Summary auto-generated
This study investigated whether rhesus cytomegalovirus (RhCMV) can infect brain microvascular endothelial cells (BrMVEC) isolated from fetal rhesus macaques. Researchers purified BrMVEC using biotin-labeled lectin selection, achieving a 99% pure population confirmed by expression of endothelial markers including von Willebrand factor, CD105, and acetylated LDL uptake. These cells formed capillary-like structures on Matrigel, demonstrating characteristic endothelial behavior. When infected with RhCMV strain 68-1, BrMVEC were fully permissive for viral replication, producing detectable plaques within 5 days with peak viral titers by 96 hours post-infection. Treatment of cells with pro-inflammatory mediators (TNF-α, IL-1β, or PMA) prior to or during infection significantly reduced RhCMV infectivity, suggesting these activation signals interfere with early infection steps such as viral attachment or entry. However, post-infection treatment had no effect, indicating the activation-mediated inhibition is specific to early viral processes. These findings establish rhesus BrMVEC as a valuable model system for studying CMV neuropathogenesis in a primate system.
Key findings
- Rhesus brain microvascular endothelial cells (BrMVEC) are fully permissive for RhCMV infection, supporting efficient viral replication with plaque formation within 5 days
- BrMVEC isolated from fetal rhesus macaque brain tissue can be purified to 99% purity using biotin-labeled lectin selection and maintain characteristic endothelial phenotype and function
- Pro-inflammatory mediators (TNF-α, IL-1β, and PMA) significantly reduce RhCMV infectivity when applied before or during infection but not after, indicating these factors inhibit early infection steps
- RhCMV replication kinetics in BrMVEC are comparable to infection patterns in rhesus fibroblasts, demonstrating robust viral propagation in endothelial cells
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Abstract
Endothelial cells (EC) are an important cell type for human cytomegalovirus (CMV) pathogenesis. To characterize better the role of EC in primate CMV natural history, rhesus macaque microvascular EC (MVEC) were purified from fetal brain and analysed for infectivity by rhesus cytomegalovirus (RhCMV). Rhesus brain MVEC (BrMVEC) in culture were positive for von Willebrand factor and CD105 expression, uptake of acetylated low-density lipoprotein, and formation of capillary-like tubules on Matrigel, all phenotypic hallmarks of EC. BrMVEC were fully permissive for infection by RhCMV strain 68-1, and detectable plaques formed within 5 days of infection. Infectivity of BrMVEC by RhCMV could be reduced, but not abolished, by treatment of cells either before or during infection with pro-inflammatory mediators tumour necrosis factor-α, interleukin-1β or phorbol 12-myristate 13-acetate. These results demonstrate that in vitro infection of rhesus BrMVEC is a dynamic process that is influenced by activation conditions.