dc.contributor.author | Karelehto E | |
dc.contributor.author | Merilahti P | |
dc.contributor.author | Heikkila O | |
dc.contributor.author | Sukki M | |
dc.contributor.author | Kiljunen S | |
dc.contributor.author | Hakanen M | |
dc.contributor.author | Alanko J | |
dc.contributor.author | Susi P | |
dc.date.accessioned | 2022-10-28T13:25:09Z | |
dc.date.available | 2022-10-28T13:25:09Z | |
dc.identifier.uri | https://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.iso | en | |
dc.publisher | BIOMED CENTRAL LTD | |
dc.title | Integrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells | |
dc.identifier.urn | URN:NBN:fi-fe2021042715558 | |
dc.relation.volume | 13 | |
dc.contributor.organization | fi=fysiologia ja genetiikka|en=Physiology and Genetics| | |
dc.contributor.organization | fi=PÄÄT Virusoppi|en=PÄÄT Virusoppi| | |
dc.contributor.organization | fi=Turun biotiedekeskus|en=Turku Bioscience Centre| | |
dc.contributor.organization-code | 2609201 | |
dc.contributor.organization-code | 2607108 | |
dc.contributor.organization-code | 2606404 | |
dc.converis.publication-id | 17086699 | |
dc.converis.url | https://research.utu.fi/converis/portal/Publication/17086699 | |
dc.identifier.eissn | 1743-422X | |
dc.identifier.jour-issn | 1743-422X | |
dc.okm.affiliatedauthor | Susi, Petri | |
dc.okm.affiliatedauthor | Alanko, Jonna | |
dc.okm.affiliatedauthor | Karelehto, Eveliina | |
dc.okm.affiliatedauthor | Kiljunen, Saija | |
dc.okm.affiliatedauthor | Merilahti, Pirjo | |
dc.okm.affiliatedauthor | Heikkilä, Outi | |
dc.okm.affiliatedauthor | Koivu, Marika | |
dc.okm.discipline | 1183 Kasvibiologia, mikrobiologia, virologia | fi_FI |
dc.okm.discipline | 1182 Biochemistry, cell and molecular biology | en_GB |
dc.okm.discipline | 1183 Plant biology, microbiology, virology | en_GB |
dc.okm.discipline | 1182 Biokemia, solu- ja molekyylibiologia | fi_FI |
dc.okm.internationalcopublication | not an international co-publication | |
dc.okm.internationality | Domestic publication | |
dc.okm.type | Journal article | |
dc.publisher.country | Britannia | fi_FI |
dc.publisher.country | United Kingdom | en_GB |
dc.publisher.country-code | GB | |
dc.publisher.place | London, UK | |
dc.relation.articlenumber | ARTN 171 | |
dc.relation.doi | 10.1186/s12985-016-0619-y | |
dc.relation.ispartofjournal | Virology Journal | |
dc.year.issued | 2016 | |