Pathogenesis of murine cytomegalovirus infection

CXCR3-Dependent Recruitment of Antigen-Specific T Lymphocytes to the Liver during Murine Cytomegalovirus Infection

“…Additional studies have demonstrated that CD8 T cells accumulate in the liver following infection with MCMV (12,19,20,48,51); however, this is the first report documenting the mechanisms required for promoting their recruitment and that of MCMV-specific CD8 T cells. Our results show a clear induction of CXCL9 and CXCL10 protein in the liver during MCMV infection.…”

“…It is speculated that CXCL9 induction reflects the innate NK cell-mediated IFN-␥ effects (37,40,41,43,50), as this chemokine is highly dependent on IFN-␥ for production (53,56). However, CXCL10 can be in- duced by IFN-␥ in addition to other molecules, including tumor necrosis factor alpha, which is found in the liver during MCMV infection (20,33,36,51). In addition, as antibody neutralization of these CXCR3 ligands reduced the proportions and total numbers of hepatic MCMV-specific CD8 T cells, it is probable that the combined effects of these chemokines initiate the CD8 T-cell inflammatory response but CXCL10 may exert distinct functions during late acute MCMV infection in the liver that remain to be determined.…”

“…Several studies have demonstrated the accumulation and development of effective CD8 T-cell responses in various tissues during acute infections with MCMV that become maximally apparent by day 7 postinfection (12,20). To evaluate the kinetics of CD8 T-cell accumulation in the liver, flow cytometric analyses were used to document the expression of cell surface markers for CD8 T cells (CD8␣ ϩ CD4 Ϫ TCR␤ ϩ ) in liver leukocytes from uninfected and MCMV-infected C57BL/6 mice.…”

“…Additionally, T-cell depletion studies demonstrated a role for these cells in controlling hepatic damage and promoting host survival (34,51), suggesting that the MCMV-infected liver is sensitive to immune control by CD8 T cells. Furthermore, studies have demonstrated the accumulation and development of an effective CD8 T-cell response in various tissues that becomes maximally apparent 7 days after infection with MCMV (12,20). Thus, it is clear that CD8 T cells support hepatic immunity; however, the mechanisms promoting the recruitment of activated CD8 T lymphocytes into the liver during MCMV infection have not been evaluated.…”

Discrete Clusters of Virus-Encoded MicroRNAs Are Associated with Complementary Strands of the Genome and the 7.2-Kilobase Stable Intron in Murine Cytomegalovirus

“…CMV is highly species specific; however, the pathogenesis of mouse CMV (MCMV) in mice is remarkably similar to that of HCMV in humans. This has resulted in the widespread adoption of the MCMV model in the study of all aspects of infection and pathogenesis (19).…”