Primary neurons become less susceptible to coxsackievirus B5 following maturation: The correlation with the decreased level of CAR expression on cell surface

Abstract

Coxsackievirus B (CVB) is one of the major pathogens of aseptic meningitis and meningioencephalitis, particularly in newborn infants. To analyze the influence of neural maturation on susceptibility to CVB infection, we prepared immature and mature neurons from 16-day-old BALB/c embryonic cortex. In contrast to immature neurons, mature neurons were less susceptible to CVB5 infection, as indicated by the decrease of cytopathic features. In mature neurons, progeny virus production was significantly hindered, and virus capsid protein VP1 synthesis and virus genome amplification were concomitantly reduced. In addition, the expression of coxsackievirus and adenovirus receptor (CAR), the major receptor of CVB5, was down-regulated in mature neurons. The antibody treatment specific to CAR significantly attenuated CVB5 susceptibility of immature neurons. These findings demonstrate that mature neurons become less susceptible to CVB by the decrease of CAR level. Thus, the data strongly support the idea that the level of virus receptor in neurons is one of the crucial determinants in the age-dependency of CVB virulence in central nervous system.

Coxsackievirus Preferentially Replicates and Induces Cytopathic Effects in Undifferentiated Neural Progenitor Cells

“…Adding to the complexity, susceptibility to infection may be altered as progenitor cells differentiate into the downstream lineages. A recent publication suggests preferential coxsackievirus replication within immature neurons expressing relatively high levels of coxsackievirus-adenovirus receptor (CAR) compared to their fully differentiated counterparts (1).…”

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression

“…10,24 Coxsackievirus B5, which also uses CAR as its primary receptor, demonstrated higher levels of transduction in embryonic immature neurons than mature neurons and correlated with the downregulation of CAR with age. 25 Examination of CAR expression in human adult brains revealed low levels to no expression with only the choroid plexus and pituitary gland showing higher concentrations. 26 On the basis of this evidence, Ad5 could be viewed as a poor choice for gene delivery to the adult brain, but well suited to the fetal brain.…”

Characterization of Infections of Human Leukocytes by Non-Polio Enteroviruses

“…The ability of anti-DAF monoclonal antibodies to block EV70 binding to HeLa cells and to protect the cells against infection suggested a close association between cellular susceptibility to virus and virus receptor expression [37] . We also found that CAR expression on neural cells is required for CVB3 infection [38] . Subsets of EV receptors, such as CAR, DAF, and sialic acid, were expressed in human leukocyte lineages.…”