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Journal of Virology, January 2004, p. 798-810, Vol. 78, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.2.798-810.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

DC-SIGN from African Green Monkeys Is Expressed in Lymph Nodes and Mediates Infection in trans of Simian Immunodeficiency Virus SIVagm

Mickaël J.-Y. Ploquin,1 Ousmane M. Diop,2 Nathalie Sol-Foulon,3 Lorenzo Mortara,1,{dagger} Abdourahmane Faye,2 Marcelo A. Soares,1,{ddagger} Eric Nerrienet,4 Roger Le Grand,5 Yvette Van Kooyk,6 Ali Amara,7,§ Olivier Schwartz,3 Françoise Barré-Sinoussi,1 and Michaela C. Müller-Trutwin1*

Unité de Biologie des Rétrovirus,1 Virus et Immunité,3 Unité d'Immunologie Virale, Institut Pasteur, Paris,7 CEA, Fontenay aux Roses, France,4 Laboratoire de Rétrovirologie, Institut Pasteur, Dakar, Senegal,2 Centre Pasteur du Cameroun, Yaoundé, Cameroon,5 Department of Molecular Cell Biology, Free University Medical Center, Amsterdam, The Netherlands6

Received 19 June 2003/ Accepted 3 October 2003

African green monkeys (AGMs) infected by simian immunodeficiency virus (SIV) SIVagm are resistant to AIDS. SIVagm-infected AGMs exhibit levels of viremia similar to those described during pathogenic human immunodeficiency virus type 1 (HIV-1) and SIVmac infections in humans and macaques, respectively, but contain lower viral loads in their lymph nodes. We addressed the potential role of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN; CD209) in viral dissemination. In previous studies, it has been shown that human DC-SIGN and macaque DC-SIGN allow transmission of HIV and SIVmac to T cells. Here, we looked at the ability of DC-SIGN derived from AGM lymph nodes to interact with SIVagm. We show that DC-SIGN-expressing cells are present mainly in the medulla and often within the cortex and/or paracortex of AGM lymph nodes. We describe the isolation and characterization of at least three isoforms of dc-sign mRNA in lymph nodes of AGMs. The predicted amino acid sequence from the predominant mRNA isoform, DC-SIGNagm1, is 92 and 99% identical to the corresponding human and rhesus macaque DC-SIGN amino acid sequences, respectively. DC-SIGNagm1 is characterized by the lack of the fourth motif in the repeat domain. This deletion was also detected in the dc-sign gene derived from thirteen animals belonging to five other African monkey species and from four macaques (Macaca fascicularis and M. mulatta). Despite three- to seven-amino-acid modifications compared to DC-SIGNmac, DC-SIGNagm1 allows transmission of SIVagm to T cells. Furthermore, AGM monocyte-derived dendritic cells (MDDC) expressed at least 100,000 DC-SIGN molecules and were able to transmit SIVagm to T cells. At a low multiplicity of infection (10-5 50% tissue culture infective doses/cell), viral transmission by AGM MDDC was mainly DC-SIGN dependent. The present study reveals that DC-SIGN from a natural host species of SIV has the ability to act as an efficient attachment and transmission factor for SIVagm and suggests the absence of a direct link between this ability and viral load levels in lymph nodes.

* Corresponding author. Mailing address: Unité de Biologie des Rétrovirus, Institut Pasteur, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: (33)1-40-61-39-69. Fax: (33)1-45-68-89-57. E-mail: mmuller{at}pasteur.fr.

{dagger} Present address: Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Varese, Italy.

{ddagger} Present address: Departamento de Genética, Instituto de Biologia-Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

§ Present address: Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, NY 10016.

Journal of Virology, January 2004, p. 798-810, Vol. 78, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.2.798-810.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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