HHV-6 and oligodendrocyte cell death.


Human herpesvirus type 6 indirectly enhances oligodendrocyte cell death.

 http://www.ncbi.nlm.nih.gov/pubmed/13129768

Abstract

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

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

Popular Posts in the Last 7 Days

Dr. Bhupesh Prusty and Professor Thomas Rudel discuss their HHV-6 research

More evidence HHV-6 is the cause of Chronic Fatigue Syndrome.

If you want to know the whole truth about Chronic Fatigue Syndrome, you need to go Beyond Unrest

Popular Post in the Last 30 Days

Dr. Bhupesh Prusty and Professor Thomas Rudel discuss their HHV-6 research

If you want to know the whole truth about Chronic Fatigue Syndrome, you need to go Beyond Unrest

More evidence HHV-6 is the cause of Chronic Fatigue Syndrome.

Will Fauci screw up Zika as much as he has screwed up HHV-6, AIDS and Chronic Fatigue Syndrome?

Popular Posts from the Last Year

Dr. Bhupesh Prusty and Professor Thomas Rudel discuss their HHV-6 research

Oral Kaposi's Sarcoma looks like the Crimson Crescents in Chronic Fatigue Syndrome patients.

If you want to know the whole truth about Chronic Fatigue Syndrome, you need to go Beyond Unrest

More evidence HHV-6 is the cause of Chronic Fatigue Syndrome.

All Time Most Popular Posts

Dr. Bhupesh Prusty and Professor Thomas Rudel discuss their HHV-6 research

Anthony Fauci was part of the gang that silenced and destroyed Judy Mikovits.

Is Chronic Fatigue Syndrome the other AIDS epidemic in the gay community?

Was Judy Mikovits destroyed because her XMRV work would have ultimately shown HIV is a total fraud?