Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function

Abstract

Recruitment and activation of leukocytes are important for elimination of microbes, including viruses, from infected areas. Chemokines constitute a group of bioactive peptides that regulate leukocyte migration and also contribute to activation of these cells. Chemokines are essential mediators of inflammation and important for control of viral infections. The profile of chemokine expression contributes to shaping the immune response during viral infection, whereas viral subversion of the chemokine system allows the virus to evade antiviral activities of the host. In this review, we discuss the role of chemokines in host-defense against virus infections, and we also look deeper into the virus-cell interactions that trigger chemokine expression as well as the cellular signaling cascades involved.

Figure 1

Virus‐activated signal transduction. Cells respond to virus infection by activating a number of signal‐transduction cascades, which lead to nuclear translocation of a specific set of transcription factors. Ultimately, the activated transcription factors stimulate expression of chemokines and other proinflammatory mediators. For a more detailed description of virus‐activated signal transduction, see the text. This figure depicts the gene promoter regions of CCL5/RANTES, CCL3/MIP‐1α, CXCL8/IL‐8, and CXCL10/IP‐10, which are discussed in more detail in the text. NF‐AT, Nuclear factor of activated T cells; JNK, Jun N‐terminal kinase; ATF2, activating transcription factor 2; AP‐1, activator protein‐1; STAT, signal transducer and activator of transcription; IKK, inhibitor of κB (IκB) kinase; VAK, virus‐activated kinase; IRF, IFN regulatory factor; CRE, cyclic adenosine monophosphate response element; GAS, IFN‐γ activation site; ISRE, IFN‐stimulated response element; C/EBP, CCAAT enhancer‐binding protein; CD28RE, CD28 response element.