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Gammaherpesvirus infection modulates the temporal and spatial expression of SCGB1A1 (CCSP) and BPIFA1 (SPLUNC1) in the respiratory tract.

ABSTRACT: Murine ?-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an established model of ?-herpesvirus infection. We have previously developed an alternative system using a natural host, the wood mouse (Apodemus sylvaticus), and shown that the MHV-68 M3 chemokine-binding protein contributes significantly to MHV-68 pathogenesis. Here we demonstrate in A. sylvaticus using high-density micro-arrays that M3 influences the expression of genes involved in the host response including Scgb1a1 and Bpifa1 that encode potential innate defense proteins secreted into the respiratory tract. Further analysis of MHV-68-infected animals showed that the levels of both protein and RNA for SCGB1A1 and BPIFA1 were decreased at day 7 post infection (p.i.) but increased at day 14 p.i. as compared with M3-deficient and mock-infected animals. The modulation of expression was most pronounced in bronchioles but was also present in the bronchi and trachea. Double staining using RNA in situ hybridization and immunohistology demonstrated that much of the BPIFA1 expression occurs in club cells along with SCGB1A1 and that BPIFA1 is stored within granules in these cells. The increase in SCGB1A1 and BPIFA1 expression at day 14 p.i. was associated with the differentiation of club cells into mucus-secreting cells. Our data highlight the role of club cells and the potential of SCGB1A1 and BPIFA1 as innate defense mediators during respiratory virus infection.

SUBMITTER: Leeming GH

PROVIDER: S-EPMC4450743 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Gammaherpesvirus infection modulates the temporal and spatial expression of SCGB1A1 (CCSP) and BPIFA1 (SPLUNC1) in the respiratory tract.

Leeming Gail H GH Kipar Anja A Hughes David J DJ Bingle Lynne L Bennett Elaine E Moyo Nathifa A NA Tripp Ralph A RA Bigley Alison L AL Bingle Colin D CD Sample Jeffery T JT Stewart James P JP

Laboratory investigation; a journal of technical methods and pathology 20141222 6

Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an established model of γ-herpesvirus infection. We have previously developed an alternative system using a natural host, the wood mouse (Apodemus sylvaticus), and shown that the MHV-68 M3 chemokine-binding protein contributes significantly to MHV-68 pathogenesis. Here we demonstrate in A. sylvaticus using high-density micro-arrays that M3 influences the expression of genes involved in the host response includi ...[more]

PMID: 25531566

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Project description:BACKGROUND:Although nanoparticles and their hazardous effects on human health are well elucidated meanwhile, inhalation and distribution of these materials in the human respiratory tract still represent partly enigmatic phenomena. Main objective of the present study was the detailed description of a mathematical method, with the help of which spatial distributions of nanoparticles deposited in the tracheobronchial tree may be visualized appropriately. METHODS:The technique is founded on a stochastic model of the bronchial network, within which inhaled particles follow individual, randomly selected trajectories. The lengths of these random paths depend on the airway-specific deposition probabilities calculated for the particles and the duration of the breath cycle. Positions of the deposited material were determined by computation of the exact lengths of individual particle trajectories and the orientation of single path segments within a Cartesian coordinate system, where the z-direction corresponds with the trachea. For a better quantification of the particle distribution and its eventual comparison with experimental data particle coordinates were fitted into a voxel grid [1 voxel = (0.467 cm)(3)]. Particle deposition is chiefly controlled by diffusive processes, whereas deposition mechanisms associated with inertia or gravity play a subordinate role. RESULTS:Deposition patterns were visualized for particles with sizes of 1, 10, and 100 nm. As clearly demonstrated by the results obtained from the modeling procedure, under normal breathing conditions 1-nm particles tend to deposit in the upper airways, whilst 10- and 100-nm particles are preferably accumulated in the airways of the central and peripheral lung. The particle dose deposited in the extrathoracic and thoracic airways within one breath cycle significantly declines with increasing particle size. CONCLUSIONS:Based on the predictions presented in this study possible consequences of nanoparticle inhalation to the health of subjects increasingly exposed to these airborne materials were discussed.

Dataset Information

Gammaherpesvirus infection modulates the temporal and spatial expression of SCGB1A1 (CCSP) and BPIFA1 (SPLUNC1) in the respiratory tract.

Publications

Gammaherpesvirus infection modulates the temporal and spatial expression of SCGB1A1 (CCSP) and BPIFA1 (SPLUNC1) in the respiratory tract.

Similar Datasets

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