Hexamethylbisacetamide Remodels the Human Immunodeficiency Virus Type 1 (HIV-1) Promoter and Induces Tat-Independent HIV-1 Expression but Blunts Cell Activation

Klichko, Vladimir I.; Archin, Nancy M; Kaur, Rupinderjeet; Lehrman, Ginger; Margolis, David M.

doi:10.1128/jvi.80.9.4570-4579.2006

Cited by 40 publications

(40 citation statements)

References 79 publications

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“…Nonselective HDAC inhibition with potent agents such as TSA can induce HIV-1 expression in cell line models of latency (15,16,24). Furthermore, HDAC inhibitors induce viral expression in resting CD4 ϩ T cells obtained from aviremic, HIV-1-positive patients (1,27).…”

Section: Persistent Proviral Human Immunodeficiency Virus Type 1 (Hivmentioning

confidence: 99%

A Limited Group of Class I Histone Deacetylases Acts To Repress Human Immunodeficiency Virus Type 1 Expression

Keedy¹,

Archin²,

Gates

et al. 2009

J Virol

179

168

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Section: Persistent Proviral Human Immunodeficiency Virus Type 1 (Hivmentioning

confidence: 99%

A Limited Group of Class I Histone Deacetylases Acts To Repress Human Immunodeficiency Virus Type 1 Expression

Keedy¹,

Archin²,

Gates

et al. 2009

J Virol

179

168

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“…HMBA is a polar compound shown previously to enhance replication of HSV-1 via enhancing IE gene transcription and can promote the propagation of VP16-deficient HSV-1 clones [15]. The structure of HMBA resembles that of HDAC inhibitors but the compound itself does not inhibit histone deacetylase (HDAC) activity or induce histone hyperacetylation [16]. The exact mechanism by which HMBA exerts its activity on HSV gene transcription is unknown, while its overall effects on patterns of HSV gene expression have been deemed significant [17].…”

Section: Introductionmentioning

confidence: 99%

Hexamethylene bisacetamide leads to reduced helper virus‐free HSV‐1 amplicon expression titers via suppression of ICP0

Burris

Silva

Narrow

et al. 2007

The Journal of Gene Medicine

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The Herpes simplex virus (HSV)-derived amplicon vector has evolved into a promising gene transfer platform for widespread DNA delivery in gene replacement strategies and vaccine development given its ease of molecular manipulation, large transgene capacity, and transduction efficiencies of numerous cell types in vivo. The recent development of helper virus-free packaging methodologies bodes well for this vector system in its eventual implementation as a clinically viable therapeutic modality. For realization of clinical application, efforts have been made to enhance yields and quality of helper-free amplicon stocks. Hexamethylene bisacetamide (HMBA), a hybrid polar compound that exhibits stimulatory activity of HSV-1 immediate-early gene expression, has been employed as a standard reagent in helper virus-free packaging given its purported mode of action on virus gene expression kinetics. Unexpectedly, we have found that HMBA exhibits no titer-enhancing activity; in contrast, the compound enhances the proportion of amplicon virions that are non-expressive. Omission of HMBA during vector packaging led to a marked reduction in the ratios of vector genometransducing to transgene-expressing virions. This effect was neither packaging cell-specific nor amplicon promoter-dependent. Analysis of resultant vector stocks indicated amplicon genome replication/concatenation was unaffected, but the level of particle-associated ICP0 was reduced in stocks packaged in the presence of HMBA. Inclusion of a co-transfected, ICP0-expressing plasmid into the packaging process led to significant rescue of amplicon expression titers, indicating that regulation of ICP0 concentrations is critical for maintenance of the amplicon genome expressive state.

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“…The NF-B pathway is turned on by activating protein kinase C. Several drugs, such as TNF-␣ (16), prostratin (17), and bryostatin (18), are currently under investigation for treating HIV-1 latency through this mechanism. P-TEFb is activated by some small compounds to trigger its release from the inhibitory form in the 7SK small nuclear ribonucleoprotein complex, which allows more accessibility to HIV-1 Tat protein, such as hexamethylene bisacetamide (19) and disulfiram (20). However, most of these drugs are less potent when used individually in the in vitro resting CD4ϩ T cells or in vivo settings of clinical trials.…”

mentioning

confidence: 99%

FACT Proteins, SUPT16H and SSRP1, Are Transcriptional Suppressors of HIV-1 and HTLV-1 That Facilitate Viral Latency

Huang

Santoso

Power

et al. 2015

Journal of Biological Chemistry

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Background: FACT proteins SUPT16H and SSRP1 are identified as host factors that restrict HIV-1 replication. Results: Biochemical and genetic evidences that SUPT16H and SSRP1 affect HIV-1/HTLV-1 transcription and latency are provided. Conclusion: SUPT16H and SSRP1 suppress transcription of HIV-1/HTLV-1, and their presence may promote HIV-1 latency. Significance: Identification of host factors necessary for HIV-1 latency is critical, which may benefit the development of novel HIV-1 latency-reversing agents.

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Hexamethylbisacetamide Remodels the Human Immunodeficiency Virus Type 1 (HIV-1) Promoter and Induces Tat-Independent HIV-1 Expression but Blunts Cell Activation

Cited by 40 publications

References 79 publications

A Limited Group of Class I Histone Deacetylases Acts To Repress Human Immunodeficiency Virus Type 1 Expression

A Limited Group of Class I Histone Deacetylases Acts To Repress Human Immunodeficiency Virus Type 1 Expression

Hexamethylene bisacetamide leads to reduced helper virus‐free HSV‐1 amplicon expression titers via suppression of ICP0

FACT Proteins, SUPT16H and SSRP1, Are Transcriptional Suppressors of HIV-1 and HTLV-1 That Facilitate Viral Latency

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