Virus-encoded members of the chemokine superfamily of ligands have been discovered in the genomes of certain poxviruses and herpesviruses. The MC148R gene of molluscum contagiosum virus, a human-specific poxvirus that induces benign skin lesions which can become clinically serious in immunocompromised patients, encodes for amemberof theCCchemokinesuperfamily that can antagonize the activities of several human CC chemokines tested. The MC148R protein lacks certain amino acid motifs at the N-terminus that are believed to be required for signaling from cognate chemokine receptors, and this feature is believed to be important for its activity as a CC chemokine antagonist.