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Inhibition of influenza viral neuraminidase activity by collectins

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Summary

The collectins, lung surfactant proteins A and D (SP-A and SP-D), contribute to innate host defense against influenza A virus (IAV) in vivo. Although collectins bind to the viral hemagglutinin (HA) and inhibit early stages of viral infection in vitro, they also bind to the neuraminidase (NA) and inhibit NA activity. We used a variety of NA functional assays, viral strains and recombinant (mutant or wild type) collectins to characterize the mechanism of NA inhibition. NA inhibition by SP-D correlates with binding of its carbohydrate recognition domain (CRD) to oligomannose oligosaccharides on the viral hemagglutinin (HA). The effects of SP-D are additive with oseltamivir, consistent with differences in mechanism of action. NA inhibition was observed using fetuin or MDCK cells as a substrate, but not in assays using a soluble sialic acid analogue. Collectin multimerization and CRD binding properties are key determinants for NA inhibition. SP-D had greater NA inhibitory activity than mannose-binding lectin, which in turn had greater activity than SP-A. The markedly greater NA inhibitory activity of SP-D compared to SP-A may partly account for the finding that deletion of the SP-D gene in mice has a greater effect on viral replication in vivo.

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References

  • SJ Baigent JW McCauley (2001) ArticleTitleGlycosylation of haemagglutinin and stalk-length of neuraminidase combine to regulate the growth of avian influenza viruses in tissue culture Virus Res 79 177–185 Occurrence Handle11551658 Occurrence Handle10.1016/S0168-1702(01)00272-6 Occurrence Handle1:CAS:528:DC%2BD3MXmsleitbg%3D

    Article  PubMed  CAS  Google Scholar 

  • CA Benne CA Kraaijeveld JAG van-Strijp E Brouwer M Harmsen J Verhoef LMG van-Golde JF van-Iwaarden (1995) ArticleTitleInteractions of surfactant protein A with influenza A viruses: binding and neutralization J Infect Dis 171 335–341 Occurrence Handle7844369 Occurrence Handle1:CAS:528:DyaK2MXktVejurw%3D

    PubMed  CAS  Google Scholar 

  • E Crouch Y Tu D Briner B McDonald K Smith U Holmskov K Hartshorn (2005) ArticleTitleLigand binding of human surfactant protein D: expression of a mutant trimeric collectin that shows enhanced interactions with influenza A virus J Biol Chem 280 17046–17056 Occurrence Handle15711012 Occurrence Handle10.1074/jbc.M413932200 Occurrence Handle1:CAS:528:DC%2BD2MXjsFOgt70%3D

    Article  PubMed  CAS  Google Scholar 

  • D Fleury B Barrere T Bizebard RS Daniels JJ Skehel M Knossow (1999) ArticleTitleA complex of influenza hemagglutinin with a neutralizing antibody that binds outside the virus receptor binding site Nat Struct Biol 6 530–534 Occurrence Handle10360354 Occurrence Handle10.1038/9299 Occurrence Handle1:CAS:528:DyaK1MXjs1ykt7o%3D

    Article  PubMed  CAS  Google Scholar 

  • L Gubareva R Webster F Hayden (2001) ArticleTitleComparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants Antimicrobial Agents Chemo 45 3403–3408 Occurrence Handle10.1128/AAC.45.12.3403-3408.2001 Occurrence Handle1:CAS:528:DC%2BD3MXovVOlsLk%3D

    Article  CAS  Google Scholar 

  • CA Hartley DC Jackson ME Anders (1992) ArticleTitleTwo distinct serum mannose-binding lectins functions as B inhibitors of influenza virus: identification of bovine serum B inhibitor as conglutinin J Virol 66 4358–4363 Occurrence Handle1602549 Occurrence Handle1:CAS:528:DyaK38XksVKmsb8%3D

