HIV Infection Decreases Intracellular Nicotinamide Adenine Dinucleotide [NAD]

Murray, Michael F.; Nghiem, My Ngoc; Srinivasan, Alagarsamy

doi:10.1006/bbrc.1995.1945

Cited by 55 publications

(46 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have recently discovered that this NAD+ depletion is due to elevated poly-ADP-ribose polymerase activity (L. Vastag, unpublished work). The activation of poly-ADP-ribose polymerase has also been observed in HIV-1 and Sindbis Virus infected cells [42], [43], [44]. Understanding the significance of such observations requires further study.…”

Section: Discussionmentioning

confidence: 96%

Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism

et al. 2011

View full text Add to dashboard Cite

Viruses rely on the metabolic network of the host cell to provide energy and macromolecular precursors to fuel viral replication. Here we used mass spectrometry to examine the impact of two related herpesviruses, human cytomegalovirus (HCMV) and herpes simplex virus type-1 (HSV-1), on the metabolism of fibroblast and epithelial host cells. Each virus triggered strong metabolic changes that were conserved across different host cell types. The metabolic effects of the two viruses were, however, largely distinct. HCMV but not HSV-1 increased glycolytic flux. HCMV profoundly increased TCA compound levels and flow of two carbon units required for TCA cycle turning and fatty acid synthesis. HSV-1 increased anapleurotic influx to the TCA cycle through pyruvate carboxylase, feeding pyrimidine biosynthesis. Thus, these two related herpesviruses drive diverse host cells to execute distinct, virus-specific metabolic programs. Current drugs target nucleotide metabolism for treatment of both viruses. Although our results confirm that this is a robust target for HSV-1, therapeutic interventions at other points in metabolism might prove more effective for treatment of HCMV.

show abstract

Section: Discussionmentioning

confidence: 96%

Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism

et al. 2011

View full text Add to dashboard Cite

show abstract

“…4B), it suggests that the Rossmann fold may constitute only a part of the 3Ј-GS-RNA binding site in GAPDH. HPIV3 infection may also lead to a significant decrease in the intracellular concentration of NAD ϩ , as observed recently in human immunodeficiency virus, type I-infected cells (29) leading to inhibition of GAPDH activity with impairment of cellular functions. Thus, it remains to be determined whether HPIV3 may utilize some other activity of this cellular enzyme for its own replication while inhibiting glycolytic function of GAPDH.…”

Section: Discussionmentioning

confidence: 97%

Specific Interaction in Vitro and in Vivo of Glyceraldehyde-3-phosphate Dehydrogenase and LA Protein with Cis-acting RNAs of Human Parainfluenza Virus Type 3

