The role of CXCL9 in host defense during acute viral infection of the CNS and liver in mice: Perspectives using a recombinant mouse hepatitis virus

We investigated the role that the murine chemokine CXCL9 plays in host defense against viral infections of the central nervous system (CNS) and liver. A recombinant virus derived from the A59 strain of MHV (MHV-A59) was engineered to encode the murine CXCL9 coding sequence (MHV-CXCL9). An isogenetic non-CXCL9-expressing virus (MHV-cCXCL9) was also created. Intracranial administration of either virus into susceptible RAG1-/- or CXCL9-/- mice resulted in acute viral infection and replication within both the CNS and liver. Virally-directed ectopic-expression of the CXCL9 chemokine resulted in improved immune control of viral replication in both mouse strains. Mice receiving the MHV-CXCL9 virus had lower viral titers, less liver disease and increased immune cell infiltration into infected tissues resulting in dramatic reductions in mortality rates compared to MVH-cCXCL9 infected mice. These data demonstrate that CXCL9 plays an important role in host defense against viral infections of the CNS and liver.