Longitudinal imaging of HIV-1 spread in humanized mice with parallel 3D immunofluorescence and electron tomography

  1. Collin Kieffer
  2. Mark S Ladinsky
  3. Allen Ninh
  4. Rachel P Galimidi
  5. Pamela J Bjorkman  Is a corresponding author
  1. California Institute of Technology, United States
  2. Icahn School of Medicine at Mount Sinai, United States

Abstract

Dissemination of HIV-1 throughout lymphoid tissues leads to systemic virus spread following infection. We combined tissue clearing, 3D-immunofluorescence, and electron tomography (ET) to longitudinally assess early HIV-1 spread in lymphoid tissues in humanized mice. Immunofluorescence revealed peak infection density in gut at 10-12 days post-infection when blood viral loads were low. Human CD4+ T-cells and HIV-1-infected cells localized predominantly to crypts and the lower third of intestinal villi. Free virions and infected cells were not readily detectable by ET at 5-days post-infection, whereas HIV-1-infected cells surrounded by pools of free virions were present in ~10% of intestinal crypts by 10-12 days. ET of spleen revealed thousands of virions released by individual cells and discreet cytoplasmic densities near sites of prolific virus production. These studies highlight the importance of multiscale imaging of HIV-1-infected tissues and are adaptable to other animal models and human patient samples.

Article and author information

Author details

  1. Collin Kieffer

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, 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.
  3. Allen Ninh

    Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    No competing interests declared.
  4. Rachel P Galimidi

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  5. Pamela J Bjorkman

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

Funding

National Institute of General Medical Sciences (2 P50 GM082545-06)

  • Pamela J Bjorkman

California HIV/AIDS Research Program (ID15-CT-017)

  • Pamela J Bjorkman

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

Reviewing Editor

  1. Jeremy Luban, University of Massachusetts Medical School, United States

Ethics

Animal experimentation: This study was performed according to the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#1702) of the California Institute of Technology. Full effort was made to minimize suffering during animal sacrifice.

Version history

  1. Received: November 15, 2016
  2. Accepted: February 13, 2017
  3. Accepted Manuscript published: February 15, 2017 (version 1)
  4. Version of Record published: March 6, 2017 (version 2)

Copyright

© 2017, Kieffer 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. Collin Kieffer
  2. Mark S Ladinsky
  3. Allen Ninh
  4. Rachel P Galimidi
  5. Pamela J Bjorkman
(2017)
Longitudinal imaging of HIV-1 spread in humanized mice with parallel 3D immunofluorescence and electron tomography
eLife 6:e23282.
https://doi.org/10.7554/eLife.23282

Share this article

https://doi.org/10.7554/eLife.23282

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