In Vitro Derived Dendritic Cells trans-Infect CD4 T Cells Primarily with Surface-Bound HIV-1 Virions
Open accessAbstract
In the prevailing model of HIV-1 trans-infection, dendritic cells (DCs) capture and internalize intact virions and transfer these virions to interacting T cells at the virological synapse. Here, we show that HIV-1 virions transmitted in trans from in vitro derived DCs to T cells principally originate from the surface of DCs. Selective neutralization of surface-bound virions abrogated trans-infection by monocyte-derived DCs and CD34-derived Langerhans cells. Under conditions mimicking antigen recognition by the interacting T cells, most transferred virions still derived from the cell surface, although a few were transferred from an internal compartment. Our findings suggest that attachment inhibitors could neutralize trans-infection of T cells by DCs in vivo.
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Later, immature DCs become productively infected and transmit viral particles produced de novo to T cells in the cis-infection process.
“Later, immature DCs become productively infected, and transmit viral particles produced de novo to T cells in the cis-infection process [66,67,69,70].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [66]
The Introduction defines the de novo pathway as infection of DCs followed by budding and spread of new virions to CD4 T cells. The Results/Discussion report that immature monocyte-derived DCs transmit R5-tropic HIV-1 through this pathway in the later phase (days 1–5). The claim omits that viral-strain qualification: the paper says immature DCs transmit X4-tropic HIV-1 principally through the trans pathway. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNeutralization of DC surface-bound HIV-1 virions with soluble CD4 completely prevents trans-infection of T cells.
“This model is based on a report by Cavrois et al. showing that neutralization of the DC surface-bound HIV-1 virions with soluble CD4 completely prevented the trans-infection of T cells [66].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [66]
In Results/Discussion, under “Neutralizing Surface-Bound Virions on DCs Abrogates trans-Infection” (page unavailable), the paper reports that soluble CD4 blocked transmission of surface-bound HIV-1. But it also notes low levels of transmission in the presence of soluble CD4; under “trans-Infection in the Context of Superantigen Stimulation,” a few virions were transmitted from an sCD4-resistant compartment. Thus, “completely prevented” overstates the finding across the reported conditions. (LLM, conf=0.91)
Experimental — accuracy not yet measuredDifferent mechanisms of HIV-1 transmission are possible at different anatomic sites in vivo.
“Therefore, different mechanisms of HIV-1 transmission are possible at different anatomic sites in vivo [66].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [66]
In trans-infection, immature and mature DCs transmit captured HIV-1 to T cells within the first 24 h without being infected themselves.
“In trans-infection, immature and mature DCs transmit captured HIV-1 to T cells within the first 24 h without being infected themselves [66,67,68].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [66]
The healthy mucosa contains immature DCs, whereas the lymph nodes and gut-associated lymphoid tissue contain mature DCs.
“The healthy mucosa contains immature DCs, whereas the lymph nodes and gut-associated lymphoid tissue contain mature DCs.”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [66]
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Cites
DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T cell infection
Kwon, D. S., Gregorio, G., Bitton, N., Hendrickson, W. A., & Littman, D. R. (2002) · Immunity · doi:10.1016/s1074-7613(02)00259-5 · Cited by 523 · cited 3× · see citing works
“These results in MDDCs and LCs sharply contrast with the report that formed the basis for the prevailing model of transinfection [21].”
MethodResultBurleigh, L., Lozach, P.-Y., Schiffer, C., Staropoli, I., Pezo, V., Porrot, F., Canque, B., Virelizier, J.-L., Arenzana-Seisdedos, F., & Amara, A. (2006) · Journal of Virology · doi:10.1128/jvi.80.6.2949-2957.2006 · Cited by 151 · cited 6× · see citing works
“Since the immature MDDCs used in that study are highly susceptible to fusion with the R5-tropic BaL envelopes [12] and efficiently replicate CCR5-tropic HIV-1 [15,22], the luciferase activity may have derived from infected immature MDDCs, not T cells, in the coculture.”
ResultInfluential
Flagged first, then by citations
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Avoiding the void: Cell-to-cell spread of human viruses
Sattentau, Q. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1972 · Cited by 614 · see citing works
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Bitter-sweet symphony: glycan–lectin interactions in virus biology
Van Breedam, W., Pöhlmann, S., Favoreel, H. W., de Groot, R. J., & Nauwynck, H. J. (2014) · FEMS Microbiology Reviews · doi:10.1111/1574-6976.12052 · Cited by 141 · see citing works
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HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread
Kalinichenko, S., Komkov, D., & Mazurov, D. (2022) · Viruses · doi:10.3390/v14010152 · Cited by 68 · see citing works
“Therefore, different mechanisms of HIV-1 transmission are possible at different anatomic sites in vivo [66].”
Background
- Authors
- Cavrois, M., Neidleman, J., Kreisberg, J. F., & Greene, W. C.
- Affiliations
- Gladstone Institutes (US)
- Corresponding author
- Greene, Warner C.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007
- Volume
- 3
- Issue
- 1
- Pages
- e4
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC1779297
- OpenAlex
- W2043152270
- Cited by
- 141
- References
- 2
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 5 · 2021: 2 · 2020: 7 · 2019: 8 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 8 · 2014: 10 · 2013: 16 · 2012: 14
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (AMD3100, 1c06rr018928-01)
- Center for AIDS Research, University of Washington
- University of California, San Francisco
- National Institute of Allergy and Infectious Diseases (P30-AI-27763, R03AI062263, P30AI027763)
- National Center for Research Resources (RR 18928-01, S10RR022448, C06-RR-018928)
- National Institute on Minority Health and Health Disparities (L60 MD003100)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01 HD40543, P01HD040543)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Keywords
- dendritic cells, CD4+ T cells, virological synapse, Langerhans cells, monocyte-derived dendritic cells, virus transmission
- MeSH terms
- Animals, Dendritic Cells, Humans, Virion, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, In Vitro Techniques
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