was weak against the plant pathogens Colletotrichum acutatum, C. fragariae, and C. gloeosporioides in direct bioautography assay. The E. capillifolium oil showed promising repellent activity against the yellow fever mosquito Aedes aegypti, whereas the oil exhibited moderate activity against the mosquito’s first instar larvae in a high throughput bioassay. Topical applications of the oil showed no activity against the blood-feeding female adults of A. aegypti. Eupatorium capillifolium essential oil showed a linear dose response between adult lace bug (Stephanitis pyrioides) mortality and increasing oil concentration in an adulticidal activity bioassay. The dog-fennel oil was more potent than the conventional insecticide malathion. In conclusion, these combined results showed Eupatorium capillifolium oil is a promising novel source of a biological insecticide with multiple modes of action