Epstein-Barr Virus Infection of Human Astrocyte Cell Lines

Abstract

Epstein-Barr virus (EBV) is implicated in different central nervous system syndromes. The major cellular receptor for EBV, complement receptor type 2 (CR2) (CD21), is expressed by different astrocyte cell lines and human fetal astrocytes, suggesting their susceptibility to EBV infection. We demonstrated the infection of two astrocyte cell lines, T98 and CB193, at low levels. As infection was mediated by CR2, we used two stable CR2 transfectant astrocyte cell lines (T98CR2 and CB193CR2) to achieve a more efficient infection. We have monitored EBV gene expression for 2 months and observed the transient infection of T98 and T98CR2 cells and persistent infection of CB193 and CB193CR2 cells. The detection of BZLF1, BALF2, and BcLF1 mRNA expression suggests that the lytic cycle is initiated at early time points postinfection. At later time points the pattern of mRNA expressed (EBER1, EBNA1, EBNA2, and LMP1) differs from latency type III in the absence of LMP2A transcription and in the expression of BALF2 and BcLF1 but not BZLF1. A reactivation of the lytic cycle was achieved in CB193CR2 cells by the addition of phorbol esters. These studies identify astrocyte cell lines as targets for EBV infection and suggest that this infection might play a role in the pathology of EBV in the brain.

Epstein–Barr Virus in Gliomas: Cause, Association, or Artifact?

“…Further, EBV is causally associated with a number of other CNS disorders [infectious mononucleosis, acute encephalitis, acute cerebellar ataxia, demyelinating disease, myelitis or meningitis, and some CNS neuropathies ( 72 )]. The major cellular receptor for EBV, compliment receptor 2 (CR2) appears to be present on astrocytes ( 73 ) facilitates entry to infect astrocyte cell lines ( 74 ), and leads to increased proliferation. Importantly, primary CNS lymphomas (e.g., diffuse large B-cell lymphomas and lymphoid granulomatosis) are frequently EBV-positive ( 75 ).…”

Episomal vectors for gene expression in mammalian cells

“…Besides infectious mononucleosis, EBV may also cause a variety of other neurological syndromes. The capability of infecting astrocyte cell lines suggests that the virus may also play a role in the pathology of EBV in the brain [87].…”

Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…In support of this premise, several studies have found that EBV can infect and undergo lytic replication in neuronal cell lines as well as primary human neurons 20 and abortively replicates in human astrocytes. 21 Although acute infections of EBV are known to cause neurologic complications in immunocompetent patients with infectious mononucleosis, generally, they are benign. Conversely, in patients co-infected with HIV-1, EBV is associated with primary central nervous system (CNS) lymphoma, which has a poor prognosis.…”