Human immunodeficiency virus type 1 infection of the brain.

Atwood, Walter J.; Berger, Joseph R.; Kaderman, R; Tornatore, Carlo; Major, Eugene O.

doi:10.1128/cmr.6.4.339-366.1993

Cited by 3 publications

(3 citation statements)

References 195 publications

(257 reference statements)

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“…GRS probes were end labeled with y_32P by using T4 polynucleotide kinase and then gel purified. A 100,000-cpm level of labeled GRS probe was incubated with 5 Vig of nuclear extracts in a binding buffer containing 1.0 [ig of the nonspecific competitor poly(dI-dC), 5 mM dGTP, 12 mM HEPES (pH 7.9), 4 mM Tris (pH 7.5), 60 mM KCl, 5 mM MgCl2, and 0.8 mM dithiothreitol. The reaction mixture was incubated at 40C for 30 min to allow assembly of DNA-protein complexes.…”

Section: Methodsmentioning

confidence: 99%

Identification and Characterization of a Novel GGA/C-Binding Protein, GBP-i, That Is Rapidly Inducible by Cytokines

Raj

Khalili

1994

Molecular and Cellular Biology

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Immunosuppressive states with accompanying alterations in cytokine profiles have been postulated to play a vital role in the reactivation of viruses from latency. Cytokines regulate gene expression by activating transcription factors via well-characterized signal transduction pathways. In this study, we report the identification of a novel inducible protein, GBP-i, that binds to a double-stranded GGA/C-rich region of the transcriptional control region of the human papovavirus JC virus (JCV), specifically within the origin of viral DNA replication. GBP-i is distinct from previously characterized GC-box-binding proteins with respect to both its sequence specificity and its electrophoretic mobility on native and denaturing gels. GBP-i responds within 90 min to phorbol myristate acetate stimulation; however, unlike typical phorbol myristate acetate-inducible factors, this rapid induction is regulated primarily at the transcriptional level. Further, the induction of GBP-i appears to be widespread and mediated by many inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, gamma interferon, and transforming growth factor beta. Interestingly, the induced protein acts as a transcriptional repressor in its native context in the JCVL promoter. However, when its binding sequence is transposed to a heterologous promoter, GBP-i appears to function as a transcriptional activator. The data presented here suggest a role for GBP-i in cytokine-mediated induction of viral and cellular genes.

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Section: Methodsmentioning

confidence: 99%

Identification and Characterization of a Novel GGA/C-Binding Protein, GBP-i, That Is Rapidly Inducible by Cytokines

Raj

Khalili

1994

Molecular and Cellular Biology

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“…The relationship between HIV and psychosis is complex. Psychosis may occur as a consequence of HIV replication in the central nervous system (CNS) [3]; earlier studies in the 1990s report a high incidence of psychosis among people with HIV (PWH), with reported rates varying between 0.5 and 15% [4,5], and greater risk if HIV is left untreated [6]. Conversely, HIV risk may be increased among people living with psychosis [7].…”

Section: Introductionmentioning

confidence: 99%

A 20-year population-based study of all-cause and cause-specific mortality among people with concurrent HIV and psychotic disorders

