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

  1. Kelsey A Haugh
  2. Mark S Ladinsky
  3. Irfan Ullah
  4. Helen M Stone
  5. Ruoxi Pi
  6. Alexandre Gilardet
  7. Michael W Grunst
  8. Priti Kumar
  9. Pamela J Bjorkman
  10. Walther Mothes  Is a corresponding author
  11. Pradeep D Uchil  Is a corresponding author
  1. Yale University, School of Medicine, United States
  2. California Institute of Technology, United States
  3. Yale University, United States
  4. Yale University School of Medicine, United States

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.

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 pradeep.uchil@yale.edu, walther.mothes@yale.edu , 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 doi:10.5061/dryad.hhmgqnkgw.

The following data sets were generated

Article and author information

Author details

  1. Kelsey A Haugh

    Department of Microbial Pathogenesis, Yale University, School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  2. Mark S Ladinsky

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1036-3513
  3. Irfan Ullah

    Department of Internal Medicine, Section of Infectious Diseases, Yale University, School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  4. Helen M Stone

    Yale University, New Haven, United States
    Competing interests
    No competing interests declared.
  5. Ruoxi Pi

    Microbial Pathogenesis, Yale University, School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  6. Alexandre Gilardet

    Department of Microbial Pathogenesis, Yale University, School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  7. Michael W Grunst

    Yale University, New Haven, United States
    Competing interests
    No competing interests declared.
  8. Priti Kumar

    Department of Internal Medicine, Section of Infectious diseases, Yale University, School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  9. Pamela J Bjorkman

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    Pamela J Bjorkman, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2277-3990
  10. Walther Mothes

    Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States
    For correspondence
    walther.mothes@yale.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3367-7240
  11. Pradeep D Uchil

    Department of Microbial Pathogenesis, Yale University, School of Medicine, New Haven, United States
    For correspondence
    pradeep.uchil@yale.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7236-858X

Funding

National Cancer Institute (R01 CA098727)

  • Walther Mothes

National Institute of Allergy and Infectious Diseases (5P50AI150464-14)

  • Pamela J Bjorkman
  • Walther Mothes

National Institute of Allergy and Infectious Diseases (5R33AI122384-05)

  • Priti Kumar

National Institute of Allergy and Infectious Diseases (5R01AI145164-03)

  • Priti Kumar

National Institute of Allergy and Infectious Diseases (T32AI055403)

  • Kelsey A Haugh
  • Priti Kumar
  • Walther Mothes

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mark Marsh, University College London, United Kingdom

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.

Version history

  1. Received: October 20, 2020
  2. Accepted: June 15, 2021
  3. Accepted Manuscript published: July 5, 2021 (version 1)
  4. Version of Record published: July 22, 2021 (version 2)

Copyright

© 2021, Haugh et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Kelsey A Haugh
  2. Mark S Ladinsky
  3. Irfan Ullah
  4. Helen M Stone
  5. Ruoxi Pi
  6. Alexandre Gilardet
  7. Michael W Grunst
  8. Priti Kumar
  9. Pamela J Bjorkman
  10. Walther Mothes
  11. Pradeep D Uchil
(2021)
In vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission
eLife 10:e64179.
https://doi.org/10.7554/eLife.64179

Share this article

https://doi.org/10.7554/eLife.64179

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