Ion-abrasion scanning electron microscopy reveals surface-connected tubular conduits in HIV-infected macrophages
Open accessAbstract
HIV-1-containing internal compartments are readily detected in images of thin sections from infected cells using conventional transmission electron microscopy, but the origin, connectivity, and 3D distribution of these compartments has remained controversial. Here, we report the 3D distribution of viruses in HIV-1-infected primary human macrophages using cryo-electron tomography and ion-abrasion scanning electron microscopy (IA-SEM), a recently developed approach for nanoscale 3D imaging of whole cells. Using IA-SEM, we show the presence of an extensive network of HIV-1-containing tubular compartments in infected macrophages, with diameters of approximately 150-200 nm, and lengths of up to approximately 5 microm that extend to the cell surface from vesicular compartments that contain assembling HIV-1 virions. These types of surface-connected tubular compartments are not observed in T cells infected with the 29/31 KE Gag-matrix mutant where the virus is targeted to multi-vesicular bodies and released into the extracellular medium. IA-SEM imaging also allows visualization of large sheet-like structures that extend outward from the surfaces of macrophages, which may bend and fold back to allow continual creation of viral compartments and virion-lined channels. This potential mechanism for efficient virus trafficking between the cell surface and interior may represent a subversion of pre-existing vesicular machinery for antigen capture, processing, sequestration, and presentation.
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Viruses have evolved several mechanisms, including cell-cell fusion, synapse formation, actin tails, filopodial bridges, and nanotubes, to facilitate secure and rapid cell-to-cell dissemination.
“Viruses have evolved several mechanisms, including cell-cell fusion, synapse formation, and induction of actin tails, filopodial bridges, or nanotubes, and are equipped with the necessary information to facilitate a secure and rapid cell-to-cell dissemination (Aubert et al., 2009; Bennett et al., 2009; Sherer et al., 2007; Sowinski et al., 2008).”
From Equid Herpesvirus-1 Exploits the Extracellular Matrix of Mononuclear Cells to Ensure Transport to Target Cells (2020) · cites this paper as Bennett et al., 2009
The Results describe HIV-1-containing channels connecting macrophage compartments to the cell surface, and the Discussion proposes that they may enable sequestered virus to be released for efficient, directed transmission to other cells. The paper does not establish the broader list of mechanisms—cell-cell fusion, actin tails, filopodial bridges, and nanotubes—or show that they evolved to make dissemination secure and rapid. No page numbers are available in our copy. (LLM, conf=0.86)
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“…fusion, synapse formation, and induction of actin tails, filopodial bridges, or nanotubes, and are equipped with the necessary information to facilitate a secure and rapid cell-to-cell dissemination (Aubert et al., 2009; Bennett et al., 2009; Sherer et al., 2007; Sowinski et al., 2008).”
- Authors
- Bennett, A. E., Narayan, K., Shi, D., Hartnell, L. M., Gousset, K., He, H., Lowekamp, B. C., Yoo, T. S., Bliss, D., Freed, E. O., & Subramaniam, S.
- Affiliations
- National Institutes of Health (US)
- National Cancer Institute (US)
- Corresponding author
- Subramaniam, Sriram
- ORCID
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-09-25
- Volume
- 5
- Issue
- 9
- Pages
- e1000591
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2743285
- OpenAlex
- W2114225085
- Cited by
- 163
- References
- 30
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 7 · 2023: 3 · 2022: 2 · 2021: 9 · 2020: 7 · 2019: 7 · 2018: 11 · 2017: 8 · 2016: 8 · 2015: 12 · 2014: 15 · 2013: 16 · 2012: 20
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Cancer Institute
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- HIV-1, macrophages, cryo-electron tomography, viral assembly, vesicular compartments, antigen presentation, HIV-1 virions
- MeSH terms
- Humans, Macrophages, Microscopy, Electron, Scanning, Video Recording, Virion, HIV-1, HIV Infections, Jurkat Cells, Imaging, Three-Dimensional
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