Cooperative anti-influenza activities of respiratory innate immune proteins and neuraminidase inhibitor.
The surfactant collectins, surfactant proteins A and D (SP-A and D), and scavenger receptor-rich glycoprotein 340 (gp340) inhibit influenza A virus (IAV) in the following order of potency: SP-D>gp340>SP-A. SP-D binds in a calcium-dependent manner to carbohydrate attachments on the viral hemagglutinin (HA) and neuraminidase (NA). By contrast, gp340 and SP-A act like mucins in that they provide sialic acid ligands that bind to the viral HA. In this study, SP-D, SP-A, and gp340 showed cooperative antiviral interactions. These cooperative effects were most evident in viral aggregation but were also observed in at least some hemagglutination inhibition and viral neutralization assays. The mechanism of binding between gp340 and SP-D was further characterized using monoclonal antibodies. Although gp340 can bind to SP-D at a site distinct from the mannan-binding site, binding of gp340 to SP-D did not contribute to cooperative antiviral interactions. SP-D and mucin showed cooperative interactions, apparently dependent on NA inhibition by SP-D. The commercial NA inhibitor oseltamivir had a similar effect and also enhanced the neutralizing activity of SP-A and bronchoalveolar lavage fluid. Hence, oseltamivir collaborates with innate immune proteins in inhibiting the initial infection of epithelial cells.
White
Mitchell R
MR
Department of Medicine, Section of Hematology/Oncology, Boston University, School of Medicine, Boston, MA 02118, USA.
Crouch
Erika
E
van Eijk
Martin
M
Hartshorn
Max
M
Pemberton
Lily
L
Tornoe
Ida
I
Holmskov
Uffe
U
Hartshorn
Kevan L
KL
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D016466:CHO Cells; D002642:Chick Embryo; D002645:Chickens; D006224:Cricetinae; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology*; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology*; D009077:Mucins / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology* / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism
D000081:Acetamides; D000998:Antiviral Agents; D006388:Hemagglutinins; D009077:Mucins; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011971:Receptors, Immunologic; C116303:glycoprotein 340; D053139:Oseltamivir; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid