The viral chemokine MCK-2 of murine cytomegalovirus promotes infection as part of a gH/gL/MCK-2 complex.

The viral chemokine MCK-2 of murine cytomegalovirus promotes infection as part of a gH/gL/MCK-2 complex.

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Human cytomegalovirus (HCMV) forms two gH/gL glycoprotein complexes, gH/gL/gO and gH/gL/pUL(128,130,131A), which determine the tropism, the entry pathways and the mode of spread of the virus.For murine cytomegalovirus (MCMV), which serves as a model for HCMV, a gH/gL/gO complex functionally homologous to the HCMV gH/gL/gO complex has been described.Knock-out Oxygen Therapy Accessories of MCMV gO does impair, but not abolish, virus spread indicating that also MCMV might form an alternative gH/gL complex.Here, we show that the MCMV CC chemokine MCK-2 forms a complex with the glycoprotein gH, a complex which is incorporated into the virion.We could additionally show that mutants lacking both, gO and MCK-2 are not able to produce infectious virus.

Trans-complementation of these double mutants with either gO or MCK-2 showed that both proteins can promote infection of host cells, although through different entry pathways.MCK-2 has been extensively studied in vivo by others.It has been shown to be involved in attracting cells for virus dissemination and in regulating antiviral host responses.We now show that MCK-2, by forming a complex with gH, strongly promotes infection of Polos macrophages in vitro and in vivo.Thus, MCK-2 may play a dual role in MCMV infection, as a chemokine regulating the host response and attracting specific target cells and as part of a glycoprotein complex promoting entry into cells crucial for virus dissemination.