JCPyV T-Antigen Activation of the Anti-Apoptotic Survivin Promoter-Its Role in the Development of Progressive Multifocal Leukoencephalopathy.

Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease of the CNS, resulting from the lytic infection of oligodendrocytes by the human neurotropic polyomavirus JC (JCPyV), typically associated with severe immunocompromised states and, in recent years, with the use of immunotherapies. Apoptosis is a homeostatic mechanism to dispose of senescent or damaged cells, including virally infected cells, triggered in the vast majority of viral infections of the brain. Previously, we showed upregulation of the normally dormant anti-apoptotic protein Survivin in cases of PML, which-in vitro-resulted in protection from apoptosis in JCPyV-infected primary cultures of astrocytes and oligodendrocytes.

Mediation of HIV/STI risk by mental health disorders among persons living in the United States reporting childhood sexual abuse.

Background: Individuals who experience childhood sexual abuse (CSA) have higher rates of unsafe sexual behaviors and/or HIV or sexually transmitted infection (STI) incidence. Accordingly, sexual minorities also have higher rates of HIV/STI incidence compared with heterosexuals among those abused as children and those who were not. However, little is known concerning the mechanisms by which CSA confers increased sexual risk.

Associations of sexual identity or same-sex behaviors with history of childhood sexual abuse and HIV/STI risk in the United States.

Objective: To measure associations of childhood sexual abuse (CSA) with sexual orientation, behaviors, and attractions and HIV/sexually transmitted infection (STI) incidence in a nationally representative sample of men and women.

Methods: Data from the 2004-2005 Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were analyzed, including frequencies of CSA and HIV/STI incidence for 5 subgroups defined by sexual orientation based on identity and behaviors and attraction to the same sex or opposite sex.

Results: Overall, 14.

Activation of the oxidative stress pathway by HIV-1 Vpr leads to induction of hypoxia-inducible factor 1alpha expression.

The detection of biomarkers of oxidative stress in brain tissue and cerebrospinal fluid of patients with human immunodeficiency virus, type 1 (HIV)-associated dementia indicates the involvement of stress pathways in the neuropathogenesis of AIDS. Although the biological importance of oxidative stress on events involved in AIDS neuropathogenesis and the HIV-1 proteins responsible for oxidative stress remain to be elucidated, our results point to the activation of hypoxia-inducible factor 1 (HIF-1) upon HIV-1 infection and its elevation in brain cells of AIDS patients with dementia. HIF-1 is a transcription factor that is responsive to oxygen.

Evidence for activation of the TGF-beta1 promoter by C/EBPbeta and its modulation by Smads.

The transforming growth factor-beta1 (TGF-beta1) is a cytokine involved in many biological events inlcuding immunosuppression, angiogenesis, cell growth, and apoptosis. Expression of TGF-beta1 at the transcriptional level is controlled by a series of ubiquitous and specialized factors whose activities can be modulated by a variety of signaling events. Here we demonstrate that activity of the TGF-beta1 promoter is increased by C/EBPbeta, a DNA-binding transcription factor whose activity can be influenced by several immunomodulators, in astrocytes and microglial cells.

Evidence for involvement of NFBP in processing of ribosomal RNA.

Ribosomal RNA (rRNA) in vertebrates is initially transcribed as a single 47S precursor which is modified by the addition of 2'-O-methyl ribose moieties, pseudouridines, and methyl groups, followed by cleavage at several sites to produce the mature 28S, 18S, and 5.8S rRNAs. Cleavage of the rRNA precursor to generate the 18S rRNA is mediated by a ribonucleoprotein (RNP) complex termed the processome containing U3, a box C/D small nucleolar RNA (snoRNA), and at least 28 cellular proteins.

Effects of JC virus infection on anti-apoptotic protein survivin in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system resulting from the productive infection of oligodendrocytes by the opportunistic polyomavirus JC virus (JCV). Apoptosis is a host defense mechanism to dispose of damaged cells; however, certain viruses have the ability to deregulate apoptotic pathways to complete their life cycles. One such pathway involves survivin, a member of the inhibitor of apoptosis family, which is abundantly expressed during development in proliferating tissues but should be absent in normal, terminally differentiated cells.

