Mechanisms of anti-influenza activity of surfactant proteins A and D: comparison with serum collectins

Abstract

The present study provides the first direct comparison of anti-influenza A virus (IAV) activities of the collectins surfactant protein (SP) A and SP-D, mannose-binding lectin (MBL), and conglutinin. SP-D, MBL, and conglutinin inhibited IAV hemagglutination activity with a greater potency than and by a distinct mechanism from SP-A. Although isolated trimeric SP-D carbohydrate recognition domains inhibited hemagglutination activity, preparations of SP-D also containing the collagen domain and NH2 terminus caused greater inhibition. In contrast to SP-A (or nonmultimerized SP-D), absence of the N-linked attachment did not effect interactions of multimerized SP-D with IAV. SP-D, SP-A, and conglutinin caused viral precipitation through formation of massive viral aggregates, whereas MBL formed aggregates of smaller size that did not precipitate. All of the collectins enhanced IAV binding to neutrophils; however, in the case of MBL, this effect was modest compared with the binding enhancement induced by SP-D or conglutinin. These studies clarify the structural requirements for viral inhibition by SP-D and reveal significant differences in the mechanisms of anti-IAV activity among the collectins.

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

“…SP-D, a collectin present in respiratory fluids, and the short pentraxin SAP bind to influenza viruses in a Ca 2ϩ -dependent manner (4,6,22,23) and mediate antiviral activity by binding to mannose residues on the viral HA/NA glycoproteins. Therefore, studies were undertaken to assess the ability of the long pentraxin PTX3 to bind influenza virus by ELISA.…”

“…The antiviral activities of collectins have been well described with strong evidence to suggest that surfactant protein-D (SP-D) 4 is of particular importance during influenza infections. Both surfactant protein-A (SP-A) and SP-D mediate a range of activities against influenza virus, including inhibition of hemagglutination, virus neutralization, virus aggregation, and opsonizaton of the virus for interaction with neutrophils (2)(3)(4)(5)(6)(7)(8), with SP-D acting as a more potent inhibitor than SP-A in vitro (4).…”

“…Both surfactant protein-A (SP-A) and SP-D mediate a range of activities against influenza virus, including inhibition of hemagglutination, virus neutralization, virus aggregation, and opsonizaton of the virus for interaction with neutrophils (2)(3)(4)(5)(6)(7)(8), with SP-D acting as a more potent inhibitor than SP-A in vitro (4). Levels of SP-D recovered from the airways by lavage increase significantly following infection of mice with influenza virus (3, 9 -11), and SP-D Ϫ/Ϫ mice exhibit enhanced viral replication and illness (9,11).…”

Transcriptional expression levels of chicken collectins are affected by avian influenza A virus inoculation

“…For mammalian collectins, several in vitro studies have described a strong neutralizing activity against influenza A virus (Hartshorn et al, 1997;Van Eijk et al, 2003;White et al, 2008). Collectins are thought to bind carbohydrate residues present on influenza hemagglutinin and neuraminidase, thereby aggregating viral particles and preventing invasion of host cells (Reading et al, 2007).…”

Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus

“…Whereas SP-D-mediated viral inhibition depends on binding of SP-D to high-mannose oligosaccharides on the viral envelope proteins, SP-A-and gp-340-mediated inhibition involves binding of the viral hemagglutinin to sialylated carbohydrates on SP-A or gp-340 (3,15,16). For this reason both SP-A and gp-340 have antiviral activity against strains of IAV that are resistant to SP-D (15,16).…”