Varied Persistent Life Cycles of Borna Disease Virus in a Human Oligodendroglioma Cell Line

Abstract

Borna disease virus (BDV) establishes a persistent infection inBorna disease virus (BDV) causes progressive meningoencephalomyelitis in horses and sheep, in addition to several other vertebrate species (4,26,41). BDV is a single nonsegmented, negative-stranded (NNS) RNA virus (7,11,14,42) that is unique among members of the order Mononegaverales, in that it uses the nucleus as a site for replication and transcription (10, 43). BDV is a highly neurotropic virus that persists in the central nervous system (CNS) of infected animals. In adult rats, BDV infection is associated with massive brain inflammation and extensive neuronal damage (33). Neonatal infection, by contrast, results in life-long persistence without encephalitis (2,3,8,16,33). However, infected rats of all ages express a variety of behavioral abnormalities. Therefore, BDV provides an important model for the investigation of the mechanisms and consequences of viral persistence in the CNS.Generally, the CNS is known to be unique in its response to viral infections. This may be because of the lack of specialized lymphatic drainage, potentially limiting and delaying viral antigen recognition, in addition to the lack of dendritic cells and the use of microglia for the initial recognition and presentation of viral antigens, as well as the lack of expression of major histocompatibility molecules by normal neurons and glial cells (36). Thus, these factors result in immune limitations, which could contribute to the fate of viral persistence in the CNS, in general and for BDV as well. In addition, persistent BDV infection in the CNS is due to its noncytolytic strategy for replication (25).Persistent infection with BDV has been established in a variety of neuronal and glial cell lines during which viral antigens are continuously detected (9). The choice of a cell line for the in vitro characterization of BDV appears to depend on the in vivo tropism of the virus, as well as on the functional importance and abundance of cells in the CNS such as neurons and glial cells (astrocytes and oligodendrocytes). The rat astrocytoma cell line (C6) is frequently used for such a purpose (9, 17), in addition to the neuronal cell lines SK-N-SH and SK-N-SHEP (9).The cell-specific variations in BDV replication in vitro have been studied. BDV persistence in the C6 cell line is characterized by high-level expression of BDV-specific proteins and RNA and low-level production of infectious virions (9). Such an expression is related in part to the secretion of several neurotrophic factors into the culture medium by the cells (9, 35). Although BDV is characterized by high genomic stability, a recent report demonstrated the possibility of isolating stable virus variants from a persistently infected C6 cell line (17).Although oligodendrocytes are a major cellular component of the white matter in the CNS and have a pivotal role in neuronal cell functions, they have not been well studied in terms of BDV characterization. Oligodendrocytes have been shown to support experimental and natural i...

Interleukin‐4 Up‐Regulates T‐Tropic Human Immunodeficiency Virus Type 1 Transcription in Primary CD4+ CD38+ T‐Lymphocyte Subset

“…Northern blot hybridization was performed as described previously (11). Total RNA was extracted from infected CD38 subsets by using Isogen (Nippon Gene Co., Tokyo).…”

Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

“…OL cells are a cell line derived from fetal human oligodendrocytes, which are a major cellular component of the brain white matter that play a pivotal role in maintaining neurological function. OL cells are targets of several neurotropic NNS RNA viruses, including canine distemper virus (Muller et al, 1995), measles virus (Baczko et al, 1988), and BDV (Ibrahim et al, 2002;Zhai et al, 2013). Although neurons are the primary targets of BDV, astroglia and oligodendroglia can be infected by BDV as well (Carbone et al, 1993).…”

Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

“…Oligodendroglia (OL) cells, a cell line derived from human fetal oligodendrocytes, are a major component of the brain white matter that play a pivotal role in maintaining neurological function. OL cells support both natural and experimental infection with several neurotropic NNS RNA viruses including BDV (Ibrahim et al, 2002;Koster-Patzlaff et al, 2007), canine distemper virus (Muller et al, 1995), and measles virus (Baczko et al, 1988). Laboratory-adapted and wild-type (e.g.…”