HHV-6 and oligodendrocyte cell death.
Human herpesvirus type 6 indirectly enhances oligodendrocyte cell death.
http://www.ncbi.nlm.nih.gov/pubmed/13129768Abstract
Accumulating
evidence suggests that human herpesvirus type 6 (HHV-6) plays a
pathogenic role in diseases of the central nervous system including
multiple sclerosis (MS). Recent studies have indicated that HHV-6 DNA is
detected with high frequency in MS lesions compared to normal-appearing
white matter, implicating a role for HHV-6 in MS pathogenesis. It
appears that T cells, which infiltrate into the brain in MS patients,
and resident oligodendrocytes harbor HHV-6 virus in MS lesions. Because T
cells infected with HHV-6 have elevated proinflammatory gene
expression, we hypothesized that HHV-6 could be indirectly cytotoxic to
glial cells, including oligodendrocytes. Supernatants from SupT1 cells
infected with HHV-6 variant A (GS or U1102) or variant B (Z29)
significantly reduced MO3.1 cell proliferation by 75% +/- 10%, 78% +/-
8% or 51% +/- 9%, respectively. HHV-6 viral supernatants (GS or U1102 or
Z29) significantly increased MO3.1 or primary human oligodendrocyte
precursor cells (OPCs) cell death, whereas primary human fetal
astrocytes were not affected. Removal of HHV-6 virions or proteins by
trypsin treatment from culture supernatants did not reverse the loss in
oligodendrocyte proliferation or viability. Supernatants from HHV-6 GS
or U1102 cultures were significantly more cytotoxic to MO3.1 cells or
OPCs compared to supernatants from T cells infected with Z29. Dying
oligodendrocytes did not have an apoptotic-like phenotype and toxicity
was not inhibited by general inhibitor of apoptosis, ZVAD. Further,
oligodendrocytes had minimal caspase-3 activation even in the presence
of staurosporine, suggesting that cell death followed
caspase-independent pathways. These results indicate that HHV-6 is
indirectly cytotoxic to oligodendrocytes and that cell death is driven
primarily by caspase-independent pathways.
The effect of human herpesvirus-6 (HHV-6) on cultured human neural cells: oligodendrocytes and microglia.
http://www.ncbi.nlm.nih.gov/pubmed/9839646
The effect of human herpesvirus-6 (HHV-6) on cultured human neural cells: oligodendrocytes and microglia.
http://www.ncbi.nlm.nih.gov/pubmed/9839646
Abstract
Human
herpesvirus-6 (HHV-6) is a betaherpesvirus that has been frequently
associated with pediatric encephalitis. In 1995 Challoner et al reported
that HHV-6 variant B (HHV-6B) was linked to multiple sclerosis (MS) due
to the presence of viral DNA and antigen in the oligodendrocytes
surrounding MS plaques. These findings led us to examine HHV-6B's in
vitro tropism for primary neural cells. HIV-6B mediated cell-to-cell
fusion in cultured adult oligodendroglia. Infection of oligodendrocytes
was further confirmed by transmission electron microscopy (EM), which
showed the presence of intracellular HHV-6 particles, and by PCR for
HHV-6 DNA. However, the release of infectious virus was low or
undetectable in multiple experiments. Microglia were also susceptible to
infection by HHV-6B, as demonstrated by an antigen capture assay. We
did not detect infection of a differentiated neuronal cell line (NT2D).
Our findings suggest that HHV-6B infection of oligodendrocytes and/or
microglia could potentially play a role in neuropathogenesis.
Infection of murine oligodendroglial precursor cells with Human Herpesvirus 6 (HHV-6)--establishment of a murine in vitro model.
http://www.ncbi.nlm.nih.gov/pubmed/17276361
CONCLUSIONS:
Infection of murine OPCs by HHV-6 reproduces the critical phenotypes of cell cycle arrest and altered differentiation seen in human cells. The murine system provides a highly defined, accessible, and reproducible source of cells permitting the elucidation of specific viral and cell cycle genes involved in CNS viral infections of OPCs.Background on Oligodendrocytes:
http://en.wikipedia.org/wiki/Oligodendrocyte