The Extent Of Human Cytomegalovirus Replication In Primary Neurons Is Dependent On Host Cell Differentiation

Poland, S.D; Bambrick, Linda L.; Dekaban, Gregory A.; Rice, George P.

doi:10.1093/infdis/170.5.1267

Cited by 41 publications

(33 citation statements)

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“…These include (i) that neuronal stem cells and neuronal precursor cells may be more susceptible to CMV infection than other cells in the developing brain, and/or (ii) that CMV may readily reach the CNS through the blood-cerebrospinal fluid route during early gestation. It has been reported that CNS stem cells and undifferentiated neurons are permissive to HCMV and MCMV replication (20,29,34). Identification of the choroid plexus as another major target for RhCMV replication early after inoculation (Fig.…”

Section: Discussionmentioning

confidence: 97%

A Recombinant Rhesus Cytomegalovirus Expressing Enhanced Green Fluorescent Protein Retains the Wild-Type Phenotype and Pathogenicity in Fetal Macaques

Chang¹,

Tarantal

Zhou³

et al. 2002

J Virol

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Section: Discussionmentioning

confidence: 97%

A Recombinant Rhesus Cytomegalovirus Expressing Enhanced Green Fluorescent Protein Retains the Wild-Type Phenotype and Pathogenicity in Fetal Macaques

Chang¹,

Tarantal

Zhou³

et al. 2002

J Virol

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“…Moreover, there are similar reports concerning neurons. While the ability of the neuronal HCN-1A cell line to support HCMV replication is reported to be elevated in connection with differentiation (45), cultures of highly enriched and purified mature neuronal cultures from the fetal cortex do not support viral growth or exhibit any morphological changes following viral infection (33,45). In the present study, NPCs and cells that had already begun to differentiate for 1 or 3 days were both permissive for infection and exhibited cytopathic effect, at similar levels, which is in concordance with previous reported data (11).…”

Section: Discussionmentioning

confidence: 99%

“…Human neural precursor cells can be expanded as neurospheres, giving rise to both phenotypic neuronal and glial cells following differentiation in vitro. Although astrocytes (31,33), neurons (35), the neuronal cell line HCN-A1 (45), and an oligodendrocytic cell line (54) can all be infected with HCMV, only astrocytes and neurons appear to be fully permissive for such infection. In mixed cultures of the latter two types of cells, HCMV seems to preferentially infect astrocytes (33,57).…”

mentioning

confidence: 99%

Human Cytomegalovirus Inhibits Neuronal Differentiation and Induces Apoptosis in Human Neural Precursor Cells

Odeberg

Wolmer

Falci

et al. 2006

J Virol

144

165

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Human cytomegalovirus (HCMV) is the most common cause of congenital infections in developed countries, with an incidence varying between 0.5 and 2.2% and consequences varying from asymptomatic infection to lethal conditions for the fetus. Infants that are asymptomatic at birth may still develop neurological sequelae, such as hearing loss and mental retardation, at a later age. Infection of neural stem and precursor cells by HCMV and consequent disruption of the proliferation, differentiation, and/or migration of these cells may be the primary mechanism underlying the development of brain abnormalities. In the present investigation, we demonstrate that human neural precursor cells (NPCs) are permissive for HCMV infection, by both the laboratory strain Towne and the clinical isolate TB40, resulting in 55% and 72% inhibition of induced differentiation of human NPCs into neurons, respectively, when infection occurred at the onset of differentiation. This repression of neuronal differentiation required active viral replication and involved the expression of late HCMV gene products. This capacity of HCMV to prevent neuronal differentiation declined within 24 h after initiation of differentiation. Furthermore, the rate of cell proliferation in infected cultures was attenuated. Surprisingly, HCMV-infected cells exhibited an elevated frequency of apoptosis at 7 days following the onset of differentiation, at which time approximately 50% of the cells were apoptotic at a multiplicity of infection of 10. These findings indicate that HCMV has the capacity to reduce the ability of human NPCs to differentiate into neurons, which may offer one explanation for the abnormalities in brain development associated with congenital HCMV infection.

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“…Regarding the susceptibility of brain cells to HCMV, various human brain-derived cultured cells, including glial (32), microglial (40), neuronal (37), or endothelial (36) cells, have been reported to support HCMV replication, However, the infectious dynamics of human brain cells in vivo are unknown, aside from speculation based on autopsy cases (4,35). We have reported the infectious dynamics of neuronal and glial cells in acute and subacute phases of infection in the developing mouse brain (48,57).…”

mentioning

confidence: 99%

Reactivation of Latent Cytomegalovirus Infection in Mouse Brain Cells Detected after Transfer to Brain Slice Cultures

Tsutsui

Kawasaki

Kosugi

2002

J Virol

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Cytomegalovirus (CMV) is the most significant infectious cause of brain disorders in humans involving the developing brain. It is hypothesized that the brain disorders occur after recurrent reactivation of the latent infection in some kinds of cells in the brains. In order to test this hypothesis, we examined the reactivation of latent murine CMV (MCMV) infection in the mouse brain by transfer to brain slice culture. We infected neonatal and young adult mice intracerebrally with recombinant MCMV in which the lacZ gene was inserted into a late gene. The brains were removed 6 months after infection and used to prepare brain slices that were then cultured for up to 4 weeks. Reactivation of latent infection in the brains was detected by ␤-galactosidase (␤-Gal) staining to assess ␤-galactosidase expression. Viral replication was also confirmed by the plaque assay. Reactivation was observed in about 75% of the mice infected during the neonatal period 6 months after infection. Unexpectedly, reactivation was also observed in 75% of mice infected as young adults, although the infection ratio in the brain slices was significantly lower than that in neonatally infected mice. ␤-Gal-positive cells were observed in marginal regions of the brains or immature neural cells in the ventricular walls. Immunohistochemical staining showed that the ␤-Gal-positive reactivated cells were neural stem or progenitor cells. These results suggest that brain disorders may occur long after infection by reactivation of latent infection in the immature neural cells in the brain.

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The Extent Of Human Cytomegalovirus Replication In Primary Neurons Is Dependent On Host Cell Differentiation

Cited by 41 publications

References 0 publications

A Recombinant Rhesus Cytomegalovirus Expressing Enhanced Green Fluorescent Protein Retains the Wild-Type Phenotype and Pathogenicity in Fetal Macaques

A Recombinant Rhesus Cytomegalovirus Expressing Enhanced Green Fluorescent Protein Retains the Wild-Type Phenotype and Pathogenicity in Fetal Macaques

Human Cytomegalovirus Inhibits Neuronal Differentiation and Induces Apoptosis in Human Neural Precursor Cells

Reactivation of Latent Cytomegalovirus Infection in Mouse Brain Cells Detected after Transfer to Brain Slice Cultures

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