TY - JOUR
T1 - Human adenovirus modulates surfactant phospholipid trafficking
AU - Miakotina, Olga L.
AU - McCoy, Diann M.
AU - Shi, Lei
AU - Look, Dwight C.
AU - Mallampalli, Rama K.
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
KW - Epithelia
KW - Export
KW - Phospholipid
KW - Surfactant
KW - Virus
UR - http://www.scopus.com/inward/record.url?scp=35949003560&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0854.2007.00641.x
DO - 10.1111/j.1600-0854.2007.00641.x
M3 - Article
C2 - 17897321
AN - SCOPUS:35949003560
SN - 1398-9219
VL - 8
SP - 1765
EP - 1777
JO - Traffic
JF - Traffic
IS - 12
ER -