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Human Adenovirus Modulates Surfactant Phospholipid Trafficking
Author(s) -
Miakotina Olga L.,
Look Dwight C.,
Mallampalli Rama K.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a84-a
Subject(s) - abca1 , phospholipid , phosphatidylcholine , biology , pulmonary surfactant , microbiology and biotechnology , adenoviridae , chemistry , genetic enhancement , biochemistry , gene , membrane , transporter
Adenovirus targets alveolar epithelia and causes acute respiratory illness. We hypothesized that pulmonary infection with replication‐competent adenovirus impairs surfactant phospholipid metabolism. Adenoviral infection decreased levels of alveolar disaturated phosphatidylcholine (DSPC), the major surfactant phospholipid secreted apically into the alveolus by epithelia. Adenovirus did not alter phosphatidylcholine (PC) synthesis or degradation, but stimulated basolateral phospholipid efflux. These effects were not observed with replication‐deficient adenovirus. Adenoviral stimulation of basolateral PC efflux was inhibited using inhibitors of ATP‐binding cassette proteins and ABCA1 siRNA. The effects of adenovirus on efflux were attenuated in distal lung epithelia isolated from ABCA1 knockout mice and completely abolished in ABCA1‐defective human Tangier disease fibroblasts. Adenovirus increased ABCA1 mRNA and protein levels primarily via increased ABCA1 gene transcription. Like replication‐competent adenovirus, early region I (E1A) also transcriptionally activated the ABCA1 gene. Thus, adenovirus lowers surfactant, in part, by triggering ABCA1‐directed basolateral PC export, limiting the PC pool destined for alveolar secretion. The results support a novel pathway whereby a virus exploits surfactant trafficking. This study was supported by a Merit Review Award, Department of Veteran’s Affairs, The Cystic Fibrosis Foundation, and NIH Grants HL55584 and HL68135 (to RKM).