Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and CMV UL130 originate from chemokines

Abstract

Herpesviridae is a large family of DNA viruses divided into three subfamilies: Alpha-, Beta- and Gammaherpesvirinae. The process of herpesvirus transmission is mediated by a range of proteins, one of which is glycoprotein L (gL). Based on our analysis of the solved structures of HSV2 and EBV gH/gL complexes, we propose that Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and Betaherpesvirinae UL130 originate from chemokines. Herpes simplex virus type 2 gL and human cytomegalovirus homolog (UL130) adopt a novel C chemokine-like fold, while Epstein-Barr virus gL mimics a CC chemokine structure. Hence, it is possible that gL interface with specific chemokine receptors during the transmission of Herpesviridae. We conclude that the further understanding of the function of viral chemokine-like proteins in Herpesviridae infection may lead to development of novel prophylactic and therapeutic treatment.

Figure 1

Superimposed native structures of C-C motif chemokine 5 (green; PDB entry: 1U4L A) and EBV glycoprotein L (cyan; PDB entry 3PHF B). The cysteine residues are marked in red (C-C motif chemokine 5) and magenta (gL).

Figure 2

Superimposed native structures of the CC-type chemokine eotaxin-2 (green; PDB entry: 1EIG A) and EBV glycoprotein L (light-green; PDB entry 3PHF B). The hydrophobic surfaces are marked in blue (eotaxin-2) and light-blue (gL), cysteine residues in magenta (eotaxin-2) and light-pink (gL).

Figure 3

Multiple sequence alignment of lymphotactin (XCL1) and interleukin-8 (IL-8). The corresponding sequences were labeled with their GenBank entries (denoted by the GenBank identifier - gi) and organism of origin. The numbers in brackets refer to the positions of the presented sequence fragments. The observed (Protein Data Bank entries 1J8I_A for XCL1 and 1IL8_A for IL-8) and predicted (Psipred) secondary structure elements are coded with letters (H - a-helix, G - 3₁₀ helix, E - b-strands). Disulphide bridges in IL-8 has been marked with arrows and numbered.

Figure 4

Multiple sequence alignment of glycoprotein L (found in Alphaherpesvirinae) and interleukin-8 (IL-8). The corresponding sequences were labeled with their GenBank entries (denoted by the GenBank identifier - gi) and organism of origin. The numbers in brackets refer to the positions of the presented sequence fragments. The observed (Protein Data Bank entries 3M1C_B for gL and 1IL8_A for IL-8) and predicted (Psipred) secondary structure elements are coded with letters (H - a-helix, G - 3₁₀ helix, E - b-strands). Disulphide bridges in IL-8 has been marked with arrows and numbered.

Figure 5

Multiple sequence alignment of UL130 (found in Betaherpesvirinae) and interleukin-8 (IL-8). The corresponding sequences were labeled with their GenBank entries (denoted by the GenBank identifier - gi) and organism of origin. The numbers in brackets refer to the positions of the presented sequence fragments. The observed (Protein Data Bank entry 1IL8_A for IL-8) and predicted (Psipred) secondary structure elements are coded with letters (H - a-helix, G - 3₁₀ helix, E - b-strands). Disulphide bridges in IL-8 has been marked with arrows and numbered.