Suppressive and stimulatory host processes during virus infection fate decisions

The processes and mechanisms of virus infection fate decisions that are the result of a dynamic virus - immune system interaction with either an efficient effector response and virus elimination or an alleviated immune response and chronic infection are poorly understood. Here we characterized the host response to acute and chronic lymphocytic choriomeningitis virus (LCMV) infections by gene coexpression network analysis of time-resolved splenic transcriptomes. We found first, an early attenuation of inflammatory monocyte/macrophage prior to the onset of T cell exhaustion and second, a critical role of the XCL1-XCR1 communication axis during the functional adaptation of the T cell response to the chronic infection state. These findings not only reveal an important feedback mechanism that couples T cell exhaustion with the maintenance of a lower level of effector T cell response but also suggest therapy options to better control virus levels during the chronic infection phase. Overall design: mRNA profiles of spleens (in duplicate, days 0, 3, 5, 6, 7, 9 and 31 post-infection) and macrophages (in triplicate, day 6 post-infection) from C57BL/6 mice infected with 2x10E2 (acute) or 2x10E6 (chronic) pfu of LCMV strain Docile, generated by deep sequencing.

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Argilaguet J, Pedragosa M, Esteve-Codina A, Riera G, Vidal E, Peligero-Cruz C, Casella V, Andreu D, Kaisho T, Bocharov G, Ludewig B, Heath S, Meyerhans A