Yazdani

Salters

Shen

et al. 2022

Aids

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Objective:We aimed to characterize mortality among people with HIV (PWH) and psychotic disorders (PWH/psychosis+) vs. PWH alone (PWH/psychosis−).Method:A population-based analysis of mortality in PWH (age ≥19) in British Columbia (BC) from April 1996 to March 2017 was conducted using data from the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) study. Deaths were identified from the Vital Statistics Data (classified as HIV vs. non-HIV causes). Mortality trends across all fiscal years were examined. Cox models assessed the hazard of psychotic disorders on mortality; possible differences between schizophrenia and nonschizophrenia types of psychotic disorders were also evaluated.Results:Among 13 410 PWH included in the analysis, 1572 (11.7%) met the case definition for at least one psychotic disorder. Over the study period, 3274 deaths (PWH/psychosis−: n = 2785, PWH/psychosis+: n = 489) occurred. A decline over time in all-cause mortality and HIV-related mortality was observed in both PWH/psychosis+ and PWH/psychosis− (P value <0.0001). A decline in non-HIV mortality was observed among PWH/psychosis− (P value = 0.003), but not PWH/psychosis+ (P value = 0.3). Nonschizophrenia psychotic disorders were associated with increased risk of mortality; adjusted hazard ratios with (95% confidence intervals): all-cause 1.75 (1.46–2.09), HIV-related 2.08 (1.60–2.69), non-HIV-related 1.45 (1.11–1.90). Similar associations between schizophrenia and mortality were not observed.Conclusion:People with co-occurring HIV and nonschizophrenia psychotic disorders experienced a significantly higher risk of mortality vs. PWH without any psychotic disorder. Implementing care according to syndemic models considering interactions between HIV and particularly episodic psychotic disorders could help manage mortality risk more effectively among PWH/psychosis+.

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“…HIV infection of the central nervous system (CNS) and the attendant AIDS-related dementia remains a major problem for people with AIDS . Although significant progress has been made in the discovery of new therapeutic approaches to the systemic treatment of HIV infection, a continuing effort is needed for the specific problem of CNS HIV infection 4a.…”

Section: Introductionmentioning

confidence: 99%

Lipophilic, Acid-Stable, Adenosine Deaminase-Activated Anti-HIV Prodrugs for Central Nervous System Delivery. 3. 6-Amino Prodrugs of 2‘-β-Fluoro-2‘,3‘-dideoxyinosine

et al. 1996

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A series of 6-substituted amino analogs of 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl) purines (F-ddN) has been synthesized and characterized with the objective of finding compounds which might be superior to existing drugs for the treatment of HIV in the central nervous system. These compounds are intended to be more lipophilic than the currently approved anti-HIV drugs for better blood-brain barrier penetration. Subsequent adenosine deaminase (ADA)-catalyzed hydrolysis of these prodrugs in the brain is expected to produce the anti-HIV agent, 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)hypoxanthine (F-ddI). The new compounds, synthesized from the corresponding 6-chloro analog, include F-ddN which contain methylamino, ethylamino, dimethylamino, hydroxylamino, methoxyamino, benzyloxyamino, hydrazino, and nitro substituents in the 6-position. The 6-nitro analog was isolated as an unexpected product during the preparation of the 6-chloro derivative. Among the analogs with anti-HIV activity, the ethylamino and dimethylamino compounds are ca. 100 times more lipophilic than ddI or F-ddI. As expected, 2'-fluoro substitution protects the compounds from acid-catalyzed glycosylic cleavage. Only the hydroxylamino and nitro analogs underwent any nonenzymatic hydrolysis at pH 1.0 or 7.4. This reaction, however, results in hydrolysis of the group in the 6-position rather than glycosylic bond cleavage. ADA catalyzes the hydrolysis of the 6-substituents at rates which vary from slightly slower (NO2, 1.7x) to much slower (NHEt, 5000x) than F-ddA. The 6-dimethylamino analog is the only compound which possesses anti-HIV activity (ED50 18 microM) without ADA hydrolysis. With the exception of the two inactive alkoxyamino compounds, the other prodrugs exhibited cellular protection in the HIV-1/PHA-PBM system with IC50 potencies of 7-40 microM.

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Human immunodeficiency virus type 1 infection of the brain.

Cited by 3 publications

References 195 publications

Identification and Characterization of a Novel GGA/C-Binding Protein, GBP-i, That Is Rapidly Inducible by Cytokines

Identification and Characterization of a Novel GGA/C-Binding Protein, GBP-i, That Is Rapidly Inducible by Cytokines

A 20-year population-based study of all-cause and cause-specific mortality among people with concurrent HIV and psychotic disorders

Lipophilic, Acid-Stable, Adenosine Deaminase-Activated Anti-HIV Prodrugs for Central Nervous System Delivery. 3. 6-Amino Prodrugs of 2‘-β-Fluoro-2‘,3‘-dideoxyinosine

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