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Journal of Virology, July 2007, p. 7559-7570, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.02572-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Maturation of Blood-Derived Dendritic Cells Enhances Human Immunodeficiency Virus Type 1 Capture and Transmission{triangledown} ,{dagger}

Nuria Izquierdo-Useros,1 Julià Blanco,1 Itziar Erkizia,1 Maria Teresa Fernández-Figueras,2 Francesc E. Borràs,3 Mar Naranjo-Gómez,3 Margarita Bofill,1,4 Lidia Ruiz,1 Bonaventura Clotet,1 and Javier Martinez-Picado1,4*

IrsiCaixa Foundation,1 Department of Pathology,2 Laboratory of Immunobiology for Research and Application to Diagnosis, Blood and Tissue Bank, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain,3 Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain4

Received 21 November 2006/ Accepted 20 April 2007

Dendritic cells (DCs) are specialized antigen-presenting cells. However, DCs exposed to human immunodeficiency virus type 1 (HIV-1) are also able to transmit a vigorous cytopathic infection to CD4+ T cells, a process that has been frequently related to the ability of DC-SIGN to bind HIV-1 envelope glycoproteins. The maturation of DCs can increase the efficiency of HIV-1 transmission through trans infection. We aimed to comparatively study the effect of maturation in monocyte-derived DCs (MDDCs) and blood-derived myeloid DCs during the HIV-1 capture process. In vitro capture and transmission of envelope-pseudotyped HIV-1 and its homologous replication-competent virus to susceptible target cells were assessed by p24gag detection, luciferase activity, and both confocal and electron microscopy. Maturation of MDDCs or myeloid DCs enhanced the active capture of HIV-1 in a DC-SIGN- and viral envelope glycoprotein-independent manner, increasing the life span of trapped virus. Moreover, higher viral transmission of mature DCs to CD4+ T cells was highly dependent on active viral capture, a process mediated through cholesterol-enriched domains. Mature DCs concentrated captured virus in a single large vesicle staining for CD81 and CD63 tetraspanins, while immature DCs lacked these structures, suggesting different intracellular trafficking processes. These observations help to explain the greater ability of mature DCs to transfer HIV-1 to T lymphocytes, a process that can potentially contribute to the viral dissemination at lymph nodes in vivo, where viral replication takes place and there is a continuous interaction between susceptible T cells and mature DCs.

* Corresponding author. Mailing address: IrsiCaixa Foundation, Hospital Germans Trias i Pujol, Ctra. de Canyet s/n, 08916 Badalona, Spain. Phone: 34 93 4656374. Fax: 34 93 4653968. E-mail: jmpicado{at}irsicaixa.es

{triangledown} Published ahead of print on 2 May 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, July 2007, p. 7559-7570, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.02572-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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