    PubMed  CAS  Google Scholar 

  • K Hartshorn D Chang K Rust M White J Heuser E Crouch (1996) ArticleTitleInteractions of recombinant human pulmonary surfactant protein D and SPD multimers with influenza A Amer J Physiol 271 L753–L762 Occurrence Handle8944718 Occurrence Handle1:CAS:528:DyaK28XntFyqurs%3D

    PubMed  CAS  Google Scholar 

  • K Hartshorn K Reid M White S Morris J Jensenius E Crouch (1996) ArticleTitleNeutrophil deactivation by influenza A viruses: mechanisms of protection after viral opsonization with collectins and hemagglutination-inhibiting antibodies Blood 87 3450–3461 Occurrence Handle8605364 Occurrence Handle1:STN:280:BymC1cvotVM%3D

    PubMed  CAS  Google Scholar 

  • K Hartshorn M White V Shepherd K Reid J Jensenius E Crouch (1997) ArticleTitleMechanisms of anti-influenza activity of pulmonary surfactant proteins A and D: comparison with other collectins Amer J Physiol 273 L1156–L1166 Occurrence Handle9435570 Occurrence Handle1:CAS:528:DyaK1cXjvFaqtA%3D%3D

    PubMed  CAS  Google Scholar 

  • K Hartshorn K Sastry D Chang M White E Crouch (2000) ArticleTitleEnhanced antinfluenza activity of a recombinant pulmonary surfactant protein D and serum conglutinin fusion protein Amer J Physiol 278 L90–L98 Occurrence Handle1:CAS:528:DC%2BD3cXht1GitL0%3D

    CAS  Google Scholar 

  • K Hartshorn M White D Voelker J Coburn K Zaner E Crouch (2000) ArticleTitleMechanism of binding of surfactant surfactant protein D to influenza A viruses: importance of binding to hemagglutinin to antiviral activity Biochem J 351 449–458 Occurrence Handle11023831 Occurrence Handle10.1042/0264-6021:3510449 Occurrence Handle1:CAS:528:DC%2BD3cXnvFSqtLc%3D

    Article  PubMed  CAS  Google Scholar 

  • KL Hartshorn M Collamer M Auerbach JB Myers N Pavlotsky AI Tauber (1988) ArticleTitleEffects of influenza A virus on human neutrophil calcium metabolism J Immunol 141 1295–1301 Occurrence Handle3135328 Occurrence Handle1:CAS:528:DyaL1cXltVyrsro%3D

    PubMed  CAS  Google Scholar 

  • KL Hartshorn K Sastry MR White EM Anders M Super RA Ezekowitz AI Tauber (1993) ArticleTitleHuman mannose-binding protein functions as an opsonin for influenza A viruses J Clin Invest 91 1414–1420 Occurrence Handle7682571 Occurrence Handle1:CAS:528:DyaK3sXisFeht7w%3D Occurrence Handle10.1172/JCI116345

    Article  PubMed  CAS  Google Scholar 

  • KL Hartshorn EC Crouch MR White P Eggleton AI Tauber D Chang K Sastry (1994) ArticleTitleEvidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses J Clin Invest 94 311–319 Occurrence Handle8040272 Occurrence Handle1:CAS:528:DyaK2cXlsFGms7k%3D

    PubMed  CAS  Google Scholar 

  • KL Hartshorn LS Liou MR White MM Kazhdan JL Tauber (1995) ArticleTitleNeutrophil deactivation by influenza A virus: role of hemagglutinin binding to specific sialic acid-bearing cellular proteins J Immunol 154 3952–3960 Occurrence Handle7706733 Occurrence Handle1:CAS:528:DyaK2MXkvFOrtbs%3D

    PubMed  CAS  Google Scholar 

  • KL Hartshorn U Holmskov S Hansen P Zhang J Meschi T Mogues MR White EC Crouch (2002) ArticleTitleDistinctive anti-influenza properties of recombinant collectin 43 Biochem J 366 87–96 Occurrence Handle11971759 Occurrence Handle1:CAS:528:DC%2BD3sXptFOhtrs%3D

