Human Adenovirus Modulates Surfactant Phospholipid Trafficking

Surfactant, highly enriched with phosphatidylcholine (PC), is secreted into the airspace by a classic apical secretory route, thereby maintaining lung stability. Herein, we show that adenoviral infection decreases surfactant PC in lungs by inhibiting its apical secretion and redirecting its export i...

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Bibliographic Details
Published in:Traffic (Copenhagen, Denmark) Denmark), 2007-12, Vol.8 (12), p.1765-1777
Main Authors: Miakotina, Olga L, McCoy, Diann M, Shi, Lei, Look, Dwight C, Mallampalli, Rama K
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - chemistry
Adenoviridae - metabolism
Adenovirus
Animals
ATP Binding Cassette Transporter 1
ATP-Binding Cassette Transporters - metabolism
Cell Line
Dose-Response Relationship, Drug
epithelia
Epithelial Cells - metabolism
export
exports
Fibroblasts - metabolism
Gene Expression Regulation
Human adenovirus
Humans
Mice
Mice, Inbred C57BL
Models, Biological
phospholipid
Phospholipids - chemistry
Surface-Active Agents - metabolism
surfactant
Time Factors
Up-Regulation
virus
viruses
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Summary:Surfactant, highly enriched with phosphatidylcholine (PC), is secreted into the airspace by a classic apical secretory route, thereby maintaining lung stability. Herein, we show that adenoviral infection decreases surfactant PC in lungs by inhibiting its apical secretion and redirecting its export in alveolar cells by a basolateral route. These effects were not observed with replication-deficient adenovirus (Ad), specifically lacking early region 1 (E1) gene products. Adenoviral stimulation of basolateral PC export from cells was not observed after pharmacologic inhibition of ATP-binding cassette proteins, after introduction of small interfering RNA to the lipid pump ATP-binding cassette transporter A1 (ABCA1) or in ABCA1-defective human Tangier disease fibroblasts. Adenovirus and its E1A gene product increased ABCA1 levels by transcriptionally activating the ABCA1 gene. Thus, Ad lowers surfactant, in part, by triggering ABCA1-directed basolateral PC export, thereby limiting the cellular pool of surfactant PC destined for apical secretion. The results support a novel pathway, whereby a viral pathogen disrupts surfactant trafficking.
ISSN:1398-9219
1600-0854
DOI:10.1111/j.1600-0854.2007.00641.x