The murine cytomegalovirus chemokine homolog, m131/129, is a determinant of viral pathogenicity

Chemokines are important mediators of the early inflammatory response to in fection and modify a wide range of host immune responses. Functional homolo gs of cellular chemokines have been identified in a number of herpesviruses , suggesting that the subversion of the host chemokine response contributes to the pathogenesis of these viruses. Transcriptional and reverse transcri ption-PCR analyses demonstrated that the murine cytomegalovirus (MCMV) chem okine homolog, m131, was spliced at the 3' end to the adjacent downstream o pen reading frame, m129, resulting in a predicted product of 31 kDa, which is significantly larger than most known chemokines. The in vivo impact of m 131/129 was investigated by comparing the replication of MCMV mutants havin g m131/129 deleted (Delta m131/129) with that of wild-type (wt) MCMV. Our s tudies demonstrate that both wt and Delta m131/129 viruses replicated to eq uivalent levels during the first 2 to 3 days following in vivo infection. H owever, histological studies demonstrated that the early inflammatory respo nse elicited by Delta m131/129 was reduced compared with that of wt MCMV. F urthermore, the Delta m131/129 mutants failed to establish a high-titer inf ection in the salivary glands, These results suggest that m131/129 possesse s proinflammatory properties in vivo and is important for the dissemination of MCMV to or infection of the salivary gland. Notably, the Delta m131/129 mutants were cleared more rapidly from the spleen and liver during acute i nfection compared with wt MCMV. The accelerated clearance of the mutants wa s dependent on NK cells and cells of the CD4(+) CD8(+) phenotype. These dat a suggest that m131/129 may also contribute to virus mechanisms of immune s ystem evasion during early infection, possibly through the interference of NK cells and T cells.