Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4+ T cells
Abstract
Cell-free human T-lymphotropic virus type 1 (HTLV-1) virions are poorly infectious in vitro for their primary target cells, CD4(+) T cells. Here, we show that HTLV-1 can efficiently infect myeloid and plasmacytoid dendritic cells (DCs). Moreover, DCs exposed to HTLV-1, both before and after being productively infected, can rapidly, efficiently and reproducibly transfer virus to autologous primary CD4(+) T cells. This DC-mediated transfer of HTLV-1 involves heparan sulfate proteoglycans and neuropilin-1 and results in long-term productive infection and interleukin-2-independent transformation of the CD4(+) T cells. These studies, along with observations of HTLV-1-infected DCs in the peripheral blood of infected individuals, indicate that DCs have a central role in HTLV-1 transmission, dissemination and persistence in vivo. In addition to altering the current paradigm concerning how HTLV-1 transmission occurs, these studies suggest that impairment of DC function after HTLV-1 infection plays a part in pathogenesis.
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Purified HTLV-1 virions, though having low infectivity for T lymphocytes, efficiently infect DCs of monocytic origin (MDDCs), as well as plasmacytoid and immature myeloid DCs.
“In 2008, Kathryn Jones and colleagues demonstrated for the first time that purified HTLV-1 virions, though having low infectivity for T lymphocytes, efficiently infect DCs of monocytic origin (MDDCs), as well as plasmacytoid and immature myeloid DCs [71].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [71]
There are two phases of HTLV-1 transmission between immature DCs and T cells: trans-infection immediately after virion capture, followed later by cis-infection by viral particles synthesized de novo.
“As with HIV-1 transmission, there are two phases of HTLV-1 transmission between immature DCs and T cells. Trans-infection takes place immediately after the virions are captured, followed later by cis-infection by viral particles synthesized de novo [71].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [71]
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- Authors
- Jones, K. S., Petrow-Sadowski, C., Huang, Y. K., Bertolette, D. C., & Ruscetti, F. W.
- Affiliations
- Science Applications International Corporation (United States) (US)
- Frederick National Laboratory for Cancer Research (US)
- Corresponding author
- Jones, Kathryn S
- Venue
- Nature Medicine
- Published
- 2008-03-23
- Volume
- 14
- Issue
- 4
- Pages
- 429-436
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2122782505
- Cited by
- 284
- References
- 50
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 12 · 2023: 9 · 2022: 12 · 2021: 7 · 2020: 7 · 2019: 14 · 2018: 15 · 2017: 21 · 2016: 10 · 2015: 14 · 2014: 28 · 2013: 23 · 2012: 19
- FWCI
- 11.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01co12400-79-0-22)
- National Cancer Institute (N01CO12400)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- HTLV-1, dendritic cells, heparan sulfate proteoglycans, neuropilin-1, viral dissemination, viral persistence, myeloid dendritic cells, plasmacytoid dendritic cells
- MeSH terms
- Cell Communication, Cell Line, Cell Transformation, Viral, Cell-Free System, Dendritic Cells, Humans, Lymphocyte Activation, Human T-lymphotropic virus 1, HTLV-I Infections, CD4-Positive T-Lymphocytes, Heparan Sulfate Proteoglycans, Immunophilins, In Vitro Techniques
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