RT Journal
A1 Argilaguet, Jordi
A1 Pedragosa, Mireia
A1 Esteve-Codina, Anna
A1 Riera, Graciela
A1 Vidal, Enric
A1 Peligero-Cruz, Cristina
A1 Casella, Valentina
A1 Andreu, David
A1 Kaisho, Tsuneyasu
A1 Bocharov, Gennady
A1 Ludewig, Burkhard
A1 Heath, Simon
A1 Meyerhans, Andreas
T1 Systems analysis reveals complex biological processes during virus infection fate decisions
JF Genome Research 
JO Genome Research 
YR 2019 
FD June 01 
VO 29 
IS 6 
SP 907 
OP 919 
DO 10.1101/gr.241372.118 
UL http://genome.cshlp.org/content/29/6/907.abstract 
AB 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.