    PubMed  CAS  Google Scholar 

  • KL Hartshorn MR White T Mogues T Ligtenberg E Crouch U Holmskov (2003) ArticleTitleLung and salivary scavenger receptor glycoprotein-340 contribute to the host defense against influenza A viruses Am J Physiol Lung Cell Mol Physiol 285 L1066–L1076 Occurrence Handle12871854 Occurrence Handle1:CAS:528:DC%2BD3sXpt1Kisbk%3D

    PubMed  CAS  Google Scholar 

  • KL Hartshorn A Ligtenberg MR White M van Eijk M Hartshorn L Pemberton U Holmskov E Crouch (2006) ArticleTitleSalivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation Biochem J 393 545–553 Occurrence Handle16190864 Occurrence Handle10.1042/BJ20050695 Occurrence Handle1:CAS:528:DC%2BD28Xht1KqsLg%3D

    Article  PubMed  CAS  Google Scholar 

  • KL Hartshorn MR White T Tecle U Holmskov EC Crouch (2006) ArticleTitleInnate defense against influenza A virus: activity of human neutrophil defensins and interactions of defensins with surfactant protein D J Immunol 176 6962–6972 Occurrence Handle16709857 Occurrence Handle1:CAS:528:DC%2BD28XkslWhu74%3D

    PubMed  CAS  Google Scholar 

  • S Hawgood C Brown J Edmondson A Stumbaugh L Allen J Goerke H Clark F Poulain (2004) ArticleTitlePulmonary collectins modulate strain-specific influenza A virus infection and host responses J Virol 78 8565–8572 Occurrence Handle15280465 Occurrence Handle10.1128/JVI.78.16.8565-8572.2004 Occurrence Handle1:CAS:528:DC%2BD2cXmslSmsL8%3D

    Article  PubMed  CAS  Google Scholar 

  • R Kandel KL Hartshorn (2005) ArticleTitleNovel strategies for prevention and treatment of influenza Expert Opin Ther Targets 9 1–22 Occurrence Handle15757479 Occurrence Handle10.1517/14728222.9.1.1 Occurrence Handle1:CAS:528:DC%2BD2MXhs1ansr8%3D

    Article  PubMed  CAS  Google Scholar 

  • E Leikina H Delanoe-Ayari K Melikov MS Cho A Chen AJ Waring W Wang Y Xie JA Loo RI Lehrer LV Chernomordik (2005) ArticleTitleCarbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins Nat Immunol 6 995–1001 Occurrence Handle16155572 Occurrence Handle10.1038/ni1248 Occurrence Handle1:CAS:528:DC%2BD2MXhtVajsL7M

    Article  PubMed  CAS  Google Scholar 

  • R Leth-Larsen P Garred H Jensenius J Meschi K Hartshorn J Madsen I Tornoe HO Madsen G Sorensen E Crouch U Holmskov (2005) ArticleTitleA common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D J Immunol 174 1532–1538 Occurrence Handle15661913 Occurrence Handle1:CAS:528:DC%2BD2MXlsFymtw%3D%3D

    PubMed  CAS  Google Scholar 

  • A LeVine K Hartshorn J Elliot J Whitsett T Korfhagen (2001) ArticleTitleSurfactant protein A modulates both innate and adaptive defense responses to pulmonary influenza A virus infection Am J Physiol Lung Cell Mol Physiol 282 L563–L572

    Google Scholar 

  • A LeVine J Whitsett K Hartshorn T Korfhagen (2001) ArticleTitleSurfactant protein D enhances clearance of influenza A virus from the lung in vivo J Immunol 167 5868–5873 Occurrence Handle11698462 Occurrence Handle1:CAS:528:DC%2BD3MXotlamurg%3D

