Human astrocytic cells support persistent coxsackievirus B3 infection

Area of Science:

• Neurovirology
• Molecular Virology
• Immunology

Background:

• Enteroviruses frequently cause central nervous system diseases.
• Despite being cytolytic, enteroviruses can establish persistent infections.
• Understanding persistent enterovirus infections is crucial for chronic neuropathogenesis.

Purpose of the Study:

• Investigate the susceptibility of human brain cell lines to enterovirus infection.
• Identify mechanisms of persistent enterovirus infection in the central nervous system.
• Establish a novel cell model for studying enterovirus-central nervous system interactions.

Main Methods:

• Infection of CCF-STTG1, T98G, and SK-N-SH cell lines with coxsackievirus B3 (CVB3), enterovirus 71, and coxsackievirus A9.
• Detection of infectious virions, viral RNA, and viral antigens to assess persistent infection.
• Analysis of viral receptor usage (CAR, DAF, chondroitin sulfate) and interferon induction.
• Measurement of proinflammatory chemokine and cytokine (VCAM-1, IL-8, IL-6) upregulation.

Main Results:

• Persistent infection was observed in CVB3-infected CCF-STTG1 cells.
• CVB3 replication was inhibited by removing cell surface chondroitin sulfate, indicating its role in persistence.
• CVB3 curtailed beta interferon induction in CCF-STTG1 cells.
• Proinflammatory mediators were upregulated in infected CCF-STTG1 cells and astrocytes.

Conclusions:

• CCF-STTG1 cells are susceptible to persistent CVB3 infection, serving as a novel cell model.
• Chondroitin sulfate and impaired interferon response are key factors in CVB3 persistence.
• This model aids in understanding CVB3-induced chronic neuropathogenesis.