HIV-1 in the Developing CNS: Developmental Differences in Gene Expression

Buzy, Jeanine M.; Lindstrom, Lynn; Zink, M. Christine; Clements, Janice E.

doi:10.1006/viro.1995.1352

Cited by 14 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have demonstrated that B elements within the HIV-LTR promoter are sensitive to neuronal NF-B activity in vitro (Rattner et al, 1993) and in vivo (Corboy et al, 1992;Buzy et al, 1995). To produce a reporter construct that would reflect endogenous NF-B activity in neurons, we generated an NF-B responsive minigene containing three tandem HIV-derived B binding element repeats placed proximal to a minimal promoter derived from SV40.…”

Section: Resultsmentioning

confidence: 99%

Constitutive Nuclear Factor-κB Activity Is Required for Central Neuron Survival

et al. 2002

View full text Add to dashboard Cite

The function of nuclear factor (NF)-kappaB within the developing and mature CNS is controversial. We have generated transgenic mice to reveal NF-kappaB transcriptional activity in vivo. As expected, constitutive NF-kappaB activity was observed within immune organs, and tumor necrosis factor-inducible NF-kappaB activity was present in mesenchymal cells. Intriguingly, NF-kappaB activity was also prominent in the CNS throughout development, especially within neocortex, olfactory bulbs, amygdala, and hippocampus. NF-kappaB in the CNS was restricted to neurons and blocked by overexpression of dominant-negative NF-kappaB-inducible kinase or the IkappaBalphaM super repressor. Blocking endogenous neuronal NF-kappaB activity in cortical neurons using recombinant adenovirus induced neuronal death, whereas induction of NF-kappaB activity increased levels of anti-apoptotic proteins and was strongly neuroprotective. Together, these data demonstrate a physiological role for NF-kappaB in maintaining survival of central neurons.

show abstract

Section: Resultsmentioning

confidence: 99%

Constitutive Nuclear Factor-κB Activity Is Required for Central Neuron Survival

et al. 2002

View full text Add to dashboard Cite

show abstract

“…In contrast, Kaposi's sarcoma and AIDS dementia complex are complications that are secondary to cofactors (human herpesvirus 8) or a consequence of a more direct viral effect (tropism for the central nervous system [CNS]) (38)(39)(40). The pathological basis for the development of renal disease has been enigmatic.…”

Section: Discussionmentioning

confidence: 99%

“…Recent work by Ray and coworkers has provided evidence that not only do renal cells become infected, but HIVAN patients appear to have viral isolates that have adapted to replication in renal cells (12). The evolution of HIV-1 strains with altered tropism has precedence in AIDS dementia (39,40). AIDS patients with dementia complex have macrophage tropic strains of HIV-1 that have adapted to replication in microglial cells through mutations in envelope as well as the LTR, allowing for viral gene expression in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression.

Bruggeman¹,

Dikman²,

Meng³

et al. 1997

J. Clin. Invest.

226

155

View full text Add to dashboard Cite

HIV-associated nephropathy (HIVAN) is a progressive glomerular and tubular disease that is increasingly common in AIDS patients and one of the leading causes of end stage renal disease in African Americans. A major unresolved issue in the pathogenesis of HIVAN is whether the kidney disease is due to renal cell infection or a "bystander" phenomenon mediated by systemically dysregulated cytokines. To address this issue, we have used two different experimental approaches and an HIV-1 transgenic mouse line that develops a progressive renal disease histologically similar to HIVAN in humans. In the murine model, kidney tissue expresses the transgene and in heterozygous adults, renal disease develops shortly thereafter. We demonstrate by terminal deoxynucleotide transferase-mediated dUTP-biotin nick-end labeling assay that similar to the disease in humans, apoptosis of renal tubular epithelial cells is a component of the molecular pathogenesis. To determine whether apoptosis is due to transgene expression or environmental factors, we treated fetal kidney explants (normal and transgenic) with UV light to induce transgene expression. Apoptosis occurred in transgenic but not normal littermates after stimulation of transgene expression. To confirm a direct effect of HIV expression on the production of HIVAN, we transplanted kidneys between normal and transgenic mice. HIVAN developed in transgenic kidneys transplanted into nontransgenic littermates. Normal kidneys remained disease free when transplanted into transgenic littermates. Thus, the renal disease in the murine model is intrinsic to the kidney. Using two different experimental approaches, we demonstrate a direct effect of transgene expression on the development of HIVAN in the mouse. These studies suggest that in humans, a direct effect of HIV-1 expression is likely the essential cause of HIVAN, rather than an indirect effect of cytokine dysregulation. ( J. Clin. Invest. 1997. 100:84-92.)

show abstract

“…Besides differences in envelope sequences of the virus that influence the occurrence of nervous system disease (9), the LTR region is also able to contribute to HIV-1 cell type-specific expression. This was demonstrated by transgenic mouse studies which revealed that the LTR of neurotropic HIV-1 strains JR-FL and JR-CSF directs gene expression in CNS neurons (10,11); in contrast, the lymphotropic LAI strain was unable to direct gene expression in the CNS of transgenic mice (12,13). These transgenic data strongly suggest the importance of cellular transcription factors present in brain cells, different from those in non neural cells.…”

mentioning

confidence: 96%

Chicken Ovalbumin Upstream Promoter Transcription Factor, a Transcriptional Activator of HIV-1 Gene Expression in Human Brain Cells

Sawaya

Rohr

Aunis

et al. 1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

Viral infection of the central nervous system by the human immunodeficiency virus type 1 leads to a wide range of neuropathological disorders. However, the molecular mechanisms governing transcription of the human immunodeficiency virus type 1 genome in brain remain unclear. We have recently established that in brain cells, proteins belonging to the steroid/thyroid/retinoic acid receptor family bind to the -352 to -320 region of the long terminal repeat (LTR). Here, by supershift experiments, we have identified chicken ovalbumin upstream promoter transcription factor (COUP-TF), an orphan member of this nuclear receptor family, as one of the major proteins interacting with this LTR site. Cotransfection studies revealed that COUP-TF is able to dramatically activate LTR-directed gene transcription in human oligodendroglioma but not in astrocytoma cells. This activation occurs through two mechanisms, depending on the LTR sequence. Moreover, in neuronal cells COUP-TF and dopamine, a catecholamine neurotransmitter, enhance LTR-directed transcription by acting on the proximal LTR region. These results reveal the importance of COUP-TF and the dopamine signaling pathway as activators of human immunodeficiency virus type 1 gene expression in brain.

show abstract

HIV-1 in the Developing CNS: Developmental Differences in Gene Expression

Cited by 14 publications

References 0 publications

Constitutive Nuclear Factor-κB Activity Is Required for Central Neuron Survival

Constitutive Nuclear Factor-κB Activity Is Required for Central Neuron Survival

Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression.

Chicken Ovalbumin Upstream Promoter Transcription Factor, a Transcriptional Activator of HIV-1 Gene Expression in Human Brain Cells

Contact Info

Product

Resources

About