Interactions of Surfactant Protein a with Influenza A Viruses: Binding and Neutralization

Benne, C. A.; Kraaijeveld, C. A.; Strijp, Jos A. G. van; Brouwer, Eric; Harmsen, M.; Verhoef, J.; Golde, L.M.G. Van; Iwaarden, J. Freek van

doi:10.1093/infdis/171.2.335

Cited by 181 publications

(141 citation statements)

References 31 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…This difference may reflect steric hindrance of receptor-binding sites on adjacent monomers of the trimeric HA molecule. This function is reminiscent of the naturally occurring g-inhibitors of IAV, such as surfactant protein A 41 and PTX3, 42 which inhibit IAV infection by blocking HA receptor-binding function. It will be interesting to compare these synthetic inhibitors with the natural inhibitors in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

The cell surface mucin MUC1 limits the severity of influenza A virus infection

et al. 2017

View full text Add to dashboard Cite

Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency. Utilizing human lung epithelial cells, we found that IAV associates with the cs-mucin MUC1 but not MUC13 or MUC16. Overexpression of MUC1 by epithelial cells or the addition of sialylated synthetic MUC1 constructs, reduced IAV infection in vitro. In addition, Muc1 À / À mice infected with IAV exhibited enhanced morbidity and mortality, as well as greater inflammatory mediator responses compared to wild type mice. This study implicates the cs-mucin MUC1 as a critical and dynamic component of the innate host response that limits the severity of influenza and provides the foundation for exploration of MUC1 in resolving inflammatory disease.

show abstract

Section: Discussionmentioning

confidence: 99%

The cell surface mucin MUC1 limits the severity of influenza A virus infection

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In contrast, ␣2-macroglobulin and collectin SP-A mediate antiviral activity by providing sialic acid residues that are recognized by the HA glycoprotein of influenza viruses and are classified as ␥ inhibitors (13,14,30). Oligosaccharide analysis of PTX3 has indicated the presence of complex type sugars displaying varying degrees of sialylation attached to the single N-linked glycosylation site at Asn220 in the pentraxin domain of the PTX3 molecule (25).…”

Section: Recognition Of Sialic Acid On Ptx3 By Influenza Virus Hamentioning

confidence: 99%

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Reading

Bozza

Gilbertson

et al. 2008

The Journal of Immunology

178

210

View full text Add to dashboard Cite

Proteins of the innate immune system can act as natural inhibitors of influenza virus, limiting growth and spread of the virus in the early stages of infection before the induction of adaptive immune responses. In this study, we identify the long pentraxin PTX3 as a potent innate inhibitor of influenza viruses both in vitro and in vivo. Human and murine PTX3 bound to influenza virus and mediated a range of antiviral activities, including inhibition of hemagglutination, neutralization of virus infectivity and inhibition of viral neuraminidase. Antiviral activity was associated with binding of the viral hemagglutinin glycoprotein to sialylated ligands present on PTX3. Using a mouse model we found PTX3 to be rapidly induced following influenza infection and that PTX3−/− mice were more susceptible than wild-type mice to infection by PTX3-sensitive virus strains. Therapeutic treatment of mice with human PTX3 promoted survival and reduced viral load in the lungs following infection with PTX3-sensitive, but not PTX3-resistant, influenza viruses. Together, these studies describe a novel antiviral role for PTX3 in early host defense against influenza infections both in vitro and in vivo and describe the therapeutic potential of PTX3 in ameliorating disease during influenza infection.

show abstract

“…We first proposed that SP-A interacted with the glycans of F 2 and enhanced the fusion activity of F protein. It has been reported that SP-A enhanced uptake of HSV [29] and influenza A virus [30] by alveolar macrophages, and a viral and SP-A glyco-conjugate interaction was suggested in these studies. Carbohydrate recognition and opsonization of viruses may be an important role of SP-A in viral clearance.…”

Section: Discussionmentioning

confidence: 61%

Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

et al. 2003

View full text Add to dashboard Cite

Surfactant protein A (SP-A) and lactoferrin (LF) play important roles in innate immune systems in the respiratory mucous membranes. We investigated how SP-A and LF act against respiratory syncytial virus (RSV) infection. The present study indicated that RSV-induced IL-8 secretion from HEp-2 cells was up-regulated by SP-A (170% of control) but downregulated by LF (23% of control). RSV infectivity determined by viral titers and the uptake of FITC-labeled RSV were also increased by SP-A, but decreased by LF. To clarify the mechanism of these opposite effects, we examined the interactions of SP-A and LF with RSV F protein, the most important surface glycoprotein for viral penetration. RSV F protein was found to be the ligand for both SP-A and LF, but the manners of binding were different. LF directly interacted with the F 1 subunit, which involved antigenic sites of F protein. Contrarily, SP-A associated with the F 2 subunit, which was highly glycosylated. SP-A but not LF failed to interact with deglycosylated F protein. Moreover, SP-A initiated the hemolyzing fusion activity of F protein. These results suggest that SP-A and LF modulate RSV infection by different binding specificity to F protein.

show abstract

Interactions of Surfactant Protein a with Influenza A Viruses: Binding and Neutralization

Cited by 181 publications

References 31 publications

The cell surface mucin MUC1 limits the severity of influenza A virus infection

The cell surface mucin MUC1 limits the severity of influenza A virus infection

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

Contact Info

Product

Resources

About