Interplay between NFBP and NF-kappaB modulates tat activation of the LTR.

Interplay of the HIV-1 regulatory protein, Tat, with several cellular factors plays an important role in transcriptional regulation of the viral promoter, the long terminal repeat (LTR). Special attention has been paid to NF-kappaB, a family of inducible transcription factors, which interact with a specific DNA motif within the LTR. Here, we report on the physical and functional interaction of NFBP, a recently identified protein that interacts with the P65 subunit of NF-kappaB, with HIV-1 Tat.

Cooperative interaction of C/EBP beta and Tat modulates MCP-1 gene transcription in astrocytes.

The chemoattractant protein 1 (MCP-1) is one of the most potent monocyte chemoattractants whose level is elevated during the course of AIDS dementia. Earlier studies showed that HIV-1 Tat protein is able to induce transcription of the MCP-1 promoter in astrocytic cells. Furthermore, the TGFbeta-1 signaling pathway through its regulatory proteins, Smads, modulates Tat activation of MCP-1.

Evidence for involvement of transforming growth factor beta1 signaling pathway in activation of JC virus in human immunodeficiency virus 1-associated progressive multifocal leukoencephalopathy.

Context: Progressive multifocal leukoencephalopathy is a fatal demyelinating disease of the central nervous system frequently seen in patients with impaired immune systems, particularly acquired immunodeficiency syndrome. JC virus (JCV), a human neurotropic polyomavirus, is the etiologic infectious agent of this disease.

Objective: The significantly higher incidence of progressive multifocal leukoencephalopathy in patients with acquired immunodeficiency syndrome than in patients with other immunosuppressive conditions suggests that molecular interactions between human immunodeficiency virus 1 and JCV, via the Tat protein, are responsible for the activation of the JCV enhancer/promoter and the development of progressive multifocal leukoencephalopathy.

Identification of a novel protein from glial cells based on its ability to interact with NF-kappaB subunits.

Nuclear factor kappaB (NF-kappaB) represents a family of inducible DNA-binding transcription factors whose activity is critical for expression of the HIV-1 genome in a broad range of cells. In addition to its interaction with the kappaB DNA sequence, the association of NF-kappaB subunits with other cellular proteins plays an important role in stimulation of HIV-1 gene transcription in astrocytic cells. Here, we utilized a yeast two-hybrid system to screen a cDNA library from a human astrocytic cell line and were able to isolate a partial cDNA belonging to a gene with an open reading frame of 1,871 amino acid residues which binds to both the p50 and p65 subunits of NF-kappaB.

Developmental expression of Wnt signaling factors in mouse brain.

The Wnt signaling pathway has been implicated in a variety of biological events inducing neurogenesis. In this study, we aim to investigate the expression pattern of various components of the Wnt pathway including b-catenin and its partners LEF-1/TCF-4, GSK-3beta and their nuclear target genes such as c-myc and cyclin D1 during mouse brain development. We performed a series of Western blot and immunohistochemistry of brain cortex, brainstem, and cerebellum which revealed differential accumulation of these proteins in different types of brain cells including neurons, astrocytes, and oligodendrocytes at different developmental stages.

Interaction between TGFbeta signaling proteins and C/EBP controls basal and Tat-mediated transcription of HIV-1 LTR in astrocytes.

Signal transduction pathways induced by cytokines can modulate the level of HIV-1 gene transcription and replication in a variety of cells including those from the central nervous system. Here, we investigated the effect of TGFbeta-1 signaling the factors, including Smads, on transcription of the viral LTR in human astrocytic cells. Ectopic expression of Smad-3 increased activity of the viral promoter, while its partner protein, Smad-4, caused a slight decrease in viral gene transcription.

Molecular biology and immunoregulation of human neurotropic JC virus in CNS.

The human polyomavirus, JC virus (JCV), provides an excellent model system to investigate the reciprocal interaction of the immune and nervous systems. Infection with JCV occurs during childhood and the virus remains in the latent state with no apparent clinical symptoms. However, under immunosuppressed conditions, the virus enters the lytic cycle and upon cytolytic destruction of glial cells, causes the fatal demyelinating disease of the central nervous system (CNS), named progressive multifocal leukoencephalopathy (PML).