Figure 4. CD163 is a dynamic barrier to host-switching of SHFV, but the human ortholog is fully functional for virus entry.

(A) Illustration of the CD163 receptor, showing the extracellular scavenger receptor cysteine-rich (SRCR domains 1–9) and proline domains rich with serine threonine (PST) I and II, and the short cytoplasmic tail. Residues evolving under positive selection are shown with red circles, and the putative arterivirus interaction domain is denoted with a black line. The N-terminus (amine terminus; NH₂) and C-terminus (carboxyl terminus; COOH) denote the beginning and end of the protein polypeptide chain, respectively. (B) MA-104 ΔCD163 cells stably expressing the indicated primate CD163 ortholog (X-axis) were exposed to SHFV at a multiplicity of infection (MOI) of 3. Viral titers in cell supernatants 12 h post-exposure were assessed by plaque assay. Bars are color-coded by log-fold differences in SHFV titers compared to cells expressing the receptor of the presumed natural host (patas monkey; #7). The data show the mean +/− standard error of the mean (SEM) from three independent experiments, with one replicate per experiment. One-way analysis of variance (ANOVA) with Dunnett’s post-test compared to control cells (*P < 0.05, **P < 0.01, ****P < 0.0001, NS not significant). The dotted line represents the limit of detection for the assay. CD163 receptor expression was confirmed by western blotting, and actin beta served as a protein loading control. See also Figure S5. SHFV, simian hemorrhagic fever virus.