Infection of Specific Dendritic Cells by CCR5-tropic Human Immunodeficiency Virus Type 1 Promotes Cell-mediated Transmission of Virus Resistant to Broadly Neutralizing Antibodies

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2004 Oct 14

PMID 15479838

Citations 85

Authors

Lakshmanan Ganesh

Kwanyee Leung

Karin Lore

Reuven Levin

Amos Panet

Owen Schwartz

Richard A Koup

Gary J Nabel

Affiliations

Soon will be listed here.

Abstract

The tropism of human immunodeficiency virus type 1 for chemokine receptors plays an important role in the transmission of AIDS. Although CXCR4-tropic virus is more cytopathic for T cells, CCR5-tropic strains are transmitted more frequently in humans for reasons that are not understood. Phenotypically immature myeloid dendritic cells (mDCs) are preferentially infected by CCR5-tropic virus, in contrast to mature mDCs, which are not susceptible to infection but instead internalize virus into a protected intracellular compartment and enhance the infection of T cells. Here, we define a mechanism to explain preferential transmission of CCR5-tropic viruses based on their interaction with mDCs and sensitivity to neutralizing antibodies. Infected immature mDCs differentiated normally and were found to enhance CCR5-tropic but not CXCR4-tropic virus infection of T cells even in the continuous presence of neutralizing antibodies. Infectious synapses also formed normally in the presence of such antibodies. Infection of immature mDCs by CCR5-tropic virus can therefore establish a pool of infected cells that can efficiently transfer virus at the same time that they protect virus from antibody neutralization. This property of DCs may enhance infection, contribute to immune evasion, and could provide a selective advantage for CCR5-tropic virus transmission.

Citing Articles

Role of Rab13, Protein Kinase A, and Zonula Occludens-1 in Hepatitis E Virus Entry and Cell-to-Cell Spread: Comparative Analysis of Quasi-Enveloped and Non-Enveloped Forms.

Nagashima S, Primadharsini P, Takahashi M, Nishiyama T, Murata K, Okamoto H Pathogens. 2025; 13(12.

PMID: 39770389 PMC: 11678111. DOI: 10.3390/pathogens13121130.

Cytoskeletal Vimentin Directs Cell-Cell Transmission of Hepatitis C Virus.

Xing Y, Wen Z, Mei J, Huang X, Zhao S, Zhong J Adv Sci (Weinh). 2024; 12(3):e2408917.

PMID: 39611409 PMC: 11744697. DOI: 10.1002/advs.202408917.

Exploiting hosts and vectors: viral strategies for facilitating transmission.

Yu X, Zhu Y, Yin G, Wang Y, Shi X, Cheng G EMBO Rep. 2024; 25(8):3187-3201.

PMID: 39048750 PMC: 11315993. DOI: 10.1038/s44319-024-00214-6.

Mucosal application of the broadly neutralizing antibody 10-1074 protects macaques from cell-associated SHIV vaginal exposure.

Suphaphiphat K, Desjardins D, Lorin V, Dimant N, Bouchemal K, Bossevot L Nat Commun. 2023; 14(1):6224.

PMID: 37803011 PMC: 10558491. DOI: 10.1038/s41467-023-41966-4.

Tight junction protein occludin is an internalization factor for SARS-CoV-2 infection and mediates virus cell-to-cell transmission.

Zhang J, Yang W, Roy S, Liu H, Roberts R, Wang L Proc Natl Acad Sci U S A. 2023; 120(17):e2218623120.

PMID: 37068248 PMC: 10151465. DOI: 10.1073/pnas.2218623120.

References

Geijtenbeek T, Kwon D, Torensma R, van Vliet S, van Duijnhoven G, Middel J . DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 2000; 100(5):587-97. DOI: 10.1016/s0092-8674(00)80694-7. View

Pope M, Gezelter S, Gallo N, Hoffman L, Steinman R . Low levels of HIV-1 infection in cutaneous dendritic cells promote extensive viral replication upon binding to memory CD4+ T cells. J Exp Med. 1995; 182(6):2045-56. PMC: 2192232. DOI: 10.1084/jem.182.6.2045. View

Turville S, Arthos J, Donald K, Lynch G, Naif H, Clark G . HIV gp120 receptors on human dendritic cells. Blood. 2001; 98(8):2482-8. DOI: 10.1182/blood.v98.8.2482. View

