Seminar

Modulation of chemokine activity by poxviruses and herpesviruses

Antonio Alcami, PhD

One of the main functions of the immune system is to prevent invasion by pathogens such as viruses. The relevant function of the chemokine system in anti-viral defense is emphasized by the identification of virus-encoded proteins that mimic chemokines and chemokine receptors, and viral secreted proteins that bind chemokines (chemokine binding proteins, CKBPs). These immune evasion strategies are employed by complex DNA viruses (poxviruses and herpesviruses) that can accommodate a large number of genes in their genomes. The CKBPs encoded by pathogens have unique amino acid sequence and structure unrelated to host seven-transmembrane chemokine receptors. Two families of CKBPs encoded by poxviruses and herpesviruses will be presented. The different properties of the virus-encoded CKBPs illustrate that viruses have adapted the properties of these chemokine modulators to their specific needs in the infected host. The implications for viral pathogenesis and immune modulation will be discussed. Virus-encoded secreted chemokine decoy receptors represent a unique and alternative strategy to modulate chemokine activity in vivo, and may be used to treat inflammatory conditions.