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Integrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells

Karelehto E; Merilahti P; Heikkila O; Sukki M; Kiljunen S; Hakanen M; Alanko J; Susi P

dc.contributor.authorKarelehto E
dc.contributor.authorMerilahti P
dc.contributor.authorHeikkila O
dc.contributor.authorSukki M
dc.contributor.authorKiljunen S
dc.contributor.authorHakanen M
dc.contributor.authorAlanko J
dc.contributor.authorSusi P
dc.date.accessioned2022-10-28T13:25:09Z
dc.date.available2022-10-28T13:25:09Z
dc.identifier.urihttps://www.utupub.fi/handle/10024/165048
dc.description.abstract<p> </p><p><b>Background:</b> Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family <i>Picornaviridae</i>. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the aVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the capsid protein VP1 in all studied clinical isolates. However, genetically-modified CV-A9 that lacks the RGD motif (CV-A9-RGDdel) has been shown to be infectious in some cell lines but not in A549, suggesting that RGD-mediated integrin binding is not always essential for efficient entry of CV-A9.</p> <p><b> </b></p> <p><b>Methods: </b>Two cell lines, A549 and SW480, were used in the study. SW480 was the study object for the integrin-independent entry and A549 was used as the control for integrin-dependent entry. Receptor levels were quantitated by cell sorting and quantitative PCR. Antibody blocking assay and siRNA silencing of receptor-encoding genes were used to block virus infection. Peptide phage display library was used to identify peptide binders to CV-A9. Immunofluorescence and confocal microscopy were used to visualize the virus infection in the cells.</p> <p><b> </b></p> <p><b>Results:</b> We investigated the receptor use and early stages of CV-A9 internalization to SW480 human epithelial colon adenocarcinoma cells. Contrary to A549 infection, we showed that both CV-A9 and CV-A9-RGDdel internalized into SW480 cells and that function-blocking anti-αV integrin antibodies had no effect on the binding and entry of CV-A9. Whereas siRNA silencing of β6 integrin subunit had no influence on virus infection in SW480, silencing of β2-microglobulin (b2M) inhibited the virus infection in both cell lines. By using a peptide phage display screening, the virus-binding peptide identical to the N-terminal sequence of HSPA5 protein was identified and shown to block the virus infection in both A549 and SW480 cell lines. HSPA5 was also found to co-localize with CV-A9 at the SW480 cell periphery during the early stages of infection by confocal microscopy.</p> <p><b> </b></p> <p><b>Conclusions:</b> The data suggest that while aVβ6 integrin is essential for CV-A9 in A549 cell line, it is not required in SW480 cell line in which β2M and HSPA5 alone are sufficient for CV-A9 infection. This suggests that the choice of CV-A9 receptor(s) is dependent on the tissue/cellular environment.</p>
dc.language.isoen
dc.publisherBIOMED CENTRAL LTD
dc.titleIntegrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells
dc.identifier.urnURN:NBN:fi-fe2021042715558
dc.relation.volume13
dc.contributor.organizationfi=fysiologia ja genetiikka|en=Physiology and Genetics|
dc.contributor.organizationfi=PÄÄT Virusoppi|en=PÄÄT Virusoppi|
dc.contributor.organizationfi=Turun biotiedekeskus|en=Turku Bioscience Centre|
dc.contributor.organization-code2609201
dc.contributor.organization-code2607108
dc.contributor.organization-code2606404
dc.converis.publication-id17086699
dc.converis.urlhttps://research.utu.fi/converis/portal/Publication/17086699
dc.identifier.eissn1743-422X
dc.identifier.jour-issn1743-422X
dc.okm.affiliatedauthorSusi, Petri
dc.okm.affiliatedauthorAlanko, Jonna
dc.okm.affiliatedauthorKarelehto, Eveliina
dc.okm.affiliatedauthorKiljunen, Saija
dc.okm.affiliatedauthorMerilahti, Pirjo
dc.okm.affiliatedauthorHeikkilä, Outi
dc.okm.affiliatedauthorKoivu, Marika
dc.okm.discipline1183 Kasvibiologia, mikrobiologia, virologiafi_FI
dc.okm.discipline1182 Biochemistry, cell and molecular biologyen_GB
dc.okm.discipline1183 Plant biology, microbiology, virologyen_GB
dc.okm.discipline1182 Biokemia, solu- ja molekyylibiologiafi_FI
dc.okm.internationalcopublicationnot an international co-publication
dc.okm.internationalityDomestic publication
dc.okm.typeJournal article
dc.publisher.countryBritanniafi_FI
dc.publisher.countryUnited Kingdomen_GB
dc.publisher.country-codeGB
dc.publisher.placeLondon, UK
dc.relation.articlenumberARTN 171
dc.relation.doi10.1186/s12985-016-0619-y
dc.relation.ispartofjournalVirology Journal
dc.year.issued2016


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