Kantonsspital St.Gallen

Systems analysis reveals complex biological processes during virus infection fate decisions

Jordi Argilaguet, Mireia Pedragosa, Anna Esteve-Codina, Graciela Riera, Enric Vidal, Cristina Gil Cruz, Valentina Casella, David Andreu, Tsuneyasu Kaisho, Gennady Bocharov, Burkhard Ludewig, Simon Heath & Andreas Meyerhans

abstract 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. First, we found 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.
citation Argilaguet J, Pedragosa M, Esteve-Codina A, Riera G, Vidal E, Gil Cruz C, Casella V, Andreu D, Kaisho T, Bocharov G, Ludewig B, Heath S, Meyerhans A. Systems analysis reveals complex biological processes during virus infection fate decisions. Genome Res 2019; 29:907-919.
type journal paper/review (English)
date of publishing 28-05-2019
journal title Genome Res (29/6)
ISSN electronic 1549-5469
pages 907-919
PubMed 31138618
DOI 10.1101/gr.241372.118