Surfactant protein A binding to cytomegalovirus proteins enhances virus entry into rat lung cells.
The role of surfactant protein (SP)-A in cytomegalovirus (CMV) infection of the lung was investigated. We found that SP-A binds to various immobilized human CMV proteins and those exposed on the surface of infected embryonal lung fibroblasts. The interaction between SP-A and immobilized CMV proteins was found to be calcium-dependent and inhibited by mannan, suggesting involvement of the carbohydrate recognition domain of SP-A and high-mannose carbohydrate residues of viral envelope glycoproteins. Using flow cytometry and confocal laser fluorescence microscopy in the rat model we showed that preincubation of rat CMV with SP-A stimulates its binding and internalization by rat type II pneumocytes and alveolar tissue macrophages. This effect was concentration- and Ca(2+)-dependent but was not inhibited by mannan. Therefore, the domains of SP-A involved in SP-A CMV interaction and in interaction of the SP-A/virus complex with rat lung cells are distinct. Additionally, in the human CMV model, sheep as well as human proteinosis SP-A did not significantly affect human CMV replication in embryonal lung fibroblasts. Thus, SP-A may contribute to CMV-associated pathology of the lung by increasing the efficiency of target cell infection.
Weyer
C
C
Departments of Virology, Medical Immunology, and Neonatology, Humboldt University, Medical School (Charité), Berlin, Germany.
Sabat
R
R
Wissel
H
H
Krüger
D H
DH
Stevens
P A
PA
Prösch
S
S
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000821:virology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008297:Male; D008351:Mannans / Q000378:metabolism / Q000494:pharmacology; D018613:Microscopy, Confocal; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011649:Pulmonary Alveolar Proteinosis / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D008351:Mannans; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D014759:Viral Envelope Proteins; D016650:Fluorescein-5-isothiocyanate; D002118:Calcium