De¹,

Gupta²,

Zhao³

et al. 1996

Journal of Biological Chemistry

109

View full text Add to dashboard Cite

Human parainfluenza virus type 3 (HPIV3) genome RNA is transcribed and replicated by the virus-encoded RNA-dependent RNA polymerase, and specific cellular proteins play a regulatory role in these processes. To search for cellular proteins potentially interacting with HPIV3 cis-acting regulatory RNAs, a gel mobility shift assay was used. Two cellular proteins specifically interacted with the viral cis-acting RNAs containing the genomic 3 -noncoding region and the plus-sense leader sequence region. Surprisingly, by biochemical and immunological analyses, one of the cellular proteins was identified as the key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The other protein was characterized as the autoantigen, LA protein. Both GAPDH and LA protein also interacted with the same cis-acting RNA sequences in vivo and were found to be associated with the HPIV3 ribonucleoprotein complex in the infected cells. By double immunofluorescent labeling, GAPDH was found to be co-localized with viral ribonucleoprotein in the perinuclear region. These observations strongly suggest that cellular GAPDH and LA Protein participate in the regulation of HPIV3 gene expression.The human parainfluenza virus type 3 (HPIV3), 1 belonging to the paramyxovirus family, is one of the major causes of pneumonia and bronchiolitis in infants (1). HPIV3 contains a negative strand RNA genome that is encapsidated by a nucleocapsid protein NP (68 kDa) and tightly associated with two RNA polymerase subunits, a large protein L (251 kDa) and a phosphoprotein P (90 kDa), to form the viral ribonucleoprotein (RNP) core (2, 3). The encapsidated genome RNA serves as a template for transcription to synthesize a leader RNA and six mRNAs as well as in replication to synthesize full-length genome RNA, both mediated by the viral RNA-dependent RNA polymerase. Recent studies demonstrate that participation of specific cellular proteins is critical for the regulation of gene expression of HPIV3 (4, 5). Protein kinase C-has been implicated in the phosphorylation of the virion-associated RNA polymerase subunit, the phosphoprotein P (5). Introduction of protein kinase C--specific peptide inhibitor in cultured cells abrogated HPIV3 replication providing strong evidence that protein kinase C-is involved in the HPIV3 life cycle (5). Another cellular protein, actin, was found to be required in transcription of purified viral RNP in vitro and was found to be involved in maintaining a moderately coiled structure of the RNP that appeared to facilitate transcription of the genome RNA by the RNA polymerase (4). The productive infection of HPIV3, thus, appears to require a close encounter between the viral genome and several cellular proteins. A detailed search of such putative cellular proteins and their characterization would lead to better understanding of their roles in the regulation of the intricate steps in viral gene expression.Sequence analysis of HPIV3 genome RNA reveals the presence of a sequence element at the 3Ј-end that serves as the binding site o...

show abstract

“…Schrauffstatter et al (1986) reported that DNA strand breaks, developed after H202-induced injury, activate PARP within macrophages and lymphocytes with a resulting loss of >80% of cellular NAD within 20-30 min. Human peripheral blood lymphocytes infected with human immunodeficiency virus have reportedly increased PARP activity and significantly decreased intracellular NAD levels (Murray et al, 1995). It has been suggested that the PARP-mediated depletion of intracellular NAD in the CNS seen in NMDA toxicity may contribute significantly to the death of neuronal cells (Zhang et al, 1994).…”

mentioning

confidence: 99%

Murine Glial Cells Regenerate NAD, After Peroxide‐Induced Depletion, Using Either Nicotinic Acid, Nicotinamide, or Quinolinic Acid as Substrates

Grant

Kapoor

1998

Journal of Neurochemistry

View full text Add to dashboard Cite

Abstract:The potential for regeneration of intracellular pyridine nucleotide levels from different precursors, after peroxide-induced NAD depletion, in cultured glial cells was investigated. Cultured murine glial cells showed a decrease in intracellular NAD levels of >40% after treatment with H 202 (100 pM). Removal of the H202 followed by a 2-h incubation did not result in NAD recovery in the absence of precursors. However, NAD levels increased significantly in these cells after the following substrate additions, at minimum effective concentrations of 1 mM for quinolinic acid (QUIN), 500 p~M for nicotinamide, and 2~uMfor nicotinic acid. The regeneration of significant amounts of NAD from nicotinic acid at doses 250 and 500 times lower than either nicotinamide or QUIN indicates a preferred route for NAD biosynthesis in glial cells in vitro, probably via nicotinic acid phosphoribosylation. Key Words: Glia-Nicotinic acid-Nicotinamide-Nicotinamide adenine dinucleotide-Peroxide-Quinolinic acid.

show abstract

HIV Infection Decreases Intracellular Nicotinamide Adenine Dinucleotide [NAD]

Cited by 55 publications

References 0 publications

Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism

Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism

Specific Interaction in Vitro and in Vivo of Glyceraldehyde-3-phosphate Dehydrogenase and LA Protein with Cis-acting RNAs of Human Parainfluenza Virus Type 3

Murine Glial Cells Regenerate NAD, After Peroxide‐Induced Depletion, Using Either Nicotinic Acid, Nicotinamide, or Quinolinic Acid as Substrates

Contact Info

Product

Resources

About