    PubMed  CAS  Google Scholar 

  • C Liu G Air (1993) ArticleTitleSelection and characterization of a neuraminidase minus mutant of influenza virus and its rescue by cloned neuraminidase genes Virology 194 403–407 Occurrence Handle8480427 Occurrence Handle10.1006/viro.1993.1276 Occurrence Handle1:CAS:528:DyaK3sXisFWhu7k%3D

    Article  PubMed  CAS  Google Scholar 

  • R Malhotra J Haurum S Thiel R Sim (1994) ArticleTitleBinding of human collectins (SP-A and MBP) to influenza virus Biochem J 304 455–461 Occurrence Handle7998980 Occurrence Handle1:CAS:528:DyaK2MXitlCntLc%3D

    PubMed  CAS  Google Scholar 

  • MN Matrosovich TY Matrosovich T Gray NA Roberts HD Klenk (2004) ArticleTitleNeuraminidase is important for the initiation of influenza virus infection in human airway epithelium J Virol 78 12665–12667 Occurrence Handle15507653 Occurrence Handle10.1128/JVI.78.22.12665-12667.2004 Occurrence Handle1:CAS:528:DC%2BD2cXhtVWhu7fJ

    Article  PubMed  CAS  Google Scholar 

  • VP Mishin D Novikov FG Hayden LV Gubareva (2005) ArticleTitleEffect of hemagglutinin glycosylation on influenza virus susceptibility to neuraminidase inhibitors J Virol 79 12416–12424 Occurrence Handle16160169 Occurrence Handle10.1128/JVI.79.19.12416-12424.2005 Occurrence Handle1:CAS:528:DC%2BD2MXhtVGlsL7M

    Article  PubMed  CAS  Google Scholar 

  • LJ Mitnaul MN Matrosovich MR Castrucci AB Tuzikov NV Bovin D Kobasa Y Kawaoka (2000) ArticleTitleBalanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus J Virology 74 6015–6020 Occurrence Handle10846083 Occurrence Handle10.1128/JVI.74.13.6015-6020.2000 Occurrence Handle1:CAS:528:DC%2BD3cXkt1eiuro%3D

    Article  PubMed  CAS  Google Scholar 

  • P Reading L Morey E Crouch E Anders (1997) ArticleTitleCollectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice J Virol 71 8204–8212 Occurrence Handle9343171 Occurrence Handle1:CAS:528:DyaK2sXmvV2iurY%3D

    PubMed  CAS  Google Scholar 

  • JJ Skehel DC Wiley (2000) ArticleTitleReceptor binding and membrane fusion in virus entry: the influenza hemagglutinin Annu Rev Biochem 69 531–569 Occurrence Handle10966468 Occurrence Handle10.1146/annurev.biochem.69.1.531 Occurrence Handle1:CAS:528:DC%2BD3cXnt1ajtbY%3D

    Article  PubMed  CAS  Google Scholar 

  • M Super S Gillis S Foley K Sastry JE Schweinle VJ Silverman RAB Ezekowitz (1992) ArticleTitleDistinct and overlapping functions of allelic forms of human mannose binding protein Nature Genet 2 50–55 Occurrence Handle1303250 Occurrence Handle10.1038/ng0992-50 Occurrence Handle1:CAS:528:DyaK38XlvFSju78%3D

    Article  PubMed  CAS  Google Scholar 

  • T Tecle MR White KL Hartshorn (2005) ArticleTitleInnate immunity to influenza A virus infection Current Respiratory Med Rev 1 127–145 Occurrence Handle10.2174/1573398054023073 Occurrence Handle1:CAS:528:DC%2BD2MXmt1Cktr0%3D

    Article  CAS  Google Scholar 

  • TM Tumpey A Garcia-Sastre JK Taubenberger P Palese DE Swayne MJ Pantin-Jackwood S Schultz-Cherry A Solorzano N Van Rooijen JM Katz CF Basler (2005) ArticleTitlePathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice J Virol 79 14933–14944 Occurrence Handle16282492 Occurrence Handle10.1128/JVI.79.23.14933-14944.2005 Occurrence Handle1:CAS:528:DC%2BD2MXht1CgsbrP

