Fig. 6. EphA2 may serve as an entry receptor for multiple γ-herpesviruses.

a The structure of KSHV gL shows hydrophobic (orange) surfaces on both the EphA2 and the gH-binding faces. Molecular surfaces are colored according to hydrophobicity, with blue, white, and orange corresponding to the most hydrophilic, neutral, and hydrophobic patches, respectively. b Phylogenetic analysis of the gL proteins from 29 γ-herpesviruses, as generated by MEGA 10.1⁴⁶. Analyses were performed using the neighbor-joining method. The viruses selected for the cell fusion experiments are shown in red ellipses. c Conserved gL sequences mapped onto the protein surface. The gL surface is gradiently colored by the ConSurf server⁴⁷, based on degree of conservation as indicated by the alignment of gL sequences from 29 γ-herpesviruses: the most conserved regions are dark magenta and the most divergent regions are dark cyan. d Cell-based fusion assays were performed by co-culturing of HEK-293T cells transfected with EphA2 and HEK-293T cells transfected with plasmids expressing viral gHgL and gB. The Macavirus AIHV-1, Percavirus EHV-2, and Rhadinovirus MuHV-4 were randomly selected for testing. KSHV was used as the positive control and HSV-2 was used as the negative control. Representative results from three experiments are shown. Relative fusion was normalized to the empty vector. The data are presented as mean ± SEM (n = 3 independent replicates). Unpaired Student’s t-test was used for comparing two groups and ordinary one-way ANOVA with Dunnett’s multiple comparison test for multiple comparisons. boEphA2: bovine EphA2; hoEphA2: horse EphA2; huEphA2: human EphA2; moEphA2: mouse EphA2. The GenBank accession codes of gH, gL, and gB are shown in the Supplementary Table 3. Source data are provided as a Source Data file.