Molluscum contagiosum poxvirus (MCV) type 1 and type 2 encode two chemokine-like 
proteins MC148R1 and MC148R2. It is believed that MC148R proteins function by 
blocking the inflammatory response. However, the mechanism of the proposed 
biological activities of MC148R proteins and the role of the additional 
C-terminal cysteines that do not exist in other chemokines are not understood. 
Here, we demonstrated in two different assay systems that His-tagged MC148R1 
displaces the interaction between CXCL12α and CXCR4. The N-terminal cysteines 
but not the additional C-terminal cysteines modulate this displacement. 
His-tagged MC148R1 blocked both CXCL12α-mediated and MIP-1α-mediated chemotaxis. 
In contrast, MC148R2 blocked MIP-1α-mediated but not CXCL12α-mediated 
chemotaxis. Immunoprecipitation by antibodies to MC148R1 or CXCL12α followed by 
immunoblotting and detection by antibodies to the other protein demonstrated 
physical interaction of His-tagged CXCL12α and His-tagged MC148R1. Interaction 
with chemokines might mask the receptor interaction site resulting in decreased 
binding and impairment of the biological activities.