    Article  PubMed  CAS  Google Scholar 

  • M van Eijk MR White JJ Batenburg AB Vaandrager LM van Golde HP Haagsman KL Hartshorn (2004) ArticleTitleInteractions of influenza A virus with sialic acids present on porcine surfactant protein D Am J Respir Cell Mol Biol 30 871–879 Occurrence Handle14672916 Occurrence Handle10.1165/rcmb.2003-0355OC Occurrence Handle1:CAS:528:DC%2BD2cXkvVyjsbw%3D

    Article  PubMed  CAS  Google Scholar 

  • J Varghese W Laver P Colman (1983) ArticleTitleStructure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution Nature 303 35–40 Occurrence Handle6843658 Occurrence Handle10.1038/303035a0 Occurrence Handle1:CAS:528:DyaL3sXktVags7w%3D

    Article  PubMed  CAS  Google Scholar 

  • RG Webster GM Air DW Metzger PM Colman JN Varghese AT Baker WG Laver (1987) ArticleTitleAntigenic structure and variation in an influenza virus N9 neuraminidase J Virol 61 2910–2916 Occurrence Handle3612957 Occurrence Handle1:CAS:528:DyaL2sXmtFCisL0%3D

    PubMed  CAS  Google Scholar 

  • M White E Crouch D Chang K Sastry N Guo G Engelich K Takahashi R Ezekowitz K Hartshorn (2000) ArticleTitleEnhanced antiviral and opsonic activity of a human mannose binding lectin and surfactant protein D fusion protein J Immunol 165 2108–2155 Occurrence Handle10925296 Occurrence Handle1:CAS:528:DC%2BD3cXls1Kmsbk%3D

    PubMed  CAS  Google Scholar 

  • M White E Crouch D Chang K Hartshorn (2001) ArticleTitleIncreased antiviral and opsonic activity of a highly multimerized collectin chimera Biochem Biophys Res Comm 286 206–213 Occurrence Handle11485330 Occurrence Handle10.1006/bbrc.2001.5373 Occurrence Handle1:CAS:528:DC%2BD3MXls1egsbc%3D

    Article  PubMed  CAS  Google Scholar 

  • MR White E Crouch M van Eijk M Hartshorn L Pemberton I Tornoe U Holmskov KL Hartshorn (2005) ArticleTitleCooperative anti-influenza activities of respiratory innate immune proteins and neuraminidase inhibitor Am J Physiol Lung Cell Mol Physiol 288 L831–L840 Occurrence Handle15608147 Occurrence Handle10.1152/ajplung.00365.2004 Occurrence Handle1:CAS:528:DC%2BD2MXktlSnt7w%3D

    Article  PubMed  CAS  Google Scholar 

  • L Zhang K Hartshorn E Crouch M Ikegami J Whitsett (2002) ArticleTitleComplementation of pulmonary abnormalities in SP-D (−/−) mice with an SP-D/Conglutinin fusion protein J Biol Chem 277 22453–22459 Occurrence Handle11956209 Occurrence Handle10.1074/jbc.M201632200 Occurrence Handle1:CAS:528:DC%2BD38XltVGkt74%3D

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Medicine, Boston University School of Medicine, Boston, MA, USA

    T. Tecle, M. R. White & K. L. Hartshorn

  2. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

    E. C. Crouch

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  1. T. Tecle
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  2. M. R. White
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  3. E. C. Crouch
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  4. K. L. Hartshorn
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Tecle, T., White, M., Crouch, E. et al. Inhibition of influenza viral neuraminidase activity by collectins. Arch Virol 152, 1731–1742 (2007). https://doi.org/10.1007/s00705-007-0983-4

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