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In vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission

Haugh, Kelsey A. and Ladinsky, Mark S. and Ullah, Irfan and Stone, Helen M. and Pi, Ruoxi and Gilardet, Alexandre and Grunst, Michael W. and Kumar, Priti and Bjorkman, Pamela J. and Mothes, Walther and Uchil, Pradeep D. (2021) In vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission. eLife, 10 . Art. No. e64179. ISSN 2050-084X. PMCID PMC8298093. doi:10.7554/eLife.64179. https://resolver.caltech.edu/CaltechAUTHORS:20201021-151807622

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Abstract

Early events in retrovirus transmission are determined by interactions between incoming viruses and frontline cells near entry sites. Despite their importance for retroviral pathogenesis, very little is known about these events. We developed a bioluminescence imaging (BLI)-guided multiscale imaging approach to study these events in vivo. Engineered murine leukemia reporter viruses allowed us to monitor individual stages of retrovirus life cycle including virus particle flow, virus entry into cells, infection and spread for retroorbital, subcutaneous, and oral routes. BLI permitted temporal tracking of orally administered retroviruses along the gastrointestinal tract as they traversed the lumen through Peyer’s patches to reach the draining mesenteric sac. Importantly, capture and acquisition of lymph-, blood-, and milk-borne retroviruses spanning three routes was promoted by a common host factor, the I-type lectin CD169, expressed on sentinel macrophages. These results highlight how retroviruses co-opt the immune surveillance function of tissue-resident sentinel macrophages for establishing infection.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.7554/eLife.64179DOIArticle
https://doi.org/10.1101/2020.10.20.347427DOIDiscussion Paper
https://medicine.yale.edu/profile/pradeep_uchil/Related ItemData
https://medicine.yale.edu/profile/walther_mothes/Related ItemData
https://doi.org/10.5061/dryad.hhmgqnkgwDOIData
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8298093/PubMed CentralArticle
ORCID:
AuthorORCID
Haugh, Kelsey A.0000-0002-4277-2493
Ladinsky, Mark S.0000-0002-1036-3513
Kumar, Priti0000-0002-6901-5601
Bjorkman, Pamela J.0000-0002-2277-3990
Mothes, Walther0000-0002-3367-7240
Uchil, Pradeep D.0000-0002-7236-858X
Additional Information:© 2021, Haugh et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Received: 20 October 2020; Accepted: 15 June 2021; Published: 05 July 2021. This work was supported by NIH grants R01 CA098727 to WM and P50AI150464 to WM and PJB; R33AI122384 and R01AI145164 to PK, the Flow Cytometry Shared Resource of the Yale Cancer Center P30 CA016359, Yale Center for Cellular and Molecular Imaging S10 OD020142, Virology Training Grant fellowship T32AI055403 to KAH, the Gruber Foundation to MWG, and a fellowship from the China Scholarship Council – Yale World Scholars to RP. We thank the Kavli Nanoscience Institute at Caltech for maintenance of the TF-30 electron microscope. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Data Availability: Data is plotted as individual points wherever possible. We can provide Graphpad prism files that was used to plot all the graphs for each figure upon request. Raw datasets are freely available upon request. Interested parties should contact https://medicine.yale.edu/profile/pradeep_uchil/, https://medicine.yale.edu/profile/walther_mothes/, and we will place requested dataset onto an externally accessible Yale Box Server. Requestors will then be provided with a direct URL link from which they can download the files at their convenience. All the images acquired using confocal microscopy are available at Dryad https://doi.org/10.5061/dryad.hhmgqnkgw. Author contributions: Kelsey A Haugh, Conceptualization, Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing - original draft, Writing - review and editing; Mark S Ladinsky, Conceptualization, Data curation, Formal analysis, Validation, Investigation, Methodology, Writing - review and editing; Irfan Ullah, Data curation, Formal analysis, Investigation; Helen M Stone, Alexandre Gilardet, Investigation; Ruoxi Pi, Formal analysis, Investigation, Methodology, Writing - review and editing; Michael W Grunst, Investigation, Writing - review and editing; Priti Kumar, Resources, Funding acquisition, Project administration; Pamela J Bjorkman, Resources, Methodology, Project administration; Walther Mothes, Conceptualization, Resources, Supervision, Funding acquisition, Visualization, Methodology, Writing - original draft, Project administration, Writing - review and editing, co-corresponding author; Pradeep D Uchil, Conceptualization, Formal analysis, Supervision, Validation, Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review and editing. Competing interests: Pamela J Bjorkman: Reviewing editor, eLife. The other authors declare that no competing interests exist. Ethics: Animal experimentation: All experiments were approved by the Institutional Animal Care and Use Committees (IACUC) protocols 2020-10649 and Institutional Biosafety Committee of Yale University (IBSCYU). All the animals were housed under specific pathogen-free conditions in the facilities provided and supported by Yale Animal Resources Center (YARC). All IVIS imaging, blood draw and virus inoculation experiments were done under anesthesia using regulated flow of isoflurane:oxygen mix to minimize pain and discomfort to the animals. Animals were housed under specific pathogen-free conditions in the Yale Animal Resources Center (YARC) in the same room of the vivarium. Yale University is registered as a research facility with the United States Department of Agriculture, License and Registration number 16-R-0001 Registered until March 20, 2023. It also is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) AAALAC Accreditation: April 3, 2019. An Animal Welfare Assurance (#D16-0014) is on file with OLAW-NIH; effective May 1, 2019-May 31, 2023.
Group:Kavli Nanoscience Institute
Funders:
Funding AgencyGrant Number
NIHR01 CA098727
NIHP50AI150464
NIHR33AI122384
NIHR01AI145164
NIHP30 CA016359
NIHS10 OD020142
NIH Predoctoral FellowshipT32AI055403
Gruber FoundationUNSPECIFIED
China Scholarship CouncilUNSPECIFIED
Yale World ScholarsUNSPECIFIED
Subject Keywords:Retrovirus transmission, oral route, bioluminescence imaging, CD169
PubMed Central ID:PMC8298093
DOI:10.7554/eLife.64179
Record Number:CaltechAUTHORS:20201021-151807622
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201021-151807622
Official Citation:In vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission. Haugh et al. eLife 2021; 10:e64179. DOI: https://doi.org/10.7554/eLife.64179
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106192
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:22 Oct 2020 13:59
Last Modified:02 Aug 2021 16:26

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