Cytomegalovirus expresses the chemokine homologue vXCL1 capable of attracting XCR1+CD4- dendritic cells

Abstract

Cytomegaloviruses (CMV) have developed various strategies to escape the immune system of the host. One strategy involves the expression of virus-encoded chemokines to modulate the host chemokine network. We have identified in the English isolate of rat CMV (murid herpesvirus 8; MuHV8) an open reading frame encoding a protein homologous to the chemokine XCL1, the only known C-chemokine. Viral XCL1 (vXCL1), a glycosylated protein of 96 amino acids, can be detected 13 hours post infection in the supernatant of MuHV8-infected rat embryo fibroblasts. vXCL1 exclusively binds to CD4- rat dendritic cells (DC), a DC subset that expresses the corresponding chemokine-receptor XCR1. Like endogenous rat XCL1, vXCL1 selectively chemoattracts XCR1+ CD4- DC. Since XCR1+ DC in mice and humans have been shown to excel in antigen cross-presentation and thus in the induction of cytotoxic CD8+ T lymphocytes, the virus has apparently hijacked this gene to subvert cytotoxic immune responses. The biology of vXCL1 offers an interesting opportunity to study the role of XCL1 and XCR1+ DC in the cross-presentation of viral antigens.