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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 Pi, Ruoxi and Gilardet, Alexandre and Kumar, Priti and Bjorkman, Pamela J. and Mothes, Walther and Uchil, Pradeep D. (2020) In vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20201021-151807622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 the 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 Patch 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:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.10.20.347427DOIDiscussion Paper
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:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This work was supported by NIH grants R01 CA098727 to W.M. and P50GM082545 to W.M. and P.J.B.; R33AI122384 and R01AI145164 to P. K., the Flow Cytometry Shared Resource of the Yale Cancer Center P30 CA016359, Yale Center for Cellular and Molecular Imaging S10 OD020142, and a fellowship from the China Scholarship Council – Yale World Scholars to R.P. We thank the Kavli Nanoscience Institute at Caltech for maintenance of the TF-30 electron microscope. Author Contributions. K.A.H. carried out all the BLI imaging. KA.H and P.D.U. contributed to executing experiments, data analysis, and figure generation. K.A.H. P.D.U., and W.M. shared the conceptualization, experimental design, interpretation, and manuscript preparation. M.S.L. carried out electron tomography of tissue samples. R.P. assisted in carrying out experiments, primer design and maintaining mouse colonies. A.G. assisted with cloning and generation of reporter constructs. P.J.B. and P.K. contributed to interpretation and discussion of the work. The authors have declared no competing interest.
Group:Kavli Nanoscience Institute
Funders:
Funding AgencyGrant Number
NIHR01 CA098727
NIHP50GM082545
NIHR33AI122384
NIHR01AI145164
NIHP30 CA016359
NIHS10 OD020142
China Scholarship CouncilUNSPECIFIED
Yale World ScholarsUNSPECIFIED
Subject Keywords:Retrovirus transmission, oral route, bioluminescence imaging, CD169
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 Kelsey A Haugh, Mark S. Ladinsky, Irfan Ullah, Ruoxi Pi, Alexandre Gilardet, Priti Kumar, Pamela Bjorkman, Walther Mothes, Pradeep D Uchil bioRxiv 2020.10.20.347427; doi: https://doi.org/10.1101/2020.10.20.347427
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:22 Oct 2020 13:59

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