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Journal of Virology, May 2005, p. 5386-5399, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5386-5399.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Covert Human Immunodeficiency Virus Replication in Dendritic Cells and in DC-SIGN-Expressing Cells Promotes Long-Term Transmission to Lymphocytes

Cinzia Nobile,1 Caroline Petit,2 Arnaud Moris,1 Katharina Skrabal,3 Jean-Pierre Abastado,4 Fabrizio Mammano,3 and Olivier Schwartz1*

Groupe Virus et Immunité, URA CNRS 1930, Institut Pasteur,1 Institut Cochin,2 INSERM U552-Recherche Antivirale, Hôpital Bichat,3 IDM Research Laboratories, Institut des Cordeliers, Paris, France4

Received 27 September 2004/ Accepted 6 December 2004

HIV-1 virions are efficiently captured by monocyte-derived immature dendritic cells (iDCs), as well as by cell lines expressing the lectin DC-SIGN. Viral infectivity can be retained for several days, and even enhanced, before transmission to CD4+ lymphocytes. The role of DC-SIGN in viral retention and enhancement of infection is not fully understood and varies according to the cell line expressing the lectin. We studied here the mechanisms underlying this process. We focused our study on X4-tropic human immunodeficiency virus (HIV) strains, since they were widely believed not to replicate in iDCs. However, we first show that X4 HIV replicates covertly and slowly in iDCs. This is also the case in Raji-DC-SIGN cells, which are classically used to study HIV transmission. We used either single-cycle or replicative HIV and measured viral RT and replication to further demonstrate that transfer of incoming virions from iDCs or DC-SIGN+ cells occurs only on the short-term (i.e., a few hours after viral exposure). There is no long-term storage of original HIV particles in these cells. A few days after viral exposure, replicative viruses, and not single-cycle virions, are transmitted to CD4+ cells. The cell-type-dependent activity of DC-SIGN reflects the ability of HIV to replicate covertly in some cells, and not in others.

* Corresponding author. Mailing address: Institut Pasteur, Groupe Virus et Immunité, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: 33 1 45 68 83 53. Fax: 33 1 40 61 34 65. E-mail: schwartz{at}pasteur.fr.

Journal of Virology, May 2005, p. 5386-5399, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5386-5399.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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