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Journal of Virology, October 2004, p. 10516-10524, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10516-10524.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Macrophages, but Not Dendritic Cells, Are Activated and Produce Alpha/Beta Interferons in Response to Mopeia Virus Infection

Delphine Pannetier,1 Caroline Faure,1 Marie-Claude Georges-Courbot,1 Vincent Deubel,1 and Sylvain Baize1*

Unité de Biologie des Infections Virales Emergentes, Institut Pasteur—IFR 128 Biosciences Lyon-Gerland, Lyon, France1

Received 5 March 2004/ Accepted 21 May 2004

Lassa virus (LV) and Mopeia virus (MV) are closely related members of the Arenavirus genus, sharing 75% amino acid sequence identity. However, LV causes hemorrhagic fever in humans and nonhuman primates, whereas MV cannot induce disease. We have previously shown that antigen-presenting cells (APC)—macrophages (MP) and dendritic cells (DC)—sustain high replication rates of LV but are not activated, suggesting that they play a role in the immunosuppression observed in severe cases of Lassa fever. Here, we infected human APC with MV and analyzed the cellular responses induced. MV infection was productive in MP and even more so in DC. Apoptosis was not induced in either cell type. Moreover, unlike DC, MP were early and strongly activated in response to MV, as shown by the increased surface expression of CD86, CD80, CD54, CD40, and HLA-abc and by the production of mRNA encoding alpha interferon (IFN-{alpha}), IFN-ß, tumor necrosis factor alpha and interleukin-6. In addition, MV-infected MP produced less of the virus than DC, which was related to the fact that these cells secreted IFN-{alpha}. Thus, the strong activation of MP is probably a major event in the control of MV infection and may be involved in the induction of an adaptive immune response in infected hosts. These results may explain the difference in pathogenicity between LV and MV.

* Corresponding author. Mailing address: UBIVE, Institut Pasteur, 21, avenue Tony Garnier, 69365 Lyon Cedex 07, France. Phone: 33 4 37 28 24 44. Fax: 33 4 37 28 24 41. E-mail: baize{at}cervi-lyon.inserm.fr.

Journal of Virology, October 2004, p. 10516-10524, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10516-10524.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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