Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake
Arenaviruses are enveloped viruses that cause hemorrhagic fever outbreaks in humans and still lack an effective antiviral treatment. Upon early infection, these viruses target dendritic cells (DCs), which can promote systemic viral dissemination, contributing to pathogenesis. We have previously desc...
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MDPI AG
2020-06-01
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| Online Access: | https://www.mdpi.com/2504-3900/50/1/90 |
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| author | Xabier Muniz-Trabudua Cristina Borio Marcos Bilen Itziar Erkizia Daniel Perez-Zsolt Susana Benet Javier Martinez-Picado Nuria Izquierdo-Useros |
| author_facet | Xabier Muniz-Trabudua Cristina Borio Marcos Bilen Itziar Erkizia Daniel Perez-Zsolt Susana Benet Javier Martinez-Picado Nuria Izquierdo-Useros |
| author_sort | Xabier Muniz-Trabudua |
| collection | DOAJ |
| description | Arenaviruses are enveloped viruses that cause hemorrhagic fever outbreaks in humans and still lack an effective antiviral treatment. Upon early infection, these viruses target dendritic cells (DCs), which can promote systemic viral dissemination, contributing to pathogenesis. We have previously described that Siglec-1, a sialic acid Ig-like binding lectin-1 expressed on DCs interacts with different enveloped viruses and promotes their capture within a virus-containing compartment. Such is the case of HIV-1 or Ebola virus, which display sialylated gangliosides on their viral envelope that are effectively recognized by Siglec-1. Here, we aimed to study if Siglec-1 on DCs also interacts with arenaviruses such as Junin. We produced non-infectious Junin viral-like particles (Junin-VLPs) tagged with fluorescent Egfp by transfecting a plasmid encoding the structural Junin Z protein on HEK-293T cells. Junin-VLPs were added to a Raji cell line stably transfected with Siglec-1 or to monocyte-derived DCs activated or not with either Interferon-α or lipopolysaccharide. Viral uptake was analyzed by FACS or confocal microscopy in the presence of an anti-Siglec-1 monoclonal antibody (mAb) or an isotype control. Statistical differences were assessed with the indicated tests. Raji Siglec-1 cells captured a higher number of Junin-VLPs than Raji cells, and this was blocked with an anti-Siglec-1 mAb (<i>P </i>= 0.0159; Mann–Whitney). On primary DCs, activation enhanced Junin-VLP capture (<i>P =</i> 0.0024<i>; </i>paired <i>t</i>-test) and Siglec-1 expression. Furthermore, pre-incubation with an anti-Siglec-1 mAb on activated DCs blocked Junin-VLP uptake (<i>P </i>≤ 0.0002; one sample <i>t</i>-test), while an isotype control did not. Forty-nine percent of the activated DCs analyzed by confocal microscopy captured Junin-VLPs within a Siglec-1+ virus-containing compartment. Moreover, when HIV-1 was also added, 97% of those compartments retained both viruses. Thus, we conclude that Siglec-1 is a new receptor involved in arenavirus uptake in DCs and could represent a novel target for an anti-arenavirus treatment. |
| first_indexed | 2024-03-10T19:02:38Z |
| format | Article |
| id | doaj.art-dc978371b1dd4b078b267581aace14dd |
| institution | Directory Open Access Journal |
| issn | 2504-3900 |
| language | English |
| last_indexed | 2024-03-10T19:02:38Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
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| spelling | doaj.art-dc978371b1dd4b078b267581aace14dd2023-11-20T04:19:01ZengMDPI AGProceedings2504-39002020-06-015019010.3390/proceedings2020050090Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus UptakeXabier Muniz-Trabudua0Cristina Borio1Marcos Bilen2Itziar Erkizia3Daniel Perez-Zsolt4Susana Benet5Javier Martinez-Picado6Nuria Izquierdo-Useros7IrsiCaixa AIDS Research Institute, 08916 Badalona, SpainLaboratorio de Ingeniería Genética y Biología Celular y Molecular—Area Virosis Emergentes y Zoonóticas, Department of Science and Technology, UniversidadNacional de Quilmes, Bernal, B1876 Buenos Aires, ArgentinaLaboratorio de Ingeniería Genética y Biología Celular y Molecular—Area Virosis Emergentes y Zoonóticas, Department of Science and Technology, UniversidadNacional de Quilmes, Bernal, B1876 Buenos Aires, ArgentinaIrsiCaixa AIDS Research Institute, 08916 Badalona, SpainIrsiCaixa AIDS Research Institute, 08916 Badalona, SpainIrsiCaixa AIDS Research Institute, 08916 Badalona, SpainIrsiCaixa AIDS Research Institute, 08916 Badalona, SpainIrsiCaixa AIDS Research Institute, 08916 Badalona, SpainArenaviruses are enveloped viruses that cause hemorrhagic fever outbreaks in humans and still lack an effective antiviral treatment. Upon early infection, these viruses target dendritic cells (DCs), which can promote systemic viral dissemination, contributing to pathogenesis. We have previously described that Siglec-1, a sialic acid Ig-like binding lectin-1 expressed on DCs interacts with different enveloped viruses and promotes their capture within a virus-containing compartment. Such is the case of HIV-1 or Ebola virus, which display sialylated gangliosides on their viral envelope that are effectively recognized by Siglec-1. Here, we aimed to study if Siglec-1 on DCs also interacts with arenaviruses such as Junin. We produced non-infectious Junin viral-like particles (Junin-VLPs) tagged with fluorescent Egfp by transfecting a plasmid encoding the structural Junin Z protein on HEK-293T cells. Junin-VLPs were added to a Raji cell line stably transfected with Siglec-1 or to monocyte-derived DCs activated or not with either Interferon-α or lipopolysaccharide. Viral uptake was analyzed by FACS or confocal microscopy in the presence of an anti-Siglec-1 monoclonal antibody (mAb) or an isotype control. Statistical differences were assessed with the indicated tests. Raji Siglec-1 cells captured a higher number of Junin-VLPs than Raji cells, and this was blocked with an anti-Siglec-1 mAb (<i>P </i>= 0.0159; Mann–Whitney). On primary DCs, activation enhanced Junin-VLP capture (<i>P =</i> 0.0024<i>; </i>paired <i>t</i>-test) and Siglec-1 expression. Furthermore, pre-incubation with an anti-Siglec-1 mAb on activated DCs blocked Junin-VLP uptake (<i>P </i>≤ 0.0002; one sample <i>t</i>-test), while an isotype control did not. Forty-nine percent of the activated DCs analyzed by confocal microscopy captured Junin-VLPs within a Siglec-1+ virus-containing compartment. Moreover, when HIV-1 was also added, 97% of those compartments retained both viruses. Thus, we conclude that Siglec-1 is a new receptor involved in arenavirus uptake in DCs and could represent a novel target for an anti-arenavirus treatment.https://www.mdpi.com/2504-3900/50/1/90arenavirusdendritic cellsSiglec-1 |
| spellingShingle | Xabier Muniz-Trabudua Cristina Borio Marcos Bilen Itziar Erkizia Daniel Perez-Zsolt Susana Benet Javier Martinez-Picado Nuria Izquierdo-Useros Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake Proceedings arenavirus dendritic cells Siglec-1 |
| title | Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake |
| title_full | Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake |
| title_fullStr | Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake |
| title_full_unstemmed | Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake |
| title_short | Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake |
| title_sort | siglec 1 expressed on dendritic cells is a new receptor implicated in arenavirus uptake |
| topic | arenavirus dendritic cells Siglec-1 |
| url | https://www.mdpi.com/2504-3900/50/1/90 |
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