Chemokine-binding activities of M3 protein encoded by Murine gammaherpesvirus 72

Murine gammaherpesvirus 68 (MHV-68) contains gene-encoding M3 protein expressed during the acute and persistent phase of infection. This protein features a chemokine-binding activities (Parry et al., 2000; van Berkel et al., 2000). In this study, we demonstrated that the Murine gammaherpesvirus 72 (MHV-72) also contained M3 gene with the codon-changing mutation at the position 920 nt converting amino acid (aa) 307 Asp (GAC) to Gly (GGC). The mutation in the M3 protein was localized near chemokine-binding domain and was able to change the secondary structure of M3 protein. We examined the binding activities of M3 proteins of MHV-72 and MHV-68 to five human chemokines (CCL3, CCL5, CCL11, CCL2, and CXCL8). Binding activity of MHV-72 M3 protein to CCL5 as well as to CXCL8 reached only 11.1% (day 3 p.i.) to 20% (day 4 p.i.) of the activity detected for MHV-68 M3 protein. On the other hand, MHV-72 M3 protein bound to human cytokines CCL11 and CCL2 reached about 90% of the binding detected for MHV-68 M3 protein. The binding activity of both M3 proteins to human CCL3 was similar. These data implied that mutation identified in MHV-72 M3 protein might be involved in attenuation of immune response to infection with MHV-72.