Insertion of the CXC chemokine ligand 9 (CXCL9) into the mouse hepatitis virus genome results in protection from viral-induced encephalitis and hepatitis.
The role of the CXC chemokine ligand 9 (CXCL9) in host defense following infection with mouse hepatitis virus (MHV) was determined. Inoculation of the central nervous system (CNS) of CXCL9-/- mice with MHV resulted in accelerated and increased mortality compared to wild type mice supporting an important role for CXCL9 in anti-viral defense. In addition, infection of RAG1-/- or CXCL9-/- mice with a recombinant MHV expressing CXCL9 (MHV-CXCL9) resulted in protection from disease that correlated with reduced viral titers within the brain and NK cell-mediated protection in the liver. Survival in MHV-CXCL9-infected CXCL9-/- mice was associated with reduced viral burden within the brain that coincided with increased T cell infiltration. Similarly, viral clearance from the livers of MHV-CXCL9-infected mice was accelerated but independent of increased T cell or NK cell infiltration. These observations indicate that CXCL9 promotes protection from coronavirus-induced neurological and liver disease.
Muse
Michael
M
Department of Molecular Biology and Biochemistry, University of California, Irvine 92619-3900, USA.
Kane
Joy A C
JA
Carr
Daniel J J
DJ
Farber
Joshua M
JM
Lane
Thomas E
TE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D054370:Chemokine CXCL9 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D018352:Coronavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018792:Encephalitis, Viral / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D016679:Genome, Viral; D006524:Hepatitis, Viral, Animal / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D011995:Recombination, Genetic; D014779:Virus Replication
D054370:Chemokine CXCL9; C485969:Cxcl9 protein, mouse; D018398:Homeodomain Proteins; C064658:RAG-1 protein