Dissecting the Epstein–Barr virus entry pathway into astrocytes: unfolding the involvement of endosomal trafficking

Aim: Previous reports have suggested successful infection by Epstein–Barr virus (EBV) in various brain cells; however, the entry mechanism is still elusive. In the present study, we investigated the entry pathway of EBV into astrocytes.
Materials & methods: For virus entry, receptors are considered as a instrumental moieties for infection. Upon EBV infection, the expression of receptors such as Ephrin, neuropilin and nonmuscle myosin heavy chain-II were assessed in a time-dependent manner. Then, by using inhibitors, we investigated the role of membrane cholesterol, the dynamin protein and, eventually, EBV colocalization in endosomal vesicles.
Results: EBV induced changes in the expression of numerous receptors, especially EphA4, EphA10 and NMHC-IIB. Upon binding to its receptor, the virus translocates into the lipid raft region of the plasma membrane, and its depletion results in decreased EBV internalization. The inhibition of dynamin also mitigated EBV entry. Subsequently, EBV colocalized in the endosomal compartment with markers such as EEA1, Rab5, Rab7 and LAMP1.
Conclusion: The current work implicitly indicates that EBV follows the endocytic pathway to enter brain cells, although further validation by knocking down these proteins is needed. These findings will further enable us to pinpoint therapeutic targets.
Epstein–Barr virus (EBV) is linked to neurodegenerative diseases like multiple sclerosis (MS). Immune cells responding to EBV infection have been found in the brain of these patients. The exact way in which the virus enters cells in the brain is unknown. Our study looks at how EBV enters a type of brain cells called astrocytes.
Epstein–Barr virus enters astrocytes via different receptors, such as EphA4 and NMHC-IIB.
EBV internalization decreased upon depletion of the lipid rafts.
The dynamin protein plays a crucial role in EBV entry into astrocytes, and its depletion indicates a decrease in EBV entry.
The colocalization of EBV with endosomal vesicles was detected via markers such as EEA1, Rab5, Rab7 and LAMP1.