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J Virol, July 1998, p. 5852-5861, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Contact with Thymic Epithelial Cells as a Prerequisite for Cytokine-Enhanced Human Immunodeficiency Virus Type 1 Replication in Thymocytes

Maurice Rothe, Laurent Chêne, Marie-Thérèse Nugeyre, Joséphine Braun, Françoise Barré-Sinoussi, and Nicole Israël*

Unité de Biologie des Rétrovirus, Institut Pasteur, 75724 Paris Cedex 15, France

Received 28 October 1997/Accepted 2 April 1998

We report here that human immunodeficiency virus type 1 (HIV-1)-infected human thymocytes, in the absence of any exogenous stimulus but cocultivated with autologous thymic epithelial cells (TEC), obtained shortly (3 days) after thymus excision produce a high and sustained level of HIV-1 particles. The levels and kinetics of HIV-1 replication were similar for seven distinct viral strains irrespective of their phenotypes and genotypes. Contact of thymocytes with TEC is a critical requirement for optimal viral replication. Rather than an inductive signal resulting from the contact itself, soluble factors produced in the mixed culture are responsible for this effect. Specifically, the synergistic effects of tumor necrosis factor, interleukin-1 (IL-1), IL-6, and granulocyte-macrophage colony-stimulating factor may account by themselves for the high level of HIV-1 replication in thymocytes observed in mixed cultures. In conclusion, the microenvironment generated by TEC-thymocyte interaction might greatly favor optimal HIV-1 replication in the thymus.

* Corresponding author. Mailing address: Unité de Biologie des Rétrovirus, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 33 1 4568 8944/8733. Fax: 33 1 4568 8957. E-mail: nisrael{at}pasteur.fr.

J Virol, July 1998, p. 5852-5861, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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