Abstract
Background
The antiviral role of glycosaminoglycans in human milk (HM-GAGs) has been poorly investigated. They are highly sulfated polysaccharides, which were proposed to act as decoy receptors according to their structure. The aim of this study is to evaluate the antiviral potential and the mechanism of action of total and individual HM-GAGs against three pediatric clinically relevant viruses: respiratory syncytial virus (RSV), cytomegalovirus (HCMV), and rotavirus.
Methods
HM-GAGs were isolated from HM and a library of individual GAGs, structurally related to HM-GAGs, was prepared. The antiviral activity of HM-GAGs and the impact of thermal treatment were investigated in vitro by specific antiviral assays.
Results
We demonstrated that HM-GAGs are endowed with anti-HCMV and anti-RSV activity and that they act by altering virus attachment to cell. We clarified the contribution of individual HM-GAGs, showing a specific structure-related activity. We did not observe any alteration of HM-GAG antiviral activity after thermal treatment.
Conclusions
We showed that HM-GAGs contribute to the overall antiviral activity of HM, likely exerting a synergic action with other HM antiviral agents. HM-GAGs can now be added to the list of endogenous factors that may reduce breast-milk-acquired HCMV symptomatic infections and protecting infants from respiratory tract infections by RSV.
Impact
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HM-GAGs have been poorly investigated for their antiviral action so far.
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We demonstrated that HM-GAGs are endowed with significant anti-HCMV and anti-RSV activity and that they are able to alter virus binding to the cell.
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The contribution of individual HM-GAGs is mainly exerted by the FMHep and is not based on a simple charge interaction between the virus and sulfate groups but involves a specific GAG structural configuration.
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Our results contribute to identifying the multiple factors synergically acting in mediating HM antiviral properties and to clarifying their specific mechanism of action.
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Data availability
All data generated or analyzed during this study are included in this published article.
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Funding
D.L. was supported by Fondazione Cassa di Risparmio di Torino (http://www.fondazionecrt.it/) grant No 2019.0495 and by Banca d’Italia grant No 0835924/20 (https://www.bancaditalia.it/). D.L. was also supported by kind donations from Italian Association of Human Milk Banks (AIBLUD: https://www.aiblud.com/) and from Silvana Legnani. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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D.L., N.V., M.D., R.F., E.B., P.T., G.E.M.: substantial contributions to conception and design. R.F., M.D., M.R., P.T., F.C., V.M., F.M.: acquisition of data. R.F., M.D., M.R., D.L., N.V., G.E.M.: analysis and interpretation of data. R.F., M.D., M.R.: drafting the article; D.L., N.V.: revising the article critically for important intellectual content. All authors: final approval of the version to be published.
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Francese, R., Donalisio, M., Rittà , M. et al. Human milk glycosaminoglycans inhibit cytomegalovirus and respiratory syncytial virus infectivity by impairing cell binding. Pediatr Res (2022). https://doi.org/10.1038/s41390-022-02091-y
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DOI: https://doi.org/10.1038/s41390-022-02091-y
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