Chemokine Subversion by Human Herpesviruses

Abstract

Viruses use diverse molecular mechanisms to exploit and evade the immune response. Herpesviruses, in particular, encode functional chemokine and chemokine receptor homologs pirated from the host, as well as secreted chemokine-binding proteins with unique structures. Multiple functions have been described for herpesvirus chemokine components, including attraction of target cells, blockade of leukocyte migration, and modulation of gene expression and cell entry by the virus. Here we review current concepts about how human herpesvirus chemokines, chemokine receptors, and chemokine-binding proteins may be used to shape a proviral state in the host.

Keywords: Chemokine receptors; Chemokines; Viral infection.

Fig. 1

vCKBP encoded by HHV. Graphic representation of the vCKBP identified in alphaherpesvirus (HSV1, HSV2, and VZV) and betaherpesvirus (HCMV). The chemokines bound by each vCKBP are indicated. Since it has been shown that HCMV UL21.5 mRNA is packaged into virions, the expression of UL21.5 protein from this encapsidated mRNA as well as from the viral DNA genome is represented. vCKBP are depicted in the color of the corresponding HHV. sgG2, soluble gG2.

Fig. 2

vCKR encoded by HHV. Graphic representation of the vCKR identified in betaherpesvirus (HCMV, HHV6, and HHV7) and gammaherpesvirus (EBV and KSHV). Chemokines bound by each vCKR are indicated. Unknown ligands for orphan vCKR are shown in gray. The lightning bolt symbol indicates vCKR with reported constitutive activity.

Fig. 3

vCK encoded by HHV. Graphic representation of the vCK identified in alphaherpesvirus (HSV1, HSV2, and VZV), betaherpesvirus (HCMV, HHV6A, and HHV6B) and gammaherpesvirus (EBV and KSHV). vCK are shown in the same color as the corresponding virus. Other non-chemokine viral proteins (gH and HCMV gL and UL131A) are shown in gray. Cellular receptors for each vCK are indicated. Agonistic and antagonistic activities are represented with green and red arrows, respectively. Unknown receptors for vCK are shown in red. s-vCCL4a/b, spliced variants of vCCL4a/b.