Chemokines, or chemotactic cytokines are secreted protein playing an important role in migration of immune cells to a site of viral infection, Th1/Th2 differentiation, and T cell co-stimulation.
Due to the importance of chemokines in immunity, viruses have evolved mechanisms to counter the chemokine network. The level of regulating chemokines can occur at different levels. Some viruses encode viral cytokines, such as cytomegalovirus UL146 (vCXCL1 that targets both CXCR1 and CXCR2 as an agonist), or Molluscum contagiosum virus MC148R that displaces the interaction between CXCL12alpha and CXCR4. These proteins interfere with proper chemokine signaling. Viruses also encode chemokine receptors. For example, HCMV encodes four proteins US27, US28, UL33 and UL78 homologous to human chemokine receptors. US28 receptor expression leads to constitutive activation of the host Galphaq/phospholipase C pathway. HHV-6 and HHV-7 possess also two proteins homologous to chemokine receptor namely U12 and U51 that can function in concert with CCR4 and CCR7 in host-cell signalling pathways. Finally, viruses also interfere with the host chemokines by encoding viral chemokine-binding proteins. For instance, Myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines. Glycoprotein G from pseudorabies also virus binds to chemokines with high affinity and inhibits their function.