The Story behind The Lady Upstairs

Monday, December 01, 2014

World AIDS Day

cartoon, AIDS, CFS,

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

Mitochondrial Dysfunction and Chronic Fatigue Syndromes: Issues in Clinical Care

http://figshare.com/articles/Mitochondrial_Dysfunction_and_Chronic_Fatigue_Syndromes_Issues_in_Clinical_Care_modified_version_/1254859

New HHV-6 cartoon

cartoon, aids, ms, cfs, chronic fatigue syndrome, cancer, gallo, ablashi
Julian Lake's CFS cartoon book on Kindle (free on Kindle Unlimited).

Dharam Ablashi on HHV-6 and AIDS

HHV-6 infection in HIV-infected asymptomatic and AIDS patients.

 http://www.ncbi.nlm.nih.gov/pubmed/9705559

Abstract

In order to investigate the levels of HHV-6 infection and elevated antibodies to HHV-6 in HIV-1-infected asymptomatic and symptomatic patients, peripheral blood mononuclear cells were (PBMC) cultured. As patients progressed from asymptomatic HIV infection to AIDS, there was a concurrent increase in replicating HHV-6. Plasma obtained from several of these patients showed the presence of IgM antibody and a significantly elevated level of HHV-6 IgG antibody. Serial samples of plasma from 10 AIDS patients collected over a period of 4 years were assayed for the detection of HHV-6 core protein (gp116/64/54) by antigen capture ELISA. The results demonstrated that either a persistent infection or reactivation can occur based on the degree of fluctuation in HHV-6 antigen detected. ELISA to HHV-6 purified viral proteins, i.e., early (p41/38) and late (gp110), demonstrated that IgG antibody to gp110 did not differentiate between HIV-1-infected and healthy donors. IgG and IgM antibody to p41/38, however, showed a significantly higher prevalence in HIV-1-infected individuals (56.7-85.3%) than in normal healthy donors (19.0%), suggesting virus activation. PBMC culture from the AIDS patients expressing significant peaks of HHV-6 core antigen (gp116/64/54) in their plasma showed that in most cases, HHV-6 early and late antigens were detectable; however, those patients with consistently low antigen peaks had no detectable antigens in their PBMC. Only 55% of PBMC cultures established from IgM antibody-positive HIV-1-infected asymptomatic and AIDS patients expressed HHV-6 antigens in the short-term cultures, but HHV-6 antigens could not be demonstrated in PBMC culture from 4 IgM-antibody-positive healthy donors. HHV-6 isolates obtained from the HIV-1-positive patients were predominantly HHV-6 variant A, compared to healthy donors. Based on the data presented here, it is evident that the levels of HHV-6 infection increased in HIV-1-infected asymptomatic individuals as they progressed to AIDS. Our immunovirological data on HHV-6-infected individuals with HIV infection support a role for HHV-6 in the pathogenesis of AIDS. We believe that simultaneous active infection with HIV-1 and HHV-6 may contribute to enhanced immune suppression perhaps leading to disease manifestations.

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