Epstein-Barr virus latent membrane protein 2 induces autophagy to promote abnormal acinus formation.

Epstein-Barr virus latent membrane protein 2A (LMP2A) induces many characteristics of carcinoma, including transformation, migration, invasion, and impaired differentiation. The MCF10A cell line differentiates to form hollow acini when grown in Matrigel, and expression of LMP2A inhibited differentiation and anoikis induced by loss of matrix attachment. LMP2A-infected cells formed large, lobular structures rather than hollow acini.

Epstein-Barr virus latent membrane protein 2 effects on epithelial acinus development reveal distinct requirements for the PY and YEEA motifs.

Epstein-Barr virus (EBV) is a gammaherpesvirus associated with numerous cancers, including the epithelial cancers nasopharyngeal carcinoma (NPC) and gastric carcinoma. The latent membrane protein 2 (LMP2) encoded by EBV is consistently detected in NPC tumors and promotes a malignant phenotype when expressed in epithelial cells by inducing transformation and migration and inhibiting differentiation. Grown in three dimensions (3D) on Matrigel, the nontumorigenic mammary epithelial cell line MCF10A forms hollow, spherical acinar structures that maintain normal glandular features.

Epstein-Barr virus latent membrane protein-2A induces ITAM/Syk- and Akt-dependent epithelial migration through αv-integrin membrane translocation.

Epstein-Barr virus (EBV) is a highly prevalent herpesvirus associated with epithelial cancers, including nasopharyngeal carcinoma (NPC). The EBV protein latent membrane protein 2 (LMP2) is expressed in NPC tumor tissue and has been shown to induce transformation, inhibit differentiation, and promote migration of epithelial cells. In this study, the effect of LMP2A on migration of human epithelial cells was further analyzed.

Reactivation of human herpesvirus-6 in natalizumab treated multiple sclerosis patients.

The alpha(4) integrin antagonist natalizumab was shown to be effective in patients with immune-mediated disorders but was unexpectedly associated with JC polyomavirus associated progressive multifocal leukoencephalopathy (PML) in two multiple sclerosis (MS) and one Crohn's disease patients. Impaired immune surveillance due to natalizumab treatment may have contributed to the JCV reactivation. As HHV-6 has been suggested to play a role in MS, we asked whether this virus could also have been reactivated during natalizumab therapy.

Human herpesvirus 6 (HHV-6) induces dysregulation of glutamate uptake and transporter expression in astrocytes.

Human herpesvirus 6 (HHV-6) infects and establishes latency in the central nervous system (CNS). Reactivation of latent HHV-6 has been associated with neurologic diseases including epilepsy and multiple sclerosis (MS). In vivo, HHV-6 has been localized to astrocytes and can infect human astrocytes in vitro, suggesting that this virus may have a tropism for glial cells and may affect glial cell function.

Association of human herpesvirus-6B with mesial temporal lobe epilepsy.

Background: Human herpesvirus-6 (HHV-6) is a beta-herpesvirus with 90% seroprevalence that infects and establishes latency in the central nervous system. Two HHV-6 variants are known: HHV-6A and HHV-6B. Active infection or reactivation of HHV-6 in the brain is associated with neurological disorders, including epilepsy, encephalitis, and multiple sclerosis.

Detection of HHV-6B in post-mortem central nervous system tissue of a post-bone marrow transplant recipient: a multi-virus array analysis.

Background: HHV-6 has been implicated in a number of neurological disorders. Recent evidence has suggested high incidence of HHV-6 infection in patients (46%) undergoing allogeneic bone marrow transplant (BMT).

Objective: To investigate whether HHV-6 plays a role in the development of fatal encephalopathy in an allogeneic post-BMT patient using an unbiased approach.

Detection of active human herpesvirus-6 infection in the brain: correlation with polymerase chain reaction detection in cerebrospinal fluid.

One-half of bone-marrow transplant (BMT) and stem-cell transplant recipients have reactivation of latent human herpesvirus (HHV)-6 2-4 weeks after transplant. Although the detection of viral DNA, RNA, and antigen in brain material confirmed active HHV-6 variant B infection, peak viral loads in cerebrospinal fluid (CSF) and serum occurred 2-4 weeks before death and decreased to low levels before or at autopsy. All autopsy samples consistently demonstrated HHV-6 active infection in the hippocampus.

Efficacy of antiviral compounds in human herpesvirus-6-infected glial cells.

The beta-herpesvirus human herpesvirus-6 (HHV-6) is becoming increasingly recognized as an important pathogen in immunocompromised patients, particularly in post bone marrow transplant (BMT). Reactivation of latent HHV-6 resulting in encephalitis has been reported in BMT and stem cell transplant (SCT) patients. The development of HHV-6 encephalitis can be a fatal complication, the frequency of which is increasing likely due to improved diagnosis with quantitative polymerase chain reaction (PCR) of cerebrospinal fluid.

Differential HHV-6A gene expression in T cells and primary human astrocytes based on multi-virus array analysis.

Human herpesvirus 6 (HHV-6) is a ubiquitous virus that has been associated with a wide spectrum of diseases, such as exanthem infantum, multiple sclerosis, seizures, encephalitis/meningitis, and more recently, mesial temporal lobe sclerosis. Although HHV-6 is known to predominately infect CD4+ T lymphocytes, its ability to infect neural glial cells has been demonstrated both in vitro and in vivo. Reactivation of latent HHV-6 infection in the brain has recently been suggested to play a role in the development of neuropathogenesis.

Differential tropism of human herpesvirus 6 (HHV-6) variants and induction of latency by HHV-6A in oligodendrocytes.

Human herpesvirus 6 (HHV-6) is a ubiquitous beta -herpesvirus associated with a number of clinical disorders. Two closely but biologically distinct variants have been described. HHV-6 variant B causes the common childhood disease exhanthem subitum, and although the pathologic characteristics for HHV-6 variant A are less well defined, HHV-6A has been suggested to be more neurotropic.

Human herpesvirus 6 and multiple sclerosis: potential mechanisms for virus-induced disease.

Multiple sclerosis (MS) is a debilitating neurological disease of unknown cause that affects people between 20 and 40 years of age. While several viruses have been associated with MS, none has proven causative. Human herpesvirus 6 (HHV-6) is one agent that may play a role in MS.

Activation of adenosine receptors inhibits tumor necrosis factor-alpha release by decreasing TNF-alpha mRNA stability and p38 activity.

Adenosine receptor agonists have anti-inflammatory properties and modulate immune responses partly by inhibiting pro-inflammatory cytokine production by monocytes. We investigated signal transduction mechanisms by which adenosine receptor activation inhibits tumor necrosis factor-alpha (TNF-alpha) production. Phorbol-12-myristate-13-acetate (PMA) and phytohemagglutinin treatment of human pro-monocytic U937 cells increased TNF-alpha protein release.