Human Immunodeficiency Virus type 1 Endocytic Trafficking Through Macrophage Bridging Conduits Facilitates Spread of Infection
Open accessAbstract
Bridging conduits (BC) sustain communication and homeostasis between distant tethered cells. These are also exploited commonly for direct cell-to-cell transfer of microbial agents. Conduits efficiently spread infection, effectively, at speeds faster than fluid phase exchange while shielding the microbe against otherwise effective humoral immunity. Our laboratory has sought to uncover the mechanism(s) for these events for human immunodeficiency virus type one (HIV-1) infection. Indeed, in our prior works HIV-1 Env and Gag antigen and fluorescent virus tracking were shown sequestered into endoplasmic reticulum-Golgi organelles but the outcomes for spreading viral infection remained poorly defined. Herein, we show that HIV-1 specifically traffics through endocytic compartments contained within BC and directing such macrophage-to-macrophage viral transfers. Following clathrin-dependent viral entry, HIV-1 constituents bypass degradation by differential sorting from early to Rab11(+) recycling endosomes and multivesicular bodies. Virus-containing endocytic viral cargoes propelled by myosin II through BC spread to neighboring uninfected cells. Disruption of endosomal motility with cytochalasin D, nocodasole and blebbistatin diminish intercellular viral spread. These data lead us to propose that HIV-1 hijacks macrophage endocytic and cytoskeletal machineries for high-speed cell-to-cell spread.
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Viral proteins and RNA can be found in endosomes within macrophage TNTs.
“According to a study by Kadiu and Gendelman, viral proteins and RNA can be even found in endosomes within macrophage TNTs [111].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [111]
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- Authors
- Kadiu, I., & Gendelman, H. E.
- Affiliations
- Nebraska Medical Center (US)
- Corresponding author
- Gendelman, Howard E.
- ORCID
- Gendelman, Howard E.
- Venue
- Journal of Neuroimmune Pharmacology
- Published
- 2011-07-26
- Volume
- 6
- Issue
- 4
- Pages
- 658-675
- ISSN
- 1557-1890 (ISSN-L)
- 1557-1904
- PMC
- PMC3232570
- OpenAlex
- W2062874567
- Cited by
- 100
- References
- 58
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 9 · 2013: 6 · 2012: 8
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of Neuroimmune Pharmacology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (RR15635, DA028555)
- National Institute of Mental Health (P01 MH 64570, P30MH062261, P01MH064570)
- National Institute on Drug Abuse (P01DA028555, P20DA026146, P01DA026146)
- National Institute of Neurological Disorders and Stroke (R01-NS-36126, P01-NS31492, P01 NS 43985, R01NS036126, P01NS031492, P01NS043985, R01NS034239)
- National Center for Research Resources (P20 RR-15635, P20RR015635)
- National Institute on Minority Health and Health Disparities (G12MD007600)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Keywords
- HIV-1, macrophages, cell-to-cell viral spread, endosomal trafficking, multivesicular bodies, myosin II, cytoskeleton
- MeSH terms
- Cell Communication, Endocytosis, Humans, Immunohistochemistry, Macrophages, Microscopy, Electron, Endosomes, HIV-1, HIV Infections, In Situ Hybridization, Fluorescence, Microscopy, Confocal
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