Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published October 28, 2019 | Supplemental Material + Published
Journal Article Open

Mechanisms of virus dissemination in bone marrow of HIV-1-infected humanized BLT mice


Immune progenitor cells differentiate in bone marrow (BM) and then migrate to tissues. HIV-1 infects multiple BM cell types, but virus dissemination within BM has been poorly understood. We used light microscopy and electron tomography to elucidate mechanisms of HIV-1 dissemination within BM of HIV-1–infected BM/thymus/liver (BLT) mice. Tissue clearing combined with confocal and light sheet fluorescence microscopy revealed distinct populations of HIV-1 p24-producing cells in BM early after infection, and quantification of these populations identified macrophages as the principal subset of virus-producing cells in BM over time. Electron tomography demonstrated three modes of HIV-1 dissemination in BM: (i) semi-synchronous budding from T-cell and macrophage membranes, (ii) mature virus association with virus-producing T-cell uropods contacting putative target cells, and (iii) macrophages engulfing HIV-1–producing T-cells and producing virus within enclosed intracellular compartments that fused to invaginations with access to the extracellular space. These results illustrate mechanisms by which the specialized environment of the BM can promote virus spread locally and to distant lymphoid tissues.

Additional Information

© 2019 eLife Sciences Publications Ltd. Subject to a Creative Commons Attribution license, except where otherwise noted. Data availability: Source data files have been provided for graphs from Figure 1. We thank Andres Collazo at the Caltech Biological Imaging Facility for use of confocal and light sheet microscopes and help with image capture and analysis, Carol Garland and the Caltech Kavli Nanoscience Institute for aid in maintaining the TF30 electron microscope, and the Gordon and Betty Moore and Beckman Foundations for gifts to Caltech to support electron microscopy. This research was supported by the Rosalind W. Alcott post-doctoral fellowship (Caltech) and startup funding from the University of Illinois at Urbana-Champaign School of Molecular and Cellular Biology (C.K.), NIAID 1R01AI100652-01A1, the UCLA AIDS Institute, and the UCLA Center for AIDS Research NIH/NIAID AI028697 (D.S.A.), and the National Institute of General Medical Sciences (2 P50 GM082545-08) and California HIV/AIDS Research Program (ID15-CT-017) (P.J.B.) The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The opinions, findings, and conclusions herein are those of the authors and do not necessarily represent those of The Regents of the University of California, or any of its programs. The authors declare no competing interests.

Attached Files

Published - elife-46916-v2.pdf

Supplemental Material - elife-46916-supp-v1.zip


Files (260.4 MB)
Name Size Download all
250.2 MB Preview Download
10.2 MB Preview Download

Additional details

August 19, 2023
October 18, 2023