Lassa virus activates myeloid dendritic cells but suppresses their ability to stimulate T cells.

Justine Schaeffer,Caroline Picard,Marie-Agnès Dillies,Stéphanie Reynard,Natalia Pietrosemoli,Xavier Carnec,Mathieu Mateo,Sylvain Baize,Stefan Kunz

doi:10.1371/journal.ppat.1007430

Abstract

Lassa virus (LASV) is responsible for a viral hemorrhagic fever in humans and the death of 3,000 to 5,000 people every year. The immune response to LASV is poorly understood, but type I interferon (IFN-I) and T-cell responses appear to be critical for the host. We studied the response of myeloid dendritic cells (mDC) to LASV, as mDCs are involved in both IFN-I production and T-cell activation. We compared the response of primary human mDCs to LASV and Mopeia virus (MOPV), which is similar to LASV, but non-pathogenic. We showed that mDCs produced substantial amounts of IFN-I in response to both LASV and MOPV. However, only MOPV-infected mDCs were able to activate T cells. More surprisingly, coculture with T cells completely inhibited the activation of LASV-infected mDCs. These differences between LASV and MOPV were mostly due to the LASV nucleoprotein, which has major immunosuppressive properties, but the glycoprotein was also involved. Overall, these results suggest that mDCs may be important for the global response to LASV and play a role in the outcome of Lassa fever.

Highlights

Viral hemorrhagic fevers (VHF) are an important global health problem with a significant yearly death toll
We showed that primary human myeloid dendritic cells are activated by Lassa virus infection, and produce type I interferon
Results myeloid dendritic cells (mDC) are activated by Mopeia virus (MOPV) and Lassa virus (LASV) infection

Summary

Introduction

Viral hemorrhagic fevers (VHF) are an important global health problem with a significant yearly death toll. Among VHFs, Lassa fever (LF) is endemic in West Africa, with an estimated 300,000 to 500,000 cases and 3,000 to 5,000 deaths every year [1]. Lassa virus (LASV), the causative agent of LF, is listed by the World Health Organization (WHO) as one of the emerging pathogens likely to cause severe outbreaks in the near future, and for which there are few or no medical countermeasures [3]. This enveloped virus contains two segments of negative strand RNA (S and L) coding for four proteins. ORFs are coded in ambisense and separated by a hairpin structure containing termination sites

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