Donaghy H, Pozniak A, Gazzard B, Qazi N, Gilmour J, Gotch F . Loss of blood CD11c(+) myeloid and CD11c(-) plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load. Blood. 2001; 98(8):2574-6. DOI: 10.1182/blood.v98.8.2574. View

Zwick M, Labrijn A, Wang M, Spenlehauer C, Saphire E, Binley J . Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J Virol. 2001; 75(22):10892-905. PMC: 114669. DOI: 10.1128/JVI.75.22.10892-10905.2001. View

Folcik R, Merrill J, Li Y, Guo C, Douglas S, Starr S . HIV-1 infection of placental cord blood monocyte-derived dendritic cells. J Hematother Stem Cell Res. 2001; 10(5):609-20. PMC: 4009687. DOI: 10.1089/152581601753193823. View

Steinman R, Nussenzweig M . Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci U S A. 2002; 99(1):351-8. PMC: 117564. DOI: 10.1073/pnas.231606698. View

Kwon D, Gregorio G, Bitton N, Hendrickson W, Littman D . DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity. 2002; 16(1):135-44. DOI: 10.1016/s1074-7613(02)00259-5. View

Mascola J, Louder M, Winter C, Prabhakara R, De Rosa S, Douek D . Human immunodeficiency virus type 1 neutralization measured by flow cytometric quantitation of single-round infection of primary human T cells. J Virol. 2002; 76(10):4810-21. PMC: 136170. DOI: 10.1128/jvi.76.10.4810-4821.2002. View

10.

Wu L, Martin T, Vazeux R, Unutmaz D, KewalRamani V . Functional evaluation of DC-SIGN monoclonal antibodies reveals DC-SIGN interactions with ICAM-3 do not promote human immunodeficiency virus type 1 transmission. J Virol. 2002; 76(12):5905-14. PMC: 136240. DOI: 10.1128/jvi.76.12.5905-5914.2002. View

11.

Alvarez C, Lasala F, Carrillo J, Muniz O, Corbi A, Delgado R . C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans. J Virol. 2002; 76(13):6841-4. PMC: 136246. DOI: 10.1128/jvi.76.13.6841-6844.2002. View

12.

Engering A, van Vliet S, Geijtenbeek T, van Kooyk Y . Subset of DC-SIGN(+) dendritic cells in human blood transmits HIV-1 to T lymphocytes. Blood. 2002; 100(5):1780-6. DOI: 10.1182/blood-2001-12-0179. View

13.

Turville S, Cameron P, Handley A, Lin G, Pohlmann S, Doms R . Diversity of receptors binding HIV on dendritic cell subsets. Nat Immunol. 2002; 3(10):975-83. DOI: 10.1038/ni841. View

14.

Gummuluru S, KewalRamani V, Emerman M . Dendritic cell-mediated viral transfer to T cells is required for human immunodeficiency virus type 1 persistence in the face of rapid cell turnover. J Virol. 2002; 76(21):10692-701. PMC: 136613. DOI: 10.1128/jvi.76.21.10692-10701.2002. View

15.

McDonald D, Vodicka M, Lucero G, Svitkina T, Borisy G, Emerman M . Visualization of the intracellular behavior of HIV in living cells. J Cell Biol. 2002; 159(3):441-52. PMC: 2173076. DOI: 10.1083/jcb.200203150. View

16.

Halary F, Amara A, Lortat-Jacob H, Messerle M, Delaunay T, Houles C . Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection. Immunity. 2002; 17(5):653-64. DOI: 10.1016/s1074-7613(02)00447-8. View

17.

Lin G, Simmons G, Pohlmann S, Baribaud F, Ni H, Leslie G . Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR. J Virol. 2002; 77(2):1337-46. PMC: 140807. DOI: 10.1128/jvi.77.2.1337-1346.2003. View

18.

Ketas T, Frank I, Klasse P, Sullivan B, Gardner J, Spenlehauer C . Human immunodeficiency virus type 1 attachment, coreceptor, and fusion inhibitors are active against both direct and trans infection of primary cells. J Virol. 2003; 77(4):2762-7. PMC: 141110. DOI: 10.1128/jvi.77.4.2762-2767.2003. View

19.

Tassaneetrithep B, Burgess T, Granelli-Piperno A, Trumpfheller C, Finke J, Sun W . DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. J Exp Med. 2003; 197(7):823-9. PMC: 2193896. DOI: 10.1084/jem.20021840. View

20.

Donaghy H, Gazzard B, Gotch F, Patterson S . Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1. Blood. 2003; 101(11):4505-11. DOI: 10.1182/blood-2002-10-3189. View